FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Lowenstein, E AF Lowenstein, E TI Cardiac anesthesiology, professionalism and ethics: A microcosm of anesthesiology and medicine SO ANESTHESIA AND ANALGESIA LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-of-Cardiolovascular-Anesthesiologists CY APR, 2003 CL Miami Beach, FL SP Soc Cardiovascular Anesthesiologists ID MYOCARDIAL-INFARCTION; SURGERY; SOCIETY; LEAD; CARE AB The granting of professional status to medicine by society at large entails obligations by physicians. Those physicians in the young subspecialty of cardiac anesthesiology have fulfilled these obligations by developing a body of scientific and clinical knowledge and the technical bases to increase survival and decrease morbidity of patients with heart disease undergoing either cardiac or noncardiac surgery. Furthermore, they have contributed effectively to the broad practice of medicine. However, a strong argument can be made that these contributions, though benefiting many individual patients, do not by themselves completely fulfill our obligations. The concept of Civic Professionalism states that our moral responsibilities as physicians must be expanded beyond our immediate patients. Physicians have the obligation to use their knowledge and influence to promote the common good. The Universal Declaration of Human Rights includes access to health care as a basic tenet. The present health care system of the United States excludes many people. Thus, cardiac anesthesiologists have a moral obligation to actively advocate for universal access to health care until it is achieved. Doing so will make the specialty of cardiac anesthesiology an example to the entire profession of medicine. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Med Eth, Boston, MA 02114 USA. RP Lowenstein, E (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Clin 3,55 Fruit St, Boston, MA 02114 USA. EM elowenstein1@partners.org NR 37 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD APR PY 2004 VL 98 IS 4 BP 927 EP 934 DI 10.1213/01.ANE.0000105870.71753.FA PG 8 WC Anesthesiology SC Anesthesiology GA 807HD UT WOS:000220491700009 PM 15041574 ER PT J AU Lowenstein, E AF Lowenstein, E TI The birth of opioid anesthesia SO ANESTHESIOLOGY LA English DT Editorial Material ID INTRAVENOUS MORPHINE; FENTANYL; SURGERY; OXYGEN C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Lowenstein, E (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care Med, 55 Fruit St, Boston, MA 02114 USA. EM elowenstein1@partners.org OI Yang, Shuman/0000-0002-9638-0890 NR 10 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2004 VL 100 IS 4 BP 1013 EP 1015 DI 10.1097/00000542-200404000-00036 PG 3 WC Anesthesiology SC Anesthesiology GA 806LZ UT WOS:000220436700035 PM 15087641 ER PT J AU Phipatanakul, W Cronin, B Wood, RA Eggleston, PA Shih, MC Song, L Tachdjian, R Oettgen, HC AF Phipatanakul, W Cronin, B Wood, RA Eggleston, PA Shih, MC Song, L Tachdjian, R Oettgen, HC TI Effect of environmental intervention on mouse allergen levels in homes of inner-city Boston children with asthma SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID COCKROACH ALLERGEN; SODIUM-HYPOCHLORITE; DUST MITE; EXPOSURE; EXTERMINATION; MORBIDITY; REMOVAL; CAT AB Background: Recent studies have suggested that mouse allergen exposure and sensitization are common in urban children with asthma. The effectiveness of environmental intervention in reducing mouse allergen exposure has not been established. Objective: To evaluate whether environmental intervention of mouse extermination and cleaning results in a reduction in mouse allergen levels. Methods: Eighteen homes of children with positive mouse allergen skin test results and at least mild persistent asthma in urban Boston, MA, with evidence of mouse infestation or exposure were randomized in a 2:1 ratio (12 intervention and 6 control homes). The intervention homes received an integrated pest management intervention, which consisted of filling holes with copper mesh, vacuuming and cleaning, and using low-toxicity pesticides and traps. Dust samples were collected and analyzed for major mouse allergen (Mus m 1) and cockroach allergen (Bla a 1) at baseline and 1, 3, and 5 months after the intervention was started and compared with control homes. Results: Mouse allergen levels were significantly decreased compared with control homes by the end of the intervention period at month 5 in the kitchen and bedroom (kitchen intervention, 78.8% reduction; control, 319% increase; P = .02; bedroom intervention, 77.3% reduction; control, 358% increase; P < .01; and living room intervention, 67.6% reduction; control, 32% reduction; P = .07). Conclusions: Mouse allergen levels were significantly reduced during a 5-month period using an integrated pest management intervention. C1 Harvard Univ, Childrens Hosp, Sch Med,Dept Pediat, Div Allergy & Immunol, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Div Allergy & Immunol, Baltimore, MD 21205 USA. Harvard Univ, Childrens Hosp, Clin Res Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Phipatanakul, W (reprint author), Harvard Univ, Childrens Hosp, Sch Med,Dept Pediat, Div Allergy & Immunol, Boston, MA 02115 USA. EM wanda.phipatanakul@childrens.harvard.edu FU NIAID NIH HHS [K-23 AI054972, K23 AI054972] NR 17 TC 62 Z9 64 U1 1 U2 3 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD APR PY 2004 VL 92 IS 4 BP 420 EP 425 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 812ZI UT WOS:000220877000006 PM 15104193 ER PT J AU Herbert, MR Ziegler, DA Makris, N Filipek, PA Kemper, TL Normandin, JJ Sanders, HA Kennedy, DN Caviness, VS AF Herbert, MR Ziegler, DA Makris, N Filipek, PA Kemper, TL Normandin, JJ Sanders, HA Kennedy, DN Caviness, VS TI Localization of white matter volume increase in autism and developmental language disorder SO ANNALS OF NEUROLOGY LA English DT Article ID CORPUS-CALLOSUM SIZE; TOPOGRAPHIC PARCELLATION; HEAD CIRCUMFERENCE; CEREBRAL-CORTEX; GROWTH-PATTERNS; HUMAN BRAIN; CHILDREN; MRI; IMPAIRMENT; AGE AB Increased brain volume in autism appears to be driven mainly by an unexplained white matter enlargement, and we have reported a similar phenomenon in developmental language disorder (DLD). Localization of this enlargement would strongly guide research into its cause, tissue basis, and functional implications. We utilized a white matter parcellation technique that divides cerebral white matter into an outer zone containing the radiate compartment and an inner zone containing sagittal and bridging system compartments. In both high-functioning autism and DLD, enlargement localized to the radiate white matter (all lobes in autism, all but parietal in DLD), whereas inner zone white matter compartments showed no volume differences from controls. Furthermore, in both autism and DLD, later or longer-myelinating regions showed greater volume increases over controls. Neither group showed cerebral cortex, corpus callosum, or internal capsule volume differences from control. Radiate white matter myelinates later than deep white matter; this pattern of enlargement thus is consistent with striking postnatal head circumference percentile increases reported in autism. These findings suggest an ongoing postnatal process in both autism and DLD that is probably intrinsic to white matter, that primarily affects intrahemispheric and corticocortical connections, and that places these two disorders on the same spectrum. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Morphometr Anal, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Cambridge, MA 02138 USA. Univ Calif Irvine, Coll Med, Dept Pediat, Irvine, CA 92717 USA. Univ Calif Irvine, Coll Med, Dept Neurol, Irvine, CA 92717 USA. Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02215 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Herbert, MR (reprint author), Ctr Morphometr Anal, 149 13th St,Room 6012, Charlestown, MA 02129 USA. EM mherbert1@partners.org RI Kennedy, David/H-3627-2012 FU NIDA NIH HHS [DA09467, DA34189]; NINDS NIH HHS [NS20489, NS02126, NS27950, NS34189] NR 48 TC 364 Z9 374 U1 1 U2 17 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2004 VL 55 IS 4 BP 530 EP 540 DI 10.1002/ana.20032 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 806ME UT WOS:000220437200010 PM 15048892 ER PT J AU Schmahmann, JD Rosene, DL Pandya, DN AF Schmahmann, JD Rosene, DL Pandya, DN TI Ataxia after pontine stroke: Insights from pontocerebellar fibers in monkey SO ANNALS OF NEUROLOGY LA English DT Article ID RHESUS-MONKEY; BRAIN-STEM; PROJECTIONS; HEMIPARESIS; ORGANIZATION; CORTICES AB Basis pontis lacunes cause contralateral but rarely ipsilateral ataxia. We explored this phenomenon with isotope tract tracing in the rhesus monkey. Labeled pontocerebellar fibers cross midline and disperse widely in the opposite hemipons before coalescing in the brachium pontis. This anatomical arrangement suggests that small pontine strokes spare sufficient decussating pontocerebellar fibers to prevent ipsilateral dysmetria, and that ipsilateral dysmetria after large pontine stroke represents a disconnection syndrome. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol, VBK 915,Fruit St, Boston, MA 02114 USA. EM jschmahmann@partners.org RI Rosene, Douglas/G-1973-2015; OI Rosene, Douglas/0000-0001-8719-1441 NR 20 TC 18 Z9 18 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2004 VL 55 IS 4 BP 585 EP 589 DI 10.1002/ana.20060 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 806ME UT WOS:000220437200018 PM 15048900 ER PT J AU Zeitels, SM Franco, RA Dailey, SH Burns, JA Hillman, RE Anderson, RR AF Zeitels, SM Franco, RA Dailey, SH Burns, JA Hillman, RE Anderson, RR TI Office-based treatment of glottal dysplasia and papillomatosis with the 585-nm pulsed dye laser and local anesthesia SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Laryngological-Association CY MAY 02-03, 2003 CL NASHVILLE, TN SP Amer Laryngol Assoc DE dysphonia; dysplasia; glottis; hoarseness; keratosis; laryngoscopy; papillomatosis; pulsed dye laser; vocal cord; vocal fold ID LARYNGEAL PAPILLOMAS; INITIAL EXPERIENCE; SCARS; ENDOSCOPE AB Treatment of galottal papillomatosis and dysplasia was mirror-guided and performed in surgeons' offices in the 19th century. It migrated to the operating room in the 20th century to accommodate direct laryngoscopic surgery, which required assistants to administer anesthesia and procedural support. Presently, the primary treatment goals, which are disease regression and voice restoration or maintenance. are tempered by the morbidity of general anesthesia and potential treatment-induced vocal deterioration. In fact, general anesthesia has been appropriately considered to be an acceptable source of morbidity for the promise of a precise procedure, which usually ensures airway safety and an optimal vocal outcome. However, patients with recurrent glottal papillomatosis and keratosis with dysplasia are typically monitored with various degrees of watchful waiting until there is a subjective judgment (on the part of the patient and surgeon) that the disease is more of a liability than is the procedure to treat it. Innovations in the 585-nm pulsed dye laser delivery system have allowed for its use in the clinic with local anesthesia through the working channel of a flexible fiberoptic laryngoscope. A prospective assessment was done on 51 patients in 82 cases of recurrent glottal papillomatosis (30) and dysplasia (52). All individuals had previously undergone microlaryngoscopic management with histopathologic evaluation. Five procedures could not be completed because of impaired exposure (2) or discomfort (3). Of those patients who could be treated, there was at least a 50% disease involution in 68 of 77 cases (88%) and 25% to 50% disease regression in the remaining 9 (12%). Patient self-assessment of the voice revealed that 34 of 77 were improved, 39 were unchanged, 4 were slightly worse, and none were substantially worse. These data confirm that diseased mucosa can be normalized without resection or substantial loss of vocal function. The putative mechanisms, which vary according to the fluence (energy) delivered by the laser, are photoangiolysis of sublesional microcirculation, denaturing of epithelial basement membrane linking proteins, and cellular destruction. Furthermore, this relatively safe, effective technique allowed for treatment of many patients (in a clinic setting) in whom classic surgery-related morbidity would have often delayed intervention. C1 Massachusetts Eye & Ear Infirm, Div Laryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Voice & Speech Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Dermatol, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Div Otolaryngol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02115 USA. RP Zeitels, SM (reprint author), Massachusetts Eye & Ear Infirm, Div Laryngol, Boston, MA 02114 USA. NR 47 TC 63 Z9 64 U1 1 U2 3 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 APR PY 2004 VL 113 IS 4 BP 265 EP 276 PG 12 WC Otorhinolaryngology SC Otorhinolaryngology GA 811FK UT WOS:000220757600003 PM 15112968 ER PT J AU Thatte, HS Rhee, JH Zagarins, SE Treanor, PR Birjiniuk, V Crittenden, MD Khuri, SF AF Thatte, HS Rhee, JH Zagarins, SE Treanor, PR Birjiniuk, V Crittenden, MD Khuri, SF TI Acidosis-induced apoptosis in human and porcine heart SO ANNALS OF THORACIC SURGERY LA English DT Article ID FAILURE; CASPASE-3; MYOCYTES AB Background. Acidosis-mediated injury to cardiac myocytes during surgery may lead to progressive heart failure. The nature of this injury, although not well defined, may be caused by induction of apoptosis in cardiac myocytes. We applied fluorescence imaging and biochemical techniques to assess apoptosis in cardiac myocytes excised from human patients and porcine subjects maintained on cardiopulmonary bypass to demonstrate the relationship between acidosis and apoptosis. Methods. Multiphoton microscopy was used to image fluorescence signals generated in myocytes deep within atrial and ventricular biopsies for identification of apoptotic changes. The biopsies, obtained during cardiac surgery, were subjected to ex vivo or in vivo acidosis. Proapoptotic markers such as exposure of phosphatidyl serine, cytochrome c, apoptotic protease-activating factor-1, and caspase-3 were identified using fluorescence-based imaging and biochemical assays. Results. Within 30 minutes of storage in low pH (<7) buffers, apoptosis was detected in human atrial samples, the severity of which correlated well with low pH. Apoptosis was also detected in atrial and ventricular biopsy samples obtained from three porcine subjects maintained on cardiopulmonary bypass and undergoing 110 minutes of aortic cross-clamp and 10 minutes of reperfusion, in which the cardiac pH was 6.36, 7.14, and 7.48. The apoptosis level detected in postacidotic reperfused cardiac tissue was pH dependent and approximately threefold greater than the precross-clamp levels. Conclusions. Using fluorescence multiphoton microscopy and biochemical techniques we have assessed a direct correlation between low pH and induction of apoptosis in cardiac samples obtained both from human patients undergoing cardiac surgery and porcine subjects maintained on cardiopulmonary bypass simulating cardiac surgery. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, VA Boston Healthcare Syst,Dept Surg, Boston, MA USA. RP Khuri, SF (reprint author), VA Boston Healthcare Syst, Dept Surg, MC 112, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM shukri.khuri@med.va.gov NR 25 TC 34 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD APR PY 2004 VL 77 IS 4 BP 1376 EP 1383 DI 10.1016/j.athoracsur.2003.07.047 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 807YA UT WOS:000220535600052 PM 15063270 ER PT J AU Pignon, JP Syz, N Posner, M Olivares, R Le Lann, L Yver, A Dunant, A Lewin, F Dalley, DN Paccagnella, A Taylor, SG Domenge, C Bourhis, J Mazumdar, M AF Pignon, JP Syz, N Posner, M Olivares, R Le Lann, L Yver, A Dunant, A Lewin, F Dalley, DN Paccagnella, A Taylor, SG Domenge, C Bourhis, J Mazumdar, M TI Adjusting for patient selection suggests the addition of docetaxel to 5-fluorouracil-cisplatin induction therapy may offer survival benefit in squamous cell cancer of the head and neck SO ANTI-CANCER DRUGS LA English DT Article DE cisplatin; docetaxel; head and neck cancer; pooled analysis ID PHASE-I/II TRIAL; NEOADJUVANT CHEMOTHERAPY; CLINICAL-TRIALS; ACTIVE-DRUG; II TRIAL; CARCINOMA; CISPLATIN; FLUOROURACIL; LEUCOVORIN; CARBOPLATIN AB When induction chemotherapy is used in locally advanced squamous cell cancer of the head and neck (SCCHN), patients often receive cisplatin-5-fluorouracil (PF) followed by radical loco-regional therapy. Phase II studies of docetaxel-cisplatin-5-fluorouracil (TPF) induction therapy, with or without leucovorin (L), have achieved high survival rates versus those reported in phase III PF trials. However, the distribution of prognostic factors may vary between phase II and phase III study populations, making the extrapolation of phase II TPF/L results to phase III PF populations difficult This study used a patient selection standardization method and Cox model to adjust for potential selection bias. Thus, the survival benefit from adding docetaxel into PF induction regimens in SCCHN could be more accurately assessed. The TPF/L dataset comprised 195 patients from six phase II trials. The PF dataset of 585 patients was derived from five large randomized trials included in the Meta-Analysis of Chemotherapy in Head and Neck Cancer (MACH-NC) database. TPF/L and PF datasets differed significantly concerning the distribution of several prognostic factors. Adjusting for these differences, the relative risk of death in the PF versus TPF/L datasets was 1.85 (95% confidence interval 1.37-2.49), corresponding to a 20% 2-year survival benefit (p < 0.0001). Sensitivity analyses confirmed that this improved 2-year survival rate of TPF/L over PF was robust, irrespective of the distribution of studied prognostic factors between treatment datasets. We conclude that this improved survival might be due either to docetaxel's pharmacologic effect or to uncontrolled prognostic factors. (C) 2004 Lippincott Williams Wilkins. C1 Inst Gustave Roussy, Unit Biostat & Epidemiol, F-94805 Villejuif, France. Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. Aventis Pharma, Bridgewater, NJ USA. Huddinge Univ Hosp, Karolinska Inst, Dept Oncol, Stockholm, Sweden. St Vincents Hosp, Dept Med Oncol, Sydney, NSW 2010, Australia. Osped S Giovanni & Paolo, Dept Med Oncol, Venice, Italy. Illinois Masonic Med Ctr, Dept Oncol, Chicago, IL 60657 USA. Inst Gustave Roussy, Dept Head & Neck Surg, F-94805 Villejuif, France. Inst Gustave Roussy, Dept Radiotherapy, F-94805 Villejuif, France. Mem Sloan Kettering Canc Ctr, Div Epidemiol & Biostat, New York, NY 10021 USA. RP Pignon, JP (reprint author), Inst Gustave Roussy, Unit Biostat & Epidemiol, Rue Camille Desmoulins, F-94805 Villejuif, France. EM jppignon@igr.fr NR 32 TC 43 Z9 45 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD APR PY 2004 VL 15 IS 4 BP 331 EP 340 DI 10.1097/00001813-200404000-00004 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 814VF UT WOS:000221001500004 PM 15057136 ER PT J AU Wang, MG Sahm, DF Jacoby, GA Hooper, DC AF Wang, MG Sahm, DF Jacoby, GA Hooper, DC TI Emerging plasmid-mediated quinolone resistance associated with the qnr gene in Klebsiella pneumoniae clinical isolates in the United States SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID SPECTRUM BETA-LACTAMASE; ESCHERICHIA-COLI; EPIDEMIOLOGY; DNA AB Although quinolone resistance commonly results from chromosomal mutation, recent studies indicate that such resistance can also be transferred on plasmids carrying the gene responsible, qnr. One hundred ten ciprofloxacin-resistant clinical isolates of Klebsiella pneumoniae and Escherichia coli from the United States were screened for the qnr gene by PCR and Southern hybridization of plasmid DNA. Conjugation experiments were done with azide-resistant E. coli J53 as the recipient and selection with azide and sulfonamide, a resistance frequently linked to qnr. EcoRI and BamHI digests of qnr-hybridizing plasmids were subjected to electrophoresis on agarose gels and probed with qnr by Southern hybridization. qnr was detected in 8 (11.1%) of 72 K. pneumoniae strains. These eight positive strains were from six states in the United States. qnr was not found in any of the 38 E. coli strains tested. Quinolone resistance was transferred from seven of the eight probe-positive strains. Transconjugants with qnr-hybridizing plasmids had 32-fold increases in ciprofloxacin MICs relative to E. coli J53. For all eight strains, the sequence of qnr was identical to that originally reported. By size and restriction digests, four plasmids were related to the first-reported plasmid, pMG252, and three were different. Five new qnr plasmids encoded FOX-5 beta-lactamase, as did pMG252, but two others produced SRV-7 extended-spectrum beta-lactamase. Transferable plasmid-mediated quinolone resistance associated with qnr is now widely distributed in quinolone-resistant clinical strains of K. pneumoniae in the United States. Plasmid-determined quinolone resistance contributes to the increasing quinolone resistance of K. pneumoniae isolates and to the linkage previously observed between resistance to quinolones and the latest beta-lactam antibiotics. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Fudan Univ, Huashan Hosp, Inst Antiobiot, Shanghai 200040, Peoples R China. Focus Technol, Herndon, VA 20171 USA. Lahey Clin Fdn, Dept Infect Dis, Burlington, MA 01805 USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org OI Wang, Minggui/0000-0001-7682-5859 FU NIAID NIH HHS [R01 AI043312, R01 AI057576, AI43312] NR 20 TC 157 Z9 199 U1 3 U2 9 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 APR PY 2004 VL 48 IS 4 BP 1295 EP 1299 DI 10.1128/AAC.48.4.1295-1299.2004 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 809TI UT WOS:000220658600029 PM 15047532 ER PT J AU Wang, MG Sahm, DF Jacoby, GA Zhang, YY Hooper, DC AF Wang, MG Sahm, DF Jacoby, GA Zhang, YY Hooper, DC TI Activities of newer quinolones against Escherichia coli and Klebsiella pneumoniae containing the plasmid-mediated quinolone resistance determinant qnr SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID FLUOROQUINOLONES AB Seventeen qnr-containing transconjugants were constructed with azide-resistant Escherichia coli J53 as the recipient, and the MICs of 12 quinolones were tested by agar dilution methods. Sitafloxacin, BAYy3118, and premafloxacin had higher activity in vitro than ciprofloxacin against transconjugants and donors containing qnr. The donors had higher quinolone MICs than the transconjugants. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Fudan Univ, Huashan Hosp, Inst Antibiot, Shanghai 200040, Peoples R China. Focus Technol, Herndon, VA 20171 USA. Lahey Clin Fdn, Dept Infect Dis, Burlington, MA 01805 USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org OI Wang, Minggui/0000-0001-7682-5859 FU NIAID NIH HHS [AI43312, R01 AI043312, R01 AI057576] NR 11 TC 31 Z9 37 U1 2 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 2004 VL 48 IS 4 BP 1400 EP 1401 DI 10.1128/AAC.48.4.1400-1401.2004 PG 2 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 809TI UT WOS:000220658600049 PM 15047552 ER PT J AU Trehan, M Taylor, CR AF Trehan, M Taylor, CR TI Low-dose excimer 308-nm laser for the treatment of oral lichen planus SO ARCHIVES OF DERMATOLOGY LA English DT Article ID HEPATITIS-C VIRUS; UV-B PHOTOTHERAPY; TOPICAL TACROLIMUS; PARANEOPLASTIC PEMPHIGUS; CLINICAL-FEATURES; DRAMATIC RESPONSE; OPEN TRIAL; PSORIASIS; PHOTOCHEMOTHERAPY; MANAGEMENT AB Background: Lichen planus is a difficult-to-treat chronic inflammatory disorder that affects mucous membranes, causing inanition, halitosis, and dyspareunia. Objective: To evaluate the novel use of low-dose 308-nm excimer laser radiation for the treatment of symptomatic oral lichen planus (OLP). Design: A single-center, before-after trial. Setting: Academic clinical research center Patients: Nine patients with symptomatic, biopsy-proven OLP, unresponsive to conventional therapies, were recruited from the dermatology clinics of the Massachusetts General Hospital in Boston. Eight participants completed the entire study, and 1, despite early improvement, did not complete the study because of hospitalization for an unrelated reason. Intervention: With a narrow, fiberoptic handpiece to target precisely only diseased sites, 308-nm excimer laser radiation was delivered at an initial dose of 100 mJ/cm(2) once a week. Main Outcome Measure: A visual analog scale was used to grade subjective disease severity. Clinical improvement was graded in quartiles as follows: poor (<25%), fair (25%-50%), good (51%-75%), and excellent (>75%). Follow-up visits occurred for up to 18 months. A paired t test was performed to evaluate efficacy of treatment. Results: Treatments were painless and well tolerated. Five patients demonstrated overall excellent clinical and subjective improvement after 7 treatments. Two participants with nonerosive OLP were deemed fair responders. The only poor responder in the study also had chronic active hepatitis C infection. Overall improvement was statistically significant (P<.05), and for the responders, remission times ranged from 2 to 17 months. Conclusion: Low-dose treatment with the excimer 308-nm laser can be very effective in treating symptomatic and especially erosive OLP, an otherwise notoriously difficult-to-control disease. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Dermatol, Wellman Labs Photomed,Gange Photomed Res Ctr, Boston, MA 02114 USA. RP Trehan, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Dermatol, Wellman Labs Photomed,Gange Photomed Res Ctr, 55 Fruit St,Bartlett 622, Boston, MA 02114 USA. NR 56 TC 46 Z9 49 U1 0 U2 3 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 APR PY 2004 VL 140 IS 4 BP 415 EP 420 DI 10.1001/archderm.140.4.415 PG 6 WC Dermatology SC Dermatology GA 922BU UT WOS:000228811600004 PM 15096369 ER PT J AU Wells, K Sherbourne, C Schoenbaum, M Ettner, S Duan, N Miranda, J Unutzer, J Rubenstein, L AF Wells, K Sherbourne, C Schoenbaum, M Ettner, S Duan, N Miranda, J Unutzer, J Rubenstein, L TI Five-year impact of quality improvement for depression - Results of a group-level randomized controlled trial SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID PRIMARY-CARE PATIENTS; MANAGED PRIMARY-CARE; COST-EFFECTIVENESS; COLLABORATIVE MANAGEMENT; HEALTH-CARE; AFRICAN-AMERICAN; CHRONIC ILLNESS; IMPROVING CARE; UNITED-STATES; RACE AB Background: Quality improvement (QI) programs for depressed primary care patients can improve health outcomes for 6 to 28 months; effects for longer than 28 months are unknown. Objective: To assess how QI for depression affects health outcomes, quality of care, and health outcome disparities at 57-month follow-up. Design: A group-level randomized controlled trial. Setting: Forty-six primary care practices in 6 managed care organizations. Patients: Of 1356 primary care patients who screened positive for depression and enrolled in the trial, 991 (73%, including 451 Latinos and African Americans) completed 57-month telephone follow-up. Interventions: Clinics were randomly assigned to usual care or to I of 2 QI programs supporting QI teams, provider training, nurse assessment, and patient education, plus resources to support medication management (QI-meds) or psychotherapy (QI-therapy) for 6 to 12 months. Main Outcome Measures: Probable depressive disorder in the previous 6 months, mental health-related quality of life in the previous 30 days, primary care or mental health specialty visits, counseling or antidepressant medications in the previous 6 months, and unmet need, defined as depressed but not receiving appropriate care. Results: Combined QI-meds and QI-therapy, relative to usual care, reduced the percentage of participants with probable disorder at 5 years by 6.6 percentage points (P=.04). QI-therapy improved health outcomes and reduced unmet need for appropriate care among Latinos and African Americans combined but provided few long-term benefits among whites, reducing outcome disparities related to usual care (P=.04 for QI-ethnicity interaction for probable depressive disorder). Conclusions: Programs for QI for depressed primary care patients implemented by managed care practices can improve health outcomes 5 years after implementation and reduce health outcome disparities by markedly improving health outcomes and unmet need for appropriate care among Latinos and African Americans relative to whites; thus, equity was improved in the long run. C1 RAND Corp, Hlth Program, Santa Monica, CA 90407 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Biobehav Serv, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Hlth Serv Res Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Ctr Community Hlth, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Dept Med, Div Gen Internal Med & Hlth Serv Res, Sepulveda, CA USA. RP Wells, K (reprint author), RAND Corp, Hlth Program, 1700 Main St, Santa Monica, CA 90407 USA. EM kwells@ucla.edu FU AHRQ HHS [R01-HS08349]; NIMH NIH HHS [P50MH54623, R01MH57992] NR 64 TC 139 Z9 139 U1 1 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD APR PY 2004 VL 61 IS 4 BP 378 EP 386 DI 10.1001/archpsyc.61.4.378 PG 9 WC Psychiatry SC Psychiatry GA 811CD UT WOS:000220749100007 PM 15066896 ER PT J AU DeAngelis, MM Lane, AM Shah, CP Ott, J Dryja, TP Miller, JW AF DeAngelis, MM Lane, AM Shah, CP Ott, J Dryja, TP Miller, JW TI Extremely discordant sib-pair study design to determine risk factors for neovascular age-related macular degeneration SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID QUANTITATIVE TRAIT LOCI; BEAVER DAM EYE; ALCOHOL-CONSUMPTION; MACULOPATHY; SMOKING; DISEASE AB Objective: To search for factors that contribute to the development of neovascular age-related macular degeneration (AMD). Methods: In a matched-pair case-control study, we studied sib pairs in which the index sibling had neovascular AMD in at least 1 eye and the unaffected sibling had normal maculae (or at most only a few small drusen) and was past the age at which the index case was diagnosed. Factors studied included sex, iris color, education, alcohol consumption, body mass index, vitamin use, smoking history, hypercholesterolemia, aspirin use, hypertension, other cardiovascular disease, any autoimmune disease, and non-insulin-dependent diabetes mellitus. Conditional logistic regression was performed to identify predictors of neovascular AMD. Results: On the basis of 73 sib pairs, multivariate regression analysis revealed statistically significant 2% increase in risk of neovascular AMD with each pack-year of smoking (odds ratio, 1.02; 95% confidence interval, 1.01-1.04; P=.007). Suggestive but nonsignificant associations were also observed for mean lifetime alcohol consumption, adult lifetime body mass index, and hypertension in multivariate regression analyses. Conclusion: Using extremely discordant sib pairs to study risk factors for AMD, a novel approach in epidemiological design, we found evidence that smoking is a risk factor for neovascular AMD. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Ocular Mol Genet Inst, Boston, MA USA. Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA. RP Miller, JW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM jwmiller@meei.harvard.edu RI DeAngelis, e/J-7863-2015 FU NEI NIH HHS [EY 07076]; NHGRI NIH HHS [HG 00008] NR 18 TC 22 Z9 24 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 APR PY 2004 VL 122 IS 4 BP 575 EP 580 DI 10.1001/archopht.122.4.575 PG 6 WC Ophthalmology SC Ophthalmology GA 812GT UT WOS:000220828700017 PM 15078676 ER PT J AU Loewenstein, JI Montezuma, SR Rizzo, JF AF Loewenstein, JI Montezuma, SR Rizzo, JF TI Outer retinal degeneration - An electronic retinal prosthesis as a treatment strategy SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID SUBRETINAL ELECTRICAL-STIMULATION; EPIRETINAL MICROELECTRODE ARRAYS; CHARGE INJECTION LIMITS; LONG-TERM IMPLANTATION; RETINITIS-PIGMENTOSA; MORPHOMETRIC-ANALYSIS; CORTICAL RESPONSES; VISUAL-PERCEPTION; CHICKEN RETINA; RABBIT RETINA AB Objective: To review progress toward an electronic retinal prosthesis for outer retinal degeneration. Method: Literature review. Results: Retinal degenerations such as retinitis pigmentosa result in a loss of photoreceptors. There is a secondary loss of inner retinal cells, but significant numbers of bipolar and ganglion cells remain for many years. Electrical stimulation can produce phosphenes in the eyes of individuals who are blind as a result of retinitis pigmentosa. Several research groups are trying to exploit this phenomenon to produce artificial vision with electronic retinal prostheses. Two groups, with private company sponsorship, have recently implanted first-generation devices in subjects with advanced retinitis pigmentosa. They have reported limited preliminary results. This article seeks to put these results in a broader context and review potential obstacles to successful prosthesis development. These include inner retinal cell viability, high thresholds, signal encoding, power requirements, biocompatibility, and device encapsulation. Conclusion: There has been substantial progress toward an electronic retinal prosthesis, but fully functional, long-lasting devices are not on the immediate horizon. C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. Vet Adm Ctr Innovat Rehabil, Boston, MA USA. RP Loewenstein, JI (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM john_loewenstein@meei.harvard.edu NR 79 TC 50 Z9 52 U1 2 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 APR PY 2004 VL 122 IS 4 BP 587 EP 596 DI 10.1001/archopht.122.4.587 PG 10 WC Ophthalmology SC Ophthalmology GA 812GT UT WOS:000220828700019 PM 15078678 ER PT J AU Anzai, Y Weymuller, EA Yueh, B Maronian, N Jarvik, JG AF Anzai, Y Weymuller, EA Yueh, B Maronian, N Jarvik, JG TI The impact of sinus computed tomography on treatment decisions for chronic sinusitis SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID CHRONIC RHINOSINUSITIS; RECURRENT SINUSITIS; SURGERY; HEALTH; CARE; ANTROSTOMY; DIAGNOSIS; OUTCOMES AB Objectives: To determine the impact of sinus computed tomography (CT) on treatment decisions by otolaryngologists and to explore the factors leading to choice of surgical treatment for patients suspected of having chronic sinusitis. Design: Prospective cohort study. Setting: A tertiary academic medical center Patients: Questionnaires were administered to 3 otolaryngologists in a tertiary academic institution regarding diagnosis and treatment decisions in 27 patients suspected of having chronic sinusitis, before and after they reviewed sinus CT scans. Main Outcome Measures: The dichotomous decisions regarding surgical or nonsurgical treatment and the agreement of treatment decisions among surgeons were evaluated. The factors strongly influencing surgeons' treatment decisions regarding patients selected for surgery were also determined. Results: The dichotomous treatment decisions were changed in one third of patients (9 of 27) after the sinus CT scans were reviewed. The agreement of treatment decisions among the 3 surgeons was markedly improved after they reviewed sinus CT scans. The factors favorably influencing surgical treatment were obstruction of the ostiomeatal complex on CT and concordance of CT abnormality with a patient's symptoms. Lund-Mackay stage, symptoms, and corticosteroid or antibiotic use were not significant predictors. Conclusions: Despite the common belief that treatment decisions for chronic sinusitis should be solely based on clinical grounds, with sinus CT providing only anatomic detail before surgery, our study indicates that the decision to perform surgery was altered by CT in a substantial portion of the patients. In our preliminary study, CT increased the tendency to elect surgical treatment by all 3 surgeons. C1 Univ Washington, Dept Radiol, Seattle, WA 98195 USA. Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Anzai, Y (reprint author), Univ Washington, Dept Radiol, Box 357115,RR-215,1959 NE Pacific St, Seattle, WA 98195 USA. EM anzai@u.washington.edu OI Yueh, Bevan/0000-0003-1380-1053 NR 29 TC 17 Z9 18 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 APR PY 2004 VL 130 IS 4 BP 423 EP 428 DI 10.1001/archotol.130.4.423 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 812GS UT WOS:000220828600005 PM 15096424 ER PT J AU Weaver, EM Kapur, V Yueh, B AF Weaver, EM Kapur, V Yueh, B TI Polysomnography vs self-reported measures in patients with sleep apnea SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT Meeting of teh Association-of-Professional-Sleep-Societies CY JUN 19, 2000 CL LAS VEGAS, NV SP Assoc Profess Sleep Societies ID QUALITY-OF-LIFE; DAYTIME SLEEPINESS; HEALTH-STATUS; RATED HEALTH; SCALE; HYPERTENSION; ASSOCIATION; INDEX; MORTALITY; COMMUNITY AB Background: While obstructive sleep apnea syndrome is defined by both polysomnographic (PSG) abnormalities and symptoms, severity is quantified primarily by the apnea-hypopnea index (AHI) alone. Objective: To determine the correlation between standard PSG indices (AHI and others) and self-reported sleepiness, mental health status, and general health in patients with sleep apnea. Design: Cross-sectional study. Setting: University-affiliated outpatient sleep laboratory Patients: Ninety-six consecutive patients with PSG-confirmed sleep apnea (AHI; : 5). Measurements: Patients completed a questionnaire that included the Epworth Sleepiness Scale, Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) mental health domain, and self-rated health on the evening of diagnostic PSG. Spearman correlation coefficients were computed. This sample had 85% power to detect a correlation of 0.3 or greater. The associations between PSG indices and self-reported measures were further assessed with multivariable regression techniques, adjusting for age, sex, body mass index, comorbidity, and PSG type. Results: The PSG parameters correlated poorly with self-reported measures (15 correlations; range of magnitude, 0.004-0.24; mean, 0.09). AHI was not associated with self-reported sleepiness or general health, and it was associated with the SF-36 Health Status mental health domain only on multiple linear regression (P=.04) but not on multiple logistic regression (adjusted odds ratio, 1.02; 95% confidence interval, 1.00-1.04; P=.09). Conclusions: In general, PSG measures, and AHI in particular, correlated poorly with self-reported measures in a clinical sleep laboratory sample. After adjustment for potentially confounding variables, weak associations were found between some PSG indices and selected self-reported measures. These findings suggest that sleep apnea disease burden should be quantified with both physiologic and subjective measures. C1 Univ Washington, Dept Otolaryngol Head & Neck Surg, Sleep Disorders Ctr, Seattle, WA 98195 USA. Univ Washington, Ctr Cost & Outcomes, Seattle, WA 98195 USA. Univ Washington, Div Pulm & Crit Care Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA USA. RP Weaver, EM (reprint author), 1660 S Columbian Way 112 OTO, Seattle, WA 98108 USA. EM eweaver@u.washington.edu RI Kapur, Vishesh/K-1054-2014; OI Kapur, Vishesh/0000-0002-5417-1097; Yueh, Bevan/0000-0003-1380-1053 FU NHLBI NIH HHS [K23 HL068849, K23 HL068849-01A2]; ODCDC CDC HHS [CD-98318] NR 34 TC 48 Z9 52 U1 1 U2 3 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 APR PY 2004 VL 130 IS 4 BP 453 EP 458 DI 10.1001/archotol.130.4.453 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 812GS UT WOS:000220828600011 PM 15096430 ER PT J AU Austin, SB Ziyadeh, N Fisher, LB Kahn, JA Colditz, GA Frazier, AL AF Austin, SB Ziyadeh, N Fisher, LB Kahn, JA Colditz, GA Frazier, AL TI Sexual orientation and tobacco use in a cohort study of US adolescent girls and boys SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID SMOKING INITIATION; WEIGHT CONCERNS; CIGARETTE-SMOKING; PARENTAL SMOKING; BISEXUAL YOUTH; RISK BEHAVIORS; SUBSTANCE USE; HEALTH; LESBIANS; ASSOCIATION AB Objective: To examine sexual-orientation group disparities in tobacco use in adolescent girls and boys. Design: Survey data from 10685 adolescent girls and boys participating in 1999 in the Growing Up Today Study were examined cross-sectionally. Setting: Community-based population of adolescents living throughout the United States. Main Outcome Measure: Prevalence of tobacco use. Results: Ninety-two percent of the participants described themselves as heterosexual (n=9296), 5% as mostly heterosexual (n=511), 1% as lesbian/gay/bisexual (n=103), and 2% as unsure (n=226). Ages ranged from 12 to 17 years. Compared with heterosexuals, mostly heterosexual girls were 2.5 (95% confidence interval, 1.8-3.5), lesbian/bisexual girls were 9.7 (95% confidence interval, 5.1-18.4), and mostly heterosexual boys were 2.5 (95% confidence interval, 1.4-4.6) times more likely to smoke at least weekly. In contrast, gay/bisexual boys were not more likely to smoke. Findings persisted even when controlling for multiple sociodemographic and psychosocial covariates. Conclusion: Our findings indicate that mostly heterosexual adolescents of both sexes and lesbian/bisexual girls are at heightened risk for tobacco use. C1 Childrens Hosp, Div Adolescent & Young Adult Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Med Ctr, Div Adolescent Med, Cincinnati, OH 45229 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Austin, SB (reprint author), Childrens Hosp, Div Adolescent Med, 300 Longwood Ave, Boston, MA 02115 USA. EM bryn.austin@tch.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NHLBI NIH HHS [HL03533]; NIDDK NIH HHS [DK46384]; PHS HHS [6T71-MC00009-11-01] NR 46 TC 87 Z9 88 U1 8 U2 14 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 APR PY 2004 VL 158 IS 4 BP 317 EP 322 DI 10.1001/archpedi.158.4.317 PG 6 WC Pediatrics SC Pediatrics GA 810DJ UT WOS:000220684700005 PM 15066869 ER PT J AU Pulsifer, MB Salorio, CF Niparko, JK AF Pulsifer, MB Salorio, CF Niparko, JK TI Developmental, audiological, and speech perception functioning in children after cochlear implant surgery: A reply - In reply SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Pulsifer, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 5 Emerson Pl,Suite 105, Boston, MA 02114 USA. EM mpulsifer@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2004 VL 158 IS 4 BP 401 EP 402 DI 10.1001/archpedi.158.4.401-b PG 2 WC Pediatrics SC Pediatrics GA 810DJ UT WOS:000220684700021 ER PT J AU Rentschler, AJ Cooper, RA Fitzgerald, SG Boninger, ML Guo, SF Ammer, WA Vitek, M Algood, D AF Rentschler, AJ Cooper, RA Fitzgerald, SG Boninger, ML Guo, SF Ammer, WA Vitek, M Algood, D TI Evaluation of selected electric-powered wheelchairs using the ANSI/RESNA standards SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE reference standards; rehabilitation; safety; wheelchairs ID OCCUPIED WHEELCHAIRS; MANUAL WHEELCHAIRS; STABILITY; LOADS; LIFE; REAR AB Objectives: To compare the performance characteristics of different electric-powered wheelchairs (EPWs) and to evaluate the effectiveness of the American National Standards Institute/Rehabilitation Engineering and Assistive Technology Society of North America (ANSI/RESNA) wheelchair standards. Design: Five types of EPWs were selected. Three wheelchairs of each type were tested according to the ANSI/RESNA wheelchair standards. Setting: Rehabilitation engineering center. Specimens: Fifteen wheelchairs. Interventions: Not applicable. Main Outcome Measures: Static tipping angle; dynamic tipping score; braking distance; energy consumption; static, impact, and fatigue strength; and climatic conditioning. Results: There were significant differences (P<.05) among the 5 types of EPWs for static stability when facing both uphill and downhill in the most-stable and least-stable configurations. There were significant differences (P<.05) among the EPWs on most of the dynamic stability tests. There were also significant differences (P<.05) among EPWs for all the effectiveness of brakes conditions, as well as between 2 wheelchairs for the energy consumption testing. There were several failures among the wheelchairs during the static, impact, and fatigue strength testing and during the climatic testing. Conclusions: The results show that EPWs can vary greatly with respect to static and dynamic stability, braking distance, range, strength testing, and climatic conditioning. All these factors have a substantial effect on safety and performance. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, 151-RI,7180 Highland Dr, Pittsburgh, PA 15206 USA. EM rcooper@pitt.edu OI Boninger, Michael/0000-0001-6966-919X NR 16 TC 16 Z9 17 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD APR PY 2004 VL 85 IS 4 BP 611 EP 619 DI 10.1016/j.apmr.2003.06.023 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 810MM UT WOS:000220708400013 PM 15083438 ER PT J AU Elias, N Tanabe, KK Sober, AJ Gadd, MA Mihm, MC Goodspeed, B Cosimi, AB AF Elias, N Tanabe, KK Sober, AJ Gadd, MA Mihm, MC Goodspeed, B Cosimi, AB TI Is completion lymphadenectomy after a positive sentinel lymph node biopsy for cutaneous melanoma always necessary? SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 84th Annual Meeting of the New-England-Surgical-Society CY SEP 19, 2003 CL Newport, RI SP New England Surg Soc ID AMERICAN JOINT COMMITTEE; EARLY-STAGE MELANOMA; MALIGNANT-MELANOMA; INTRAOPERATIVE RADIOLYMPHOSCINTIGRAPHY; PROGNOSTIC-FACTORS; RANDOMIZED-TRIAL; DISSECTION; LOCALIZATION; METASTASIS; MANAGEMENT AB Hypothesis: Completion lymph node dissection (CLND) has usually been recommended after metastatic disease is identified in the sentinel lymph node (SLN) biopsy to eradicate further metastases in nonsentinel nodes. We hypothesized that patients with negative lymph nodes included in the initial SLN specimen have low risk of metastases in the residual draining basin and may not require CLND. Design: Chart review. Setting: University-affiliated tertiary care referral center. Patients: Between January 1, 1997, and May 31, 2003, 506 consecutive patients underwent SLN biopsy for staging of primary cutaneous melanoma. Intervention: The SLN biopsy identified 87 patients (17.2%) with metastatic melanoma, of whom 80 underwent CLND. Results: In 28 patients, all SLNs were found to contain metastatic melanoma. Seven (25%) of these patients had additional metastases identified in the CLND specimen. In 52 patients, 1 or more SLNs did not contain metastatic melanoma. Five (10%) of these patients had additional metastases in the CLND specimen (P = .02). Conclusions: Although no evidence of metastatic melanoma was found on CLND in most patients in whom negative nodes had been removed with positive SLNs at the initial biopsy, 10% of these patients did have further metastases. This subgroup of patients (positive SLNs and negative nodes in the SLN biopsy specimen) is at significantly lower risk for further metastasis, but CLND cannot be safely omitted even for these patients. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Elias, N (reprint author), Massachusetts Gen Hosp, Dept Surg, White 515,55 Fruit St, Boston, MA 02114 USA. EM nelias1@partners.org NR 25 TC 27 Z9 28 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 2004 VL 139 IS 4 BP 400 EP 404 DI 10.1001/archsurg.139.4.400 PG 5 WC Surgery SC Surgery GA 812CK UT WOS:000220817400016 PM 15078708 ER PT J AU Salemi, VMC Pires, MD Cestari, IN Cestari, IA Picard, MH Leirner, AA Mady, C AF Salemi, VMC Pires, MD Cestari, IN Cestari, IA Picard, MH Leirner, AA Mady, C TI Echocardiographic assessment of global ventricular function using the myocardial performance index in rats with hypertrophy SO ARTIFICIAL ORGANS LA English DT Article DE myocardial perfor-mance index; hypertrophy; rats; chronic pressure overload; diastolic function ID DOPPLER INDEX; DILATED CARDIOMYOPATHY; PROGNOSTIC VALUE; ASCENDING AORTA; TEI INDEX; DISEASE; HYPERTENSION; INFARCTION; QUANTITATION; GROWTH AB Myocardial hypertrophy is the hallmark of chronic pressure overload and the myocardial performance index (MPI) is an easily recordable measurement of Doppler time intervals. In this study, the utility of using MPI to assess the progression of hypertrophy in the aortic-banded rat model was evaluated. Male Wistar rats (70-90 g) underwent ascending aorta constriction (n = 4) or a sham operation (n = 5). High-resolution echocardiography was performed 4, 7, 10, and 12 weeks after the surgery. Over this follow-up interval, animals in the aortic-banded group demonstrated an increase in their mean left ventricular (LV) mass and MPI compared with controls. MPI reflects ventricular performance in small animals with LV hypertrophy, showing alterations early after aorta constriction. C1 Univ Sao Paulo, Cardiomyopathy Unit, Heart Inst InCor, Sch Med, Sao Paulo, Brazil. Univ Sao Paulo, Bioengn Div, Heart Inst InCor, Sch Med, Sao Paulo, Brazil. Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, Sao Paulo, Brazil. Massachusetts Gen Hosp, Clin Echocardiog & Cardiol Div, Boston, MA 02114 USA. RP Salemi, VMC (reprint author), Av Jandira 185,AP 41B, BR-04080000 Sao Paulo, Brazil. EM verasalemi@uol.com.br RI Cestari, Ismar /B-7286-2012; Cestari, Idagene/D-1012-2012; Mady, Charles/C-8870-2012; Salemi, Vera/C-9104-2013; OI Mady, Charles/0000-0002-8838-199X; Salemi, Vera/0000-0002-7152-1810; Picard, Michael/0000-0002-9264-3243 NR 26 TC 14 Z9 14 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0160-564X J9 ARTIF ORGANS JI Artif. Organs PD APR PY 2004 VL 28 IS 4 BP 332 EP 337 DI 10.1111/j.1525-1594.2004.47350.x PG 6 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 810KQ UT WOS:000220703600003 PM 15084191 ER PT J AU Salemi, VMC Picard, MH Mady, C AF Salemi, VMC Picard, MH Mady, C TI Assessment of diastolic function in endomyocardial fibrosis: Value of flow propagation velocity SO ARTIFICIAL ORGANS LA English DT Article DE heart failure; echocardiography; diastolic function; endomyocardial fibrosis; restrictive cardiomyopathy; flow propagation velocity ID CARDIOMYOPATHIES; CLASSIFICATION AB Endomyocardial fibrosis is manifested mainly by diastolic heart failure. However, diastolic function has not been well characterized in this disease. The aim of this study was to characterize left ventricular (LV) diastolic function in endomyocardial fibrosis (EMF) by echocardiography. Eighteen patients with LV EMF and 18 healthy subjects were studied. Cardiac volumes and ejection fraction were assessed by Simpson's method. Pulsed-wave Doppler was used to obtain mitral and pulmonary venous flow velocities and grade diastolic function. Pulsed-wave tissue Doppler imaging velocities along the septal side of mitral annulus, flow propagation velocity (V-p) of the early diastolic mitral inflow, and myocardial performance index were obtained. According to this grading method, four patients with normal diastolic function, five with impaired relaxation, five with pseudonormal, and four with a restrictive pattern were found. A positive correlation of these diastolic function grades and NYHA functional class was found (r = 0.66, P = 0.003). By "stepwise" logistic regression the best index that discriminated EMF patients from controls was V-p. The probability of occurrence of EMF = exp(7.9288 - 0.1366 V-p)/1 + exp(7.9288 - 0.1366 V-p). A wide range of diastolic function grades is found in patients with EMF and these correlated with functional class. Delayed myocardium relaxation, as reflected by altered V-p, was a frequent finding, making V-p the most useful index to discriminate EMF patients. C1 Univ Sao Paulo, Inst Heart, InCor, Sch Med, Sao Paulo, Brazil. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Salemi, VMC (reprint author), Ave Jandira 185,Ap 41B, BR-04080000 Sao Paulo, Brazil. EM verasalemi@uol.com.br RI Mady, Charles/C-8870-2012; Salemi, Vera/C-9104-2013; OI Mady, Charles/0000-0002-8838-199X; Salemi, Vera/0000-0002-7152-1810; Picard, Michael/0000-0002-9264-3243 NR 7 TC 5 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0160-564X J9 ARTIF ORGANS JI Artif. Organs PD APR PY 2004 VL 28 IS 4 BP 343 EP 346 DI 10.1111/j.1525-1594.2004.47352.x PG 4 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 810KQ UT WOS:000220703600005 PM 15084193 ER PT J AU Fox, CS Parise, H Vasan, RS Levy, D O'Donnell, CJ D'Agostino, RB Plehn, JF Benjamin, EJ AF Fox, CS Parise, H Vasan, RS Levy, D O'Donnell, CJ D'Agostino, RB Plehn, JF Benjamin, EJ TI Mitral annular calcification is a predictor for incident atrial fibrillation SO ATHEROSCLEROSIS LA English DT Article DE mitral annular calcification; epidemiology; atrial fibrillation; echocardiography; cohort study; prognosis ID ANULUS CALCIFICATION; RISK-FACTORS; FRAMINGHAM; DISEASE; CALCIUM; STROKE; PREVALENCE; COHORT; OLDER; SIZE AB Background Mitral annular calcification (MAC) has been associated with adverse cardiovascular disease outcomes and stroke in longitudinal and community-based cohorts. Prospective data are limited on its association with atrial fibrillation (AF). Methods: We examined the association between MAC and the long-term risk of AF over 16 years of follow-up in participants in the original cohort of the Framingham Heart Study who attended a routine examination between 1979 and 1981. MAC was assessed by M-mode echocardiography. Cox proportional-hazards models were used to estimate hazard ratios (HR) for incident AF. Results: Of 1126 subjects who had adequate echocardiographic assessment and were AF-free at baseline, 149 (13%) had MAC. There were 217 cases of incident AF (42 in subjects with MAC). The age- and sex-adjusted incidence rate was 362 per 10,000 person-years in subjects with MAC compared with 185 per 10,000 person-years in those without MAC. In multivariable-adjusted analyses, MAC was associated with an increased risk of AF (HR 1.6, 95% Cl 1.1-2.2). This association was attenuated upon further adjustment for left atrial size (HR 1.4, 95% Cl 0.9-2.0). Conclusions: The association between MAC and incident AF may be mediated partially through left atrial enlargement. These data suggest the importance of better understanding the mechanisms involved in cardiac valvular calcification. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 NHLBI, Framington Heart Study, Framingham, MA 01702 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Boston Univ, Sch Med, Cardiol Sect, Dept Med & Prevent Med Sect, Boston, MA 02215 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Benjamin, EJ (reprint author), NHLBI, Framington Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM emelia@fram.nhlbi.nih.gov OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [K24 HL 04334, N01-HC-25195]; NINDS NIH HHS [5R01-NS-17950] NR 19 TC 44 Z9 45 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD APR PY 2004 VL 173 IS 2 BP 291 EP 294 DI 10.1016/j.athersclerosis.2003.12.018 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 825KL UT WOS:000221755700016 PM 15064104 ER PT J AU Homik, JE Suarez-Almazor, M AF Homik, JE Suarez-Almazor, M TI An economic approach to health care SO BEST PRACTICE & RESEARCH IN CLINICAL RHEUMATOLOGY LA English DT Article DE cost-effectiveness; economic analysis; rheumatoid arthritis; anti-tumor necrosis factor agents; COX-2 inhibitors ID COST-EFFECTIVENESS ANALYSIS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RHEUMATOID-ARTHRITIS; TREATMENT OPTIONS; 2ND-LINE DRUGS; ACCES MODEL; OSTEOARTHRITIS; METHOTREXATE; MISOPROSTOL; CELECOXIB AB Economic analyses have the potential to put all of the positive and negative outcomes of an intervention into perspective to aid decision making. The quality of the data upon which the analysis is based has an impact on the resulting quality of the analysis itself. Analysis of cost-effectiveness requires the input of many types of data, and where data are not available, assumptions must be made. There are many instances where the analysis may go wrong, and it is important to remain cognizant of these. The critical parts of the analysis, which have also been identified in quality assessment tools, include the following: design of the study question, sources of probability estimates and cost data, sensitivity analysis, and the interpretation of results. If the readers are able to identify the assumptions of the analysis they are better equipped to judge the validity. We have reviewed economic analyses relating to two hot economic topics in rheumatology. These are the cost-effectiveness of cyclooxygenase-2 (COX-2) inhibitors for 'arthritis' and cost-effectiveness of anti-tumor necrosis factor alpha (anti-TNF) agents for rheumatoid arthritis (KA). The results of the COX-2 analyses vary by review. Some show cost savings, while others calculate a significant cost in order to achieve any change in quality of life. Given the unanswered questions that still exist, it seems reasonable to conclude that COX-2 inhibitors may be cost effective when used in patients at a high risk of GI complications. Unanswered questions remain regarding the concomitant use of low-dose ASA and proton pump inhibitors and how they may affect the results of these economic analyses. The cost-effectiveness of anti-TNF agents has not been explored in as much detail as that of the COX-2 agents. Two studies have presented cost-effectiveness models that include a hypothetical biologic agent. Two economic analyses report on the cost-effectiveness of etanercept compared with traditional disease-modifying anti-rheumatic drugs (DMARDs) in methotrexate-resistant and methotrexate-naive patients with RA. Both the analyses show that etanercept has a cost-effectiveness ratio of around US$40 000 for every patient who achieves an American College of Rheumatology 20% improvement score (ACR 20) within a 6-month period. A cost-utility analysis was published regarding the use of infliximab in methotrexate resistant RA. It showed a cost-utility ratio of 3400:34 000 Euro per quality adjusted life year (QALY) gained, depending on the country evaluated (Sweden and the UK, respectively). An important finding in all three studies was that indirect costs dominate costs in RA; therefore, they should be included in all future analyses of this disease. C1 Univ Alberta, Heritage Med Res Ctr 562, Edmonton, AB T6G 2S2, Canada. Houston Vet Affairs Med Ctr 152, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. RP Homik, JE (reprint author), Univ Alberta, Heritage Med Res Ctr 562, Edmonton, AB T6G 2S2, Canada. EM joanne.homik@ualberta.ca NR 41 TC 5 Z9 5 U1 1 U2 1 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1521-6942 J9 BEST PRACT RES CL RH JI Best Pract. Res. Clin. Rheumatol. PD APR PY 2004 VL 18 IS 2 BP 203 EP 218 DI 10.1016/j.berh.2004.02.001 PG 16 WC Rheumatology SC Rheumatology GA 825NM UT WOS:000221765200008 PM 15121040 ER PT J AU Riley, DE Krieger, JN AF Riley, DE Krieger, JN TI Short tandem repeats are associated with diverse mRNAs encoding membrane-targeted proteins SO BIOESSAYS LA English DT Article ID ANDROGEN RECEPTOR GENE; PROSTATE-CANCER; UNTRANSLATED REGION; FUNCTIONAL-ANALYSIS; MYOTONIC-DYSTROPHY; MOLECULAR-CLONING; BINDING PROTEIN; CDNA CLONING; EXPRESSION; MOUSE AB Within the genomes of multicellular organisms, short tandem repeating sequences (STRs) are ubiquitous, yet usage patterns remain obscure. The repeats (AC)n and (GU)n appear frequently in the untranslated regions (UTRs) of messenger RNAs (mRNAs). To investigate STR usage patterns, we used three approaches: (1) comparisons of individual mRNA database sequences including annotations and linked references, (2) statistical analysis of complete, UTR databases and (3) study of a large gene family, the aquaporins. Among 500 (AC)n- or (GU)n-containing mRNAs, 58 (12%) had known functions. Of these, 50 (86%) encoded proteins whose activities involved membranes or lipids, including integral membrane proteins, peripheral membrane proteins, ion channels, lipid enzymes, receptors and secreted proteins. A control sequence (AU)n also occurred in mRNAs, but only 5% encoded membrane-related functions. Investigation of all reported 3' UTR sequences, demonstrated that the STR (AC)n was 9 times more common in mRNAs encoding membrane functions than in the total UTR database (P < 0.001). Similarly, (GU)n was 8 times more common in membrane-function mRNAs than in the total database (P < 0.001). These observations suggest that (AC)n and (GU)n may be UTR signals for some mRNAs encoding membrane-targeted proteins. This article contains supplementary material which may be viewed at the BioEssays website at http://www.interscience.wiley.com/jpages/0265-9247/suppmat/index.html. (C) 2004 Wiley Periodicals, Inc. C1 VA Puget Sound Hlth Care Syst, Dept Res, Seattle, WA USA. Univ Washington, Dept Urol, Seattle, WA 98195 USA. RP Riley, DE (reprint author), Vet Adm Med Ctr, Room 517,Bldg 1,1660 S Columbian Way, Seattle, WA 98108 USA. EM dri@u.washington.edu FU NIDDK NIH HHS [R01 DK38955] NR 74 TC 7 Z9 7 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0265-9247 J9 BIOESSAYS JI Bioessays PD APR PY 2004 VL 26 IS 4 BP 434 EP 444 DI 10.1002/bies.20001 PG 11 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 808PH UT WOS:000220580500011 PM 15057941 ER PT J AU Weiss, AP Zalesak, M DeWitt, L Goff, D Kunkel, L Heckers, S AF Weiss, AP Zalesak, M DeWitt, L Goff, D Kunkel, L Heckers, S TI Impaired hippocampal function during the detection of novel words in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE functional MRI; hippocampus; memory; novelty detection; schizophrenia ID RECOGNITION MEMORY; TEMPORAL-LOBE; ALZHEIMERS-DISEASE; CONSCIOUS RECOLLECTION; DECLARATIVE MEMORY; PSYCHOTIC-PATIENTS; VOLUME REDUCTIONS; NOVELTY DETECTION; MRI; RETRIEVAL AB Background: Patients with schizophrenia have smaller hippocampal volumes and perform abnormally on most declarative memory tasks. Although these findings are likely belated, the impact of hippocampal pathology on cognitive performance in schizophrenia remains unclear. This study examined this relationship by measuring the volume of the hippocampus and its activation during memory task performance. Methods: Participants included 15 patients with schizophrenia and 16 age-matched control. subjects. Hippocampal volume was determined via three-dimensional volumetric analysis of high-resolution magnetic resonance images. Hippocampal activity was assessed by measuring changes in blood oxygen level-dependent signal during a recognition memory task. Results: Patients with schizophrenia had smaller hippocampal volumes bilaterally and demonstrated poorer performance on the recognition memory task, largely because of a heightened rate of false alarms to novel stimuli. Both groups showed robust hippocampal activity to old and new items when compared with a low-level baseline task; however, direct comparison of hippocampal activity during recognition task performance revealed that healthy control, but not the schizophrenia, subjects showed significant right anterior hippocampal activation during the evaluation of novel items. Conclusions: The impaired ability to classify new items as previously not experienced is associated with decreased recruitment and smaller volume of the hippocampus in schizophrenia. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Weiss, AP (reprint author), MGH E, Dept Psychiat, Bldg 149,Room 2606, Charlestown, MA 02129 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 FU NIMH NIH HHS [MH01 763-01] NR 85 TC 52 Z9 54 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 APR 1 PY 2004 VL 55 IS 7 BP 668 EP 675 DI 10.1016/j.biopsych.2004.01.004 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 806ON UT WOS:000220443300002 PM 15038994 ER PT J AU Biederman, J Faraone, SV Monuteaux, MC Bober, M Cadogen, E AF Biederman, J Faraone, SV Monuteaux, MC Bober, M Cadogen, E TI Gender effects on attention-deficit/hyperactivity disorder in adults, revisited SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 155th Annual Meeting of the American-Psychiatric-Association CY MAY 18-23, 2002 CL PHILADELPHIA, PA SP Amer Psychiatr Assoc DE ADHD; adult; comorbidity; clinical sample; gender; functioning ID DEFICIT HYPERACTIVITY DISORDER; CONTROLLED CLINICAL-TRIAL; AGE-DEPENDENT DECLINE; PSYCHIATRIC STATUS; FOLLOW-UP; CONDUCT DISORDER; CHILDHOOD-ONSET; RISK-FACTORS; ADHD; CHILDREN AB Background: This study reexamined gender differences in a large sample of adults with attention-deficit/hyperactivity disorder (ADHD). Methods. We assessed the effects of ADHD, gender, and their interaction on rates of psychiatric comorbidity and cognitive functioning in 219 adults with ADHD who were referred to an outpatient psychiatric clinic over the last 7 years compared with 215 control subjects group-matched to control subjects on age and gender, and ascertained from ongoing family genetic case control adults with, ADHD. Results. There was no evidence that gender moderated the association between ADHD and other psychiatric disorders. Attention-deficit/hyperactivity disorder was associated with cognitive deficits and higher rates of major depression, anxiety, substance use disorders, and antisocial personality disorder. Conclusions. Attention-deficit/hyperactivity disorder in adults is associated with psychiatric and cognitive impairment in both genders. These results bear striking similarities to findings reported in pediatric samples, supporting the validity of ADHD and stressing the importance of identifying and treating the disorder in adulthood. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Dept Psychiat, WACC 725,15 Parkman St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH 57934, R01 MH-41314-01A2] NR 60 TC 179 Z9 183 U1 6 U2 19 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 APR 1 PY 2004 VL 55 IS 7 BP 692 EP 700 DI 10.1016/j.biopsych.2003.12.003 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 806ON UT WOS:000220443300005 PM 15038997 ER PT J AU Ballen, KK Kurtzberg, J Lane, TA Lindgren, BR Miller, JP Nagan, D Newman, B Rupp, N Haley, NR AF Ballen, KK Kurtzberg, J Lane, TA Lindgren, BR Miller, JP Nagan, D Newman, B Rupp, N Haley, NR TI Racial diversity with high nucleated cell counts and CD34 counts achieved in a national network of cord blood banks SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE cord blood; minority; donor recruitment ID BONE-MARROW TRANSPLANTATION; UNRELATED DONORS; PLACENTAL-BLOOD; ACUTE-LEUKEMIA; RECIPIENTS; RECONSTITUTION; ETHNICITY; DISEASES; SURVIVAL AB Banked, unrelated, partially HLA-matched, umbilical cord blood is an alternative stem cell source for patients in need of transplantation therapy who lack traditionally matched donors. A presumed advantage of cord blood is the ability to increase recruitment of donors of minority ethnic backgrounds. The American Red Cross Cord Blood Program was established in 1999 with 6 banks and 10 collection sites throughout the country. Cord blood donors self-report racial designations on questionnaires, and donor race was collected from each site. Postprocessing nucleated cell counts and CD34(+) counts were obtained on the cord blood units, and results from each racial group (white, black, Asian, Hispanic, and Native American) were compared in the natural logarithmic scale by using analysis of variance. A total of 18878 donors consented: 64% white, 16% black, 12% Hispanic, 4% Asian, 1% Native American, and 3% other. The Detroit area consented the highest percentage of black donors (87%), San Diego consented the highest percentage of Hispanic donors (59%), and Oakland consented the highest percentage of Asian donors (15%). Seven thousand eight hundred sixty-six cord blood units have been banked for transplantation. The mean preprocessing nucleated cell count was 1220 x 106 (range, 327-7300 x 10(6)). There was no difference among racial groups when controlled for site (P =.395). The mean CD34(+) count was 3.28 x 10(6). Blacks had a significantly lower CD34(+) count than the other racial/ethnic groups in the Midwest, Northwest, and North Carolina collection sites. A racially diverse cord blood bank can be achieved. Nucleated cell counts were similar among the different racial/ethnic groups. CD34(+) counts were lower for blacks in some collection sites. (C) 2004 American Society for Blood and Marrow Transplantation. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Amer Red Cross, Cord Blood Program, Worcester, MA USA. Amer Red Cross, Cord Blood Program, Durham, NC USA. Duke Univ, Ctr Med, Durham, NC USA. Amer Red Cross, Cord Blood Program, Portland, OR USA. Univ Minnesota, Minneapolis, MN 55455 USA. Amer Red Cross, Cord Blood Program, St Paul, MN USA. Amer Red Cross, Cord Blood Program, Detroit, MI USA. Amer Red Cross, Cord Blood Program, Arlington, VA USA. RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 100 Blossom St,Cox 640, Boston, MA 02114 USA. EM kballen@partners.org NR 35 TC 25 Z9 26 U1 1 U2 2 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 APR PY 2004 VL 10 IS 4 BP 269 EP 275 DI 10.1016/j.bbmt.2003.12.003 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 814JD UT WOS:000220970100006 PM 15077225 ER PT J AU Shieh, SJ Terada, S Vacanti, JP AF Shieh, SJ Terada, S Vacanti, JP TI Tissue engineering auricular reconstruction: in vitro and in vivo studies SO BIOMATERIALS LA English DT Article DE auricular tissue engineering; chondrogenesis; animal model ID SYNTHETIC BIODEGRADABLE POLYMERS; MESENCHYMAL STEM-CELLS; RIB CARTILAGE GRAFTS; PERSONAL-EXPERIENCE; EAR RECONSTRUCTION; CHONDROCYTES; COLLAGEN; MICROTIA; INVITRO; RABBIT AB Although investigators have demonstrated that neocartilage can be constituted in a predetermined shape and in complex three-dimensional Structures, Such as a human ear, by using cell transplantation on polymer constructs, many unsolved problems still remain. The crucial issues for auricular tissue engineering consisted of optimal cell Culture environment, choice of polymers, behavior of chondrocytes, study of cell-polymer constructs in an acceptable animal model, and long-term structural integrity. Here we describe Our tissue engineering approaches for auricular reconstruction including auricular scaffold fabrication, in vitro chondrogenesis, in vivo immunocompromized xenograft and immunocompetent autologous animal models, and long-term follow-up. Though many current obstacles regarding auricular tissue engineering still exist, we demonstrate techniques of auricular scaffold fabrication with promising in vitro and in vivo neocartilage formation, optimal selection and application of animal models, and, to the best of our knowledge, the first report of different biodegradable biomaterial trials and the longest in vivo results (10 months) for auricular tissue engineering. (C) 2003 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Surg, Lab Tissue Engn & Organ Fabricat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Natl Cheng Kung Univ, Coll Med, Dept Surg, Div Plast & Reconstruct Surg, Tainan 70101, Taiwan. Tokyo Womens Med Univ, Dept Plast & Reconstruct Surg, Tokyo 1628666, Japan. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Surg, Lab Tissue Engn & Organ Fabricat, 1157 Warren,55 Fruit St, Boston, MA 02114 USA. EM sjshieh@mail.ncku.edu.tw; sterada@big.jp; jvacanti@partners.org NR 51 TC 86 Z9 93 U1 2 U2 24 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 APR PY 2004 VL 25 IS 9 BP 1545 EP 1557 DI 10.1016/S0142-9612(03)00501-5 PG 13 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 761PA UT WOS:000187916100010 PM 14697857 ER PT J AU Tuszynski, JA Portet, S Dixon, JM Luxford, C Cantiello, HF AF Tuszynski, JA Portet, S Dixon, JM Luxford, C Cantiello, HF TI Ionic wave propagation along actin filaments SO BIOPHYSICAL JOURNAL LA English DT Article ID F-ACTIN; POLYELECTROLYTE SOLUTIONS; TRANSMISSION-LINE; ENERGY-TRANSFER; MICROTUBULES; CONDENSATION; MECHANISM; SOLITONS; DNA AB We investigate the conditions enabling actin filaments to act as electrical transmission lines for ion flows along their lengths. We propose a model in which each actin monomer is an electric element with a capacitive, inductive, and resistive property due to the molecular structure of the actin filament and viscosity of the solution. Based on Kirchhoff's laws taken in the continuum limit, a nonlinear partial differential equation is derived for the propagation of ionic waves. We solve this equation in two different regimes. In the first, the maximum propagation velocity wave is found in terms of Jacobi elliptic functions. In the general case, we analyze the equation in terms of Fisher-Kolmogoroff modes with both localized and extended wave characteristics. We propose a new signaling mechanism in the cell, especially in neurons. C1 Univ Alberta, Dept Phys, Edmonton, AB T6G 2J1, Canada. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Warwick, Dept Phys, Coventry CV4 7AL, W Midlands, England. RP Tuszynski, JA (reprint author), Univ Alberta, Dept Phys, Edmonton, AB T6G 2J1, Canada. EM jtus@phys.ualberta.ca NR 50 TC 58 Z9 59 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 2004 VL 86 IS 4 BP 1890 EP 1903 PG 14 WC Biophysics SC Biophysics GA 808KI UT WOS:000220567600002 PM 15041636 ER PT J AU Marangell, LB Martinez, JM Ketter, TA Bowden, CL Goldberg, JF Calabrese, JR Miyahara, S Miklowitz, DJ Sachs, GS Thase, ME AF Marangell, LB Martinez, JM Ketter, TA Bowden, CL Goldberg, JF Calabrese, JR Miyahara, S Miklowitz, DJ Sachs, GS Thase, ME CA STEP-BD investigators TI Lamotrigine treatment of bipolar disorder: data from the first 500 patients in STEP-BD SO BIPOLAR DISORDERS LA English DT Article DE anticonvulsant; bipolar disorder; depression; lamotrigine; treatment ID DOUBLE-BLIND; MANIA; ANTIDEPRESSANT; MONOTHERAPY; TRIAL AB Objective: To describe the frequency and correlates of lamotrigine therapy among the first 500 patients enrolled into the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study. Method: Systematic recording of psychiatric history and medication data at intake into the STEP-BD project. Results: Of the participants with bipolar disorder type I or II (n = 483), 77 (15.4%) were currently taking lamotrigine (mean dose: 258.12 mg/day) and 52 (10.4%) reported prior lamotrigine use. The groups were comparable with regard to duration of illness and mood state at study entry. Compared with participants who had never taken lamotrigine, those currently treated with lamotrigine were significantly more likely to have a prior history of rapid cycling (62.5% vs. 43.1%; p < 0.01) and an antidepressant-induced switch to (hypo)mania (49.3% vs. 33.3%; p < 0.01). In contrast, only 16.9% of lamotrigine-treated participants were taking an antidepressant at study intake, as compared with 29.1% of participants with no history of lamotrigine therapy (p < 0.03). Conclusions: While noting the limitations of a cross-sectional assessment, these data suggest that lamotrigine therapy was commonly used in these academic centers for patients with bipolar disorder several years before it was recommended in the American Psychiatric Association practice guidelines, particularly in patients with a history of rapid cycling or antidepressant-induced mania. C1 Baylor Coll Med, Dept Psychiat, Mood Disorders Program, Houston, TX 77030 USA. S Cent Mental Illness Res & Educ Clin Ctr, Dept Vet Affairs, Houston, TX USA. Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Bipolar Disorders Clin, Stanford, CA 94305 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Zucker Hillside Hosp, Dept Psychiat Res, Glen Oaks, NY USA. Case Western Reserve Univ, Univ Hosp Cleveland, Dept Psychiat, Cleveland, OH 44106 USA. Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA USA. Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Partners Bipolar Res Program, Boston, MA USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. RP Marangell, LB (reprint author), 6655 Travis,Suite 560, Houston, TX 77030 USA. EM laurenm@bcm.tmc.edu FU NIMH NIH HHS [N01 MH80001] NR 12 TC 17 Z9 20 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD APR PY 2004 VL 6 IS 2 BP 139 EP 143 DI 10.1111/j.1399-5618.2004.00098.x PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 801MF UT WOS:000220099300006 PM 15005752 ER PT J AU Hirsch, B Shimamura, A Moreau, L Baldinger, S Hag-alshiekh, M Bostrom, B Sencer, S D'Andrea, AD AF Hirsch, B Shimamura, A Moreau, L Baldinger, S Hag-alshiekh, M Bostrom, B Sencer, S D'Andrea, AD TI Association of biallelic BRCA2/FANCD1 mutations with spontaneous chromosomal instability and solid tumors of childhood SO BLOOD LA English DT Article ID FANCONI-ANEMIA REGISTRY; BRCA2; RADIOSENSITIVITY; LEUKEMIA; PATHWAY; CANCER; MEDULLOBLASTOMA; RECOMBINATION; PROTEIN; PATIENT AB The clinical, cytogenetic, and molecular findings of 2 Fanconi anemia (FA) subtype D1 kindreds, initially identified through a young child with a solid tumor (medullobastoma, Wilms tumor), are described. Each kindred subsequently had a second affected child; one developed Wilms tumor followed by a medulloblastoma, and the other developed T-lineage acute lymphoblastic leukemia. Cytogenetic studies revealed an unusually high spontaneous chromosome aberration rate, contrasting with other FA subtypes. Molecular analysis revealed biallelic BRCA2/FANCD1 mutations. The patients did not exhibit bone marrow failure. Our studies suggest that the D1 subtype represents a severe end of the cytogenetic spectrum within FA, consistent with a critical downstream role of BRCA2 in the FA pathway. Furthermore, this FA subgroup may be preferentially associated with an increased predisposition to solid tumors in early childhood. Recognition of this constellation of findings has significant implications for medical management and genetic counseling of FA families. (C) 2004 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Childrens Hosp, Dana Farber Canc Inst,Dept Pediat Oncol, Boston, MA 02115 USA. Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Abbott NW Hosp, Minneapolis, MN 55407 USA. Childrens Hosp & Clin, Dept Pediat Hematol Oncol, Minneapolis, MN USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu NR 38 TC 101 Z9 104 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 APR 1 PY 2004 VL 103 IS 7 BP 2554 EP 2559 DI 10.1182/blood-2003-06-1970 PG 6 WC Hematology SC Hematology GA 830ZR UT WOS:000222163200025 PM 14670928 ER PT J AU Chen, HC Feener, EP AF Chen, HC Feener, EP TI MEK1,2 response element mediates angiotensin II-stimulated plasminogen activator inhibitor-1 promoter activation SO BLOOD LA English DT Article ID SMOOTH-MUSCLE-CELLS; GROWTH-FACTOR-BETA; PAI-1 GENE-EXPRESSION; PROTEIN-KINASE KINASE; CONVERTING ENZYME-INHIBITION; TYPE-1 RECEPTOR ANTAGONISM; SIGNAL-REGULATED KINASE; C-JUN; DNA-BINDING; FUNCTIONAL INTERACTIONS AB The MEK1,2 (MAPK/ERK kinase 1 and 2) pathway mediates the up-regulation of plasminogen activator inhibitor-1 (PAI-1) expression in vascular smooth muscle cells by a variety of hormones, including angiotensin II. Transfection of constitutively active MEKK-1, an upstream activator of the mitogen-activated protein (MAP) kinase pathways, was used to isolate an enhancer element located between -89 and -50 bp in PAI-1 promoter that was activated by MEKK-1 and selectively blocked by the MEK1,2 inhibitor PD98059. Mutational analysis revealed that the MEKK-1 response element (MRE) contained 2 cis-acting Sp1- and AP-1-like sequences, located between -75 to -70 and -63 to -52 bp, respectively. Overexpression of Sp1 enhanced MEKK-1-induced MRE promoter activity and a dominant-negative c-Fos blocked this Sp1 response. The combination of Sp1 and c-Jun or c-Fos was required to activate this MRE. Angiotensin II (Ang II) stimulation increased c-Fos, c-Jun, and Sp1 binding to the MRE by 100-, 4.9-, and 1.9-fold, respectively, and these responses were inhibited by PD98059 and AT, receptor antagonist candesartan. Intravenous Ang II infusion in rats increased aortic c-Fos binding to the MRE. This MRE sequence mediated a 4-fold increase of MEK1,2-dependent PAI-1/luciferase mRNA expression by angiotensin II stimulation. This report identifies the MEK1,2 response element that mediates angiotensin II-stimulated PAI-1 promoter activation and shows that activation of this element requires Sp1 and AP-1 co-activation. (C) 2004 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Feener, EP (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM edward.feener@joslin.harvard.edu FU NIDDK NIH HHS [P30 DK036836, DK 36836, DK 48358] NR 63 TC 22 Z9 25 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 2004 VL 103 IS 7 BP 2636 EP 2644 DI 10.1182/blood-2003-05-1737 PG 9 WC Hematology SC Hematology GA 830ZR UT WOS:000222163200037 PM 14656894 ER PT J AU Chiaretti, S Li, XC Gentleman, R Vitale, A Vignetti, M Mandelli, F Ritz, J Foa, R AF Chiaretti, S Li, XC Gentleman, R Vitale, A Vignetti, M Mandelli, F Ritz, J Foa, R TI Gene expression profile of adult T-cell acute lymphocytic leukemia identifies distinct subsets of patients with different response to therapy and survival SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; PROTEIN-KINASE; CLINICAL-SIGNIFICANCE; ANTIGEN EXPRESSION; B-CELLS; CANCER; CLASSIFICATION; LYMPHOMA; AHNAK; CD2 AB Gene expression profiles were examined in 33 adult patients with T-cell acute lymphocytic leukemia (T-ALL). Nonspecific filtering criteria identified 313 genes differentially expressed in the leukemic cells. Hierarchical clustering of samples identified 2 groups that reflected the degree of T-cell differentiation but was not associated with clinical outcome. Comparison between refractory patients and those who responded to induction chemotherapy identified a single gene, interleukin 8 (IL-8), that was highly expressed in refractory T-ALL cells and a set of 30 genes that was highly expressed in leukemic cells from patients who achieved complete remission. We next identified 19 genes that were differentially expressed in T-ALL cells from patients who either had a relapse or remained in continuous complete remission. A model based on the expression of 3 of these genes was predictive of duration of remission. The 3-gene model was validated on a further set of T-ALL samples from 18 additional patients treated on the same clinical protocol. This study demonstrates that gene expression profiling can identify a limited number of genes that are predictive of response to induction therapy and remission duration in adult patients with T-ALL. (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 Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Univ Roma La Sapienza, Dipartimento Biotecnol Cellulari & Ematol, Rome, Italy. RP Ritz, J (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM jerome_ritz@dfci.harvard.edu RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA66996] NR 53 TC 191 Z9 198 U1 3 U2 13 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 APR 1 PY 2004 VL 103 IS 7 BP 2771 EP 2778 DI 10.1182/blood-2003-09-3243 PG 8 WC Hematology SC Hematology GA 830ZR UT WOS:000222163200055 PM 14684422 ER PT J AU Cools, J Quentmeier, H Huntly, BJP Marynen, P Griffin, JD Drexler, HG Gilliland, DG AF Cools, J Quentmeier, H Huntly, BJP Marynen, P Griffin, JD Drexler, HG Gilliland, DG TI The EOL-1 cell line as an in vitro model for the study of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia SO BLOOD LA English DT Article ID IDIOPATHIC HYPEREOSINOPHILIC SYNDROME; ACUTE MYELOID-LEUKEMIA; TYROSINE KINASE; IMATINIB; FUSION; FLT3 AB We recently identified the chimeric kinase FlP1L1-platelet-derived growth factor receptor alpha (PDGFRalpha) as a cause of the hypereosinophilic syndrome and of chronic eosinophilic leukemia. To investigate the role of FIP1L1-PDGFRA in the pathogenesis of acute leukemia, we presence of FIP1L1-PDGFRA- One cell line, EOL-1, expressed the FIP1L1-PDGFRA fusion. Three structurally divergent kinase inhibitors-imatinib (STI-571), PKC412, and SU5614-inhibited the growth of EOL-1 cells. These results indicate that the fusion of FIP1L1 to lines, but they identify EOL-1 as an in vitro model for the study of FI1L1-PDGFRA-positive chronic eosinophilic leukemia and for the analysis of small molecule inhibitors of FIP1L1-PDGFRalpha. screened 87 leukemia cell lines for the PDGFRA occurs rarely in leukemia cell (C) 2004 by The American Society of Hematology. C1 Univ Leuven VIB, Ctr Human Genet, B-3000 Louvain, Belgium. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. DSMZ, German Collect Microorganisms & Cell Cultures, Dept Human & Anim Cell Cultures, Braunschweig, Germany. RP Cools, J (reprint author), Univ Leuven VIB, Ctr Human Genet, Campus Gasthuisberg O&N 06,Herestr 49, B-3000 Louvain, Belgium. EM jan.cools@med.kuleuven.ac.be RI huntly, brian/E-6725-2014; OI huntly, brian/0000-0003-0312-161X; Cools, Jan/0000-0001-6626-5843 FU NCI NIH HHS [CA66996]; NIDDK NIH HHS [DK50654] NR 20 TC 70 Z9 75 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 APR 1 PY 2004 VL 103 IS 7 BP 2802 EP 2805 DI 10.1182/blood-2003-07-2479 PG 4 WC Hematology SC Hematology GA 830ZR UT WOS:000222163200060 PM 14630792 ER PT J AU Hershey, CL Fisher, DE AF Hershey, CL Fisher, DE TI Mitf and Tfe3: members of a b-HLH-ZIP transcription factor family essential for osteoclast development and function SO BONE LA English DT Review DE Mitf; Tfe3; osteoclasts; osteopetrosis; bone; transcription factor ID NF-KAPPA-B; MOUSE MICROPHTHALMIA LOCUS; BONE-RESORPTION; RECEPTOR ACTIVATOR; CELL-DEVELOPMENT; GENE-EXPRESSION; SIGNAL-TRANSDUCTION; MILD OSTEOPETROSIS; SPLEEN-CELLS; MAST-CELLS AB The Microphthalmia-associated transcription factor (Mitf) is required for the proper development of several cell lineages including osteoclasts, melanocytes, retinal pigment epithelial cells, mast cells and natural killer cells. Mutations in Mitf in multiple organisms result in osteopetrosis clue to defective osteoclast development. Mitf is a member of the basic/helix-loop-helix/leucine zipper (b-HLH-ZIP) transcription factor subfamily named MiT, which also includes Tfe3. Genetic evidence indicates that Mitf and Tfe3 carry out essential functions in osteoclast development. Mitf has been shown to reside downstream of the macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-kappaB ligand (RANKL) signaling pathways that are critical for osteoclast proliferation, differentiation and function. Mitf and Tfe3 have been shown to regulate the expression of several target genes necessary for bone degradation by mature osteoclasts. Here, we review the bone and osteoclast phenotypes of animals with mutations in Mitf and Tfe3, Mitf's interaction partners and signaling pathways, and known target genes which, together with others yet to be identified, likely represent key effectors of bone resorption. (C) 2004 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Dept Pediat Hematol & Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Dana Farber Canc Inst, Dept Pediat Hematol & Oncol, 44 Binney St,Dana 630, Boston, MA 02115 USA. EM David_Fisher@dfci.harvard.edu FU NIAMS NIH HHS [R01AR45662] NR 71 TC 55 Z9 55 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD APR PY 2004 VL 34 IS 4 BP 689 EP 696 DI 10.1016/j.bone.2003.08.014 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 813QZ UT WOS:000220922900013 PM 15050900 ER PT J AU Chattopadhyay, M Goss, J Wolfe, D Goins, WC Huang, S Glorioso, JC Mata, M Fink, DJ AF Chattopadhyay, M Goss, J Wolfe, D Goins, WC Huang, S Glorioso, JC Mata, M Fink, DJ TI Protective effect of herpes simplex virus-mediated neurotrophin gene transfer in cisplatin neuropathy SO BRAIN LA English DT Article DE nerve growth factors; gene therapy; herpes; neuropathy ID NERVE GROWTH-FACTOR; ROOT GANGLION NEURONS; PERIPHERAL NEUROPATHY; DIABETIC NEUROPATHY; SYMPATHETIC NEURONS; INDUCED APOPTOSIS; SENSORY NEURONS; SPINAL-CORD; IN-VIVO; RECEPTORS AB Attempts to develop clinical treatments for neuropathy using neurotrophins have not been successful. We tested whether neurotrophin gene delivery to dorsal root ganglia (DRGs) using non-replicating herpes simplex virus (HSV)-based vectors could prevent the development of neuropathy caused by administration of cisplatin. Following subcutaneous inoculation of HSV vectors expressing nerve growth factor (NGF) or neurotrophin-3 (NT-3), neurons in the DRG were transduced to produce NGF or NT-3 in vivo. Inoculation of either the NGF- or the NT-3-expressing vectors 3 days before the start of a 6-week course of cisplatin treatment protected against cisplatin-induced neuropathy assessed by electrophysiological, histological and behavioural measures 2 months later. Iatrogenic neuropathy caused by administration of chemotherapeutic drugs represents an excellent target for a human trial to assess the potential of gene therapy to prevent neuropathy. C1 Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Mol Genet, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Biochem, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA 15213 USA. RP Fink, DJ (reprint author), 1914 Taubman Ctr,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM djfink@umich.edu NR 49 TC 40 Z9 44 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD APR PY 2004 VL 127 BP 929 EP 939 DI 10.1093/brain/awh103 PN 4 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 807ET UT WOS:000220485500025 PM 14749293 ER PT J AU Rigalleau, F Baudiffier, V Caplan, D AF Rigalleau, F Baudiffier, V Caplan, D TI Comprehension of sentences with stylistic inversion by French aphasic patients SO BRAIN AND LANGUAGE LA English DT Article ID BROCAS APHASIA; AGRAMMATIC APHASIA; LANGUAGE; PERFORMANCE; ACCOUNTS; DEFICITS; SYNTAX; ISSUES AB Three French-speaking agrammatic aphasics and three French-speaking Conduction aphasics were tested for comprehension of Active, Passive, Cleft-Subject, Cleft-Object, and Cleft-Object sentences with Stylistic Inversion using an object manipulation test. The agrammatic patients consistently reversed thematic roles in the latter sentence type, and the Conduction aphasics performed at chance. The results are discussed in relationship to existing models of aphasic impairments in assigning syntactic structures and using them to determine thematic roles in sentences. We conclude that the results for the agrammatic patients demonstrate the importance of compensatory mechanisms underlying aphasic comprehension and the results in the Conduction aphasics indicate the importance of working memory deficits in determining such deficits. The results are also relevant to models of normal syntactic structure. (C) 2003 Elsevier Inc. All rights reserved. C1 CNRS, UMR 6096, Lab Langage & Cognit, F-86022 Poitiers, France. Ctr Hosp & Univ Poitiers, Unit Neuropsychol, Serv Neurol, Poitiers, France. Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. RP Rigalleau, F (reprint author), CNRS, UMR 6096, Lab Langage & Cognit, F-86022 Poitiers, France. EM frigalleu@compuserve.com NR 51 TC 6 Z9 6 U1 2 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD APR PY 2004 VL 89 IS 1 BP 142 EP 156 DI 10.1016/S0093-934X(03)00334-1 PG 15 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 804FK UT WOS:000220284400017 PM 15010246 ER PT J AU Nascimento, ALTO Verjovski-Almeida, S Van Sluys, MA Monteiro-Vitorello, CB Camargo, LEA Digiampietri, LA Harstkeerl, RA Ho, PL Marques, MV Oliveira, MC Setubal, JC Haake, DA Martins, EAL AF Nascimento, ALTO Verjovski-Almeida, S Van Sluys, MA Monteiro-Vitorello, CB Camargo, LEA Digiampietri, LA Harstkeerl, RA Ho, PL Marques, MV Oliveira, MC Setubal, JC Haake, DA Martins, EAL TI Genome features of Leptospira interrogans serovar Copenhageni SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Article DE Leptospira interrogans; outer membrane proteins; lipopolysaccharides; transport; regulatory systems ID OUTER-MEMBRANE PROTEIN; PATHOGEN XYLELLA-FASTIDIOSA; BORRELIA-BURGDORFERI; SIGNAL-TRANSDUCTION; TREPONEMA-PALLIDUM; MAMMALIAN INFECTION; SEQUENCE-ANALYSIS; ESCHERICHIA-COLI; DNA-REPLICATION; DOMAINS AB We report novel features of the genome sequence of Leptospira interrogans serovar Copenhageni, a highly invasive spirochete. Leptospira species colonize a significant proportion of rodent populations worldwide and produce life-threatening infections in mammals. Genomic sequence analysis reveals the presence of a competent transport system with 13 families of genes encoding for major transporters including a three-member component efflux system compatible with the long-term survival of this organism. The leptospiral genome contains a broad array of genes encoding regulatory system, signal transduction and methyl-accepting chemotaxis proteins, reflecting the organism's ability to respond to diverse environmental stimuli. The identification of a complete set of genes encoding the enzymes for the cobalamin biosynthetic pathway and the novel coding genes related to lipopolysaccharide biosynthesis should bring new light to the study of Leptospira physiology. Genes related to toxins, lipoproteins and several surface-exposed proteins may facilitate a better understanding of the Leptospira pathogenesis and may serve as potential candidates for vaccine. C1 Inst Butantan, Ctr Biotecnol, BR-05503900 Sao Paulo, Brazil. Univ Sao Paulo, Inst Quim, BR-05508 Sao Paulo, Brazil. Univ Sao Paulo, Inst Biociencias, BR-05508 Sao Paulo, Brazil. Univ Sao Paulo, Inst Ciencias Biomed, BR-05508 Sao Paulo, Brazil. Univ Sao Paulo, Escola Super Agr Luiz Queiroz, Piracicaba, SP, Brazil. Univ Estadual Campinas, Inst Computacao, Lab Bioinformat, Campinas, SP, Brazil. Royal Trop Inst, KIT Biomed Res, NL-1105 AZ Amsterdam, Netherlands. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. Virginia Polytech Inst & State Univ, Virginia Bioinformat Inst, Blacksburg, VA 24061 USA. Virginia Polytech Inst & State Univ, Dept Comp Sci, Blacksburg, VA 24061 USA. RP Nascimento, ALTO (reprint author), Inst Butantan, Ctr Biotecnol, Av Vital Brazil,1500, BR-05503900 Sao Paulo, Brazil. EM tabet@butantan.gov.br RI IB/USP, Botanica/Q-7627-2016; Martins, Elizabeth/B-7135-2015; Marques, Marilis/C-3085-2013; Setubal, Joao/C-7305-2012; Verjovski-Almeida, Sergio/E-4082-2012; Oliveira, Mariana /G-2512-2012; Van Sluys, Marie-Anne/A-8483-2012; Nascimento, Ana Lucia/E-8488-2012; Camargo, Luis Eduardo/C-2735-2012; Ho, Paulo/P-8267-2015; Monteiro-Vitorello, Claudia/F-2436-2012; Digiampietri, Luciano/B-8597-2012 OI IB/USP, Botanica/0000-0002-4192-3747; Martins, Elizabeth/0000-0002-2333-9379; Setubal, Joao/0000-0001-9174-2816; Verjovski-Almeida, Sergio/0000-0002-6356-2401; Oliveira, Mariana /0000-0001-8495-2962; Van Sluys, Marie-Anne/0000-0002-6506-2734; Nascimento, Ana Lucia/0000-0003-4851-0870; Camargo, Luis Eduardo/0000-0002-5650-5695; Ho, Paulo/0000-0003-3652-241X; Monteiro-Vitorello, Claudia/0000-0002-1238-9354; Digiampietri, Luciano/0000-0003-4890-1548 FU NIAID NIH HHS [R01 AI034431, R01 AI034431-07] NR 60 TC 121 Z9 124 U1 1 U2 9 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, BRAZIL SN 0100-879X J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PD APR PY 2004 VL 37 IS 4 BP 459 EP 478 DI 10.1590/S0100-879X2004000400003 PG 24 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA 815MI UT WOS:000221046000003 PM 15064809 ER PT J AU Richardson, PG Barlogie, B Berenson, J Singhal, S Jagannath, S Irwin, D Rajkumar, SV Hideshima, T Bryant, B Damokosh, A Mulligan, G Xiao, H Esseltine, D Schenkein, D AF Richardson, PG Barlogie, B Berenson, J Singhal, S Jagannath, S Irwin, D Rajkumar, SV Hideshima, T Bryant, B Damokosh, A Mulligan, G Xiao, H Esseltine, D Schenkein, D TI Prognostic factors for response parameters and overall survival in patients with multiple myeloma following treatment with bortezomib SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract CT Annual Scientific Meeting of the British-Society-for-Haematology CY APR 19-21, 2004 CL Cardiff, WALES SP British Soc Haematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NW Mem Hosp, Chicago, IL 60611 USA. St Vincents Comprehens Canc Ctr, New York, NY USA. Alta Bates Canc Ctr, Berkeley, CA USA. Mayo Clin, Rochester, MN USA. Millennium Pharmaceut, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2004 VL 125 SU 1 MA 41 BP 13 EP 14 PG 2 WC Hematology SC Hematology GA 818CW UT WOS:000221224200042 ER PT J AU Crawford, L Morris, TCM Chauhan, D Anderson, KC Walker, B Irvine, AE AF Crawford, L Morris, TCM Chauhan, D Anderson, KC Walker, B Irvine, AE TI Profiling proteasome activity in multiple myeloma and lymphoma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract CT Annual Scientific Meeting of the British-Society-for-Haematology CY APR 19-21, 2004 CL Cardiff, WALES SP British Soc Haematol C1 Queens Univ Belfast, Dept Haematol, Belfast, Antrim, North Ireland. Queens Univ Belfast, Sch Pharm, Belfast, Antrim, North Ireland. Belfast City Hosp, Dept Haematol, Belfast, Antrim, North Ireland. Dana Farber Canc Inst, Boston, MA 02115 USA. RI IRVINE, ALEXANDRA/B-3497-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2004 VL 125 SU 1 MA 116 BP 37 EP 37 PG 1 WC Hematology SC Hematology GA 818CW UT WOS:000221224200117 ER PT J AU Tache, Y Martinez, V Wang, L Million, M AF Tache, Y Martinez, V Wang, L Million, M TI CRF1 receptor signaling pathways are involved in stress-related alterations of colonic function and viscerosensitivity: implications for irritable bowel syndrome SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Review DE corticotropin releasing factor; CRF; urocortin; CRF antagonists; CRF receptors; colonic motility; enteric nervous system; stress; irritable bowel syndrome ID CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENAL AXIS; WATER-AVOIDANCE STRESS; PARAVENTRICULAR NUCLEUS; RAT-BRAIN; NERVOUS-SYSTEM; MOTOR FUNCTION; COMPETITIVE ANTAGONISTS; FOS EXPRESSION; MESSENGER-RNA AB 1 The characterization of corticotropin releasing factor (CRF) and, more recently, the discovery of additional CRF-related ligands, urocortin 1, urocortin 2 and urocortin 3, the cloning of two distinct CRF receptor subtypes, 1 (CRF1) and 2 (CRF2), and the development of selective CRF receptor antagonists provided new insight to unravel the mechanisms of stress. Activation of brain CRF1 receptor signaling pathways is implicated in stress-related endocrine response and the development of anxiety-like behaviors. 2 Compelling evidence in rodents showed also that both central and peripheral injection of CRF and urocortin 1 mimic acute stress-induced colonic response ( stimulation of motility, transit, defecation, mucus and watery secretion, increased ionic permeability and occurrence of diarrhea) in rodents. Central CRF enhances colorectal distention-induced visceral pain in rats. Peripheral CRF reduced pain threshold to colonic distention and increased colonic motility in humans. 3 Nonselective CRF1/CRF2 antagonists and selective CRF1 antagonists inhibit exogenous (central or peripheral) CRF- and acute stress-induced activation of colonic myenteric neurons, stimulation of colonic motor function and visceral hyperalgesia while selective CRF2 antagonists have no effect. None of the CRF antagonists influence basal or postprandial colonic function in nonstressed animals. 4 These findings implicate CRF1 receptors in stress-related stimulation of colonic function and hypersensitivity to colorectal distention. Targeting CRF1-dependent pathways may have potential benefit against stress or anxiety-/depression-related functional bowel disorders. C1 Univ Calif Los Angeles, CURE, Digest Dis Res Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med,Div Digest Dis, W Los Angeles Vet Affairs Med Ctr, Ctr Neurovisceral Sci & Womans Hlth, Los Angeles, CA 90024 USA. AStraZeneca R&D Molndal, Integrat Pharmacol Gastrointestinal Biol, SE-43183 Molndal, Sweden. RP Tache, Y (reprint author), VA Greater Los Angeles Hlth Care Syst, CURE, Bldg 115,Room 117,1130 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@ucla.edu RI Martinez, Vicente/N-1189-2014 FU NIAMS NIH HHS [P50 AR 049550]; NIDDK NIH HHS [R01 DK 57238, P30 DK041301, DK 41301, DK 57238-01A1S1, R01 DK 33061, R01 DK033061, R01 DK057238] NR 119 TC 131 Z9 144 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD APR PY 2004 VL 141 IS 8 BP 1321 EP 1330 DI 10.1038/sj.bjp.0705760 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 817MT UT WOS:000221182300009 PM 15100165 ER PT J AU Tohen, M Chengappa, KNR Suppes, T Baker, RW Zarate, CA Bowden, CL Sachs, GS Kupfer, DJ Ghaemi, SN Feldman, PD Risser, RC Evans, AR Calabrese, JR AF Tohen, M Chengappa, KNR Suppes, T Baker, RW Zarate, CA Bowden, CL Sachs, GS Kupfer, DJ Ghaemi, SN Feldman, PD Risser, RC Evans, AR Calabrese, JR TI Relapse prevention in bipolar I disorder: 18-month comparison of olanzapine plus mood stabiliser v. mood stabiliser alone SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID TARDIVE-DYSKINESIA; RATING-SCALE; RECOVERY; MANIA; SCHIZOPHRENIA; RECURRENCE; PSYCHOSIS; EFFICACY; 6-MONTH; LITHIUM AB Background Few controlled studies have examined the use of atypical antipsychotic drugs for prevention of relapse in patients with bipolar I disorder Aims To evaluate whether olanzapine plus either lithium or valproate reduces the rate of relapse, compared with lithium or valproate alone. Method Patients achieving syndromic remission after 6 weeks' treatment with olanzapine plus either lithium (0.6- 1.2 mmol/l) or valproate (50-125 mug/ml) received lithium or valproate plus either olanzapine 5-20 mg/day (combination therapy) or placebo (monotherapy), and were followed in a double-masked trial for 18 months. Results The treatment difference in time to relapse into either mania or depression was not significant for syndromic relapse (median time to relapse: combination therapy 94 days, monotherapy 40.5 days; P=0.742), but was significant for symptomatic relapse (combination therapy 163 days, monotherapy 42 days; P=0.023). Conclusions Patients taking. olanzapine added to lithium or valproate experienced sustained symptomatic remission but not syndromic remission, for longer than those receiving lithium or valproate monotherapy. Declaration of interest M.T., R.W.B., P.D.F., A.R.E. and R.C.R. are stockholders in Eli Lilly & Company, the sponsor of this study. C1 Lilly Res Labs, Indianapolis, IN 46285 USA. Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02178 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. Lilly Res Labs, Indianapolis, IN USA. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Harvard Univ, Cambridge Hosp, Sch Med, Dept Psychiat, Cambridge, MA USA. Lilly Res Labs, Indianapolis, IN USA. Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. RP Tohen, M (reprint author), Lilly Res Labs, Indianapolis, IN 46285 USA. EM m.tohen@lilly.com RI Ghaemi, Nassir/J-4934-2013 NR 23 TC 213 Z9 217 U1 1 U2 4 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD APR PY 2004 VL 184 BP 337 EP 345 DI 10.1192/bjp.184.4.337 PG 9 WC Psychiatry SC Psychiatry GA 811EC UT WOS:000220754200011 PM 15056579 ER PT J AU Mithofer, K Giza, E AF Mithofer, K Giza, E TI Pseudarthrosis of the first rib in the overhead athlete SO BRITISH JOURNAL OF SPORTS MEDICINE LA English DT Article ID STRESS-FRACTURE; NONUNION; PITCHER; INJURY AB Fractures of the first rib are uncommon in athletes and present a different clinical entity from traumatic first rib fracture associated with high energy thoracic trauma. These fractures are stress induced and precipitated by chronic muscular forces acting on the first rib. Typically they heal with conservative treatment. This report describes a fracture of the first rib in a tennis player that developed into a symptomatic pseudarthrosis as a result of persistent overhead activities. Symptoms mimicked ipsilateral shoulder injury. Pseudarthrosis of the first rib should be included in the differential diagnosis of chronic persistent shoulder pain in the overhead athlete. C1 Hosp Special Surg, Shoulder & Sports Med Serv, New York, NY 10021 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Mithofer, K (reprint author), Hosp Special Surg, Shoulder & Sports Med Serv, 535 E 70th St, New York, NY 10021 USA. EM MithoeferK@HSS.EDU NR 10 TC 10 Z9 10 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-3674 J9 BRIT J SPORT MED JI Br. J. Sports Med. PD APR 1 PY 2004 VL 38 IS 2 BP 221 EP 222 DI 10.1136/bjsm.2002.002998 PG 2 WC Sport Sciences SC Sport Sciences GA 805XB UT WOS:000220397900027 PM 15039264 ER PT J AU Bellon, JR Shulman, LN Come, SE Li, XC Gelman, RS Silver, BJ Harris, JR Recht, A AF Bellon, JR Shulman, LN Come, SE Li, XC Gelman, RS Silver, BJ Harris, JR Recht, A TI A prospective study of concurrent cyclophosphamide/methotrexate/5-fluorouracil and reduced-dose radiotherapy in patients with early-stage breast carcinoma SO CANCER 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 breast; concurrent; cyclophosphamide/methotrexate/5-fluorouracil; radiotherapy ID RADIATION-THERAPY; CANCER PATIENTS; CONSERVATIVE SURGERY; FOLLOW-UP; CHEMOTHERAPY; RISK; CYCLOPHOSPHAMIDE; METHOTREXATE; CONCOMITANT; TRIAL AB BACKGROUND. Concurrent administration of chemotherapy and radiotherapy has the potential advantage of delaying neither treatment and providing radiation sensitization. However, the optimal approach to concurrent treatment in women with early-stage breast carcinoma remains undefined. We present updated results of a prospective protocol of concurrent cyclophosphamide/methotrexate/5-fluorouracil (CMF) and reduced-dose radiotherapy, focusing on tumor control and patient tolerance. METHODS. One hundred twelve women with AJCC Stage 1 or Stage 11 breast carcinoma with 0-3 positive axillary lymph nodes were enrolled in a prospective single-arm study of concurrent CMF and reduced-dose radiotherapy (39.6 gray [Gy] to the whole breast, 16-Gy boost). A high proportion of women had risk factors associated with an increased risk of local disease recurrence, including age < 40 (32%), close or positive margins (37%), or lymphatic/vascular invasion (51%). The median follow-up period was 94 months. RESULTS. The 5-year overall survival rate was 94%. By 60 months, 5 patients (4%) experienced local disease recurrence and 19 patients (17%) experienced distant metastasis. There were no isolated regional lymph node recurrences. Local disease recurrence occurred in 1 of 25 patients (4%), 1 of 16 patients (6%), and 3 of 70 patients (4%) with positive, close (< 1 mm), and negative margins, respectively. One patient developed acute myelogenous leukemia. An additional patient developed Grade 2 pneumonitis. Cosmetic results were not recorded uniformly for all patients and therefore could not be reliably analyzed. CONCLUSIONS. Concurrent CMF and reduced-dose radiotherapy resulted in a low level of late toxicity and excellent local tumor control, despite the large proportion of patients with substantial risk factors for local disease recurrence. Future studies of concurrent regimens, particularly in patients at high risk of local disease recurrence, are warranted. (C) 2004 American Cancer Society. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. RP Bellon, JR (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM jbellon@lroc.harvard.edu NR 39 TC 20 Z9 20 U1 2 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD APR 1 PY 2004 VL 100 IS 7 BP 1358 EP 1364 DI 10.1002/cncr.20136 PG 7 WC Oncology SC Oncology GA 805BE UT WOS:000220341000006 PM 15042668 ER PT J AU Rizzieri, DA Johnson, JL Niedzwiecki, D Lee, EJ Vardiman, JW Powell, BL Barcos, M Bloomfield, CD Schiffer, CA Peterson, BA Canellos, GP Larson, RA AF Rizzieri, DA Johnson, JL Niedzwiecki, D Lee, EJ Vardiman, JW Powell, BL Barcos, M Bloomfield, CD Schiffer, CA Peterson, BA Canellos, GP Larson, RA TI Intensive chemotherapy with and without cranial radiation for Burkitt leukemia and lymphoma - Final results of cancer and leukemia group B study 9251 SO CANCER LA English DT Article DE Burkitt leukemia; Burkitt lymphoma; chemotherapy; central nervous system prophylaxis non-Hodgkin lymphoma; small noncleaved cell lymphoma ID ACUTE LYMPHOBLASTIC-LEUKEMIA; NONCLEAVED-CELL LYMPHOMA; CHILDREN; ADULTS; CHILDHOOD; REGIMEN; TRIAL AB BACKGROUND. The objective of the current study was to evaluate the efficacy of intensive chemotherapy with and without cranial radiation for central nervous system (CNS) prophylaxis in adults with Burkitt leukemia or lymphoma. METHODS. Patients received 18 weeks of therapy. Prophylactic cranial radiation (2400 centigrays) and 12 doses of triple intrathecal chemotherapy were administered to the first cohort of patients. A subsequent cohort received the same therapy, with the exceptions that intrathecal therapy was reduced to six doses and radiotherapy was administered only to high-risk individuals. RESULTS. The median follow-up durations were 6.8 years in Cohort 1 and 4.1 years in Cohort 2. Three Occurrences of transverse myelitis, 2 severe neuropathies, 3 cases of aphasia, and 1 case of blindness were documented in the first cohort of 52 patients (Cohort 1). In the subsequent cohort of 40 patients (Cohort 2), none of these occurrences were observed, and patients experienced less neurologic toxicity overall (61% vs. 26%; P = 0.001). Responses were similar, and the 3-year event-free survival rate was 0.52 (95% confidence interval, 0.38-0.65) for Cohort 1 and 0.45 (0.29-0.60) for Cohort 2. CONCLUSIONS. intensive, short-duration chemotherapy with less intensive CNS prophylaxis led to control at this sanctuary site with little neurotoxicity and may be curative for adults with Burkitt leukemia or lymphoma. (C) 2004 American Cancer Society. C1 Duke Univ, Med Ctr, Dept Med, Div Oncol & Bone Marrow Transplantat, Durham, NC 27710 USA. Canc & Leukemia Grp B Stat Ctr, Durham, NC USA. Maryland Oncol PA, Columbia, MD USA. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Wake Forest Univ, Baptist Med Ctr, Dept Hematol & Oncol, Winston Salem, NC USA. Roswell Pk Canc Inst, Dept Pathol, Buffalo, NY 14263 USA. Roswell Pk Canc Inst, Dept Pathol, Buffalo, NY 14263 USA. Ohio State Univ, Dept Hematol & Oncol, Coll Med & Publ Hlth, Columbus, OH 43210 USA. Wayne State Univ, Sch Med, Dept Internal Med, Detroit, MI USA. Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Rizzieri, DA (reprint author), Duke Univ, Med Ctr, Dept Med, Div Oncol & Bone Marrow Transplantat, Box 3961, Durham, NC 27710 USA. OI Larson, Richard/0000-0001-9168-3203 FU NCI NIH HHS [CA47545, CA77440, CA41287, CA33601, CA26806, CA16450, CA12046, CA10-1140, CA02599, CA47642, CA47555, CA77597, CA35279, CA31946, CA12449, CA11789, CA32291, CA77658, CA03927, CA04326, CA07968, CA08025, CA21060, CA31983, CA47577] NR 27 TC 49 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 APR 1 PY 2004 VL 100 IS 7 BP 1438 EP 1448 DI 10.1002/cncr.20143 PG 11 WC Oncology SC Oncology GA 805BE UT WOS:000220341000016 PM 15042678 ER PT J AU Tuveson, DA Shaw, AT Willis, NA Silver, DP Jackson, EL Chang, S Mercer, KL Grochow, R Hock, H Crowley, D Hingorani, SR Zaks, T King, C Jacobetz, MA Wang, LF Bronson, RT Orkin, SH DePinho, RA Jacks, T AF Tuveson, DA Shaw, AT Willis, NA Silver, DP Jackson, EL Chang, S Mercer, KL Grochow, R Hock, H Crowley, D Hingorani, SR Zaks, T King, C Jacobetz, MA Wang, LF Bronson, RT Orkin, SH DePinho, RA Jacks, T TI Endogenous oncogenic K-ras(G12D) stimulates proliferation and widespread neoplastic and developmental defects SO CANCER CELL LA English DT Article ID ARF TUMOR-SUPPRESSOR; K-RAS ONCOGENE; EMBRYO FIBROBLASTS; CRE RECOMBINASE; CONDITIONAL EXPRESSION; SOMATIC ACTIVATION; MAMMALIAN-CELLS; INK4A LOCUS; STEM-CELLS; P53 AB Activating mutations in the ras oncogene are not considered sufficient to induce abnormal cellular proliferation in the absence of cooperating oncogenes. We demonstrate that the conditional expression of an endogenous k-ras(G12D) allele in murine embryonic fibroblasts causes enhanced proliferation and partial transformation in the absence of further genetic abnormalities. Interestingly, K-ras(G12D)-expressing fibroblasts demonstrate attenuation and altered regulation of canonical Ras effector signaling pathways. Widespread expression of endogenous K-ras(G12D) is not tolerated during embryonic development, and directed expression in the lung and GI tract induces preneoplastic epithelial hyperplasias. Our results suggest that endogenous oncogenic ras is sufficient to initiate transformation by stimulating proliferation, while further genetic lesions may be necessary for progression to frank malignancy. C1 MIT, Ctr Canc, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. Tufts Univ, Sch Med & Vet Med, Dept Pathol, Boston, MA 02111 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Abramson Canc Ctr, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. RP Jacks, T (reprint author), MIT, Ctr Canc, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM tjacks@mit.edu RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 FU NIDDK NIH HHS [P30 DK050306] NR 47 TC 435 Z9 448 U1 2 U2 23 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD APR PY 2004 VL 5 IS 4 BP 375 EP 387 DI 10.1016/S1535-6108(04)00085-6 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 817DG UT WOS:000221157600012 PM 15093544 ER PT J AU Xi, ZJ Klokk, TI Korkmaz, K Kurys, P Elbi, C Risberg, B Danielsen, H Loda, M Saatcioglu, F AF Xi, ZJ Klokk, TI Korkmaz, K Kurys, P Elbi, C Risberg, B Danielsen, H Loda, M Saatcioglu, F TI Kallikrein 4 is a predominantly nuclear protein and is overexpressed in prostate cancer SO CANCER RESEARCH LA English DT Article ID GENE FAMILY; MOLECULAR-CLONING; SERINE-PROTEASE; GENOMIC ORGANIZATION; HOMEOBOX GENE; EXPRESSION; ANTIGEN; LOCALIZATION; FORMS; CELLS AB Kallikreins (KLKs) are highly conserved serine proteases that play key roles in a variety of physiological and pathological processes. KLKs are secreted proteins that have extracellular substrates and function. For example, prostate-specific antigen (or KLK3) is a secreted protein that is widely used as a diagnostic marker for prostate cancer. KLK4 is a recently identified member of the kallikrein family that is regulated by androgens and is highly specific to prostate for expression. Here, we show that the gene product of KLK4, hK4, is the first member of the KLK family that is intracellularly localized. We provide strong evidence that the previously assigned first exon that was predicted to code for a signal peptide that would target hK4 for secretion is not part of the physiologically relevant form of KLK4 mRNA. In addition to detailed mapping of the KLK4 mRNA 5' end by RT-PCR, this conclusion is supported by predominantly nuclear localization of the hK4 protein in the cell, documented by both immunofluorescence and cell fractionation experiments. Furthermore, in addition to androgens, hK4 expression is regulated by estrogen and progesterone in prostate cancer cells. Finally, in situ hybridization on normal and hyperplastic prostate samples in tissue microarrays indicate that KLK4 is predominantly expressed in the basal cells of the normal prostate gland and overexpressed in prostate cancer. These data suggest that KLK4 has a unique structure and function compared with other members of the KLK family and may have a role in the biology and characterization of prostate cancer. C1 Univ Oslo, Dept Biol, N-0316 Oslo, Norway. NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. Norwegian Radium Hosp, Dept Pathol, Oslo, Norway. Univ Sheffield, Div Gen Med, Sheffield S10 2TN, S Yorkshire, England. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. RP Saatcioglu, F (reprint author), Univ Oslo, Dept Biol, PB1050, N-0316 Oslo, Norway. EM fahris@bio.uio.no RI Risberg, Bjorn/A-6447-2008; Danielsen, Havard/A-7540-2014 NR 34 TC 83 Z9 84 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 APR 1 PY 2004 VL 64 IS 7 BP 2365 EP 2370 DI 10.1158/0008-5472.CAN-03-2025 PG 6 WC Oncology SC Oncology GA 808RP UT WOS:000220586500011 PM 15059887 ER PT J AU Bockhorn, M Roberge, S Sousa, C Jain, RK Munn, LL AF Bockhorn, M Roberge, S Sousa, C Jain, RK Munn, LL TI Differential gene expression in metastasizing cells shed from kidney tumors SO CANCER RESEARCH LA English DT Article ID INTEGRIN ALPHA-3 EXPRESSION; MESSENGER-RNA LEVELS; CANCER-CELLS; ADHESION MOLECULES; CAVEOLIN-1; ADENOCARCINOMA; TUMORIGENICITY; CHOLESTEROL; PROGRESSION; RESISTANCE AB We developed a novel orthotopic mouse tumor model of renal cell carcinoma to collect and characterize cells spontaneously shed from SN12C (renal cell carcinoma) and SN12L1 (high metastatic variant of SN12C) tumors grown in kidneys of severe combined immunodeficient mice. Viability of the shed cell population was greater for SN12L1 tumors (25%) compared with SN12C tumors (11%, P < 0.05). Gene array analysis of 23 genes involved in metastasis showed that CD44, alpha3 integrin, and caveolin were down-regulated in the shed tumor cells compared with their primary counterparts, and blocking alpha3 integrin or CD44 function inhibited attachment and migration of both cell lines. These results suggest that cohesion of the cells within the primary tumor mediated by CD44 and alpha3 integrins hinders metastasis and that shedding is a passive process not necessarily mediated by cell migration in these tumors. Furthermore, resistance to apoptosis may enhance metastasis in the higher metastatic tumor. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Munn, LL (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, 100 Blossom St,COX-736, Boston, MA 02114 USA. EM lance@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NCI NIH HHS [R24 CA-85146, R01 CA085140-09] NR 20 TC 30 Z9 32 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 APR 1 PY 2004 VL 64 IS 7 BP 2469 EP 2473 DI 10.1158/0008-5472.CAN-03-0256 PG 5 WC Oncology SC Oncology GA 808RP UT WOS:000220586500024 PM 15059900 ER PT J AU Liu, WH Kaur, M Wang, G Zhu, P Zhang, YZ Makrigiorgos, GM AF Liu, WH Kaur, M Wang, G Zhu, P Zhang, YZ Makrigiorgos, GM TI Inverse PCR-based RFLP scanning identifies low-level mutation signatures in colon cells and tumors SO CANCER RESEARCH LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SINGLE NUCLEOTIDE INSTABILITY; MISMATCH REPAIR DEFICIENCY; POLYMERASE-CHAIN-REACTION; CHRONIC MYELOID-LEUKEMIA; MICROSATELLITE INSTABILITY; GENOMIC INSTABILITY; BCR-ABL; CLINICAL RESISTANCE; COLORECTAL CANCERS AB Detecting the presence and diversity of low-level mutations in human tumors undergoing genomic instability is desirable due to their potential prognostic value and their putative influence on the ability of tumors to resist drug treatment and/or metastasize. However, direct measurement of these genetic alterations in surgical samples has been elusive, because technical hurdles make mutation discovery impractical at low-mutation frequency levels (<10(-2)). Here, we describe inverse PCR-based amplified restriction fragment length polymorphism (iFLP), a new technology that combines inverse PCR, RFLP, and denaturing high-performance liquid chromatography to allow scanning of the genome at several thousand positions per experiment for low-level point mutations. Using iFLP, widespread, low-level mutations at mutation frequency 10(-2)-10(-1) were discovered in genes located on different chromosomes, e.g., OGG1, MSH2, PTEN, beta-catenin, Bcl-2, P21, ATK3, and Braf, in human colon cancer cells that harbor mismatch repair deficiency whereas mismatch repair-proficient cells were mutation free. Application of iFLP to the screening of sporadic colon cancer surgical specimens demonstrated widespread low-level mutations in seven out of 10 samples, but not in their normal tissue counterparts, and predicted the presence of millions of diverse, low-incidence mutations in tumors. Unique low-level mutational signatures were identified for each colon cancer cell line and tumor specimen. iFLP allows the high-throughput discovery and tracing of mutational signatures in human cells, precancerous lesions, and primary or metastatic tumors and the assessment of the number and heterogeneity of low-level mutations in surgical samples. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Makrigiorgos, GM (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St,Level L2, Boston, MA 02115 USA. EM mmakrigiorgos@partners.org FU NCI NIH HHS [5 T32 CA09078, CA083234] NR 53 TC 8 Z9 9 U1 3 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 APR 1 PY 2004 VL 64 IS 7 BP 2544 EP 2551 DI 10.1158/0008-5472.CAN-03-3652 PG 8 WC Oncology SC Oncology GA 808RP UT WOS:000220586500034 PM 15059910 ER PT J AU Kasuya, H Pawlik, TM Mullen, JT Donahue, JM Nakamura, H Chandrasekhar, S Kawasaki, H Choi, E Tanabe, KK AF Kasuya, H Pawlik, TM Mullen, JT Donahue, JM Nakamura, H Chandrasekhar, S Kawasaki, H Choi, E Tanabe, KK TI Selectivity of an oncolytic herpes simplex virus for cells expressing the DF3/MUC1 antigen SO CANCER RESEARCH LA English DT Article ID ACTIVATED PROTEIN-KINASE; REPLICATION-COMPETENT ADENOVIRUS; DIFFUSE LIVER METASTASES; MONOCLONAL-ANTIBODY DF3; BREAST-CARCINOMA CELLS; PHASE-I TRIAL; GENE-THERAPY; HEPATOCELLULAR-CARCINOMA; CELLULAR INHIBITOR; MALIGNANT GLIOMA AB Replication-conditional viruses destroy tumors in a process referred to as viral oncolysis. An important prerequisite for this cancer therapy strategy is use of viruses that replicate preferentially in neoplastic cells. In this study the DF3/MUC1 promoter/enhancer sequence is used to regulate expression of gamma(1)34.5 to drive replication of a Herpes simplex virus 1 (HSV-1) mutant (DF3gamma34.5) preferentially in DF3/MUC1-positive cells. HSV-1 gamma(1)34.5 functions to dephosphorylate elongation initiation factor 2alpha, which is an important step for robust HSV-1 replication. After DF3gamma34.5 infection of cells, elongation initiation factor 2a phosphatase activity and viral replication were observed preferentially in DF3/MUC1-positive cells but not in DF3/MUC1-negative cells. Regulation of gamma(1)34.5 function results in preferential replication in cancer cells that express DF3/MUC1, restricted biodistribution in vivo, and less toxicity as assessed by LD50. Preferential replication of DF3gamma34.5 was observed in DF3/MUC1-positive liver tumors after intravascular perfusion of human liver specimens. DF3gamma34.5 was effective against carcinoma xenografts in nude mice. Regulation of gamma(1)34.5 by the DF3/MUC1 promoter is a promising strategy for development of HSV-1 mutants for viral oncolysis. C1 Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Cox Bldg 626,55 Fruit St, Boston, MA 02114 USA. RI Kasuya, hideki/I-7278-2014 FU NCI NIH HHS [CA71345, CA64454, CA76183]; NIDDK NIH HHS [DK43352]; NIGMS NIH HHS [GM07035] NR 46 TC 39 Z9 42 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2004 VL 64 IS 7 BP 2561 EP 2567 DI 10.1158/0008-5472.CAN-03-3431 PG 7 WC Oncology SC Oncology GA 808RP UT WOS:000220586500036 PM 15059912 ER PT J AU Spiro, RG AF Spiro, RG TI Role of N-linked polymannose oligosaccharides in targeting glycoproteins for endoplasmic reticulum-associated degradation SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE protein quality control; free polymannose oligosaccharides; N-glycanase; endomannosidase; protein folding; ER mannosidases; lectin chaperones; protein retrotranslocation ID UNFOLDED PROTEIN RESPONSE; ALPHA-D-MANNOSIDASE; ER QUALITY-CONTROL; RAT-LIVER GOLGI; NEWLY SYNTHESIZED GLYCOPROTEINS; YEAST SACCHAROMYCES-CEREVISIAE; UBIQUITIN-PROTEASOME PATHWAY; CELL ANTIGEN RECEPTOR; GLYCOPEPTIDE EXPORT; MEMBRANE-PROTEIN AB Misfolded or incompletely assembled multisubunit glycoproteins undergo endoplasmic reticulum-associated degradation (ERAD) regulated in large measure by their N-linked polymannose oligosaccharides. In this quality control system lectin interaction with Glc(3)Man(9)GlcNAc(2) glycans after trimming with endoplasmic reticulum (ER) alpha-glucosidases and alpha-mannosidases sorts out persistently unfolded glycoproteins for N-deglycosylation and proteolytic degradation. Monoglucosylated (Glc(1)Man(9)GlcNAc(2)) glycoproteins take part in the calnexin/calreticulin glucosylation-deglucosylation cycle, while the Man(8)GlcNAc(2) isomer B product of ER mannosidase I interacts with EDEM. Proteasomal degradation requires retrotranslocation into the cytosol through a Sec61 channel and deglycosylation by peptide: N-glycosidase (PNGase); in alternate models both PNGase and proteasomes may be either free in the cytosol or ER membrane-imbedded/attached. Numerous proteins appear to undergo nonproteasomal degradation in which deglycosylation and proteolysis take place in the ER lumen. The released free oligosaccharides (OS) are transported to the cytosol as OS-GlcNAc(2) along with similar components produced by the hydrolytic action of the oligosaccharyltransferase, where they together with OS from the proteasomal pathway are trimmed to Man(5)GlcNAc(1) by the action of cytosolic endo-beta-N-acetylglucosaminidase and alpha-mannosidase before entering the lysosomes. Some misfolded glycoproteins can recycle between the ER, intermediate and Golgi compartments, where they are further processed before ERAD. Moreover, properly folded glycoproteins with mannose-trimmed glycans can be deglucosylated in the Golgi by endomannosidase, thereby releasing calreticulin and permitting formation of complex OS. A number of regulatory controls have been described, including the glucosidase-glucosyltransferase shuttle, which controls the level of Glc(3)Man(9)GlcNAc(2)-P-P-Dol, and the unfolded protein response, which enhances synthesis of components of the quality control system. C1 Harvard Univ, Sch Med, Dept Biol Chem, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA USA. RP Spiro, RG (reprint author), Harvard Univ, Sch Med, Dept Biol Chem, Boston, MA 02215 USA. EM robert.spiro@joslin.harvard.edu NR 153 TC 109 Z9 111 U1 1 U2 8 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD APR PY 2004 VL 61 IS 9 BP 1025 EP 1041 DI 10.1007/s00018-004-4037-8 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 815QK UT WOS:000221056600003 PM 15112051 ER PT J AU Ally, S Sauer, NJ Loureiro, JJ Snapper, SB Gertler, FB Goldberg, MB AF Ally, S Sauer, NJ Loureiro, JJ Snapper, SB Gertler, FB Goldberg, MB TI Shigella interactions with the actin cytoskeleton in the absence of Ena/VASP family proteins SO CELLULAR MICROBIOLOGY LA English DT Article ID VASODILATOR-STIMULATED PHOSPHOPROTEIN; LISTERIA-MONOCYTOGENES; ARP2/3 COMPLEX; N-WASP; INTRACELLULAR MOTILITY; FOCAL-ADHESION; F-ACTIN; MICROFILAMENT BUNDLES; INTERCELLULAR SPREAD; FIBROBLAST MOTILITY AB Shigella move through the cytosol of infected cells by assembly of a propulsive actin tail at one end of the bacterium. Vasodilator-stimulated phosphoprotein (VASP), a member of the Ena/VASP family of proteins, is important in cellular actin dynamics and is present on intracellular Shigella. VASP binds both profilin, an actin monomer-binding protein, and vinculin, a component of intercellular contacts that also binds the Shigella actin assembly protein IcsA. It has been postulated that VASP might serve as a linker between vinculin and profilin on intracellular Shigella, thereby delivering profilin to the Shigella actin assembly machinery. We show that Shigella actin-based motility is unaltered in cells that are deficient for the Ena/VASP family of proteins. In these cells, Shigella form normal-appearing actin tails and move at rates that are comparable to the rates of bacterial movement in Ena/VASP-deficient cells complemented with the Ena/VASP family member Mena. Finally, whereas vinculin can bind the Arp2/3 complex, we show that Arp2/3 recruitment to Shigella is not correlated with vinculin recruitment, indicating that the role of vinculin in Shigella motility is not recruitment of Arp2/3. Thus, although VASP is recruited to the surface of intracellular Shigella, it is not essential for Shigella actin-based motility. C1 Massachusetts Gen Hosp, Div Infect Dis, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Cambridge, MA 02139 USA. RP Goldberg, MB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Cambridge, MA 02139 USA. EM mgoldberg1@partners.org FU NIAID NIH HHS [F31 AI 51228, R01 AI 052354]; NIGMS NIH HHS [GM 58801]; PHS HHS [F32 G 20286] NR 66 TC 11 Z9 11 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD APR PY 2004 VL 6 IS 4 BP 355 EP 366 DI 10.1111/j.1462-5822.2003.00359.x PG 12 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 800CN UT WOS:000220006600005 PM 15009027 ER PT J AU Tootell, RBH Nelissen, K Vanduffel, W Orban, GA AF Tootell, RBH Nelissen, K Vanduffel, W Orban, GA TI Search for color 'center(s)' in macaque visual cortex SO CEREBRAL CORTEX LA English DT Article DE color; double label deoxyglucose; monkey; V4 ID MONKEY PRESTRIATE CORTEX; STRIATE CORTEX; RHESUS-MONKEY; AREA V2; SELECTIVE CELLS; TOPOGRAPHIC ORGANIZATION; FUNCTIONAL-ORGANIZATION; CEREBRAL-ACHROMATOPSIA; INFEROTEMPORAL CORTEX; HUE DISCRIMINATION AB It is often stated that color is selectively processed in cortical area V4, in both macaques and humans. However most recent data suggests that color is instead processed in region(s) antero-ventral to V4. Here we tested these two hypotheses in macaque visual cortex, where 'V4' was originally defined, and first described as color selective. Activity produced by equiluminant color-varying (versus luminance-varying) gratings was measured using double-label deoxyglucose in awake fixating macaques, in multiple areas of flattened visual cortex. Much of cortex was activated near-equally by both color- and luminance-varying stimuli. In remaining cortical regions, discrete color-biased columns were found in many cortical visual areas, whereas luminance-biased activity was found in only a few specific regions (V1 layer 4B and area MT). Consistent with a recent hypothesis, V4 was not uniquely specialized for color processing, but areas located antero-ventral to V4 (in/near TEO and anterior TE) showed more color-biased activity. C1 Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Katholieke Univ Leuven, Sch Med, Neuro & Psychofysiol Lab, B-3000 Louvain, Belgium. RP Tootell, RBH (reprint author), Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Boston, MA 02115 USA. EM tootell@nmr.mgh.harvard.edu NR 74 TC 62 Z9 63 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD APR PY 2004 VL 14 IS 4 BP 353 EP 363 DI 10.1093/cercor/bhh001 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 805AQ UT WOS:000220339600001 PM 15028640 ER PT J AU Skloot, G Goldman, M Fischler, D Goldman, C Schechter, C Levin, S Teirstein, A AF Skloot, G Goldman, M Fischler, D Goldman, C Schechter, C Levin, S Teirstein, A TI Respiratory symptoms and physiologic assessment of ironworkers at the World Trade Center disaster site SO CHEST LA English DT Article DE exposure; forced oscillation; ironworkers; September 11, 2001; spirometry; World Trade Center disaster ID FORCED OSCILLATION TECHNIQUE; LUNG-FUNCTION; IMPULSE OSCILLOMETRY; IRRITANT INHALATION; BRONCHIAL CHALLENGE; ASTHMATIC-CHILDREN; NORMAL VALUES; COLD-AIR; RESPONSIVENESS; METHACHOLINE AB Study objectives: To characterize respiratory abnormalities in a convenience sample of ironworkers exposed at the World Trade Center (WTC) disaster site for varying lengths of time between September 11, 2001, and February 8, 2002. Design: Cross-sectional study. Setting: The Mount Sinai Medical Center, a large tertiary hospital. Participants: Ninety-six ironworkers engaged in rescue and recovery with exposure onset between September 11, 2001, and September 15, 2001, who responded to an invitation to undergo respiratory evaluation. Measurements: Medical and exposure history, physical examination, spirometry, forced oscillation (FO), and chest radiographs. The relationships of prevalence of respiratory symptoms and presence of obstructive physiology to smoking, exposure on September 11, duration of exposure, and type of respiratory protection were examined using univariate and linear and logistic regression analyses. Results; Seventy-four of 96 workers (77%) had one or more respiratory symptoms (similar in smokers [49 of 63 subjects, 78%] and nonsmokers [25 of 33 subjects, 76%]). Cough was the most common symptom (62 of 96 subjects, 65%), and was associated with exposure on September 11. Chest examination and radiograph findings were abnormal in 10 subjects (10%) and 19 subjects (20%), respectively. FO revealed dysfunction in 34 of 64 subjects tested (53%), while spirometry suggested obstruction in only 11 subjects (17%). Lack of a respirator with canister was a risk factor for large airway dysfunction, and cigarette smoking was a risk factor for small airway dysfunction. No other relationships reached statistical significance. Conclusions: Respiratory symptoms occurred in the majority of ironworkers at the WTC disaster site and were not attributable to smoking. Exposure on September 11 was associated with a greater prevalence of cough. Objective evidence of lung disease was less common. Spirometry underestimated the prevalence of lung function abnormalities in comparison to FO. Continuing evaluation of symptoms, chest radiographs, and airway dysfunction should determine whether long-term clinical sequelae will exist. C1 CUNY, Mt Sinai Med Ctr, Div Pulm & Crit Care Med, New York, NY 10029 USA. Univ Calif Los Angeles, Dept Med, Sch Med, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Dept Obstet Gynecol & Gen Internal Med, Los Angeles, CA 90073 USA. Albert Einstein Coll Med, New York, NY USA. Mt Sinai Sch Med, Div Environm & Occupat Med, New York, NY USA. RP Skloot, G (reprint author), CUNY, Mt Sinai Med Ctr, Div Pulm & Crit Care Med, 1 Gustave L Levy Pl,Box 1232, New York, NY 10029 USA. EM Gwen.Skloot@msnyuhealth.org NR 43 TC 87 Z9 87 U1 1 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD APR PY 2004 VL 125 IS 4 BP 1248 EP 1255 DI 10.1378/chest.125.4.1248 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 825YB UT WOS:000221793700015 PM 15078731 ER PT J AU Byrne, JG Leacche, M Agnihotri, AK Paul, S Bueno, R Mathisen, DJ Sugarbaker, DJ AF Byrne, JG Leacche, M Agnihotri, AK Paul, S Bueno, R Mathisen, DJ Sugarbaker, DJ TI The use of cardiopulmonary bypass during resection of locally advanced thoracic malignancies - A 10-year two-center experience SO CHEST LA English DT Article DE cardiopulmonary bypass; thoracic surgery; tumor ID LUNG-CANCER; LEFT ATRIUM; GREAT-VESSELS; OPERATION; ARTERY; CARCINOMA; DISEASE AB The use of cardiopulmonary bypass (CPB) for locally advanced thoracic malignancies is highly controversial. The purpose of this study was to document the techniques and results of CPB to facilitate the resection of complex thoracic malignancies and to identify common themes that provided for successful outcomes. This was a retrospective study that took place from January 1992 to September 2002. Fourteen consecutive patients (median age, 59 years; age range, IS to 69 years; seven men and seven women) underwent CPB during the resection of locally advanced thoracic malignancies at two Boston hospitals. CPB was planned in 8 of 14 patients (57%) with centrally located tumors, while 6 of 14 patients (43%) required emergent institution of CPB due to injury of the superior vena cava (2 patients), inferior vena cava (2 patients), or pulmonary artery (2 patients). Complete microscopic resection was achieved in 12 of 14 patients (86%). The operative mortality rate was 1 of 14 patients (7%) due to pulmonary embolism (ie, the elective group). The median ICU and hospital lengths of stay were 5 and 9 days, respectively. The overall 1-year, 3-year, and 5-year survival rates were 57%, 36%, and 21%, respectively. The planned use of CPB to facilitate complete resection of thoracic malignancies should be considered only after careful patient selection. The availability of CPB also provides a safety net in the event of injury to vascular structures during tumor resection. C1 Brigham & Womens Hosp, Div Cardiac Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Cardiac Surg Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Thorac Surg Unit, Boston, MA 02114 USA. RP Byrne, JG (reprint author), Brigham & Womens Hosp, Div Cardiac Surg, 75 Francis St, Boston, MA 02115 USA. EM JBYRNE@PARTNERS.ORG NR 19 TC 24 Z9 25 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 APR PY 2004 VL 125 IS 4 BP 1581 EP 1586 DI 10.1378/chest.125.4.1581 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 825YB UT WOS:000221793700062 PM 15078778 ER PT J AU Park, JY Kob, M Prodeus, AP Rosen, FS Shcherbina, A Remold-O'Donnell, E AF Park, JY Kob, M Prodeus, AP Rosen, FS Shcherbina, A Remold-O'Donnell, E TI Early deficit of lymphocytes in Wiskott-Aldrich syndrome: possible role of WASP in human lymphocyte maturation SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE immunodeficiency; T lymphocytes; naive T-cells; B lymphocytes ID T-CELLS; NEGATIVE SELECTION; DIFFERENTIATION; POLYMERIZATION; THYMOCYTES; APOPTOSIS; SUBSETS; FAMILY; BLOOD AB Wiskott-Aldrich syndrome (WAS) is an X-linked platelet/immunodeficiency disease. The affected gene encodes WASP, a multidomain protein that regulates cytoskeletal assembly in blood cells. Patients have recurring infections, and their lymphocytes exhibit deficient proliferative responses in vitro. We report an evaluation of peripheral blood lymphocytes of 27 WAS patients, aged one month to 55 years. Whereas NK cells were normal, a significant deficit of T and B lymphocytes was observed. The number of lymphocytes was already decreased in infant patients, suggesting deficient output. Both CD4 and CD8 T lymphocytes were affected; the decrease was most pronounced for naive T cells. Naive CD4 lymphocytes of patients showed normal expression of Bcl-2, and Ki-67, and normal survival in vitro, suggesting that their in vivo survival and proliferation are normal. The collective data suggest that the patients' lymphocyte deficit results from deficient output, likely due to abnormal lymphocyte maturation in the thymus and bone marrow. We propose that WASP plays an important role not only in the function of mature T lymphocytes, but also in the maturation of human T and B lymphocytes and that impaired lymphocyte maturation is central to the aetiology of WAS immunodeficiency. C1 CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Res Inst Paediat Haematol, Moscow, Russia. RP Remold-O'Donnell, E (reprint author), CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM remold@cbr.med.harvard.edu FU NHLBI NIH HHS [HL59561, P01 HL059561]; NIAID NIH HHS [AI39574, R01 AI039574] NR 32 TC 41 Z9 44 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD APR PY 2004 VL 136 IS 1 BP 104 EP 110 DI 10.1111/j.1365-2249.2004.02409.x PG 7 WC Immunology SC Immunology GA 804NV UT WOS:000220306300015 PM 15030520 ER PT J AU Ryan, DP Eder, JP Puchlaski, T Seiden, MV Lynch, TJ Fuchs, CS Amrein, PC Sonnichsen, D Supko, JG Clark, JW AF Ryan, DP Eder, JP Puchlaski, T Seiden, MV Lynch, TJ Fuchs, CS Amrein, PC Sonnichsen, D Supko, JG Clark, JW TI Phase I clinical trial of the farnesyltransferase inhibitor BMS-214662 given as a 1-hour intravenous infusion in patients with advanced solid tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID PROTEIN TRANSFERASE; ADVANCED CANCER; CELL-GROWTH; FARNESYL; R115777; PATHWAY; PARAMETERS; APOPTOSIS; SCH-66336; L-778,123 AB Purpose: BMS-214662 is a nonsedating benzodiazepine derivative that exhibits broad spectrum cytotoxicity against human solid tumor cell lines and potently inhibits farnesylation of the H-ras and K-ras oncogenic proteins. This report describes the initial Phase I clinical trial of the compound. The main objective of the study was to determine the dose-limiting toxicities and the maximum tolerated dose of BMS-214662 when administered as a single dose i.v. over 1 h every 21 days to patients with advanced solid tumors. Experimental Design: Patients with advanced solid tumors and adequate organ function were eligible for the study. The dose was escalated according to a modified Fibonacci schedule after evaluating groups of at least three patients for toxicity during the first cycle of therapy at each dose level. Pharmacokinetic and pharmaeodynamic studies were performed after administration of the two initial doses. Results: The dose of BMS-214662 was escalated from 36 to 225 mg/m(2) through 5 intermediate dose levels in a total of 44 patients. Dose-limiting toxicities occurred in 3 of the 13 (23%) patients during the first cycle of treatment with 225 mg/m(2), consisting of grade 3 nausea/vomiting in 2 patients and grade 3 diarrhea in another patient. In addition, four of these patients experienced reversible grade 3 transaminitis, which was not considered to be dose-limiting. At the recommended dose for Phase II studies, 200 mg/m(2), the most common side effects were reversible transaminitis, nausea, and vomiting. Although there were no objective responses, one patient with pancreatic cancer continues to receive treatment more than 3.5 years after entering the study. BMS-214662 exhibited linear pharmacokinetics and had a mean biological half-life of 1.55 +/- 0.27 h and a total body clearance of 21.8 +/- 10.8 liters/h/m(2), with a low apparent volume of distribution at steady state (31.5 +/- 12.9 liters/m(2)). In patients treated with the recommended Phase II dose, the mean maximum plasma concentration of the drug was 6.57 +/- 2.94 mug/ml, and farnesyltransferase activity in peripheral blood mononuclear cells decreased to a nadir of 10.5 +/- 6.4% of baseline at the end of the infusion but fully recovered within 24 h. Conclusions: BMS-214662 can be delivered safely as a single 1-h i.v. infusion at a dose that results in pronounced inhibition of farnesyltransferase activity in peripheral blood mononuclear cells. However, the duration of enzyme inhibition was transient, recovering in parallel with the decline in plasma concentrations of this rapidly eliminated drug. Because indications of anticancer activity were observed in several patients, further optimization of the administration schedule for this promising new compound is warranted. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc, Boston, MA USA. Bristol Myers Squibb Co, Princeton, NJ USA. RP Ryan, DP (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Cox Bldg,Room 640, Boston, MA 02114 USA. EM dpryan@partners.org NR 25 TC 30 Z9 30 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 APR 1 PY 2004 VL 10 IS 7 BP 2222 EP 2230 DI 10.1158/1078-0432.CCR-0980-3 PG 9 WC Oncology SC Oncology GA 810JX UT WOS:000220701700005 PM 15073096 ER PT J AU Hutter, AM AF Hutter, AM TI Role of the cardiologist: Clinical aspects of managing erectile dysfunction SO CLINICAL CARDIOLOGY LA English DT Article DE erectile dysfunction; cardiovascular disease; phospliodiesterase type 5 inhibitors; sildenafil; tadalafil; vardenafil; nitrates ID PULMONARY ARTERIAL-HYPERTENSION; ORAL SILDENAFIL; CARDIOVASCULAR-DISEASE; HEART-FAILURE; EXERCISE; HEMODYNAMICS; THERAPY; VIAGRA; EVENTS; SAFE AB Erectile dysfunction (ED) is often a marker for serious, underlying cardiovascular disease (CVD), and cardiologists are increasingly involved in the care of men with ED. It is important to ask specifically about ED when evaluating men with CVD, since they may be embarrassed to volunteer this information. During the clinical workup, it is also important to check for contributing factors to ED such as diabetes, depression, stress, alcohol abuse, and cardiovascular risk factors. Patients should be advised that many treatment options are available for ED, including the phosphodiesterase type 5 (PDE5) inhibitors. The PDE5 inhibitors are safe and effective in most patients with CVD, including those taking multiple antihypertensive drugs. Furthermore, they have no deleterious effect on exercise capacity, heart rate, or extent of exercise-induced ischemia. In the future, the PDE5 inhibitors may have a role in reducing pulmonary hypertension in persons with primary pulmonary arterial hypertension (PAH) or congestive heart failure. The one major precaution for, men taking PDE5 inhibitors is to avoid concomitant administration of therapeutic and recreational nitrate preparations. Patients with chest pain suggestive of a heart attack need to inform emergency room (ER) personnel if they are taking a PDE5 inhibitor. Similarly, before giving nitrates, ER personnel need to ask patients if they have used PDE5 inhibitors. Nitrates should not be given for at least 24 h after a patient uses sildenafil or vardenafil and at least 48 h after a patient uses tadalafil. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cardiol, Boston, MA 02114 USA. RP Hutter, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cardiol, WACC Bldg,15 Parkman St,Suite 467, Boston, MA 02114 USA. EM ahutter@partners.org NR 19 TC 1 Z9 1 U1 0 U2 1 PU CLINICAL CARDIOLOGY PUBL CO PI MAHWAH PA PO BOX 832, MAHWAH, NJ 07430-0832 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD APR PY 2004 VL 27 IS 4 SU 1 BP I3 EP I7 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 809PD UT WOS:000220647700002 PM 15115189 ER PT J AU Hutter, AM AF Hutter, AM TI Erectile dysfunction and cardiovascular considerations: Managing patients effectively with phosphodiesterase type 5 inhibitors - Introduction SO CLINICAL CARDIOLOGY LA English DT Editorial Material ID EPIDEMIOLOGY; MEN C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hutter, AM (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU CLINICAL CARDIOLOGY PUBL CO PI MAHWAH PA PO BOX 832, MAHWAH, NJ 07430-0832 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD APR PY 2004 VL 27 IS 4 SU 1 BP I1 EP I2 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 809PD UT WOS:000220647700001 PM 15115188 ER PT J AU El-Serag, HB Garewel, H Kuebeler, M Sampliner, RE AF El-Serag, Hashem B. Garewel, Harinder Kuebeler, Mark Sampliner, Richard E. TI Is the Length of Newly Diagnosed Barrett's Esophagus Decreasing? The Experience of a VA Health Care System SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article AB Background & Aims: Secular trends in the length of newly diagnosed Barrett's esophagus (BE) are unknown. We have anecdotally noticed less frequent new diagnoses of long segments of BE. Methods: This is a retrospective analysis of prospectively collected information on a well-characterized large cohort of patients with documented BE that was diagnosed between 1981 and 2000 at Southern Arizona Department of Veterans Affairs Health Care System. We examined temporal changes in the length of BE at the time of diagnosis (frequency and proportions). We conducted correlation analyses, as well as multivariate linear regression analyses, to examine the association between year of diagnosis and BE length while adjusting for temporal differences in age, sex, ethnicity, previous use of antisecretory therapy, and the presence of intestinal metaplasia (IM) of the gastric cardia. Results: There were 340 patients with BE first diagnosed between 1981 and 2000. All cases were defined by the presence of areas of salmoncolored mucosa in the lower end of the tubular esophagus and IM in biopsy specimens obtained from these areas on at least 2 endoscopic examinations. There were no significant changes over time in mean age of patients with BE (61 yr) or proportion of white patients (84%). The mean length of BE at the time of first diagnosis declined progressively over time. In the earliest period (1981-1985), mean BE length was 6 +/- 3.8 cm, whereas mean BE length in 1996-2000 was 3.6 +/- 2.9 cm. This observation was explained not only by more frequent diagnoses of short BE, but also by less frequent diagnoses of long BE (>= 3 cm). There was a strong inverse correlation between BE length at the time of diagnosis and year of diagnosis (Pearson's correlation coefficient, -0.29; P <0.0001). In the multivariate linear regression model, a more recent year of BE diagnosis was an independent predictor of shorter BE length (P <0.0001). Similar results were obtained in analyses restricted to veteran patients or those with BE >= 3 cm. Conclusions: There has been a progressive decline in the length of newly diagnosed BE as a result of an increase in short-segment BE, but, curiously, also because of a decline in long-segment BE (>= 3 cm). These changes cannot be explained fully by changes in demographic features of patients, previous therapy, or the increasing emphasis on IM of the gastric cardia. The role of referral bias and/or temporal changes in the definitions cannot be excluded. C1 [El-Serag, Hashem B.] Gastroenterol Sect, Houston, TX USA. [El-Serag, Hashem B.; Kuebeler, Mark] Sect Hlth Serv Res, Houston, TX 77030 USA. [El-Serag, Hashem B.; Kuebeler, Mark] Houston Vet Affairs Med Ctr, Houston, TX USA. [Garewel, Harinder; Sampliner, Richard E.] Univ Arizona, Hlth Sci Ctr, Gastroenterol Sect, Tucson, AZ USA. [Garewel, Harinder; Sampliner, Richard E.] So Arizona Vet Affairs Hlth Care Syst, Gastroenterol Sect, Tucson, AZ USA. [El-Serag, Hashem B.; Kuebeler, Mark] Baylor Coll Med, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu FU Veterans Affairs [RCD00-013-2] FX H.B.E.-S. is a Veterans Affairs Health Services Research and Development Awardee (RCD00-013-2). NR 17 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD APR PY 2004 VL 2 IS 4 BP 296 EP 300 DI 10.1053/S1542-3565(04)00058-8 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V19KP UT WOS:000208071600005 PM 15067623 ER PT J AU Craig, WA AF Craig, WA TI Proof of concept: performance testing in models SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Article; Proceedings Paper CT 13th European Congress of Clinical Microbiology and Infectious Diseases CY MAY, 2003 CL GLASGOW, SCOTLAND DE amoxicillin/clavulanate; pharmacokinetics; pharmacodynamics; animal model; drug development ID PHARMACOKINETICALLY ENHANCED FORMULATION; RESPIRATORY-TRACT INFECTION; STREPTOCOCCUS-PNEUMONIAE; AMOXICILLIN-CLAVULANATE; ANTIMICROBIAL AGENTS; DOSAGE REGIMENS; PHARMACODYNAMICS; EFFICACY; STRAINS; AMOXICILLIN/CLAVULANATE AB Pharmacokinetic (PK) and pharmacodynamic (PD) principles that predict antimicrobial efficacy can be used to set targets for antimicrobial design and optimisation. Although current formulations of amoxicillin and amoxicillin/clavulanate have retained their efficacy against many, but not all, penicillin-nonsusceptible Streptococcus pneumoniae, additional coverage is required to address the growing problem of drug-resistant strains. Accordingly, two new oral formulations of amoxicillin/clavulanate, a paediatric formulation at 90/6.4 mg/kg/day and a pharmacokinetically enhanced formulation at 2000/125 mg twice daily for adults, were designed using PK/PD principles. These principles indicate that for amoxicillin and amoxicillin/clavulanate, a time above MIC of 35-40% of the dosing interval is predictive of high bacterial efficacy. In line with PK/PD predictions, simulation of human pharmacokinetics in in-vitro kinetic models and in a rat model of pneumonia, amoxicillin/clavulanate 2000/125 mg twice daily was highly effective against S. pneumoniae strains with amoxicillin MICs of 4 or 8 mg/L. Against strains with amoxicillin MICs of 4 mg/L, amoxicillin/clavulanate 2000/125 mg twice daily was significantly more effective than the conventional 875/125 mg twice daily formulation, azithromycin and levofloxacin, even though all levofloxacin MICs were less than or equal to 1 mg/L. Following infection with S. pneumoniae strains with amoxicillin MICs of 8 mg/L, the amoxicillin/clavulanate 2000/125 mg twice daily formulation was more effective than the conventional amoxicillin/clavulanate formulations of 875/125 mg twice daily and three times daily and 1000/125 mg three times daily, and had similar or better efficacy than azithromycin and levofloxacin, depending on the strain. These data indicate the potential benefit of therapy with amoxicillin/clavulanate 2000/125 mg twice daily compared with conventional formulations and other marketed antimicrobials in the treatment of respiratory tract infection. C1 William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. Univ Wisconsin, Madison, WI USA. RP Craig, WA (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace, Madison, WI 53705 USA. EM wac@medicine.wisc.edu NR 24 TC 13 Z9 13 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1198-743X J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PD APR PY 2004 VL 10 SU 2 BP 12 EP 17 DI 10.1111/j.1470-9465.2004.00865.x PG 6 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 814BT UT WOS:000220950900003 PM 14759229 ER PT J AU Schindler, S Mannstadt, M Urena, P Segre, GV Stein, G AF Schindler, S Mannstadt, M Urena, P Segre, GV Stein, G TI PTH secretion in patients, with chronic renal failure assessed by a modified CiCa clamp method: effects of 1-year calcitriol therapy SO CLINICAL NEPHROLOGY LA English DT Article DE secondary hyperparathyroidism; parathyroid hormone; calcium set point ID PARATHYROID-HORMONE RELEASE; CALCIUM RELATIONSHIP CURVE; SECONDARY HYPERPARATHYROIDISM; GLAND FUNCTION; SET-POINT; HEMODIALYSIS-PATIENTS; HYPERPLASIA; SENSITIVITY; RECEPTOR; OSTEODYSTROPHY AB Background: Secondary hyperparathyroidism (2 degreesHPT) in patients with chronic renal failure (CRF) is characterized by parathyroid gland hyperplasia and an intrinsic defect in the recognition of parathyrbid hormone (PTH) secretion. Conflicting results have been reported regarding the set point for calcium-regulated PTH release and its modification by calcitriol therapy in hemodialysis patients. Additionally, the effect of calcitriol on the calcium/PTH relationship in predialysis CRF patients with early 2 degreesHPT has not been investigated. Our objective in this controlled study was to investigate the calcium/PTH relationship and to determine the calcium set point in patients with early stages of CRF before and after a 1-year treatment with calcitriol and in normal volunteers. Methods: Nine patients with an early stage of CRF (GFR between 20 and 50 ml/min x 1.7.3 m(2) b.s.) aged 35 - 77 years and 13 healthy volunteers (HV) aged 26 - 60, years were included in the study. All participants were investigated by sequential lowering and raising of serum calcium levels comprising the following phases: blood-ionized calcium (Ca2+) was lowered by about 0.2 mmol/l (3 steps), steady-state hypocalcemia of Ca2+ 0.2 mmol/l below the baseline (step 4), stop of the infusion for 5 minutes (step 5), Ca2+ was raised to about 0.2 mmol/l above baseline (steps 6 and 7), and a steady state hypercalcemia of Ca2+ 0.2 mmol/l above baseline (step 8). Ionized calcium and intact PTH (iPTH) were measured at 30 time points during 240, minutes. The calcium set point was determined using the classical 4-parameter model. The CiCa clamp test was performed before and after a 1-year treatment with 0.5 mug of calcitriol thrice weekly. Results: No differences in the set point were observed between HV and CRF patients with early 2 degreesHPT. Four of 9 patients responded to calcitriol treatment with a decrease in basal serum iPTH levels ("responders"). There was no difference between renal function (GFR 18 +/- 6 vs. 17 +/- 8 ml/min x 1.73 m(2) b.s.), set point (Ca2+ 1.07 +/- 0.13 vs. 1.07 +/- 0.06 mmol/l) and suppressibility of PTH secretion (PTH (min%) 7.3 +/- 1.6 vs. 8.2 +/- 2.9) in responders vs non-responders, nor did these values change after treatment with calcitriol. PTHmin% decreased significantly in the whole group after treatment (10.4 +/- 8.5 vs. 7.8 +/- 2.4). Conclusions: Although the calcium set point was not different in predialysis CRF patients with early 2 degreesHPT compared to HV, calcitriol treatment improved the calcium-related suppression of PTH secretion (PTHmin%). C1 Univ Jena, Innere Med Klin 3, Dept Internal Med 3, D-07740 Jena, Germany. Univ Munich, Dept Internal Med, D-80539 Munich, Germany. Clin Orangerie, Aubervilliers, France. Lariboisiere Hosp, INSERM, U349, Paris, France. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Stein, G (reprint author), Univ Jena, Innere Med Klin 3, Dept Internal Med 3, D-07740 Jena, Germany. EM guenter.stein@med.uni-jena.de NR 32 TC 4 Z9 4 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI OBERHACHING PA BAJUWARENRING 4, D-82041 OBERHACHING, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD APR PY 2004 VL 61 IS 4 BP 253 EP 260 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 808UF UT WOS:000220593300004 PM 15125031 ER PT J AU Parsons, IM Millett, PJ Warner, JJP AF Parsons, IM Millett, PJ Warner, JJP TI Glenoid wear after shoulder hemiarthroplasty - Quantitative radiographic analysis SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID GLENOHUMERAL OSTEOARTHRITIS; ARTHROPLASTY; REPLACEMENT; ABDUCTION; FRACTURES; HUMERUS; FORCES; JOINT AB Symptomatic glenoid arthrosis may limit the long-term success of shoulder hemiarthroplasty in patients who are young and functionally demanding. The principal objective of the current study was to quantify glenoid wear after proximal humeral replacement in young, active subjects. Eight patients, ages 21 to 60 years (mean, 45 years), met inclusion criteria. The mean followup was 43 months. Functional scores for the cohort averaged 60% of age and gender-adjusted healthy subjects (range, 28%-84%). Glenohumeral joint space was measured on serial axillary radiographs using a Microscribe 3-DX digitizing device (measurement accuracy, 0.23 mm). Progressive glenoid wear was found in all eight patients. The mean decrease was 2 mm (range, 1.3-2.8 mm), a 68% decrease in glenohumeral joint space. Glenoid cartilage wear also was correlated with Constant and Murley scores. Patients with residual joint spaces less than 1 mm had a mean score of 50%, compared with a score of 71% for patients with joint spaces greater than I mm. There were no correlations between wear and mechanism of injury, duration of symptoms, and prior surgery. This study suggests that glenoid cartilage erosion can be expected routinely after humeral head replacement in young, active individuals, and that such wear may adversely affect function or necessitate conversion to total shoulder arthroplasty. C1 Harvard Univ, Massachusetts Gen Hosp, Shoulder Serv, Boston, MA 02114 USA. Univ Pittsburgh, Pittsburgh, PA USA. Harvard Univ, Brigham & Womens Hosp, Shoulder Serv, Boston, MA 02114 USA. RP Warner, JJP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Shoulder Serv, POB 403,275 Cambridge St, Boston, MA 02114 USA. EM jwarner@partners.org NR 15 TC 45 Z9 46 U1 0 U2 5 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 APR PY 2004 IS 421 BP 120 EP 125 DI 10.1097/01.blo.0000119249.61696.f1 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 817ZH UT WOS:000221214900021 PM 15123936 ER PT J AU Mankin, HJ Casas-Ganem, J Kim, JI Gebhardt, MC Hornicek, FJ Zeegen, EN AF Mankin, HJ Casas-Ganem, J Kim, JI Gebhardt, MC Hornicek, FJ Zeegen, EN TI Leiomyosarcoma of somatic soft tissues SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID SMOOTH-MUSCLE TUMORS; INFERIOR VENA-CAVA; THERAPY; ORIGIN AB Leiomyosarcoma is a rare, aggressively malignant connective tissue tumor of mature adults, which arises from smooth muscle. It occurs most frequently in the uterus, bowel, vascular tissues, and less commonly in somatic soft tissue or bone. The tumor when it arises in soft tissue has distinctive histologic features which somewhat resemble malignant fibrous histiocytoma (otherwise known as myxofibrosarcoma). The Orthopaedic Oncology Service at our institution has treated 66 patients with these lesions and thus far, 1/2 of the patients have died of disease at a mean of 3 years after discovery. Factors that increase the death rate include size of the tumor, Musculoskeletal Tumor Society Stage of disease, and to a lesser extent particularly in the lower extremities, anatomic site. Radiation and chemotherapy had little direct effect on the outcome but patients treated with surgery and adjunctive agents seemed to live longer than their cohorts treated with surgery alone. The purpose of this study is a general review of the clinical and prognostic features of this cancer. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Oncol Serv, Boston, MA 02114 USA. RP Mankin, HJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM hmankin@partners.org NR 34 TC 15 Z9 17 U1 0 U2 4 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 APR PY 2004 IS 421 BP 225 EP 231 DI 10.1097/01.blo.0000119250.08614.82 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 817ZH UT WOS:000221214900037 PM 15123952 ER PT J AU Brigman, BE Hornicek, FJ Gebhardt, MC Mankin, HJ AF Brigman, BE Hornicek, FJ Gebhardt, MC Mankin, HJ TI Allografts about the knee in young patients with high-grade sarcoma SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID LIMB-SALVAGE; BONE-TUMORS; ENDOPROSTHETIC REPLACEMENT; OSTEOARTICULAR ALLOGRAFTS; ADJUVANT CHEMOTHERAPY; DISTAL FEMUR; OSTEOSARCOMA; EXTREMITY; CHILDREN; MANAGEMENT AB Reconstruction after resections for high-grade sarcomas about the knee in children and adolescents is a challenging problem because of the large soft tissue and skeletal defects, the effects of adjuvant therapy, and the potential for long-term use of the limb. One hundred sixteen patients, all 18 years or younger, with osteosarcoma or Ewing's sarcoma located between the middle femur and middle tibia, were treated with chemotherapy, resection, and allograft reconstruction. One hundred three patients with osteosarcoma and 13 patients with Ewing's sarcoma had 105 Stage 11 and 11 Stage III tumors. There were 72 osteoarticular grafts (39 femur, 33 tibia), 28 intercalary grafts (19 femur), seven allograft-prosthetic composites (all femur,) and nine allograft-arthrodeses (seven femur, two tibia). At latest followup, 49% of all of the allograft reconstructions were rated good or excellent, 14% were rated as fair, and 37% were failures. Sixteen percent had an infection develop. Twenty-seven percent of patients had a fracture, 34% had a nonunion, and 14 patients eventually required amputation. Reconstruction of large bone defects about the knee in young patients who are being treated with chemotherapy is difficult. Although complications significantly affect outcome, allografts are a viable option for reconstruction in children with high-grade sarcomas about the knee. C1 Duke Univ, Durham, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. RP Brigman, BE (reprint author), Box 3312, Durham, NC 27710 USA. EM brigm003@mc.duke.edu NR 24 TC 74 Z9 86 U1 1 U2 6 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 APR PY 2004 IS 421 BP 232 EP 239 DI 10.1097/01.blo.0000127132.12576.05 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 817ZH UT WOS:000221214900038 PM 15123953 ER PT J AU Ross, AS Bhan, AK Pascual, M Thiim, M Cosimi, AB Chung, RT AF Ross, AS Bhan, AK Pascual, M Thiim, M Cosimi, AB Chung, RT TI Pegylated interferon alpha-2b plus ribavirin in the treatment of post-liver transplant recurrent hepatitis C SO CLINICAL TRANSPLANTATION LA English DT Article DE antiviral therapy; hepatitis C virus; liver transplantation; pegylated interferon ID VIRUS-INFECTION; COMBINATION; ALPHA; RECIPIENTS; EFFICACY; THERAPY AB Background: Histological recurrence of the hepatitis C virus (HCV) occurs in the majority of persons transplanted for cirrhosis as a result of HCV. Herein we analyze our experience with the use of both conventional and pegylated (PEG) interferon (IFN) in combination with ribavirin (RBV) in liver transplant recipients with recurrent HCV. Methods: Patients transplanted between 1992 and 2001 with post-orthotopic liver transplantation (OLT) histological recurrence of HCV, and who were treated with at least 6 months of IFN or PEG-IFN in combination with RBV were included in this analysis. A retrospective chart review was performed. Results: A total of 31 patients were included. Fifteen were treated with IFN/RBV and 16 with PEG-IFN/RBV. Of these 16, 11 had been begun on IFN/RBV and were changed to PEG-IFN/RBV because of persistent viremia. Three patients (20%) in the IFN/RBV group and six patients (37.5%) in the PEG-IFN/RBV group experienced a virologic response (VR) on therapy. Of the six patients experiencing VR in the PEG-IFN/RBV group, three (50%) were IFN/RBV non-responders. There were two sustained VRs (SVR). The 65.6% of all patients experienced a biochemical response (BR) on therapy. Seven deaths were observed. Dose modifications of IFN or PEG-IFN (87.1%) and RBV (80.6%) and the requirement for hematopoietic growth factors were frequent. Conclusions: Treatment of recurrent HCV infection with combination of IFN or PEG-IFN and RBV produced an on-therapy VR in 29% and BR in 65% of patients. Hematologic toxicity and dose modifications were frequent. Our experience with antiviral therapy for HCV post-OLT remains disappointing but PEG-IFN + RBV appears to produce VR in a sizable portion of IFN + RBV non-responders. C1 Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplant Unit, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, GRJ 825, Boston, MA 02114 USA. EM rtchung@partners.org NR 26 TC 69 Z9 70 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0063 J9 CLIN TRANSPLANT JI Clin. Transplant. PD APR PY 2004 VL 18 IS 2 BP 166 EP 173 DI 10.1046/j.1399-0012.2003.00145.x PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 801MD UT WOS:000220099100010 PM 15016131 ER PT J AU Pollack, MH Stein, MB Davidson, JRT Ginsberg, DL AF Pollack, MH Stein, MB Davidson, JRT Ginsberg, DL TI New challenges for anxiety disorders - Where treatment, resilience, and economic priority converge SO CNS SPECTRUMS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL-COMORBIDITY-SURVEY; QUALITY-OF-LIFE; PANIC DISORDER; MENTAL-HEALTH; UNITED-STATES; DOUBLE-BLIND; COMMUNITY; DEPRESSION; PREVALENCE AB Anxiety disorders are highly prevalent, are increasing in incidence, affect individuals early in life, and significantly impact health care and quality of life. As such, they are serious public health problems that deserve attention now and in the future. Over the last 10-20 years, there has been marked improvement in pharmacologic and psychosocial interventions for anxiety. Due to their broad spectrum of efficacy against common comorbidities and lack of association with abuse and dependence, serotonergic and mixed serotonergic noradrenergic antidepressants are first-line therapies for anxiety disorders. Benzodiazepines are still widely used in clinical practice because they are well tolerated and work quickly and effectively. Other medications that are emerging as potentially useful for selected populations with anxiety include atypical neuroleptics and anticonvulsants. Cognitive-behavioral therapy (CBT) is at least as effective as medication for many patients with anxiety disorders and facilitates maintenance of benefit over the long term. Resilience, the capacity to bounce back from adversity, can be reliably measured with a psychometrically valid scale, the Connor-Davidson Resilience Scale. Compared with the general population, individuals with anxiety disorders exhibit decreased resilience. Studies have shown that pharmacologic treatment combined with CBT may increase resilience within 2-3 months. Emerging neurobiologic research indicates that noradrenergic pathways and 5-HT2 transporter efficiency may mediate effects on resiliency. C1 Massachusetts Gen Hosp, Ctr Aniety & Traumat Stress Related Disorders, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Univ Calif San Diego, San Diego, CA 92103 USA. VA San Diego Healthcare Syst, Anxiety & Traumat Stress Disorders Program, San Diego, CA USA. RP Pollack, MH (reprint author), Massachusetts Gen Hosp, Ctr Aniety & Traumat Stress Related Disorders, Boston, MA 02114 USA. NR 37 TC 4 Z9 4 U1 6 U2 9 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 APR PY 2004 VL 9 IS 4 BP 1 EP 10 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 895VC UT WOS:000226890900011 ER PT J AU Schwartz, CE Rauch, SL AF Schwartz, CE Rauch, SL TI Temperament and its implications for neuroimaging of anxiety disorders SO CNS SPECTRUMS LA English DT Review ID POSTTRAUMATIC-STRESS-DISORDER; HUMAN AMYGDALA ACTIVATION; BEHAVIORAL-INHIBITION; SOCIAL ANXIETY; UNINHIBITED BEHAVIOR; SYMPTOM PROVOCATION; SENSORY STIMULATION; FACIAL EXPRESSIONS; FUNCTIONAL MRI; YOUNG-ADULTS AB We review the attributes of inhibited and uninhibited infant temperaments, and their developmental trajectories into early adulthood. Inborn individual differences in infants' propensity to respond to novel people and objects are associated with persistent differences in the responsivity of the amygdala to novelty, as measured with functional magnetic resonance imaging, after more than 20 years of development. Because an inhibited temperament is a risk factor for developing later psychiatric disorders, particularly generalized social anxiety disorder, temperamental differences are confounds in neuroimaging and genetic studies. Longitudinal studies are a unique tool for understanding the developmental and temperamental risk factors for psychiatric disorder. C1 Massachusetts Gen Hosp, Dept Psychiat, Dev Psychopathol Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. RP Schwartz, CE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Dev Psychopathol Res Grp, 13th St,Bldg 149,CNY-9102, Charlestown, MA 02129 USA. EM carl_schwartz@hms.harvard.edu NR 57 TC 12 Z9 12 U1 3 U2 9 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 APR PY 2004 VL 9 IS 4 BP 284 EP 291 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 895VC UT WOS:000226890900013 PM 15048053 ER PT J AU Shaw, CI Kacmarek, RM Hampton, RL Riggi, V El Masry, A Cooper, JB Hurford, WE AF Shaw, CI Kacmarek, RM Hampton, RL Riggi, V El Masry, A Cooper, JB Hurford, WE TI Cellular phone interference with the operation of mechanical ventilators SO CRITICAL CARE MEDICINE LA English DT Article DE cellular phones; mechanical ventilators; radio frequency; electromagnetic interference ID ELECTROMAGNETIC-INTERFERENCE; DEVICES AB Objective: To determine whether a cellular phone would interfere with the operation of mechanical ventilators. Design: Laboratory study. Setting: University medical center. Subjects: Fourteen mechanical ventilators. Interventions: We evaluated change in operation and malfunction of the mechanical ventilators. Measurements and Main Results: The cellular phone (Nokia 6120i) was computer controlled, operating at 828.750 MHz analog modulation. It was operated at 16, 40,100, 250, and 600 mW, 30 cm from the floor and 30, 15, and <3 cm from all sides of each ventilator. Six of the 14 ventilators tested malfunctioned when a cellular phone at maximum power output was placed less than or equal to15 cm from the device. None of these responses were considered immediately life threatening except for the response of the Puritan Bennett 840, which stopped ventilating when the cellular phone at maximum power output was placed less than or equal to30 cm from the ventilator. One ventilator doubled the ventilatory rate and another increased the displayed tidal volume from 350 to 1033 mL. In one of the infant ventilators, displayed tidal volume increased from 21 to 100 mL. In another ventilator, the high respiratory rate alarm sounded but the rate had not changed. Conclusions: In a controlled laboratory setting, cellular phones placed in close proximity to some commercially available intensive care ventilators can cause malfunctions, including irrecoverable cessation of ventilation. This is most likely to occur if the cellular phone is <30 cm from the device and ringing. Based on our data and the available literature, we believe it is reasonably safe to permit the use of cellular phones in the intensive care unit, as long as they are kept 3 feet from all medical devices. The current electromagnetic compatibility standards for mechanical ventilators are inadequate to prevent malfunction. Manufacturers should ensure that their products are not affected by wireless technology even when placed immediately next to the device. C1 Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biomed Engn, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Dept Resp Care, Ellison 401, Boston, MA 02114 USA. EM rkacmarek@partners.org RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 7 TC 42 Z9 42 U1 0 U2 0 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 APR PY 2004 VL 32 IS 4 BP 928 EP 931 DI 10.1097/01.CCM.0000120061.01431.DB PG 4 WC Critical Care Medicine SC General & Internal Medicine GA 812XR UT WOS:000220872700004 PM 15071380 ER PT J AU Alston, TA Lowenstein, E AF Alston, TA Lowenstein, E TI Black and white and read all over: The human genome SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE angiotensin-converting enzyme; ethnicity; genotype; nondiscrimination; race ID RACE C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Div Med Eth, Boston, MA 02115 USA. RP Alston, TA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Div Med Eth, Boston, MA 02115 USA. NR 12 TC 1 Z9 1 U1 0 U2 0 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 APR PY 2004 VL 32 IS 4 BP 1073 EP 1074 DI 10.1097/01.CCM.0000119926.81423.76 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 812XR UT WOS:000220872700027 PM 15071405 ER PT J AU Wiklund, RA AF Wiklund, RA TI Preoperative preparation of patients with advanced liver disease SO CRITICAL CARE MEDICINE LA English DT Article DE cirrhosis; anesthesia; surgery; coagulopathy; encephalopathy; ascites; renal failure; respiratory failure; liver transplantation; acute liver failure ID SPONTANEOUS BACTERIAL PERITONITIS; INTRAHEPATIC PORTOSYSTEMIC SHUNT; CENTRAL PONTINE MYELINOLYSIS; PORTAL-VEIN THROMBOSIS; MORBIDLY OBESE PATIENTS; VARICEAL HEMORRHAGE; HEPATIC-ENCEPHALOPATHY; NONALCOHOLIC STEATOHEPATITIS; STENT-SHUNT; LAPAROSCOPIC CHOLECYSTECTOMY AB Objective: To review the characteristic features of patients with advanced liver disease that may lead to increased perioperative morbidity and mortality rates. Design: Literature review. Results. Patients with end-stage liver disease are at high risk of major complications and death following surgery. The most common complications are secondary to acute liver failure and include severe coagulopathy, encephalopathy, adult respiratory distress syndrome, acute renal failure, and sepsis. The degree of malnutrition, control of ascites, level of encephalopathy, prothrombin time, concentration of serum albumin, and concentration of serum bilirubin predict the risk of complications and death following surgery. Other determinants of adverse outcome include emergency surgery, advanced age, and cardiovascular disease. Portal hypertension is a prominent feature of advanced liver disease, and it predisposes the patient to variceal hemorrhage, hepatorenal syndrome, hepatopulmonary syndrome, and uncontrolled ascites. Portal hypertension can be ameliorated by percutaneous or surgical portasystemic shunting procedures. If well-defined contraindications are not present, patients with advanced liver disease should be evaluated for orthotopic liver transplantation from a cadaver donor or possible living-related liver transplantation. Conclusions: Optimal preparation, which addresses the common features of advanced liver disease, may decrease the risk of complications or death following surgery. Preparation should include correcting coagulopathy, minimizing preexisting encephalopathy, preventing sepsis, and optimizing renal function. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Wiklund, RA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 86 TC 30 Z9 33 U1 0 U2 3 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 APR PY 2004 VL 32 IS 4 SU S BP S106 EP S115 DI 10.1097/01.CCM.0000115624.13479.E6 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 814BN UT WOS:000220950300005 PM 15064669 ER PT J AU Venanzi, ES Benoist, C Mathis, D AF Venanzi, ES Benoist, C Mathis, D TI Good riddance: thymocyte clonal deletion prevents autoimmunity SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID FAMILY-MEMBER BIM; REGULATES NEGATIVE SELECTION; PROMISCUOUS GENE-EXPRESSION; NONOBESE DIABETIC MOUSE; ACID RECEPTOR-ALPHA; T-CELL TOLERANCE; NF-KAPPA-B; IN-VIVO; MEDIATED APOPTOSIS; INSULIN EXPRESSION AB Clonal deletion is arguably the most important mechanism of eliminating self-reactive thymocytes from the T-cell repertoire. Recent work has identified new players in this process. On the thymocyte side, several molecules have been newly implicated in the pathway from initial T-cell receptor signaling through to the final result: gene transcription and thymocyte apoptosis. In addition, several proapoptotic molecules have been found to be necessary foe the death of self-reactive thymocytes. On the antigen-presenting cell side, the expression of peripheral self-antigens, regulated at least in part by the autoimmune regulator (AIRE) protein, is crucial for complete elimination of autoreactive thymocytes. The importance of thymic peripheral antigen expression and clonal deletion to self-tolerance is demonstrated in the autoimmune diseases autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy and type-1 diabetes mellitus. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med, Joslin Diabet Ctr,Sect Immunol & Immunogenet, Boston, MA 02215 USA. RP Venanzi, ES (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med, Joslin Diabet Ctr,Sect Immunol & Immunogenet, 1 Joslin Pl, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu FU NIDDK NIH HHS [2T32 DK07260-26, R01 DK60027-01] NR 36 TC 36 Z9 37 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 2004 VL 16 IS 2 BP 197 EP 202 DI 10.1016/j.coi.2004.01.008 PG 6 WC Immunology SC Immunology GA 807JX UT WOS:000220498900012 PM 15023413 ER PT J AU Macian, F Im, SH Garcia-Cozar, J Rao, A AF Macian, F Im, SH Garcia-Cozar, J Rao, A TI T-cell anergy SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID HUMAN DENDRITIC CELLS; CLASS-II CHIMERA; IN-VIVO; TOLERANCE INDUCTION; COSTIMULATORY BLOCKADE; CYCLE PROGRESSION; CLONAL ANERGY; PERIPHERAL TOLERANCE; ALLOGRAFT-REJECTION; SUPPRESSOR ACTIVITY AB Self-reactive T cells that escape negative selection in the thymus must be inactivated in the periphery. Anergy constitutes one means of imposing peripheral tolerance. Anergic T cells are functionally inactivated and unable to initiate a productive response even when antigen is encountered in the presence of full co-stimulation. Recent studies have provided new insights into the mechanisms responsible for the induction and maintenance of T-cell anergy. These studies have helped clarify the nature of the signals that induce tolerance, the cells able to deliver them and the molecular processes that underlie the unresponsive state. C1 Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. Kwangju Inst Sci & Technol, Dept Life Sci, Kwangju 500712, South Korea. Univ Cadiz, Univ Hosp, Fac Med, Puerto Real 11510, Spain. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Ctr Blood Res, Inst Biomed Res, Boston, MA 02115 USA. RP Macian, F (reprint author), Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. EM fmacianj@aecom.yu.edu; arao@cbr.med.harvard.edu RI Garcia-Cozar, Francisco/A-6212-2013; Im, Sin-Hyeog/E-6811-2013; OI Garcia-Cozar, Francisco/0000-0003-3720-259X; Im, Sin-Hyeog/0000-0002-3173-1856; Macian, Fernando/0000-0003-2666-035X FU NIAID NIH HHS [AI48213] NR 82 TC 89 Z9 94 U1 0 U2 8 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 2004 VL 16 IS 2 BP 209 EP 216 DI 10.1016/j.coi.2004.01.013 PG 8 WC Immunology SC Immunology GA 807JX UT WOS:000220498900014 PM 15023415 ER PT J AU Chowdhury, D Sen, RJ AF Chowdhury, D Sen, RJ TI Mechanisms for feedback inhibition of the immunoglobulin heavy chain locus SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID B-CELL DEVELOPMENT; ALLELIC EXCLUSION; ANTIGEN RECEPTOR; TRANSGENIC MICE; V(D)J RECOMBINATION; DEFICIENT MICE; GENE SEGMENTS; IG-BETA; SURFACE EXPRESSION; PRO-B AB The production of immunoglobulin heavy chain (IgH) protein in pro-B cells provides feedback to terminate further V-H gene recombination. This phenomenon is referred to as allelic exclusion. The chromatin structure of the V-H genes regulates their recombination potential, hence alterations in chromatin are a key factor in allelic exclusion. In pro-B cells, IL-7/lL-7R signaling induces histone hyperacetylation and nuclease accessibility of the largest family Of V-H genes (J558) and potentially activates these genes for recombination. Loss of these signals in the later stages of B-cell development reverts the V(H)J558 gene segments to a less accessible state, making them recombinationally refractive. This provides a molecular mechanism for allelic exclusion of these genes. Similar transient signals may be responsible for enforcing allelic exclusion in other V-H gene families. D-proximal V-H genes, however, appear to be less susceptible to feedback inhibition. C1 Ctr Blood Res, Boston, MA 02115 USA. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Chowdhury, D (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. EM senranja@grc.nia.nih.gov NR 51 TC 13 Z9 13 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 2004 VL 16 IS 2 BP 235 EP 240 DI 10.1016/j.coi.2004.02.003 PG 6 WC Immunology SC Immunology GA 807JX UT WOS:000220498900017 PM 15023418 ER PT J AU Ladanyi, A Sher, AC Herlitz, A Bergsrud, DE Kraeft, SK Kepros, J McDaid, G Ferguson, D Landry, ML Chen, LB AF Ladanyi, A Sher, AC Herlitz, A Bergsrud, DE Kraeft, SK Kepros, J McDaid, G Ferguson, D Landry, ML Chen, LB TI Automated detection of immunofluorescently labeled cytomegalovirus-infected cells in isolated peripheral blood leukocytes using decision tree analysis SO CYTOMETRY PART A LA English DT Article DE CMV; automated microscopy; decision tree analysis; immunofluorescence; rare event detection ID DISSEMINATED TUMOR-CELLS; EVENT IMAGING-SYSTEM; REAL-TIME PCR; BONE-MARROW; TRANSPLANT RECIPIENTS; POSITIVE CELLS; MATERNAL BLOOD; CANCER-CELLS; RARE; ANTIGENEMIA AB Background: Cytomegalovirus (CMV) infection continues to be a major problem for immunocompromised patients. Detection of viral antigens in leukocytes (antigenemia assay) is widely used for the diagnosis of CMV infection and for guiding antiviral therapy. The antigenemia technique, contingent upon the manual microscopic analysis of rare cells, is a laborious task that is subject to human error. In this study, we combine automated microscopy with artificial intelligence for reliable detection of fluorescently labeled CMV-infected cells. Methods: Cytospin preparations of peripheral blood leukocytes were immunofluorescently labeled for the CMV lower matrix phosphoprotein (pp65) and scanned in the Rare Event Imaging System (REIS), a fully automated image cytometer. The REIS detected potential positive objects and digitally recorded 49 measured cellular features for each identified case. The measurement data of these objects were analyzed by the See5 decision tree (DT) algorithm to ascertain whether they were true-positive detections. Results: The DT was built from the measurement data of 2,047 true- and 2,028 false-positive detections, collected from 32 patient samples. By designating misclassifications of false-negatives three times more costly, the 10-fold cross-validation sensitivity, specificity, and misclassification error of the assay was 94.3%, 56.2%, and 25%, respectively. The method was also validated using an independent test set of 21 patient samples, in which similar results were obtained. Conclusions: To our knowledge, this study represents the first attempt to improve the accuracy of rare event image cytometry through the implementation of artificial intelligence methodology. Results suggest that cost-sensitive decision tree analysis of digitally measured cellular features vastly improves the performance of rare event image cytometry. (C) 2004 Wiley-Liss, Inc. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Yale New Haven Med Ctr, Dept Lab Med, Clin Virol Lab, New Haven, CT 06504 USA. RP Ladanyi, A (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM andras_ladanyi@dfci.harvard.edu NR 30 TC 2 Z9 2 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOM PART A JI Cytom. Part A PD APR PY 2004 VL 58A IS 2 BP 147 EP 156 DI 10.1002/cyto.a.20016 PG 10 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 811XR UT WOS:000220805100006 PM 15057968 ER PT J AU Mak, HY Ruvkun, G AF Mak, HY Ruvkun, G TI Intercellular signaling of reproductive development by the C-elegans DAF-9 cytochrome P450 SO DEVELOPMENT LA English DT Article DE dat-9; daf-12; dauer; gonadal migration; cytochrome P450; insulin; C. elegans; TGF beta ID CAENORHABDITIS-ELEGANS; LIFE-SPAN; LARVAL DEVELOPMENT; ECDYSTEROIDOGENIC PATHWAY; GENETIC INTERFERENCE; CHEMOSENSORY NEURONS; NUCLEAR RECEPTORS; EXPRESSION; LONGEVITY; PROTEIN AB Parallel pathways control C elegans reproductive development in response to environmental cues. Attenuation of daf-2 insulin-like or daf-7 TGFbeta-Iike signaling pathways cause developmental arrest at the stress resistant and long-lived dauer stage. Loss-of-function mutations in the cytochrome P450 gene daf-9 also cause dauer arrest and defects in cell migration. A rescuing daf9::GFP fusion gene driven by the daf-9 promoter is expressed in two head cells at all stages, in the hypodermis from mid-second larval stage (L2) to the fourth larval stage (L4), and in the spermatheca of the adult hermaphrodite. Although the level of daf-9::GFP expression in the head cells and spermatheca is constant, hypodermal daf-9::GFP expression is modulated by multiple inputs. In particular, daf-9::GFP expression in the hypodermis is absolutely dependent on daf-12, the nuclear receptor that is negatively regulated by daf-9 gene activity, suggesting feedback control between daf-9 and daf-12 in this tissue. daf-9 expression exclusively in the hypodermis is sufficient to restore reproductive, development in daf-9 mutant animals, suggesting that daf-9 functions in a cell nonautonomous manner. Furthermore, constitutive expression of daf-9 in the hypodermis suppresses dauer arrest of daf-7 mutant animals and inhibits dauer remodelling of some tissues in daf-2 mutant animals. Thus, daf-9 may integrate outputs from daf-2 and daf-7 signaling pathways to relay neuroendocrine signals through synthesis of a lipophilic hormone. C1 Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu OI Mak, Ho Yi/0000-0002-1500-5328 FU NIDDK NIH HHS [R01 DK070147] NR 41 TC 65 Z9 79 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD APR PY 2004 VL 131 IS 8 BP 1777 EP 1786 DI 10.1242/dev.01069 PG 10 WC Developmental Biology SC Developmental Biology GA 817CP UT WOS:000221155900010 PM 15084462 ER PT J AU Okuyama, R Nguyen, BC Talora, C Ogawa, E di Vignano, AT Lioumi, M Chiorino, G Tagami, H Woo, M Dotto, GP AF Okuyama, R Nguyen, BC Talora, C Ogawa, E di Vignano, AT Lioumi, M Chiorino, G Tagami, H Woo, M Dotto, GP TI High commitment of embryonic keratinocytes to terminal differentiation through a notch1-caspase 3 regulatory mechanism SO DEVELOPMENTAL CELL LA English DT Article ID PROTEIN-KINASE-C; HUMAN EPIDERMAL-KERATINOCYTES; FAS-MEDIATED APOPTOSIS; SKIN DEVELOPMENT; PROTEOLYTIC ACTIVATION; FUNCTIONAL-ANALYSIS; ALZHEIMERS-DISEASE; CASPASE ACTIVATION; GENE-EXPRESSION; NOTCH PATHWAY AB Embryonic cells are expected to possess high growth/ differentiation potential, required for organ morphogenesis and expansion during development. However, little is known about the intrinsic properties of embryonic epithelial cells due to difficulties in their isolation and cultivation. We report here that pure keratinocyte populations from E15.5 mouse embryos commit irreversibly to differentiation much earlier than newborn cells. Notch signaling, which promotes keratinocyte differentiation, is upregulated in embryonic keratinocyte and epidermis, and elevated caspase 3 expression, which we identify as a transcriptional Notch1 target, accounts in part for the high commitment of embryonic keratinocytes to terminal differentiation. In vivo, lack of caspase 3 results in increased proliferation and decreased differentiation of interfollicular embryonic keratinocytes, together with decreased activation of PKC-delta, a caspase 3 substrate which functions as a positive regulator of keratinocyte differentiation. Thus, a Notch1-caspase 3 regulatory mechanism underlies the intrinsically high commitment of embryonic keratinocytes to terminal differentiation. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Tohoku Univ, Grad Sch Med, Dept Dermatol, Sendai, Miyagi 9808574, Japan. Lab Canc Pharmacogenom Fondo Edo Tempia, I-13900 Biella, Italy. Univ Toronto, St Michaels Hosp, Ontario Canc Inst, Dept Med, Toronto, ON M5G 2N9, Canada. Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. RP Dotto, GP (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM gdotto@partners.org RI Chiorino, Giovanna/K-5037-2016 OI Chiorino, Giovanna/0000-0002-9502-6400 FU NCI NIH HHS [CA16038, CA73796]; NIAMS NIH HHS [AR39190] NR 50 TC 121 Z9 127 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD APR PY 2004 VL 6 IS 4 BP 551 EP 562 DI 10.1016/S1534-5807(04)00098-X PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 834XA UT WOS:000222443000013 PM 15068794 ER PT J AU Tsai, EC Fujimoto, WY Matsumoto, AM Boyko, EJ AF Tsai, EC Fujimoto, WY Matsumoto, AM Boyko, EJ TI Association of bioavailable, free, and total testosterone with insulin resistance - Influence of sex hormone-binding globulin and body fat SO DIABETES CARE LA English DT Article ID DEPENDENT DIABETES-MELLITUS; COMPUTED-TOMOGRAPHY; STEROID-HORMONES; PLASMA-INSULIN; ADIPOSE-TISSUE; VISCERAL FAT; RISK-FACTORS; MEN; GLUCOSE; OBESITY AB OBJECTIVE - Previous reports of in association between low testosterone levels and diabetes risk were often confounded by covariation of sex hormone-binding globulin (SHBG) and testosterone measurements. Measurements of bioavailable and free testosterone, more reliable indexes of biologically active testosterone, were examined for their associations with markets of insulin resistance and body fat measures in 221 middle-aged nondiabetic men. RESEARCH DESIGN AND METHODS - Bioavailable and free testosterone were calculated from the concentrations of total testosterone, SHBG, and albumin, and they were not significantly correlated with SHBG (r = 0.07-0.1). In contrast, total testosterone Correlated significantly with SHBG (r = 0.63). We evaluated the relationship between these measures of circulating testosterone and markers for insulin resistance (i.e., fasting insulin, C-peptide, and homeostasis model assessment for insulin resistance [HOMA-IR]) as well as total body fat (assessed by dual-energy X-ray absorptiometry [DEXA]) and abdominal fat distribution (assessed by single-slice computed tomography [CT]). RESULTS - Bioavailable, free, and total testosterone and SHBG all correlated significantly with fasting insulin (age-adjusted r = -0.15[P=0.03],-0.14[P=0.03],-0.32[P<0.0001], and -0.38[P<0.0001], respectively), fasting C-peptide (r = -0.18[P=0.009] to -0.41 [P<0.0001]) HOMA-IR (r = -0.15 [P = 0.03] to -0.39 [P<0.0001]), and body fat measures (r = -0.17 [P = 0.008] to -0.44 [P < 0.0001]). Only SHBG and total testosterone were significantly associated with fasting glucose (r = -0.20 [P = 0.003] to -0.21 [P = 0.002]). In multivariate analysis bioavailable or free testosterone was significantly and inversely associated with Insulin, C-peptide, and HOMA-IR, but this was not independent of total body or abdominal fat. SHBG was a significant determinant of insulin, C-peptide, and HOMA-IR, independent of body fat. The associations between total testosterone and insulin resistance were confounded by SHBG. CONCLUSIONS - The inverse association between testosterone and insulin resistance, independent of SHBG, was mediated through body fat. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. RP Tsai, EC (reprint author), VA Puget Sound Hlth Care Syst, 152E,1660 S Columbian Way, Seattle, WA 98108 USA. EM tsaichin@u.washington.edu RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 37 TC 143 Z9 152 U1 0 U2 3 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 APR PY 2004 VL 27 IS 4 BP 861 EP 868 DI 10.2337/diacare.27.4.861 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 809AG UT WOS:000220609000001 PM 15047639 ER PT J AU Shinkai, RSA Cornell, JE Hatch, JP Yeh, CK AF Shinkai, RSA Cornell, JE Hatch, JP Yeh, CK TI Intraoral tactile sensitivity in adults with diabetes SO DIABETES CARE LA English DT Article ID MELLITUS; NEUROPATHY AB OBJECTIVE - The intraoral tactile sensitivity (ITS) of diabetic and nondiabetic subjects was compared. The effects of age, ethnicity, sex, and intraoral site were considered. RESEARCH DESIGN AND METHODS - The sample comprised 589 participants of the Oral Health: San Antonio Longitudinal Study of Aging. A total Of 107 subjects (61.8 +/- 10.0 years; 48 women, 59 men) met American Diabetes Association diagnostic criteria For diabetes and 482 subjects (58.8 +/- 11.1 years; 274 women, 208 men) did not. ITS was assessed with an oral microaesthesiometer with a cross-modality matching procedure. The dependent variable was the slope Of the psychophysical function relating physical Stimulus intensity (air pressure) and subjects' judgments of stimulus intensity. Data were analyzed using ANOVA for repeated measures with between-subject factors of age, sex, ethnicity, and diabetes and the within-subject factor of intraoral site. RESULTS - Diabetic and nondiabetic subjects. showed no significant differences in ITS at any of the three test sites. European Americans demonstrated greater soft-palate Sensitivity (mean +/- SD 0.26 +/- 0.15) compared with Mexican Americans (0.24 +/- 0.16; P = 0.046). The three intraoral test sites differed in tactile sensitivity (P < 0.001); posterior tongue (0.33 +/- 0.22) was most sensitive, followed by the soft palate (0.25 +/- 0.15) and the anterior tongue (0.23 +/- 0.13). Potentially confounding factors were not associated with ITS. CONCLUSIONS - Our results Suggest that diabetes per se may not influence ITS. C1 Pontif Cathol Univ Rio Grande do Sul, Dept Prosthodont, Porto Alegre, RS, Brazil. Univ Texas, Hlth Sci Ctr, Dept Orthodont, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, S Texas Vet Hlth Care Syst,Audie L Murphy Div, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Dent Diagnost Sci, S Texas Vet Hlth Care Syst,Audie L Murphy Div, San Antonio, TX 78284 USA. RP Shinkai, RSA (reprint author), Ave Cristovao Colombo 3084,CJ 708-709, BR-90560002 Porto Alegre, RS, Brazil. EM rshinkai@pucrs.br RI Shinkai, Rosemary/I-3510-2013 OI Shinkai, Rosemary/0000-0002-4107-5661 FU NIDCR NIH HHS [P50-DE-10756] NR 18 TC 4 Z9 4 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 APR PY 2004 VL 27 IS 4 BP 869 EP 873 DI 10.2337/diacare.27.4.869 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 809AG UT WOS:000220609000002 PM 15047640 ER PT J AU Lopes-Virella, MF Mironova, M Stephan, E Durazo-Arvizu, R Virella, G AF Lopes-Virella, MF Mironova, M Stephan, E Durazo-Arvizu, R Virella, G TI Role of simvastatin as an immunomodulator in type 2 diabetes SO DIABETES CARE LA English DT Article ID CONTAINING IMMUNE-COMPLEXES; LOW-DENSITY-LIPOPROTEIN; CORONARY-ARTERY-DISEASE; MODIFIED LDL ANTIBODIES; OXIDIZED LDL; ATHEROSCLEROTIC LESIONS; MACROVASCULAR DISEASE; HEART-DISEASE; ATHEROGENESIS; CHOLESTEROL AB OBJECTIVE - To test the hypothesis that simvastatin reduces the levels of circulating immune complexes (ICs) containing modified lipoproteins (mLDLs; mLDL-ICs), which may represent an additional mechanism for the reduced incidence of cardiovascular events in patients treated With simvastatin. RESEARCH DESIGN AND METHODS - A total of 26 patients With type 2 diabetes and triglyceride levels <400 mg/dl who were not receiving lipid-lowering medications or CYP 3A4 inhibitors were enrolled in the study. After 2 weeks on a lipid-lowering diet and exercise, the patients were started on simvastatin 20 mg/day. The dose of simvastatin was adjusted until the levels of LDL cholesterol were less than or equal to100 mg/dl. Blood was collected at baseline, 3 and 6 months after LDL cholesterol levels reached target, and 3 months after stopping simvastatin to measure advanced glycation end product LDL and oxidized LDL antibodies, mLDL-IC, intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), E-selectin, metalloprotemase-1 (MMP-1), lipid profile, liver function tests, creatinine kinase, glucose, and HbA(1c). RESULTS - Twenty-one patients completed the Study. Their HbA(1c) remained within 1% of baseline levels. There was a highly significant decrease in mLDL-IC levels after 3 and 6 months of treatment With simvastatin, with a return to near baseline levels after discontinuation. CONCLUSIONS - Simvastatin significantly reduced the concentration of mLDL-IC, probably as a consequence of both a decrease in the formation of mLDL and to a reduction in the titers of mLDL antibodies. This effect is likely to have a beneficial impact in the inflammatory reaction associated with atherosclerosis. C1 Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Dept Med, Charleston, SC 29425 USA. Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC USA. Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP Lopes-Virella, MF (reprint author), Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Dept Med, Storm Thurmond Res Bldg,114 Doughty St,Room 529, Charleston, SC 29425 USA. EM virellam@musc.edu NR 25 TC 9 Z9 10 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 2004 VL 27 IS 4 BP 908 EP 913 DI 10.2337/diacare.27.4.908 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 809AG UT WOS:000220609000009 PM 15047647 ER PT J AU Moran, A Palmas, W Field, L Bhattarai, J Schwartz, JE Weinstock, RS Shea, S AF Moran, A Palmas, W Field, L Bhattarai, J Schwartz, JE Weinstock, RS Shea, S TI Cardiovascular autonomic neuropathy is associated with microalbuminuria in older patients with type 2 diabetes SO DIABETES CARE LA English DT Article ID AMBULATORY BLOOD-PRESSURE; HEART-RATE; NEPHROPATHY; PROGRESSION; NIDDM; ALBUMINURIA; MORTALITY; DISEASE; RISK; IDDM AB OBJECTIVE - Cardiovascular autonomic neuropathy is associated with microalbuminuria in young and middle-aged patients with type 2 diabetes. We examined this relationship and the potential mediating role of blood pressure in older patients. RESEARCH DESIGN AND METHODS - At least two of three components of cardiovascular autonomic testing were completed by 132 patients (mean age 70 +/- 5.6 years). Relative rankings on each of the components were averaged to create a summary heart rate variability (HRV) measure. The urine microalbumin-to-creatinine ratio (milligrams albumin/grams creatinine) was calculated. Blood pressure was measured at rest and by 24-h ambulatory recording. RESULTS - Urine microalbumin-to-creatinine ratio was higher in those with lower HRV (mean urine microalbumin-to-creatinine ratio 28, 56, and 191 mg/g from the highest to lowest HRV; P < 0.0001). Resting and ambulatory blood pressure levels were negatively correlated with HRV and positively correlated with unne microalbuiiiin-to-creatinine ratio. In multivariate analysis adjusting for age, duration of diabetes, HbA(1c), and HDL cholesterol, HRV and blood pressure were both independently associated with urine microalbumin-to-creatinine ratio, with no evidence that either mediates the effect of the other. CONCLUSIONS - Cardiovascular autonomic neuropathy and blood pressure are independently associated with microalbuminuria in older patients with type 2 diabetes. C1 Columbia Univ Coll Phys & Surg, Dept Med, Div Gen Med, New York, NY 10032 USA. SUNY Upstate Med Univ, Joslin Diabet Ctr, Syracuse, NY USA. SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. Dept Vet Affairs Med Ctr, Syracuse, NY USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. RP Shea, S (reprint author), Columbia Univ Coll Phys & Surg, Dept Med, Div Gen Med, PH 9,E Room 105,622 W 168th St, New York, NY 10032 USA. EM ss35@columbia.edu FU PHS HHS [95-C-90998/2-01] NR 31 TC 22 Z9 29 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 2004 VL 27 IS 4 BP 972 EP 977 DI 10.2337/diacare.27.4.972 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 809AG UT WOS:000220609000020 PM 15047658 ER PT J AU Liao, YL Kwon, SH Shaughnessy, S Wallace, P Hutto, A Jenkins, AJ Klein, RL Garvey, WT AF Liao, YL Kwon, SH Shaughnessy, S Wallace, P Hutto, A Jenkins, AJ Klein, RL Garvey, WT TI Critical evaluation of adult treatment panel III criteria in identifying insulin resistance with dyslipidemia SO DIABETES CARE LA English DT Article ID NUTRITION EXAMINATION SURVEY; NUCLEAR-MAGNETIC-RESONANCE; 3RD NATIONAL-HEALTH; PARTICLE-SIZE; CARDIOVASCULAR-DISEASE; METABOLIC SYNDROME; US ADULTS; ATHEROSCLEROSIS; PREVALENCE; SECRETION AB OBJECTIVE - The goal of this study was to evaluate the efficacy of the Third Report of the National Cholesterol Education Program Expert Panel on Detection and Treatment Evaluation,, of High Blood Cholesterol in Adults (ATP III) in identifying insulin resistance. RESEARCH DESIGN AND METHODS - This study included 74 nondiabetic Caucasians who were evaluated for insulin resistance and risk factors associated with the metabolic syndrome. Glucose disposal rate (GDR) was measured by hyperinsulinemic-euglycemic clamp and was used to quantify insulin resistance. Sensitivity and specificity of ATP III criteria in detecting insulin resistance were calculated for various cutoffs of GDR. RESULTS - insulin resistance was associated with increased waist circumference, fasting glucose, blood pressure, triglycerides, and decreased levels of HDL cholesterol. Only 1.2.2% of study subjects met ATP III criteria for metabolic syndrome, and ATP III criteria exhibited low sensitivity for detecting insulin resistance. Although high in specificities (>90%), the sensitivities of ATP III criteria ranged only between 20 and 50% when insulin resistance was defined as various GDR cutoff values below 10 to 12 mg(.)kg(-1.)min(-1). The larger number of subjects who were insulin resistant but did not meet ATP III criteria were found to have an adverse cardiovascular disease risk profile, including higher BMI, waist circumference, fasting glucose, triglycerides, and an unfavorable lipoprotein subclass profile determined by nuclear magnetic resonance compared with insulin-sensitive individuals (i.e., increased large VLDL, increased small LDL, and decreased large HDL particle concentrations). CONCLUSIONS - ATP III criteria have low sensitivity for identifying insulin resistance with dyslipidemia in nondiabetic individuals who are at increased risk for cardiovascular disease and diabetes. More sensitive criteria should be developed for clinical assessment of metabolic and cardiovascular disease risk relevant to the metabolic syndrome. C1 Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. Univ Melbourne, Dept Med, Melbourne, Vic, Australia. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Garvey, WT (reprint author), Univ Alabama, Dept Nutr Sci, Webb 232,1675 Univ Blvd, Birmingham, AL 35294 USA. EM garveyt@uab.edu RI Jenkins, Alicia/N-2482-2015 FU NCRR NIH HHS [M01-RR-1070]; NHLBI NIH HHS [P01 HL-55782]; NIDDK NIH HHS [DK-38764] NR 25 TC 128 Z9 137 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 2004 VL 27 IS 4 BP 978 EP 983 DI 10.2337/diacare.27.4.978 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 809AG UT WOS:000220609000021 PM 15047659 ER PT J AU Weinberg, BM Oh, DS Ohning, GV Pisegna, JR AF Weinberg, BM Oh, DS Ohning, GV Pisegna, JR TI Reflux laryngitis in a patient with Zollinger Ellison syndrome and the role of epidermal growth factor SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE reflux laryngitis; Zollinger Ellison syndrome; epidermal growth factor ID SALIVARY; MANAGEMENT; OMEPRAZOLE; ACID; DIAGNOSIS; DISEASE C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Olive View UCLA Med Ctr, UCLA San Fernando Valley Program, Dept Med, Sylmar, CA 91342 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90073 USA. RP Pisegna, JR (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jpisegna@ucla.edu NR 19 TC 1 Z9 1 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD APR PY 2004 VL 49 IS 4 BP 693 EP 696 DI 10.1023/B:DDAS.0000026320.17006.14 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 817KY UT WOS:000221177600027 PM 15185880 ER PT J AU Shera, CA AF Shera, CA TI Mechanisms of mammalian otoacoustic emission and their implications for the clinical utility of otoacoustic emissions SO EAR AND HEARING LA English DT Article ID BASILAR-MEMBRANE NONLINEARITY; CANAL ACOUSTIC ADMITTANCE; FINE-STRUCTURE; HAIR-CELLS; REFLECTANCE MEASUREMENTS; DPOAE GENERATION; GUINEA-PIG; DISTORTION; EAR; HUMANS AB We review recent progress in understanding the physical and physiological mechanisms that generate otoacoustic emissions (OAEs). Until recently, the conceptual model underlying the interpretation of OAEs has been an integrated view that regards all OAEs as manifestations of cochlear nonlinearity. However, OAEs appear to arise by at least two fundamentally different mechanisms within the cochlea: nonlinear distortion and linear reflection. These differences in mechanism have be used to construct a new taxonomy for OAEs that identifies OAEs based on their mechanisms of generation rather than the details of their measurement. The mechanism-based taxonomy provides a useful conceptual framework for understanding and interpreting otoacoustic responses. As commonly measured in the clinic, distortion-product and other evoked OAEs comprise a mixtures of emissions produced by both mechanisms. This mixing precludes any fixed correspondence with the conventional, measurement-based nomenclature. We discuss consequences of the taxonomy for the clinical measurement and interpretation of OAEs. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Shera, CA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. EM shera@epl.meei.harvard.edu FU NIDCD NIH HHS [DC03687, R01 DC003687] NR 70 TC 76 Z9 78 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-0202 J9 EAR HEARING JI Ear Hear. PD APR PY 2004 VL 25 IS 2 BP 86 EP 97 DI 10.1097/01.AUD.0000121200.90211.83 PG 12 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 810KX UT WOS:000220704300002 PM 15064654 ER PT J AU Gensure, RC Ponugoti, B Gunes, Y Papasani, MR Lanske, B Bastepe, M Rubin, DA Juppner, H AF Gensure, RC Ponugoti, B Gunes, Y Papasani, MR Lanske, B Bastepe, M Rubin, DA Juppner, H TI Identification and characterization of two parathyroid hormone-like molecules in zebrafish SO ENDOCRINOLOGY LA English DT Article ID PHOTOAFFINITY CROSS-LINKING; PTH2 RECEPTOR; TUBEROINFUNDIBULAR PEPTIDE; GROWTH-HORMONE; OREOCHROMIS-MOSSAMBICUS; MUTATIONAL ANALYSIS; 39 RESIDUES; EXPRESSION; AGONIST; TELEOST AB Zebrafish ( Danio rerio) have receptors homologous to the human PTH (hPTH)/PTHrP receptor (PTH1R) and PTH-2 receptor (PTH2R) and an additional receptor (PTH3R) with high homology to the PTH1R. To find natural ligands for zPTH1R and zPTH3R, we searched the zebrafish genomic database and discovered two distinct regions that, when translated (zPTH1 and zPTH2), showed high homology to hPTH. Isolation of cDNAs and determination of the intron/exon boundaries revealed genomic structures which were similar to known PTHs. Peptides consisting of the first 34 amino acids after the pre-and prosequences of the zebrafish PTHs (zPTHs) were synthesized and were shown to be fully active at the hPTH1R. zPTH2(1-34) was, however, approximately 30-fold less potent at the zPTH1R than hPTH(1 - 34), hPTHrP(1 - 36), and zPTH1(1 - 34). When tested with zPTH3R, zPTH1( 1 - 34) and hPTHrP( 1 - 36) showed similar potencies, whereas the potency of zPTH2(1 - 34) was moderately (3-fold) reduced. To determine whether other fishes have multiple PTHs, we searched the genomic database of the Japanese pufferfish ( Takifugu rubripes) and identified zPTH1 and zPTH2 homologs. Phylogenetic analysis showed that PTHs from zebrafish and pufferfish are more closely related to each other than to known mammalian PTH homologs or to PTHrP and tuberoinfundibular peptide of 39 residues. This is consistent with evolution of two teleost PTH-like peptides occurring after the evolutionary divergence between fishes and mammals. Overall, the PTH system appears more complex in fishes than in mammals, providing evidence of continued evolution in nontetrapod species. The availability of multiple forms of fish PTH and their receptors provide additional tools for PTH ligand/receptor structure-function studies. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Illinois State Univ, Dept Biol Sci, Normal, IL 61790 USA. Harvard Univ, Sch Dent Med, Forsyth Inst, Dept Oral & Dev Biol, Boston, MA 02115 USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Wellman 5, Boston, MA 02114 USA. EM hjueppner@partners.org RI PONUGOTI, BHASKAR/H-2230-2011 FU NIDDK NIH HHS [DK11794, DK60513] NR 37 TC 52 Z9 52 U1 0 U2 4 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD APR 1 PY 2004 VL 145 IS 4 BP 1634 EP 1639 DI 10.1210/en.2003-0964 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 803DT UT WOS:000220212500020 PM 14684608 ER PT J AU Cariou, B Postic, C Boudou, P Burcelin, R Kahn, CR Girard, J Burnol, AF Mauvais-Jarvis, F AF Cariou, B Postic, C Boudou, P Burcelin, R Kahn, CR Girard, J Burnol, AF Mauvais-Jarvis, F TI Cellular and molecular mechanisms of adipose tissue plasticity in muscle insulin receptor knockout mice SO ENDOCRINOLOGY LA English DT Article ID ADIPOCYTE DIFFERENTIATION; OBESITY; EXPRESSION; RESISTANCE; PROTEIN; GAMMA; ADIPONECTIN; GENE; ACTIVATION; INCREASE AB White adipose tissue (WAT) plays a critical role in the development of insulin resistance via secretion of free fatty acids (FFA) and adipocytokines. Muscle-specific insulin receptor knockout (MIRKO) mice do not develop insulin resistance or diabetes under physiological conditions despite a marked increase in adiposity and plasma FFA. On the contrary, WAT of MIRKO is sensitized to insulin action during a euglycemic clamp, and WAT glucose utilization is dramatically increased. To get insight into the potential antidiabetic role of MIRKO adiposity, we have studied insulin action in WAT during a euglycemic, hyperinsulinemic clamp, and we have characterized the morphology and biology of WAT. During the clamp, there is no alteration in the expression or activation in the insulin signaling molecules involved in glucose transport through the phosphoinositide 3-kinase/Akt and CAP/Cbl pathways in WAT from MIRKO. The 53% increase in WAT mass results from a 48% increase in adipocyte number (P < 0.05) without alteration in cell size and contemporary to a 300% increase in mRNA levels of the adipogenic transcription factor CCAAT enhancer binding protein-α (C/EBP-α) (P < 0.05). There is a 39.5% increase in serum adiponectin (P < 0.01) without modification in serum leptin, resistin, and TNF-α. In conclusion, the MIRKO mouse displays muscle insulin resistance, visceral obesity, and dyslipidemia but does not develop hyperinsulinemia or diabetes. There is an accelerated differentiation of small insulin sensitive adipocytes, an increased secretion of the insulin sensitizer adiponectin, and maintenance of leptin sensitivity. The MIRKO mouse confirms the importance of WAT plasticity in the maintenance of whole body insulin sensitivity and represents an interesting model to search for new secreted molecules that positively alter adipose tissue biology. C1 Inst Cochin Genet Mol, CNRS, UMR 8104, INSERM,U567,Dept Endocrinol, F-75014 Paris, France. Univ Paris 07, Sch Med, St Louis Hosp, F-75010 Paris, France. Hop St Louis, Dept Endocrinol & Diabet, F-75010 Paris, France. Hop St Louis, Dept Hormonal Biochem, F-75010 Paris, France. Univ Toulouse 3, CNRS, UMR 5018, F-31062 Toulouse, France. Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Res Div, Boston, MA 02215 USA. RP Mauvais-Jarvis, F (reprint author), Baylor Coll Med, Dept Med, Div Endocrinol Diabet & Metab, Room 520B, Houston, TX 77030 USA. EM fmjarvis@bcm.tmc.edu RI burcelin, remy/M-6013-2014 NR 25 TC 30 Z9 32 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD APR 1 PY 2004 VL 145 IS 4 BP 1926 EP 1932 DI 10.1210/en.2003-0882 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 803DT UT WOS:000220212500053 PM 14684612 ER PT J AU Miao, DS He, B Lanske, B Bai, XY Tong, XK Hendy, GN Goltzman, D Karaplis, AC AF Miao, DS He, B Lanske, B Bai, XY Tong, XK Hendy, GN Goltzman, D Karaplis, AC TI Skeletal abnormalities in Pth-null mice are influenced by dietary calcium SO ENDOCRINOLOGY LA English DT Article ID HORMONE-RELATED PEPTIDE; CARBOXYL-TERMINAL REGION; BONE-MINERAL DENSITY; PARATHYROID-HORMONE; BLOMSTRAND-CHONDRODYSPLASIA; CHRONIC HYPOPARATHYROIDISM; TURNOVER BONE; RECEPTOR; EXPRESSION; DECREASES AB We have examined the role of PTH in the postnatal state in a mouse model of PTH deficiency generated by targeting the Pth gene in embryonic stem cells. Mice homozygous for the ablated allele, when maintained on a normal calcium intake, developed hypocalcemia, hyperphosphatemia, and low circulating 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] levels consistent with primary hypoparathyroidism. Bone turnover was reduced, leading to increased trabecular and cortical bone volume in PTH-deficient mice. When mutant mice were placed on a low-calcium diet, renal 25-hydroxyvitamin D 1 alpha-hydroxylase expression increased despite the absence of PTH, leading to a rise in circulating 1,25(OH)(2)D-3 levels, marked osteoclastogenesis, and profound bone resorption. These studies demonstrate the dependence of the skeletal phenotype in animals with genetically depleted PTH on the external environment as well as on internal hormonal and ionic circulatory factors. They also show that, although PTH action is the first defense against hypocalcemia, 1,25(OH)(2)D-3 can be mobilized, even in the absence of PTH, to guard against extreme calcium deficiency. C1 McGill Univ, Sir Mortimer B Davis Jewish Gen Hosp, Dept Med, Montreal, PQ H3T 1E2, Canada. McGill Univ, Sir Mortimer B Davis Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada. McGill Univ, Ctr Hlth, Calcium Res Lab, Montreal, PQ H3A 1A1, Canada. McGill Univ, Ctr Hlth, Dept Med, Montreal, PQ H3A 1A1, Canada. McGill Univ, Royal Victoria Hosp, Montreal, PQ H3A 1A1, Canada. Forsyth Inst, Dept Oral & Dev Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Karaplis, AC (reprint author), McGill Univ, Sir Mortimer B Davis Jewish Gen Hosp, Dept Med, 3755 Cote St Catherine Rd, Montreal, PQ H3T 1E2, Canada. EM akarapli@ldi.jgh.mcgill.ca NR 29 TC 61 Z9 77 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD APR 1 PY 2004 VL 145 IS 4 BP 2046 EP 2053 DI 10.1210/en.2003-1097 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 803DT UT WOS:000220212500066 PM 14701672 ER PT J AU Apidianakis, Y Rahme, LG Heitman, J Ausubel, FM Calderwood, SB Mylonakis, E AF Apidianakis, Y Rahme, LG Heitman, J Ausubel, FM Calderwood, SB Mylonakis, E TI Challenge of Drosophila melanogaster with Cryptococcus neoformans and role of the innate immune response SO EUKARYOTIC CELL LA English DT Article ID ANTIMICROBIAL PEPTIDE GENES; PSEUDOMONAS-AERUGINOSA; TOLL PATHWAY; MODEL HOST; IN-VITRO; VIRULENCE; INFECTION; PATHOGEN; PROTEIN; DEFENSE AB We found that the ingestion of Cryptococcus neoformans by Drosophila melanogaster resulted in the death of the fly but that the ingestion of Saccharomyces cerevisiae or the nonpathogenic Cryptococcus kuetzingii or Cryptococcus laurentii did not. The C. neoformans protein kinase A and RAS signal transduction pathways, previously shown to be involved in virulence in mammals, also played a role in killing Drosophila. Mutation of the Toll immune response pathway, the predominant antifungal pathway of the fly, did not play a role in Drosophila defense following ingestion of the yeast. However, the Toll pathway was necessary for the clearance of C. neoformans introduced directly into the hemolymph of D. melanogaster and for the survival of systemically infected flies. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Shriners Burn Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA. RP Mylonakis, E (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM emylonakis@partners.org OI Apidianakis, Yiorgos/0000-0002-7465-3560 FU NIGMS NIH HHS [GM48707, R37 GM048707, R01 GM048707] NR 57 TC 78 Z9 81 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD APR PY 2004 VL 3 IS 2 BP 413 EP 419 DI 10.1128/EC.3.2.413-419.2004 PG 7 WC Microbiology; Mycology SC Microbiology; Mycology GA 813ZP UT WOS:000220945300017 PM 15075271 ER PT J AU Geller, DA Biederman, J Faraone, S Spencer, T Doyle, R Mullin, B Magovcevic, M Zaman, N Farrell, C AF Geller, DA Biederman, J Faraone, S Spencer, T Doyle, R Mullin, B Magovcevic, M Zaman, N Farrell, C TI Re-examining comorbidity of Obsessive Compulsive and Attention-Deficit Hyperactivity Disorder using an empirically derived taxonomy SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY LA English DT Article DE CBCL; OCD; ADHD ID CHILD-BEHAVIOR-CHECKLIST; DIFFICULTIES-QUESTIONNAIRE; PSYCHIATRIC DIAGNOSES; ADOLESCENTS; CONVERGENCE; ADHD; DEPRESSION; STRENGTHS; CBCL AB Background Using an empirically derived instrument to reduce the assessor bias inherent in structured diagnostic interviews, we sought to re-examine and validate the putative comorbidity between Obsessive Compulsive Disorder (OCD) and Attention-Deficit/Hyperactivity Disorder (ADHD) in children and adolescents. Method We examined the correlation between Child Behavior Checklist (CBCL) syndrome, competence, and composite scores in children with: 1) OCD plus ADHD (OCD + ADHD), N = 47; 2) OCD without comorbid ADHD (OCD), N = 33; 3) ADHD without comorbid OCD (ADHD) N = 43; and 4) comparison controls recruited from general pediatric clinics,N = 32. Results CBCL findings in our ADHD children were similar to previous findings reported in ADHD youth, irrespective of the presence or absence of comorbid OCD. Comorbid youth generally had additive scores on the CBCL scales, reflecting the independent contribution of symptomatic and functional impairment from each disorder. Conclusion These findings suggest that when ADHD-like symptoms are seen in OCD youth, they reflect a true comorbid state of OCD plus ADHD. The CBCL may provide a rapid assessment tool to identify comorbid ADHD in OCD youth. C1 Massachusetts Gen Hosp, Pediat OCD Clin, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Joint Program Pediat Psychopharmacol, Boston, MA 02114 USA. RP Geller, DA (reprint author), Massachusetts Gen Hosp, Pediat OCD Clin, WACC 725,15 Parkman St, Boston, MA 02114 USA. EM dageller@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K08 MH 01481] NR 32 TC 22 Z9 22 U1 2 U2 3 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 1018-8827 J9 EUR CHILD ADOLES PSY JI Eur. Child Adolesc. Psych. PD APR PY 2004 VL 13 IS 2 BP 83 EP 91 DI 10.1007/s00787-004-0379-x PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 814HR UT WOS:000220966300004 PM 15103533 ER PT J AU Martinic, MM Rocha, B McCoy, KD Hengartner, H Zinkernagel, RM AF Martinic, MM Rocha, B McCoy, KD Hengartner, H Zinkernagel, RM TI Role of TCR-restricting MHC density and thymic environment on selection and survival of cells expressing low-affinity T cell receptors SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE H-Y TCR; T cell selection and survival; MHC density; thymic and athymic environment ID TRANSGENIC MICE; POSITIVE SELECTION; NEGATIVE SELECTION; ONCOSTATIN-M; MOLECULES; ANTIGEN; LYMPHOCYTES; DIFFERENTIATION; THYMOCYTES; REPERTOIRE AB H-Y-specific T cell receptor (TCR) transgenic mice express an MHC class I H-2D(b)-restricted TCR specific for a male antigen-derived peptide (H-Y). Selection and survival of cells expressing this low-affinity TCR were analyzed under optimal and sub-optimal conditions. Optimal conditions were provided by a thymic environment with high H-2D(b) density. Suboptimal conditions were provided by a thymic environment with decreased H-2D(b) density or by an athymic environment with either high or low H-2D(b) density. Whereas negative selection was still guaranteed under sub-optimal conditions, selection and survival efficiency of cells expressing the transgenic TCR were strongly dependent on optimal conditions. These results indicated that both a thymic microenvironment and a high density of TCR-restricting MHC molecules were needed to ensure selection and maintenance of cells expressing TCR with low affinity and hence a more diverse T cell repertoire. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med, Joslin Diabet Ctr,Sect Immunol & Immunogenet, Boston, MA 02215 USA. Univ Zurich Hosp, Dept Pathol, Inst Expt Immunol, CH-8091 Zurich, Switzerland. Inst Necker, INSERM, U591, Paris, France. RP Martinic, MM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med, Joslin Diabet Ctr,Sect Immunol & Immunogenet, 1 Joslin Pl, Boston, MA 02215 USA. EM marianne.martinic@joslin.harvard.edu NR 35 TC 7 Z9 7 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD APR PY 2004 VL 34 IS 4 BP 1041 EP 1049 DI 10.1002/eji.200424920 PG 9 WC Immunology SC Immunology GA 812JA UT WOS:000220834600014 PM 15048714 ER PT J AU Allen, AJ Kurlan, RM Linder, SL Lewis, DW Winner, PK Gilbert, DL Dunn, DW Sallee, FR Milton, DR Mintz, MI Ricardi, RK Erenberg, G Layton, LL Feldman, PD Kelsey, DK Spencer, TJ AF Allen, AJ Kurlan, RM Linder, SL Lewis, DW Winner, PK Gilbert, DL Dunn, DW Sallee, FR Milton, DR Mintz, MI Ricardi, RK Erenberg, G Layton, LL Feldman, PD Kelsey, DK Spencer, TJ TI Atomoxetine treatment in children with attention-deficit/hyperactivity disorder and comorbid tic disorders SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 Lilly Res Labs, Indianapolis, IN USA. Univ Rochester, Sch Med & Dent, Rochester, NY 14627 USA. Dallas Pediat Neurol Assoc, Dallas, TX USA. Monarch Res Assoc, Norfolk, VA USA. Premiere Res Inst, W Palm Beach, FL USA. Childrens Hosp, Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA. Riley Child & Adolescent Psychiat Clin, Indianapolis, IN USA. Bancroft Neurohlth, Cherry Hill, NJ USA. Arizona Family Resource Counseling Ctr, Phoenix, AZ USA. Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PD APR PY 2004 VL 19 SU 1 BP 240S EP 241S PG 2 WC Psychiatry SC Psychiatry GA 814AS UT WOS:000220948200816 ER PT J AU Michelson, D Buitelaar, JK Danckaerts, M Gillberg, C Spencer, TJ Zuddas, A Zhang, S Biederman, J AF Michelson, D Buitelaar, JK Danckaerts, M Gillberg, C Spencer, TJ Zuddas, A Zhang, S Biederman, J TI Atomoxetine in the long-term prevention of relapse in ADHD SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 Lilly Res Labs, Indianapolis, IN USA. Univ Med Ctr St Radboud, Nijmegen, Netherlands. Catholic Univ, Louvain, Belgium. Barnneuropsykiat Kliniken, Gothenburg, Sweden. Massachusetts Gen Hosp, Boston, MA 02114 USA. Clin Neuropsichiat Infantile, Cagliari, Italy. RI Buitelaar, Jan/E-4584-2012 OI Buitelaar, Jan/0000-0001-8288-7757 NR 0 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PD APR PY 2004 VL 19 SU 1 BP 240S EP 240S PG 1 WC Psychiatry SC Psychiatry GA 814AS UT WOS:000220948200814 ER PT J AU Simpson, A Kratochvil, C Spencer, TJ Buitelaar, JK Newcorn, JH Wilens, TE Allen, AJ Faries, DE Milton, DR Feldman, PD Michelson, D Biederman, J AF Simpson, A Kratochvil, C Spencer, TJ Buitelaar, JK Newcorn, JH Wilens, TE Allen, AJ Faries, DE Milton, DR Feldman, PD Michelson, D Biederman, J TI Efficacy of atomoxetine in placebo-controlled studies in children, adolescents, and adults with attention-deficit/hyperactivity disorder SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 Eli Lilly & Co Ltd, Basingstoke, Hants, England. Univ Nebraska, Med Ctr, Lincoln, NE 68583 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Med Ctr St Radboud, Nijmegen, Netherlands. Mt Sinai Med Ctr, New York, NY 10029 USA. Lilly Res Labs, Indianapolis, IN USA. RI Buitelaar, Jan/E-4584-2012 OI Buitelaar, Jan/0000-0001-8288-7757 NR 0 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PD APR PY 2004 VL 19 SU 1 BP 240S EP 240S PG 1 WC Psychiatry SC Psychiatry GA 814AS UT WOS:000220948200815 ER PT J AU Shiffman, ML Di Bisceglie, AM Lindsay, KL Morishima, C Wright, EC Everson, GT Lok, AS Morgan, TR Bonkovsky, HL Lee, WM Dienstag, JL Ghany, MG Goodman, ZD Everhart, JE AF Shiffman, ML Di Bisceglie, AM Lindsay, KL Morishima, C Wright, EC Everson, GT Lok, AS Morgan, TR Bonkovsky, HL Lee, WM Dienstag, JL Ghany, MG Goodman, ZD Everhart, JE CA HALT-C Trial Grp TI Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment SO GASTROENTEROLOGY LA English DT Article ID INITIAL TREATMENT; PLUS RIBAVIRIN; INTERFERON THERAPY; COMBINATION; TRIAL; CIRRHOSIS; VIRUS AB Background & Aims: The most effective therapy currently available for treatment of chronic hepatitis C virus (HCV) is the combination of peginterferon and ribavirin. This study evaluated the effectiveness of this treatment in patients who were nonresponders to previous interferon-based therapy. Methods: The first 604 patients enrolled in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial were evaluated. All were HCV RNA positive, previous nonresponders to interferon, with or without ribavirin, and had bridging fibrosis or cirrhosis on liver biopsy (Ishak fibrosis stage 3-6). Patients were retreated with peginterferon alfa-2a 180 mug/wk plus ribavirin 1000-1200 mg/day. Those with no detectable HCV RNA in serum at week 20 continued treatment for a total of 48 weeks and were then followed for an additional 24 weeks. Results: Thirty-five percent of patients had no detectable HCV RNA in serum at treatment week 20, and 18% achieved sustained virologic response (SVR). Factors associated with an SVR included previous treatment with interferon monotherapy, infection with genotypes 2 or 3, a lower AST:ALT ratio, and absence of cirrhosis. Reducing the dose of ribavirin from greater than or equal to80% to less than or equal to60% of the starting dose during the first 20 weeks of treatment was associated with a decline in SVR from 21% to 11% (P less than or equal to 0.05). In contrast, reducing the dose of peginterferon or reducing ribavirin after week 20, when HCV RNA was already undetectable, did not significantly affect SVR. Conclusions: Selected nonresponders to previous interferon-based therapy can achieve SVR following retreatment with peginterferon alfa-2a and ribavirin. C1 Virginia Commonwealth Univ, Hepatol Sect, Hlth Syst, Richmond, VA 23298 USA. St Louis Univ, Sch Med, Div Gastroenterol, St Louis, MO 63103 USA. Univ So Calif, Div Gastrointestinal & Liver Dis, Los Angeles, CA USA. Univ Washington, Dept Pediat & Lab Med, Seattle, WA 98195 USA. New England Res Inst, Watertown, MA 02172 USA. Univ Colorado, Sect Hepatol, Div Gastroenterol & Hepatol, Denver, CO 80202 USA. Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI USA. Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT 06030 USA. Univ Connecticut, Ctr Hlth, Gen Clin Res Ctr, Farmington, CT 06030 USA. Univ Texas, Div Digest & Liver Dis, SW Med Ctr, Dallas, TX 75230 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. NIDDKD, Liver Dis Sect, Div Digest Dis & Nutr, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Div Hepat Pathol, Washington, DC 20306 USA. Armed Forces Inst Pathol, Vet Adm Special Reference Lab Pathol, Washington, DC 20306 USA. NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Shiffman, ML (reprint author), Virginia Commonwealth Univ, Hepatol Sect, Hlth Syst, Box 980341, Richmond, VA 23298 USA. EM mshiffma@hsc.vcu.edu RI Lok, Anna /B-8292-2009; OI Yang, Shuman/0000-0002-9638-0890 FU NCRR NIH HHS [M01RR-00042, M01RR-00043, M01RR-00051, M01RR-00065, M01RR-00633, M01RR-00827, M01RR-01066, M01RR-06192]; NIDDK NIH HHS [N01-DK-9-2324, N01-DK-9-2318, N01-DK-9-2319, N01-DK-9-2320, N01-DK-9-2321, N01-DK-9-2322, N01-DK-9-2323, N01-DK-9-2325, N01-DK-9-2326, N01-DK-9-2327, N01-DK-9-2328] NR 21 TC 326 Z9 340 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2004 VL 126 IS 4 BP 1015 EP 1023 DI 10.1053/j.gastro.2004.01.014 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 810ER UT WOS:000220688100014 PM 15057741 ER PT J AU Otte, JM Cario, E Podolsky, DK AF Otte, JM Cario, E Podolsky, DK TI Mechanisms of cross hyporesponsiveness to toll-like receptor bacterial ligands in intestinal epithelial cells SO GASTROENTEROLOGY LA English DT Article ID NF-KAPPA-B; PROINFLAMMATORY GENE-EXPRESSION; ENDOTOXIN-TOLERANT CELLS; IL-1 RECEPTOR; INTERLEUKIN-1 RECEPTOR; LIPOTEICHOIC ACID; SIGNAL-TRANSDUCTION; MURINE MACROPHAGES; ESCHERICHIA-COLI; CUTTING EDGE AB Background & Aims: Despite the ability to participate in immune responses and the continuous presence of bacteria and bacterial products, functional responses of intestinal epithelial cells (IEC) seem to be muted. Previously, tolerance to Toll-like receptors (TLRs) ligands has been described in monocytic cells. However, mechanisms in the intestine are unknown. Methods: The effect of purified lipopolysaccharide (LPS) and lipoteichoicacid (LTA) on expression and function of TLRs in intestinal epithelial cells (Colo205, SW480, T84) was assessed by Northern and Western blot and FACS analysis, kinase activity assays, immunohistochemistry, and ELISA. Results: Expression of TLRs except 10 was detected in primary IEC and TLR1-10 in the cultured cells. Shortterm stimulation with LPS or LTA activated proinflammatory signaling cascades in IEC, including phosphorylation of IRAK and MAP kinases and increased IL-8 secretion, whereas prolonged incubation resulted in a state of hyporesponsiveness with no reactivation of the cells by a second challenge with either substance detected. The cells remained responsive to tumor necrosis factor (TNF). Hyporesponsive cells showed no alteration in expression of TLR or signaling molecules but revealed a decrease in TLR surface expression and IRAK activity. Toll-interacting protein (Tollip) mRNA and protein expression were increased in hyporesponsive cells, and overexpression of Tollip in IEC resulted in a significantly decreased proinflammatory response. Conclusions: Continuous presence of specific bacterial components results in a status of hyporesponsiveness in otherwise reactive IEC. Down-regulation of TLR surface expression and up-regulation of inhibitory Tollip with decreased phosphorylation of IRAK might all contribute to this hypo responsiveness. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Ctr Study Inflammatroy Bowel Dis, Boston, MA USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Ctr Study Inflammatroy Bowel Dis, 55 Fruit St, Boston, MA USA. EM dpodolsky@partners.org FU NIDDK NIH HHS [R01 DK060049, DK43351, DK60049] NR 57 TC 311 Z9 337 U1 2 U2 24 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 APR PY 2004 VL 126 IS 4 BP 1054 EP 1070 DI 10.1053/j.gastro.2004.01.007 PG 17 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 810ER UT WOS:000220688100018 PM 15057745 ER PT J AU Oshiro, N Yoshino, K Hidayat, S Tokunaga, C Hara, K Eguchi, S Avruch, J Yonezawa, K AF Oshiro, N Yoshino, K Hidayat, S Tokunaga, C Hara, K Eguchi, S Avruch, J Yonezawa, K TI Dissociation of raptor from mTOR is a mechanism of rapamycin-induced inhibition of mTOR function SO GENES TO CELLS LA English DT Article ID P70 S6 KINASE; REPRESSOR PHAS-I; MAMMALIAN TARGET; FKBP12-RAPAMYCIN-ASSOCIATED PROTEIN; CELL-GROWTH; FISSION YEAST; EIF-4E BP1; TOS MOTIF; PHOSPHORYLATION; ACTIVATION AB The mammalian target of rapamycin (mTOR) is a Ser/Thr protein kinase that plays a crucial role in a nutrient-sensitive signalling pathway that regulates cell growth. TOR signalling is potently inhibited by rapamycin, through the direct binding of a FK506-binding protein 12 (FKBP12)/rapamycin complex to the TOR FRB domain, a segment amino terminal to the kinase catalytic domain. The molecular basis for the inhibitory action of FKBP12/rapamycin remains uncertain. Raptor (regulatory associated protein of mTOR) is a recently identified mTOR binding partner that is essential for mTOR signalling in vivo, and whose binding to mTOR is critical for mTOR-catalysed substrate phosphorylation in vitro. Here we investigated the stability of endogenous mTOR/raptor complex in response to rapamycin in vivo, and to the direct addition of a FKBP12/rapamycin complex in vitro. Rapamycin diminished the recovery of endogenous raptor with endogenous or recombinant mTOR in vivo; this inhibition required the ability of mTOR to bind the FKBP12/rapamycin complex, but was independent of mTOR kinase activity. Rapamycin, in the presence of FKBP12, inhibited the association of raptor with mTOR directly in vitro, and concomitantly reduced the mTOR-catalysed phosphorylation of raptor-dependent, but not raptor-independent substrates; mTOR autophosphorylation was unaltered. These observations indicate that rapamycin inhibits mTOR function, at least in part, by inhibiting the interaction of raptor with mTOR; this action uncouples mTOR from its substrates, and inhibits mTOR signalling without altering mTOR's intrinsic catalytic activity. C1 Kobe Univ, Biosignal Res Ctr, Kobe, Hyogo 6578501, Japan. Japan Sci & Technol Agcy, CREST, Kawaguchi 3320012, Japan. Kobe Univ, Sch Med, Dept Geriatr Med, Kobe, Hyogo 6500017, Japan. Massachusetts Gen Hosp, Med Serv, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Serv, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Yonezawa, K (reprint author), Kobe Univ, Biosignal Res Ctr, Kobe, Hyogo 6578501, Japan. EM yonezawa@kobe-u.ac.jp FU NCI NIH HHS [CA73818]; NIDDK NIH HHS [DK17776] NR 33 TC 184 Z9 196 U1 1 U2 7 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1356-9597 J9 GENES CELLS JI Genes Cells PD APR PY 2004 VL 9 IS 4 BP 359 EP 366 DI 10.1111/j.1356-9597.2004.00727.x PG 8 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 809GM UT WOS:000220625200008 PM 15066126 ER PT J AU Schnelle, JF Bates-Jensen, BM Levy-Storms, L Grbic, V Yoshii, J Cadogan, M Simmons, SF AF Schnelle, JF Bates-Jensen, BM Levy-Storms, L Grbic, V Yoshii, J Cadogan, M Simmons, SF TI The minimum data set prevalence of restraint quality indicator: Does it reflect differences in care? SO GERONTOLOGIST LA English DT Article DE MDS; quality indicator; physical restraint ID NURSING-HOME RESIDENTS; VULNERABLE ELDERS; INJURIES AB Purpose: This study investigated whether the use of restraining devices and related measures of care quality are different in nursing homes that score in the upper and lower quartiles on the Minimum Data Set (MDS) "prevalence of restraint" quality indicator, which assesses daily use of restraining devices when residents are out of bed. Design and Methods: The study was a cross-sectional study, with 413 residents in 14 nursing facilities. Eight homes scored in the lower quartile (25th percentile; low prevalence, 0-5%) on the MDS restraint prevalence quality indicator, and six homes scored in the upper quartile (75th percentile; high prevalence, 28-48%). Eight care processes related to the management of restraints and gait and balance problems were defined and operationalized into clinical indicators. Research staff conducted direct observations during three 12-hr days (7 a.m. -7 p.m.) to determine the prevalence of restraining devices and identify resident and staff behaviors that may be affected by restraint use. Results: Residents in high-restraint homes were in bed during the day on more observations than residents in low-restraint homes (44% vs. 33%; p < .001), were more frequently observed with bed rails in use (74% of residents vs. 64% of residents; p < .03), and received less feeding assistance during meals (2.7 min vs. 4.1 min; p < .001). There were no differences between homes in the use of out-of-bed restraints, nor were there any differences on any care process measure related to the management of restraints, gait and balance problems, or measures of physical or social activity. Implications: A home's score on the MDS-generated prevalence of restraint quality indicator was not associated with differences in the use of restraints, physical activity, or any care process measure when residents were out of bed. However, there were differences in the use of in-bed restraining devices, and residents in high-restraint homes were in bed more often during the day. These differences were associated with poor feeding assistance and reflect important differences in quality of care between homes, even though these differences are not what the restraint prevalence quality indicator purports to measure. Methods to monitor and improve the quality of care related to exercise, in-bed times, and resident freedom of movement are discussed. C1 Univ Calif Los Angeles, JHA, Borun Ctr Gerontol Res, Reseda, CA 91335 USA. Univ Calif Los Angeles, Dept Med, Reseda, CA 91335 USA. VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Nursing, Reseda, CA 91335 USA. RP Schnelle, JF (reprint author), Univ Calif Los Angeles, JHA, Borun Ctr Gerontol Res, 7150 Tampa Ave, Reseda, CA 91335 USA. EM jschnell@ucla.edu NR 25 TC 33 Z9 33 U1 1 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD APR PY 2004 VL 44 IS 2 BP 245 EP 255 PG 11 WC Gerontology SC Geriatrics & Gerontology GA 813FA UT WOS:000220891800011 PM 15075421 ER PT J AU Penson, RT Oliva, E Skates, SJ Glyptis, T Fuller, AF Goodman, A Seiden, MV AF Penson, RT Oliva, E Skates, SJ Glyptis, T Fuller, AF Goodman, A Seiden, MV TI Expression of multidrug resistance-1 protein inversely correlates with paclitaxel response and survival in ovarian cancer patients: a study in serial samples SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 36th Meeting of the American-Society-of-Clinical-Oncology CY MAY 20-23, 2001 CL NEW ORLEANS, LA SP American Soc Clin Oncol DE P-gp; MDR-1; taxane; chemotherapy ID MDR1 GENE-EXPRESSION; P-GLYCOPROTEIN; MONOCLONAL-ANTIBODIES; CELL-LINES; CISPLATIN; BREAST; TAXOL; ADENOCARCINOMA; CHEMOTHERAPY; DOXORUBICIN AB Objective. The role of MDRI in clinical paclitaxel resistance remains poorly characterized. This study sought to identify the incidence and significance of P-glycoprotein (P-gp) over-expression on Survival, tumor response to paclitaxel and the effect of prior cytotoxic exposure on P-gp expression in patients with paired primary and recurrent ovarian cancer samples. Methods. Retrospective survival analysis. P-gp expression was evaluated immunohistochemically with antibodies c494 and c219. Results. Thirty-two patients were identified from the tumor registry. Median interval between primary and secondary surgery was 17.9 (5.7-40.9) months. Only five primary tumors (16%) demonstrated +++ staining for P-gp. First-line treatment contained paclitaxel in 17 patients (53%) and 26 patients (8 1%) had been exposed to P-gp exportable chemotherapy before second surgery. Only seven of the recurrent tumors (22%) were +++. Only one of seven (14% (95% CI 0-46%)) recurrent tumors with ++ or +++ staining responded to subsequent paclitaxel, while 8 of 10 (80% (CI 46-100%)) recurrent tumors with 0/+ staining responded (P= 0.025). In multivariate analysis of outcome following second surgery, response to paclitaxel (P= 0.004) and P-gp over-expression (P < 0.001) were significant predictors of survival. Conclusions. De novo strong P-gp over-expression is uncommon, appears to change little over time or with prior exposure to chemotherapy. However, P-gp over-expression is a significant prognostic factor, and at the time of disease, relapse is inversely correlated with tumor response to paclitaxel. (C) 2004 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Biostat, Gillette Ctr Womens Canc, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gynecol Oncol, Gillette Ctr Womens Canc, Boston, MA 02114 USA. RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 100 Blossom St,Cox 640, Boston, MA 02114 USA. EM mseiden@partners.org NR 34 TC 100 Z9 109 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 2004 VL 93 IS 1 BP 98 EP 106 DI 10.1016/j.ygyno.2003.11.053 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 812PG UT WOS:000220850800015 PM 15047220 ER PT J AU Seiden, MV Muggia, F Astrow, A Matulonis, U Campos, S Roche, M Sivret, J Rusk, J Barrett, E AF Seiden, MV Muggia, F Astrow, A Matulonis, U Campos, S Roche, M Sivret, J Rusk, J Barrett, E TI A phase II study of liposomal lurtotecan (OSI-211) in patients with topotecan resistant ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE liposomal lurtotecan; topoisomerase I inhibitors; topotecan resistant ovarian cancer ID ANTITUMOR-ACTIVITY; CHEMOTHERAPY; PHARMACOKINETICS; PLATINUM AB Objective. To determine the safety and efficacy of a novel topoisomerase I inhibitor, liposomal lurtotecan, in patients with topotecan resistant ovarian cancer. Methods. The trial was an open-label phase II study for patients stratified by resistance to either single agent topotecan or to a prior topotecan-containing regimen. Liposomal lurtotecan was delivered at a dose of 2.4 mg/m(2) on Days 1 and 8 of a 21-day cycle. Dose escalations and reductions were allowed based on hematologic toxicity. Patients were evaluated every two cycles for response to liposomal lurtotecan. Results. Twenty-two women were accrued, with 16 women resistant to single agent topotecan and 6 women resistant to topotecan given in combination with a second chemotherapy agent. Hematologic toxicity consisted of mild to moderate thrombocytopenia, anemia, and neutropenia with mild to moderate gastrointestinal toxicity and fatigue. There were no responses, although eight patients had stable disease. Conclusions. Liposomal lurtotecan at this schedule demonstrates moderate hematologic toxicity and no evidence of clinical activity in a group of heavily pretreated women previously exposed to the topoisomerase I inhibitor topotecan. The study of this agent in alternative patient populations or with alternative schedules is ongoing. (C) 2004 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Gillete Ctr Womens Canc, Div Hematol Oncol, Boston, MA 02114 USA. Dana Farber Partners Canc Care Program, Gynecol Oncol Res Program, Boston, MA 02114 USA. NYU, Div Med Oncol, New York, NY 10016 USA. St Vincents Hosp, Sect Med Oncol, New York, NY 10011 USA. St Vincents Hosp, Ctr Comprehens Canc, New York, NY 10011 USA. Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02114 USA. OSI Pharmaceut, Boulder, CO 80301 USA. RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Gillete Ctr Womens Canc, Div Hematol Oncol, 100 Blossom St,Cox 640, Boston, MA 02114 USA. EM mseiden@partners.org OI Muggia, Franco/0000-0003-0703-9146 NR 14 TC 43 Z9 47 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 2004 VL 93 IS 1 BP 229 EP 232 DI 10.1016/j.ygyno.2003.12.037 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 812PG UT WOS:000220850800036 PM 15047241 ER PT J AU Kotz, T Costello, R Li, Y Posner, MR AF Kotz, T Costello, R Li, Y Posner, MR TI Swallowing dysfunction after chemoradiation for advanced squamous cell carcinoma of the head and neck SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article; Proceedings Paper CT 6th Research Workshop on the Biology, Prevention and Treatment of Head and Neck Cancer CY OCT, 2002 CL McLean, VA DE dysphagia; organ preservation; head and neck cancer; videofluorographic swallowing assessment ID ORAL-CANCER PATIENTS; ORGAN PRESERVATION; CHEMOTHERAPY; SPEECH; RADIOTHERAPY; RADIATION; RESECTION; INTRAARTERIAL; ADJUVANT; THERAPY AB Background. Swallowing dysfunction is a common side effect of chemoradation. Methods. Twelve patients with stage III or IV squamous cell carcinoma of the head and neck were enrolled. Videofluorographic swallowing studies were performed before initiation of chemoradiation to provide baseline swallowing function data. Postchemoradiation videofluorographic swallowing studies were performed from 1 to 14 weeks after the completion of treatment (mean, 8 weeks). Results. Changes in swallowing physiology after treatment included decreased base of tongue to posterior pharyngeal wall contact (p =.0010) and reduced pharyngeal contraction (p =.0313), resulting in impaired bolus transport through the pharynx. In addition, decreased laryngeal elevation (p=.0039), decreased laryngeal vestibule closure (p =.0078), and laryngeal penetration (p =.0078) were present. Bolus volume did not have a significant effect on swallowing ability. Aspiration was observed in four patients. Conclusions. Organ preservation treatment impairs movement of structures essential for normal swallowing. Prophylactic swallowing exercises may benefit these patients. (C) 2004 Wiley Periodicals, Inc. C1 Dana Farber Canc Inst, Head & Neck Oncol Program, SW 430, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Posner, MR (reprint author), Dana Farber Canc Inst, Head & Neck Oncol Program, SW 430, 44 Binney St, Boston, MA 02115 USA. EM marshall_posner@dfci.harvard.edu NR 31 TC 99 Z9 102 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD APR PY 2004 VL 26 IS 4 BP 365 EP 372 DI 10.1002/hed.10385 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 808EW UT WOS:000220553400008 PM 15054740 ER PT J AU Schnelle, JF Simmons, SF Harrington, C Cadogan, M Garcia, E Bates-Jensen, BM AF Schnelle, JF Simmons, SF Harrington, C Cadogan, M Garcia, E Bates-Jensen, BM TI Relationship of nursing home staffing to quality of care SO HEALTH SERVICES RESEARCH LA English DT Article DE staffing; quality of care ID REFLECT DIFFERENCES; VULNERABLE ELDERS; INDICATORS; RESIDENTS; OUTCOMES AB Objective. To compare nursing homes (NHs) that report different staffing statistics on quality of care. Data Sources. Staffing information generated by California NHs on state cost reports and during onsite interviews. Data independently collected by research staff describing quality of care related to 27 care processes. Study Design. Two groups of NHs (n = 21) that reported significantly different and stable staffing data from all data sources were compared on quality of care measures. Data Collection. Direct observation, resident and staff interview, and chart abstraction methods. Principal Findings. Staff in the highest staffed homes (n = 6), according to state cost reports, reported significantly lower resident care loads during onsite interviews across day and evening shifts (7.6 residents per nurse aide [NA]) compared to the remaining homes that reported between 9 to 10 residents per NA (n = 15). The highest-staffed homes performed significantly better on 13 of 16 care processes implemented by NAs compared to lower-staffed homes. Conclusion. The highest-staffed NHs reported significantly lower resident care loads on all staffing reports and provided better care than all other homes. C1 UCLA Borun Ctr, Reseda, CA 91335 USA. Univ Calif Los Angeles, Dept Med, Div Geriatr, Los Angeles, CA USA. Jewish Home Aging Borun Ctr Gerontol Res, Reseda, CA USA. Sepulveda Geriatr Res Educ & Clin Ctr, Sepulveda, CA USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. RP Schnelle, JF (reprint author), UCLA Borun Ctr, 7150 Tampa Ave, Reseda, CA 91335 USA. FU NIA NIH HHS [AG10415, P60 AG010415] NR 32 TC 127 Z9 127 U1 3 U2 11 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD APR PY 2004 VL 39 IS 2 BP 225 EP 250 DI 10.1111/j.1475-6773.2004.00225.x PG 26 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 801MU UT WOS:000220100800002 PM 15032952 ER PT J AU Zhan, CL Miller, MR Wong, H Meyer, GS AF Zhan, CL Miller, MR Wong, H Meyer, GS TI The effects of HMO penetration on preventable hospitalizations SO HEALTH SERVICES RESEARCH LA English DT Article DE HMOs; preventable hospitalizations; quality of care ID SMALL-AREA ANALYSIS; MANAGED CARE; HEALTH-CARE; AVOIDABLE HOSPITALIZATION; COST INFLATION; UNITED-STATES; MEDICAL-CARE; RATES; QUALITY; PERFORMANCE AB Objective. To examine the effects of health maintenance organization (HMO) penetration on preventable hospitalizations. Data Source. Hospital inpatient discharge abstracts for 932 urban counties in 22 states from the Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases (SID), hospital data from American Hospital Association (AHA) annual survey, and population characteristics and health care capacity data from Health Resources and Services Administration (HRSA) Area Resource File (ARF) for 1998. Methods. Preventable hospitalizations due to 14 ambulatory care sensitive conditions were identified using the Agency for Healthcare Research and Quality (AHRQ) Prevention Quality Indicators. Multiple regressions were used to determine the association between preventable hospitalizations and HMO penetration while controlling for demographic and socioeconomic characteristics and health care capacity of the counties. Principal Findings. A 10 percent increase in HMO penetration was associated with a 3.8 percent decrease in preventable hospitalizations (95 percent confidence interval, 2.0 percent-5.6 percent). Advanced age, female gender, poor health, poverty, more hospital beds, and fewer primary care physicians per capita were significantly associated with more preventable hospitalizations. Conclusions. Our study suggests that HMO penetration has significant effects in reducing preventable hospitalizations due to some ambulatory care sensitive conditions. C1 Agcy Healthcare Res & Qual, Ctr Qual Improvement & Patient Safety, Rockville, MD USA. Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA. Agcy Healthcare Res & Qual, Rockville, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Zhan, CL (reprint author), Agcy Healthcare Res & Qual, Ctr Qual Improvement & Patient Safety, 540 Gaither Rd, Rockville, MD USA. NR 56 TC 39 Z9 39 U1 2 U2 6 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD APR PY 2004 VL 39 IS 2 BP 345 EP 361 DI 10.1111/j.1475-6773.2004.00231.x PG 17 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 801MU UT WOS:000220100800008 PM 15032958 ER PT J AU Johnson, BE Janne, PA AF Johnson, BE Janne, PA TI Basic treatment considerations using chemotherapy for patients with small cell lung cancer SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID COLONY-STIMULATING FACTOR; SEQUENTIAL THORACIC RADIOTHERAPY; CROSS-RESISTANT CHEMOTHERAPY; MULTICENTER RANDOMIZED-TRIAL; SOUTHWEST-ONCOLOGY-GROUP; PHASE-III TRIAL; RADIATION-THERAPY; FOLLOW-UP; HISTOPATHOLOGIC CLASSIFICATION; COMBINATION CHEMOTHERAPY AB Small cell lung cancer (SCLC) was initially recognized as an entity distinct from other types of lung cancer by pathologic examination in 1926 by Dr. Barnard [1]. It has been commonly referred to as oat cell carcinoma because of its cytologic resemblance to grains of oats. The World Health Organization International Histological Classification of Tumours has now adopted the designation of small cell carcinoma rather than oat cell carcinoma [2]. SCLC is recognized as a malignant epithelial tumor consisting of small cells with scant cytoplasm, ill-defined borders, finely granular nuclear chrornatin, and absent or inconspicuous nucleoli [2-4]. The cells are round, oval, and spindle-shaped, and nuclear molding is prominent (Fig. 1). The mitotic rate is high. The most effective treatment for most lung cancer is surgical resection. Most patients cured of their localized lung cancer undergo a surgical resection; nearly all have non-SCLC (NSCLC). SCLC represents approximately 15% of the lung cancers presenting in patients in the United States [5]. SCLC rarely is treated successfully with surgery because SCLC is typically disseminated at the time of presentation. The patients who appear to have localized disease and are treated with surgical resection relapse and die of their SCLC most of the time [6,7]. The natural history of SCLC from the time of diagnosis to death is very short. The survival of patients diagnosed with SCLC and followed within the Veterans Administration Medical System was 2 months for patients with extensive-stage SCLC and 3 months for patients with limited-stage SCLC [8]. These fundamental observations on the clinical behavior of SCLC have led to adoptions of combination chemotherapy as the initial effective therapy in most Fig. 1. Photomicrograph of SCLC. The specimen is a diagnostic specimen from a patient with limited-stage SCLC. The small cells are round or oval with scant cytoplasm, ill-defined borders, finely granular nuclear chromatin, and inconspicuous nucleoli with prominent nuclear molding. (Hematoxylin-eosin, original magnification x 100). C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Dept Med Oncol, Room D1234F,44 Binney St, Boston, MA 02115 USA. EM bejohnson@partners.org NR 67 TC 19 Z9 20 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2004 VL 18 IS 2 BP 309 EP + DI 10.1016/j.hoc.2003.12.008 PG 16 WC Oncology; Hematology SC Oncology; Hematology GA 819WK UT WOS:000221346600003 PM 15094173 ER PT J AU Brau, N Rodriguez-Torres, M Prokupek, D Bonacini, M Giffen, CA Smith, JJ Frost, KR Kostman, JR AF Brau, N Rodriguez-Torres, M Prokupek, D Bonacini, M Giffen, CA Smith, JJ Frost, KR Kostman, JR CA amfAR DCRI 010 Study Grp TI Treatment of chronic hepatitis C in HIV/HCV-coinfection with interferon alpha-2b+ full-course vs 16-week delayed ribavirin SO HEPATOLOGY LA English DT Article; Proceedings Paper CT 52nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases/International-Liver -Transplantation-Society CY NOV 09-13, 2001 CL DALLAS, TX SP Amer Assoc Study Liver Dis, Int Liver Transplant Soc ID HUMAN-IMMUNODEFICIENCY-VIRUS; PLACEBO-CONTROLLED TRIAL; HIV-INFECTED PATIENTS; PLUS RIBAVIRIN; COMBINATION THERAPY; INITIAL TREATMENT; DOUBLE-BLIND; RANDOMIZED-TRIAL; LIVER-DISEASE; IN-VITRO AB Human immunodeficiency virus (HIV)-infected patients increasingly experience the consequences of chronic hepatitis C virus (HCV) coinfection. This trial randomized 107 patients coinfected with HIV and HCV to receive 48 weeks of interferon alfa-2b (IFN) 3 million units three times weekly plus either a full course of ribavirin (RBV) at 800 mg/day (group A, n = 53) or 16 weeks of placebo, followed by RBV (group B; n = 54). The primary endpoint of sustained viral response (SVR) rate (undetectable HCV RNA at posttreatment week 24) was not different between groups A (11.3%) and B (5.6%; P = .32). Within group A, the SVR rate was lower in genotype 1 (2.5%) than in genotypes 2 through 4 (41.7%; P = .002). Fifty-five patients discontinued therapy prematurely, mostly because of adverse events or patient decisions. At treatment week 12, the percentage of CD4+ cells rose in group A (+4.1%; P < .001), but not in group B (-0.3%). A significant proportion (22%) of patients who were HIV viremic at baseline had undetectable HIV RNA at week 12. By week 16, the hemoglobin level decreased more in group A (-2,52 g/dL) than in group B (-1.02 g/dL; P < .001). In group A, the hemoglobin decline was steeper in patients receiving zidovudine (azidothymidine [AZT], -3.64 g/dL vs. no AZT, -2.08 g/dL), and patients receiving zidovudine had more anemia-related RBV dose reductions (AZT, 60% vs. no AZT, 16%). In conclusion, HCV therapy with IFN plus RBV is relatively safe in patients coinfected with HIV and HCV, but frequent treatment discontinuations and anemia-related RBV dose reductions contribute to a poor SVR rate. Control of HIV infection improves rather than worsens during therapy. C1 Amer Fdn AIDS Res, New York, NY 10005 USA. Bronx Vet Affairs Med Ctr, Bronx, NY USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Fdn Invest Diego, San Juan, PR USA. AIDS Healthcare Fdn, Los Angeles, CA USA. Calif Pacific Med Ctr, San Francisco, CA USA. Informat Management Serv Inc, Silver Spring, MD USA. Philadelphia FIGHT, Philadelphia, PA USA. RP Smith, JJ (reprint author), Amer Fdn AIDS Res, 120 Wall St,13th Floor, New York, NY 10005 USA. EM jeff.smith@amfar.org NR 30 TC 54 Z9 55 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD APR PY 2004 VL 39 IS 4 BP 989 EP 998 DI 10.1002/hep.20107 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 807ZL UT WOS:000220539300016 PM 15057903 ER PT J AU Zickmund, S Hillis, SL Barnett, MJ Ippolito, L LaBrecque, DR AF Zickmund, S Hillis, SL Barnett, MJ Ippolito, L LaBrecque, DR TI Hepatitis C virus-infected patients report communication problems with physicians SO HEPATOLOGY LA English DT Article ID QUALITY-OF-LIFE; PEGINTERFERON ALPHA-2A; PSYCHIATRIC-SYMPTOMS; DIFFICULT PATIENT; FAMILY PHYSICIANS; CARE; SATISFACTION; RIBAVIRIN; INTERFERON-ALPHA-2B; STIGMATIZATION AB We examined the prevalence and nature of perceived problems in the interaction between physicians and patients diagnosed with hepatitis C virus (HCV) infection. This cross-sectional study included 322 outpatients diagnosed with chronic HCV infection and treated at a tertiary referral hospital's hepatology clinic. Patients were asked to provide demographic information and to complete a semistructured interview, the Sickness Impact Profile (SIP) and Hospital Anxiety Depression (HAD) scale. A team of two blinded coders analyzed the interviews. A total of 131 (41%) study patients reported communication difficulties with physicians involved in their care. The main difficulties were the poor communication skills of physicians (91 [28%]), physician incompetence regarding the diagnosis and treatment of HCV infection (74 [23%]), feelings of being misdiagnosed, misled, or abandoned (51 [16%]), or being stigmatized by their physician (29 [9%]). Patients were twice as likely to report difficulties with subspecialists as compared with generalists. Nonresponse with anti-viral therapy correlated with perceived physician conflict even after adjusting for treatment in relation to the time of interview, whereas previous or ongoing substance abuse and mode of acquisition did not. In a multivariate model, patients' psychosocial problems were the best predictors of communication difficulties. In conclusion, a substantial number of patients with HCV infection report difficulties when interacting with physicians, which may be due to coexisting emotional or social problems. However, perceived stigmatization by physicians and a sense of abandonment reflect the need for further educational efforts. These should target both specialists and primary care providers to inform them about the psychosocial challenges facing these patients. C1 Univ Pittsburgh, Coll Med, Dept Med,Div Gen Internal Med, VA Pittsburgh Healthcare Syst,Ctr Hlth Equity Res, Pittsburgh, PA 15240 USA. Vet Affairs Med Ctr, Program Interdisciplinary Res Hlth Care Org, Iowa City, IA 52242 USA. Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. RP Zickmund, S (reprint author), Univ Pittsburgh, Coll Med, Dept Med,Div Gen Internal Med, VA Pittsburgh Healthcare Syst,Ctr Hlth Equity Res, Univ Dr C,Bldg 28 1A118, Pittsburgh, PA 15240 USA. EM susan.zickmund@med.va.gov OI Hillis, Stephen/0000-0002-4886-8584 FU NHLBI NIH HHS [HL07121] NR 44 TC 89 Z9 89 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD APR PY 2004 VL 39 IS 4 BP 999 EP 1007 DI 10.1002/hep.20132 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 807ZL UT WOS:000220539300017 PM 15057904 ER PT J AU Garavito, G Yunis, EJ Egea, E Ramirez, LA Malagon, C Iglesias, A De La Cruz, OF Uribe, O Navarro, E Martinez, P Jaraquemada, D AF Garavito, G Yunis, EJ Egea, E Ramirez, LA Malagon, C Iglesias, A De La Cruz, OF Uribe, O Navarro, E Martinez, P Jaraquemada, D TI HLA-DRB1 alleles and HLA-DRB1 shared epitopes are markers for juvenile rheumatoid arthritis subgroups in Colombian mestizos SO HUMAN IMMUNOLOGY LA English DT Article DE JRA; juvenile rheumatoid arthritis; HLA association; HLA-DRB1-DQB1 alleles; MHC class II haplotypes ID HLA; IRIDOCYCLITIS; ASSOCIATIONS; CHILDREN; DNA; IMMUNOGENETICS; FREQUENCIES; HAPLOTYPES; DISEASE; MHC AB We studied the association of human leukocyte antigen (HLA)-DRB1 and HLA-DQB1 alleles and HLA haplotypes with juvenile rheumatoid arthritis (JRA) in 65 patients and 65 controls from Colombia. The JRA subsets were distinguished on the basis of criteria established by the American College of Rheumatology. Two alleles were associated with protection, HLA-DRB1*1501 (p = 0.002) and HLA-DRB1*1402 (p = 0.01). HLA-DRB1*1602 (p = 0.0000002) was associated with susceptibility for systemic JRA and HLA-DRB1*1104 (p = 0.0002) for pauciarticular JRA. Amino acid sequences at residues 70-74 of DRB1 chain shared by HLA-DRB1 alleles (shared epitomes) were also informative. The polyarticular JRA subset revealed association with (70)QRRAA(74) which includes HLA-DRB1*04, 01, and (70)DRRAA(74), which includes DRB1*1601, 1602, 1101, and 1104. Two new findings of interest were the association of the haplotypes DRB1*1104, DQB1*0301(p = 0.0002) with pauciarticular JRA and DRB1*1602, DQB1*0301 (p = 0.0000002) association with systemic JRA. The DRB1 alleles of these two haplotypes share the epitope (70)DRRAA(74) and were associated with both the pauciarticular and the systemic subset of JRA. Our results Suggest that studies of disease susceptibility in populations of admixed genetic background should take into account the contribution of different ethnic groups or nationalities in the recruitment of controls and patients studied in order to rule out genetic stratification. C1 Univ Norte, Lab Immunol & Biol Mol, Div Ciencias Salud, Barranquilla, Colombia. Univ Antioquia, Dept Rheumatol, Medellin, Colombia. Clin Nino, Rheumatol Outpatient Clin, Bogota, Colombia. Univ Nacl Colombia, Dept Rheumatol, Bogota, Colombia. Univ Autonoma Barcelona, Inst Biol Fundamental, E-08193 Barcelona, Spain. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Garavito, G (reprint author), Univ Norte, Lab Immunol & Biol Mol, Div Ciencias Salud, Km 5 Via Pto, Barranquilla, Colombia. EM ggaravit@uninorte.edu.co OI Garavito, Gloria/0000-0002-9425-0208 FU NHLBI NIH HHS [HL59838]; PHS HHS [AL 29583] NR 41 TC 10 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD APR PY 2004 VL 65 IS 4 BP 359 EP 365 DI 10.1016/j.humimm.2004.01.016 PG 7 WC Immunology SC Immunology GA 820ML UT WOS:000221393300010 PM 15120191 ER PT J AU Ruan, QM Lesort, M MacDonald, ME Johnson, GVW AF Ruan, QM Lesort, M MacDonald, ME Johnson, GVW TI Striatal cells from mutant huntingtin knock-in mice are selectively vulnerable to mitochondrial complex II inhibitor-induced cell death through a non-apoptotic pathway SO HUMAN MOLECULAR GENETICS LA English DT Article ID CYTOCHROME-C RELEASE; INDUCED PERMEABILITY TRANSITION; DEPRIVED SYMPATHETIC NEURONS; 3-NITROPROPIONIC ACID; MOUSE MODEL; BRAIN MITOCHONDRIA; POLY(ADP-RIBOSE) POLYMERASE; MEDIATED APOPTOSIS; GENE-EXPRESSION; PROTEIN IMPORT AB Extensive striatal neuronal loss occurs in Huntington's disease (HD), which is caused by an expanded polyglutamine tract in huntingtin (htt). Evidence suggests that mutant htt directly or indirectly compromises mitochondrial function, contributing to the neuronal loss. To determine the role of compromised mitochondrial function in the neuronal cell death in HD, immortalized striatal cells established from Hdh(Q7) (wild-type) and Hdh(Q111) (mutant) mouse knock-in embryos were treated with 3-nitropropionic acid (3-NP), a mitochondrial complex II toxin. 3-NP treatment caused significantly greater cell death in mutant striatal cells compared with wild-type cells. In contrast, the extent of cell death induced by rotenone, a complex I inhibitor, was similar in both cell lines. Although evidence of apoptosis was present in 3-NP-treated wild-type striatal cells, it was absent in 3-NP-treated mutant cells. 3-NP treatment caused a greater loss of mitochondrial membrane potential (Deltapsim) in mutant striatal cells compared with wild-type cells. Cyclosporine A, an inhibitor of mitochondrial permeability transition pore (PTP), and ruthenium red, an inhibitor of the mitochondrial calcium uniporter, both rescued mutant striatal cells from 3-NP-induced cell death and prevented the loss of Deltapsim. These data show that mutant htt specifically increases cell vulnerability to mitochondrial complex II inhibition and further switched the type of cell death induced by complex II inhibition from apoptosis to a non-apoptotic form, caused by mitochondrial membrane depolarization, probably initiated by mitochondrial calcium overload and subsequent PTP opening. These findings suggest that impaired mitochondrial complex II function in HD may contribute to non-apoptotic neuronal cell death. C1 Univ Alabama, Dept Psychiat, Birmingham, AL 35294 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. RP Johnson, GVW (reprint author), Univ Alabama, Dept Psychiat, 1720 7th Ave S,SC 1061, Birmingham, AL 35294 USA. EM gvwj@uab.edu RI Johnson, Gail/K-4723-2012 OI Johnson, Gail/0000-0003-3464-0404 FU NINDS NIH HHS [NS16367, NS32765, NS41744] NR 77 TC 60 Z9 60 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 APR 1 PY 2004 VL 13 IS 7 BP 669 EP 681 DI 10.1093/hmg/ddh082 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 802RF UT WOS:000220179900001 PM 14962977 ER PT J AU Bertram, L Tanzi, RE AF Bertram, L Tanzi, RE TI Alzheimer's disease: one disorder, too many genes? SO HUMAN MOLECULAR GENETICS LA English DT Review ID AMYLOID BETA-PROTEIN; APOLIPOPROTEIN-E; GENOME SCAN; LINKAGE DISEQUILIBRIUM; CLINICAL-DIAGNOSIS; VASCULAR DEMENTIA; COMPLEX DISEASES; HAPLOTYPE BLOCKS; CANDIDATE-GENE; HFE MUTATIONS AB The research of Alzheimer's disease (AD) genetics has been extremely prolific over the past decade, and currently more than 10 genes are reported to show either positive or negative evidence for disease association per month. Here, we review all 90 studies from 2003 reporting a total of 127 association findings between candidate genes and AD. While most positive results were largely contradictory, we identified three loci-on chromosomes 6p2l, 10q24, 11q23-that yielded positive results in three or more independent studies, in addition to the well-established AD association with the gene encoding apolipoprotein E (APOE). Based on these data, we suggest that it may be prudent for investigators to pay closer attention to issues such as power, replicability and haplotype structure prior to initial publication. This should serve to greatly decrease the likelihood of false positive and false negative findings reported in future years. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Genet & Aging Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. RP Tanzi, RE (reprint author), Harvard Univ, Sch Med, 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 67 TC 112 Z9 120 U1 0 U2 2 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 APR PY 2004 VL 13 SI 1 BP R135 EP R141 DI 10.1093/hmg/ddh077 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 811TF UT WOS:000220793500014 PM 14764623 ER PT J AU Schulz, RB Ripoll, J Ntziachristos, V AF Schulz, RB Ripoll, J Ntziachristos, V TI Experimental fluorescence tomography of tissues with noncontact measurements SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE biomedical imaging; optical fluorescence tomography ID DIFFUSE OPTICAL TOMOGRAPHY; IMAGE-RECONSTRUCTION; TURBID MEDIA; SCATTERING MEDIA; BREAST-CANCER; BOUNDARY; APPROXIMATION; SPECTROSCOPY; SYSTEM; LIGHT AB Noncontact optical measurements from diffuse media could facilitate the use of large detector arrays at multiple angles that are well suited for diffuse optical tomography applications. Such imaging strategy could eliminate the need for individual fibers in contact with tissue, restricted geometries, and matching fluids. Thus, it could significantly improve experimental procedures and enhance our ability to visualize functional and molecular processes in vivo. In this paper, we describe the experimental implementation of this novel concept and demonstrate capacity to perform small animal imaging. C1 DKFZ, Dept Med Phys Radiol, German Canc Res Ctr, D-69120 Heidelberg, Germany. Massachusetts Gen Hosp, Lab Bioopt & Mol Imaging, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Fdn Res & Technol Hellas, Inst Elect Struct & Laser, Iraklion 71110, Greece. RP Schulz, RB (reprint author), DKFZ, Dept Med Phys Radiol, German Canc Res Ctr, IM Neuenheimer Feld 280, D-69120 Heidelberg, Germany. EM r.schulz@dkfz.de; jripoll@iesl.forth.gr; vasilis@helix.mgh.harvard.edu RI Ripoll, Jorge/J-8134-2012 OI Ripoll, Jorge/0000-0001-8856-7738 FU NCI NIH HHS [R21-CA91807]; NIBIB NIH HHS [R01 EB000750-1] NR 36 TC 131 Z9 137 U1 1 U2 10 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD APR PY 2004 VL 23 IS 4 BP 492 EP 500 DI 10.1109/TMI.2004.825633 PG 9 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 809BI UT WOS:000220611800009 PM 15084074 ER PT J AU Trede, NS Langenau, DM Traver, D Look, AT Zon, LI AF Trede, NS Langenau, DM Traver, D Look, AT Zon, LI TI The use of zebrafish to understand immunity SO IMMUNITY LA English DT Review ID TOLL-LIKE RECEPTOR; RECOMBINATION ACTIVATING GENE-1; X-LINKED AGAMMAGLOBULINEMIA; DANIO-RERIO; T-CELL; TRANSGENIC MICE; CAENORHABDITIS-ELEGANS; GENETIC DISSECTION; THYMUS DEVELOPMENT; GENOMIC ANALYSIS AB For decades immunologists have relied heavily on the mouse model for their experimental designs. With the realization of the important role innate immunity plays in orchestrating immune responses, invertebrates such as worms and flies have been added to the repertoire. Here, we discuss the advent of the zebrafish as a powerful vertebrate model organism that promises to positively impact immunologic research. C1 Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. RP Trede, NS (reprint author), Childrens Hosp, Dept Med, Div Hematol Oncol, 1 Blackfan Circle, Boston, MA 02115 USA. EM trede@enders.tch.harvard.edu FU NCI NIH HHS [CA-68484]; NHLBI NIH HHS [K08HL04233]; NIDDK NIH HHS [R21DK63660] NR 91 TC 291 Z9 306 U1 3 U2 43 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD APR PY 2004 VL 20 IS 4 BP 367 EP 379 DI 10.1016/S1074-7613(04)00084-6 PG 13 WC Immunology SC Immunology GA 821EK UT WOS:000221442800004 PM 15084267 ER PT J AU Salas, A Shimaoka, M Kogan, AN Harwood, C von Andrian, UH Springer, TA AF Salas, A Shimaoka, M Kogan, AN Harwood, C von Andrian, UH Springer, TA TI Rolling adhesion through an extended conformation of integrin alpha(L)beta(2) and relation to alpha I and beta I-like domain interaction SO IMMUNITY LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-1; SMALL-MOLECULE; L-SELECTIN; EXTRACELLULAR SEGMENT; ACTIVATED PLATELETS; PHYSIOLOGICAL FLOW; CRYSTAL-STRUCTURE; LIGAND-BINDING; DISULFIDE BOND; FIRM ADHESION AB In vivo, beta(2) integrins and particularly alpha(L)beta(2) (LFA-1) robustly support firm adhesion of leukocytes, but can also cooperate with other molecules in supporting rolling adhesion. Strikingly, a small molecule alpha/beta I-like allosteric antagonist, XVA143, inhibits LFA-1-dependent firm adhesion, while at the same time it enhances adhesion in shear flow and rolling both in vitro and in vivo. XVA143 appears to induce the extended conformation of integrins as shown by increased activation epitope exposure. Fab to the beta(2) I-like domain converts firm adhesion to rolling adhesion, but does not enhance adhesion. Residue alpha(L)-Glu-310 in the linker following the I domain is critical for communication to the beta(2) I-like domain, rolling, integrin extension, and activation by Mn2+ of firm adhesion. The results demonstrate the importance of integrin extension in rolling, and suggest that rolling and firm adhesion are mediated by extended conformations Of alpha(L)beta(2) that differ in the affinity of the alpha(L) I domain for ICAM-1. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Program Biophys, 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 RI von Andrian, Ulrich/A-5775-2008; OI Salas, Azucena/0000-0003-4572-2907 FU NHLBI NIH HHS [HL-48675, HL-54936]; NIAMS NIH HHS [AR-42689] NR 67 TC 132 Z9 134 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD APR PY 2004 VL 20 IS 4 BP 393 EP 406 DI 10.1016/S1074-7613(04)00082-2 PG 14 WC Immunology SC Immunology GA 821EK UT WOS:000221442800006 PM 15084269 ER PT J AU Tran, P Lee, JH Waneck, G Bishop, GA Sharland, A AF Tran, P Lee, JH Waneck, G Bishop, GA Sharland, A TI HLA-E is not expressed on LCL 13271 cells unless other HLA class-I molecules are present SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Meeting Abstract CT 22nd Annual Scientific Meeting of the Transplantation-Society-of-Australia-and-New Zealand CY MAR 31-APR 02, 2004 CL Canberra, AUSTRALIA SP Transplantat Soc Australia & New Zealand C1 Centenary Inst, Liver Immunobiol Lab, Sydney, NSW, Australia. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD APR PY 2004 VL 82 IS 2 BP A23 EP A23 PG 1 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 808CT UT WOS:000220547900095 ER PT J AU Liu, DX Gu, XG Scafidi, J Davis, AE AF Liu, DX Gu, XG Scafidi, J Davis, AE TI N-linked glycosylation is required for C1 inhibitor-mediated protection from endotoxin shock in mice SO INFECTION AND IMMUNITY LA English DT Article ID MONOPHOSPHORYL-LIPID-A; LPS BINDING-PROTEIN; LIPOPOLYSACCHARIDE (LPS)-BINDING PROTEIN; PERMEABILITY-INCREASING PROTEIN; AMINO-ACID-RESIDUES; HUMAN LACTOFERRIN; HUMAN CD14; ANTIMICROBIAL PEPTIDES; MURINE MACROPHAGES; FUNCTIONAL DOMAINS AB C1 inhibitor (C1INH) prevents endotoxin shock in mice via a direct interaction with lipopolysaccharide (LPS). This interaction requires the heavily glycosylated amino-terminal domain of C1INH. C1INH in which N-linked carbohydrate was removed by using N-glycosidase F was markedly less effective in protecting mice from LPS-induced lethal septic shock. N-deglycosylated C1INH also failed to suppress fluorescein isothiocyanate (FITC)-LPS binding to and LPS-induced tumor necrosis factor alpha mRNA expression by the murine macrophage-like cell line, RAW 264.7, and cells in human whole blood. In an enzyme linked immunosorbent assay, the N-deglycosyllated C1INH bound to LPS very poorly. In addition, C1INH was shown to bind to diphosphoryl lipid A (dLPA) but only weakly to monophosphoryl lipid A (mLPA). As with intact LPS, binding of N-deglycosylated C1INH to dLPA and mLPA was diminished in comparison with the native protein. Removal of O-linked carbohydrate had no effect on any of these activities. Neither detoxified LPS, dLPA, nor mLPA had any effect on the rate or extent of C1INH complex formation with C1s or on cleavage of the reactive center loop by trypsin. These data demonstrate that N-linked glycosylation of C1INH is essential to mediate its interaction with the LPA moiety of LPS and to protect mice from endotoxin shock. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Davis, AE (reprint author), CBR Inst, 800 Huntington Ave, Boston, MA 02115 USA. EM aldavis@cbr.med.harvard.edu FU NICHD NIH HHS [R37 HD022082, R01 HD033727, HD33727, HD22082] NR 44 TC 27 Z9 27 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2004 VL 72 IS 4 BP 1946 EP 1955 DI 10.1128/IAI.72.4.1946-1955.2004 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 807DG UT WOS:000220481600012 PM 15039314 ER PT J AU Kim, N Marcus, EA Wen, Y Weeks, DL Scott, DR Jung, HC Song, IS Sachs, G AF Kim, N Marcus, EA Wen, Y Weeks, DL Scott, DR Jung, HC Song, IS Sachs, G TI Genes of Helicobacter pylori regulated by attachment to AGS cells SO INFECTION AND IMMUNITY LA English DT Article ID GASTRIC EPITHELIAL-CELLS; MICROARRAY ANALYSIS; PROTEIN TRANSLOCATION; ESCHERICHIA-COLI; TYROSINE PHOSPHORYLATION; OLIGONUCLEOTIDE ARRAYS; CHLAMYDIA-TRACHOMATIS; DIFFERENTIAL DISPLAY; LOW-TEMPERATURE; CANCER CELLS AB Reciprocal interactions between Helicobacter pylori and cells of the gastric epithelium to which it adheres may affect colonization. Changes in gene expression of H. pylori induced by adhesion to AGS gastric cancer cells by coculture were compared to changes in gene expression of H. pylori cultured without AGS cells by using cDNA filter macroarrays. Adhesion was quantitatively verified by confocal microscopy of green fluorescent protein-expressing bacteria. Four experiments showed that 22 and 21 H. pylori genes were consistently up- and down-regulated, respectively. The up-regulated genes included pathogenicity island, motility, outer membrane protein, and translational genes. The sigma(28) factor antagonist flgM, flgG, the stress response gene,flaA, omp11, and the superoxide dismutase gene (sodB) were down-regulated. The up-regulation of cag3,flgB, tonB, rho, and deaD was confirmed by quantitative PCR, and the up-regulation of lpxD, omp6, secG, fabH, HP1285, HP0222, and HP0836 was confirmed by reverse transcription (RT)-PCR. The down-regulation of flaA, sodB, and HP0874 was confirmed by quantitative PCR, and the down-regulation of omp11 was confirmed by RT-PCR. The alteration of gene expression in H. pylori after adhesion to gastric cells in vitro suggests that changes in motility, outer membrane composition, and stress responses, among other changes, may be involved in gastric colonization. C1 VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Geffen Sch Med, Dept Physiol & Med, Los Angeles, CA 90073 USA. Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Seoungnam 464707, Gyeonggi Do, South Korea. Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 110799, South Korea. Liver Res Inst, Seoul 110799, South Korea. RP Scott, DR (reprint author), VA Greater Los Angeles Hlth Care Syst, Bldg 113,Room 32A,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM dscott@ucla.edu RI Kim, Nayoung/J-5387-2012; Jung, Hyun Chae/J-5654-2012 FU NIDDK NIH HHS [P30 DK041301, DK17294, DK46917, DK53462, R01 DK046917] NR 56 TC 48 Z9 51 U1 0 U2 2 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 APR PY 2004 VL 72 IS 4 BP 2358 EP 2368 DI 10.1128/IAI.72.4.2358-2368.2004d PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 807DG UT WOS:000220481600059 PM 15039361 ER PT J AU Anzueto, A Frutos-Vivar, F Esteban, A Alia, I Brochard, L Stewart, T Benito, S Tobin, MJ Elizalde, J Palizas, F David, CM Pimentel, J Gonzalez, M Soto, L D'Empaire, G Pelosi, P AF Anzueto, A Frutos-Vivar, F Esteban, A Alia, I Brochard, L Stewart, T Benito, S Tobin, MJ Elizalde, J Palizas, F David, CM Pimentel, J Gonzalez, M Soto, L D'Empaire, G Pelosi, P TI Incidence, risk factors and outcome of barotrauma in mechanically ventilated patients SO INTENSIVE CARE MEDICINE LA English DT Article DE barotrauma; pneumothorax; mechanical ventilation; tidal volume; PEEP; ARDS ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; PULMONARY BAROTRAUMA; MORTALITY; STRATEGY AB Objective. To determine the incidence, risk factors, and outcome of barotrauma in a cohort of mechanically ventilated patients where limited tidal volumes and airway pressures were used. Design and setting. Prospective cohort of 361 intensive care units from 20 countries. Patients and participants. A total of 5183 patients mechanically ventilated for more than 12 h. Measurements and results. Baseline demographic data, primary indication for mechanical ventilation, daily ventilator settings, multiple-organ failure over the course of mechanical ventilation and outcome were collected. Barotrauma was present in 154 patients (2.9%). The incidence varied according to the reason for mechanical ventilation: 2.9% of patients with chronic obstructive pulmonary disease; 6.3% of patients with asthma; 10.0% of patients with chronic interstitial lung disease (ILD); 6.5% of patients with acute respiratory distress syndrome (ARDS); and 4.2% of patients with pneumonia. Patients with and without barotrauma did not differ in any ventilator parameter. Logistic regression analysis identified as factors independently associated with barotrauma: asthma [RR 2.58 (1.05-6.50)], ILD [RR 4.23 (95%CI 1.78-10.03)]; ARDS as primary reason for mechanical ventilation [RR 2.70 (95%CI 1.55-4.70)]; and ARDS as a complication during the course of mechanical ventilation [RR 2.53 (95%CI 1.40-4.57)]. Case-control analysis showed increased mortality in patients with barotrauma (51.4 vs 39.2%; p=0.04) and prolonged ICU stay. Conclusions. In a cohort of patients in whom airway pressures and tidal volume are limited, barotrauma is more likely in patients ventilated due to underlying lung disease (acute or chronic). Barotrauma was also associated with a significant increased in the ICU length of stay and mortality. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Pulm Med Crit Care Med, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. Hosp Univ Getafe, Madrid, Spain. Hop Henri Mondor, F-94010 Creteil, France. Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Hosp Santa Cruz & San Pablo, E-08025 Barcelona, Spain. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Loyola Univ, Chicago, IL 60611 USA. Hosp ABC, Mexico City, DF, Mexico. Clin Bazterrica, Buenos Aires, DF, Argentina. Hosp Univ Clementito Fraga Filho, Rio De Janeiro, Brazil. Univ Hosp, Coimbra, Portugal. Hosp Gen Medellin, Medellin, Colombia. Inst Nacl Torax, Santiago, Chile. Hosp Clin, Caracas, Venezuela. Univ Insubria, Hosp Circolo, Varese, Italy. RP Anzueto, A (reprint author), 7400 Merton Minter Blvd,11E, San Antonio, TX 78229 USA. EM anzueto@uthscsa.edu OI benito, salvador/0000-0002-6333-5823; Frutos-Vivar, Fernando/0000-0002-4648-9636 NR 24 TC 50 Z9 54 U1 1 U2 6 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD APR PY 2004 VL 30 IS 4 BP 612 EP 619 DI 10.1007/s00134-004-2187-7 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 808IM UT WOS:000220562800011 PM 14991090 ER PT J AU Thom, DH Kravitz, RL Kelly-Reif, S Sprinkle, RV Hopkins, JR Rubenstein, LV AF Thom, DH Kravitz, RL Kelly-Reif, S Sprinkle, RV Hopkins, JR Rubenstein, LV TI A new instrument to measure appropriateness of services in primary care SO INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE LA English DT Article DE diagnostic tests; prescription; process assessment; referral; utilization review ID HEALTH-CARE; QUALITY; RELIABILITY; CRITERIA AB Objective. To develop a new instrument for judging the appropriateness of three key services (new prescription, diagnostic test, and referral) as delivered in primary care outpatient visits. Design. Candidate items were generated by a seven-member expert panel, using a five-step nominal technique, for each of three service categories in primary care: new prescriptions, diagnostic tests, and referrals. Expert panelists and a convenience sample of 95 community-based primary care physicians ranked items for (i) importance and (ii) feasibility of ascertaining from a typical office chart record. Resulting items were used to construct a measure of appropriateness using principals of structured implicit review. Two physician reviewers used this measure to judge the appropriateness of 421 services from 160 outpatient visits. Setting. Primary care practices in a staff model health maintenance organization and a large preferred provider network. Measures. Inter-rater agreement was measured using intraclass correlation coefficient (ICC) and kappa statistic. Results. For overall appropriateness, the ICC and kappa were 0.52 and 0.44 for new medication, 0.35 and 0.32 for diagnostic test, and 0.40 and 0.41 for referral, respectively. Only 3% of services were judged to be inappropriate by either reviewer. The proportion of services judged to be less than definitely appropriate by one or both reviewers was 56% for new medication, 31% for diagnostic test, and 22% for referral. Conclusions. This new measure of appropriateness of primary care services has fair inter-rater agreement for new medications and referrals, similar to appropriateness measures of other general services, but poor agreement for diagnostic tests. It may be useful as a tool to assess the appropriateness of common primary care services in studies of health care quality, but is not suitable for evaluating performance of individual physicians. C1 Univ Calif San Francisco, Dept Family & Community Med, San Francisco, CA USA. Univ Calif Davis, Sch Med, Dept Med, Ctr Hlth Serv Res Primary Care, Davis, CA USA. Univ Calif Davis, Sch Med, Div Gen Internal Med, Davis, CA USA. Permanente Med Grp Inc, Dept Med, Sacramento, CA USA. UC Davis Med Grp, Davis, CA USA. Stanford Univ, Sch Med, Dept Med, Palo Alto, CA 94304 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles, Dept Med, Los Angeles, CA USA. RP Thom, DH (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Dept Family & Community Med, 1001 Potrero Ave,Bldg 80-83, San Francisco, CA 94110 USA. EM dthom@itsa.ucsf.edu OI Kravitz, Richard/0000-0001-5575-529X NR 30 TC 4 Z9 5 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1353-4505 J9 INT J QUAL HEALTH C JI Int. J. Qual. Health Care PD APR PY 2004 VL 16 IS 2 BP 133 EP 140 DI 10.1093/intqhc/mzh029 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 809CJ UT WOS:000220614500003 PM 15051707 ER PT J AU Counselman, EF Weber, RL AF Counselman, EF Weber, RL TI Organizing and maintaining peer supervision groups SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article ID PSYCHOTHERAPY SUPERVISION; LEADERLESS GROUP; CONSULTATION GROUPS; GROUP-THERAPY; MODEL; SHAME; EXPERIENCE; LEADERSHIP; DYNAMICS AB Peer supervision groups (PSGs) are attractive to psychotherapists for many reasons, including ongoing consultation and support, networking; and combating professional isolation. These leaderless groups offer opportunities for interpersonal learning from peers, and the parallel process within PSGs can be an important consultative tool. Unfortunately, many PSGs fail. PSGs benefit from careful attention to contract, task, gatekeeping; and group process, including resistances and dynamics of competition, and shame. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Counselman, EF (reprint author), 42 Crestview Rd, Belmont, MA 02478 USA. EM EleanorF@Counselman.com NR 29 TC 15 Z9 15 U1 0 U2 5 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0020-7284 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD APR PY 2004 VL 54 IS 2 BP 125 EP 143 DI 10.1521/ijgp.54.2.125.40391 PG 19 WC Psychology, Clinical SC Psychology GA 808CB UT WOS:000220546100001 PM 15103999 ER PT J AU Sherman, AC Leszcz, M Mosier, J Burlingame, GM Cleary, T Ulman, KH Simonton, S Latif, U Strauss, B Hazelton, L AF Sherman, AC Leszcz, M Mosier, J Burlingame, GM Cleary, T Ulman, KH Simonton, S Latif, U Strauss, B Hazelton, L TI Group interventions for patients with cancer and HIV disease: Part II. Effects on immune, endocrine, and disease outcomes at different phases of illness SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article ID BEHAVIORAL STRESS-MANAGEMENT; METASTATIC BREAST-CANCER; INFECTED GAY MEN; STRUCTURED PSYCHIATRIC INTERVENTION; HUMAN-IMMUNODEFICIENCY-VIRUS; SEROPOSITIVE MEN; SOCIAL SUPPORT; PSYCHOLOGICAL INTERVENTIONS; PSYCHOSOCIAL SUPPORT; DEPRESSIVE SYMPTOMS AB There has been great interest in the potential impact of group interventions on medical outcomes. This article reviews the effects of professionally-led groups on immune activity, neuroendocrine function, and survival among patients with cancer or HIV disease. We examine findings concerning different types of group services at different phases of illness. Results are mixed, but the most prominent changes in immune and endocrine activity were associated with structured group interventions for patients with early-stage disease. These findings offer provocative illustrations of relevant mind-body interactions, but their clinical importance has yet to be demonstrated empirically. Group interventions have not been tied consistently to improved survival rates for patients with advanced cancer, few studies as yet have focused on survival outcomes among patients with early-stage cancer or HIV disease. C1 Univ Arkansas Med Sci, Dept Otolaryngol, Little Rock, AR 72205 USA. Univ Toronto, Dept Psychiat, Toronto, ON, Canada. Univ Toronto, Grp Psychotherapy, Toronto, ON, Canada. Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Ctr Grp Psychotherapy, Boston, MA 02114 USA. Univ Arkansas Med Sci, Program Dev Behav Med, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Otolaryngol, Little Rock, AR 72205 USA. Klinikum Univ Jena, Inst Med Psychol, Jena, Germany. Dalhousie Univ, Dept Psychiat, Halifax, NS B3H 3J5, Canada. RP Sherman, AC (reprint author), Univ Arkansas Med Sci, Dept Otolaryngol, Behav Med 756,4301 W Markham St, Little Rock, AR 72205 USA. EM ShermanAllenC@uams.edu RI Burlingame, Gary/L-2449-2014; Leszcz, Molyn/N-9043-2016 NR 80 TC 8 Z9 8 U1 2 U2 9 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0020-7284 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD APR PY 2004 VL 54 IS 2 BP 203 EP 233 DI 10.1521/ijgp.54.2.203.40390 PG 31 WC Psychology, Clinical SC Psychology GA 808CB UT WOS:000220546100004 PM 15104002 ER PT J AU Gierga, DP Chen, GTY Kung, JH Betke, M Lombardi, J Willett, CG AF Gierga, DP Chen, GTY Kung, JH Betke, M Lombardi, J Willett, CG TI Quantification of respiration-induced abdominal tumor motion and its impact on IMRT dose distributions SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE IMRT; fluoroscope; abdomen; motion; tracking ID COMPUTED-TOMOGRAPHY; GATED RADIOTHERAPY; DEEP INSPIRATION; BREATH-HOLD; LIVER; CT; PANCREAS; MOVEMENT; THERAPY; CANCER AB Purpose: The treatment of moving targets with intensity-modulated radiotherapy may introduce errors in dose delivery. The motion of tumors in the abdomen was studied using quantitative fluoroscopic analysis, and the effect on dose delivery to the target was studied. Methods and Materials: Fluoroscopy sessions for 7 patients with pancreas or liver tumors and fiducial clips were recorded, converted to digital format, and analyzed to quantify the characteristics of tumor motion. Intensity-modulated radiotherapy plans were generated for 3 patients (a total of five plans), and the dose-volume histograms for the target volume were compared between plans with and without tumor motion. Results: The average magnitude of the peak-to-peak motion for the 7 patients in the craniocaudal and AP directions was 7.4 mm and 3.8 mm, respectively. The clip motion varied widely, because the maximal clip excursions were about 47% greater than the average clip excursions for each patient. The inclusion of tumor motion did not lead to a significant degradation in the target dose-volume histogram for four of five treatment plans studied. Conclusion: The amount of tumor motion for most patients in this study was not large but could, in some instances, significantly degrade the planned target dose-volume histogram. For some patients, therefore, motion mitigation or intervention during treatment may be necessary. (C) 2004 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Boston Univ, Dept Comp Sci, Boston, MA 02215 USA. RP Gierga, DP (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Fruit St,Cox 8, Boston, MA 02114 USA. EM dgierga@partners.org NR 29 TC 114 Z9 121 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 1 PY 2004 VL 58 IS 5 BP 1584 EP 1595 DI 10.1016/j.ijrobp.2003.09.077 PG 12 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 807XA UT WOS:000220533000035 PM 15050340 ER PT J AU Weber, DC Trofimov, AV Delaney, TF Bortfeld, T AF Weber, DC Trofimov, AV Delaney, TF Bortfeld, T TI A treatment planning comparison of intensity modulated photon and proton therapy for paraspinal sarcomas SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE intensity modulated photon therapy; intensity modulated proton therapy; sarcoma; comparative treatment planning; conformity index; inhomogeneity coefficient; dose escalation ID SOFT-TISSUE SARCOMAS; RADIATION-THERAPY; RETROPERITONEAL SARCOMAS; CONFORMAL RADIOTHERAPY; THYMIC ENLARGEMENT; PROSTATE-CANCER; POTENTIAL ROLE; RECTAL-CANCER; BEAM THERAPY; FOLLOW-UP AB Purpose: A comparative treatment planning study has been undertaken between intensity modulated (IM) photon therapy and IM proton therapy (IMPT) in paraspinal sarcomas, so as to assess the potential benefits and limitations of these treatment modalities. In the case of IM proton therapy, plans were compared also for two different sizes of the pencil beam. Finally, a 10% and 20% dose escalation with IM protons was planned, and the consequential organ at risk (OAR) irradiation was evaluated. Methods and Materials: Plans for 5 patients were computed for IM photons (7 coplanar fields) and protons (3 coplanar beams), using the KonRad inverse treatment planning system (developed at the German Cancer Research Center). IMPT planning was performed assuming 2 different sizes of the pencil beam: IMPT with a beam of full width at half-maximum of 20 mm, and IMPT with a "mini-beam" (IMPTM, full width at half-maximum = 12 mm). Prescribed dose was 77.4 Gy or cobalt Gray equivalent (CGE) for protons to the gross tumor volume (GTV). Surface and center spinal cord dose constraint for all techniques was 64 and 53 Gy/CGE, respectively. Tumor and OAR dose-volume histograms were calculated. Results were analyzed using dose-volume histogram parameters, inhomogeneity coefficient, and conformity index. Results: Gross tumor volume coverage was optimal and equally homogeneous with both IM photon and IM proton plans. Compared to the IM photon plans, the use of IM proton beam therapy leads to a substantial reduction of the OAR total integral dose in the low-level to mid-dose level. Median heart, lung, kidney, stomach, and liver mean dose and dose at the 50% volume level were consistently reduced by a factor of 1.3 to 25. Tumor dose homogeneity in IMPTM plans was always better than with IMPT planning (median inhomogeneity coefficient, 0.19 vs. 0.25). IMPT dose escalation (to 92.9 CGE to the GTV) was possible in all patients without exceeding the normal-tissue dose limits. Conclusions: These results suggest that the use of IM photon therapy, when compared to IM protons, can result in similar levels of tumor conformation. IM proton therapy, however, reduces the OAR integral dose substantially, compared to IM photon radiation therapy. As a result, tumor dose escalation was always possible with IM proton planning, within the maximal OAR dose constraints. In IM proton planning, reducing the size of the proton pencil beam (using the "mini-beam") improved the dose homogeneity, but it did not have a significant effect on the dose conformity. (C) 2004 Elsevier Inc. C1 Paul Scherrer Inst, Dept Radiat Med, CH-5232 Villigen PSI, Switzerland. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Weber, DC (reprint author), Paul Scherrer Inst, Dept Radiat Med, CH-5232 Villigen PSI, Switzerland. EM damien.weber@psi.ch NR 38 TC 64 Z9 68 U1 2 U2 6 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 APR 1 PY 2004 VL 58 IS 5 BP 1596 EP 1606 DI 10.1016/j.ijrobp.2003.11.028 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 807XA UT WOS:000220533000036 PM 15050341 ER PT J AU Eder, JP Garcia-Carbonero, R Clark, JW Supko, JG Puchalski, TA Ryan, DP Deluca, P Wozniak, A Campbell, A Rothermel, J LoRusso, P AF Eder, JP Garcia-Carbonero, R Clark, JW Supko, JG Puchalski, TA Ryan, DP Deluca, P Wozniak, A Campbell, A Rothermel, J LoRusso, P TI A phase I trial of daily oral 4 '-N-benzoyl-staurosporine in combination with protracted continuous infusion 5-fluorouracil in patients with advanced solid malignancies SO INVESTIGATIONAL NEW DRUGS LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 12-15, 2001 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Clin Oncol DE clinical trials; signal transduction inhibitor; chemotherapy; pharmacokinetics ID PROTEIN-KINASE-C; PERFORMANCE LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRIC METHOD; ACUTE MYELOID-LEUKEMIA; REASSESSMENT METHOD; CANCER-PATIENTS; OKADAIC ACID; PLASMA; STAUROSPORINE; INHIBITOR AB Purpose: 4'-N-Benzoyl-staurosporine (PKC412) is an orally available staurosporine derivative that inhibits protein kinase C. The objectives of this phase I trial were to determine the maximum tolerated dose (MTD), the dose limiting toxicities (DLTs), and the pharmacokinetics of PKC412 when co-administered with 5-Fluorouracil (5-FU). Experimental design: PKC412 was given daily with a 21-day continuous i.v. infusion of 5-FU 200 mg/m(2)/day, repeated every 4 weeks. The PKC412 dose was escalated by a modified continual reassessment method. The steady-state plasma pharmacokinetics of 5-FU, PKC412, and two of its circulating metabolites were determined during the first cycle of therapy. Results: A total of 33 patients were treated with 70 cycles (median: 2, range: 1-4) of PKC412 at doses ranging from 25 to 225 mg/day. No significant toxicities were encountered with doses up to 150 mg/day. Among nine patients treated with 225 mg/day of PKC412, one experienced grade 3 fatigue and nausea, another developed grade 3 hyperglycemia, and three had grade 2 emesis and stomatitis, leading to early treatment discontinuation. Minor responses consisting of a 40-45% tumor reduction were observed in two patients, one with gall bladder carcinoma and one with breast cancer. Mean values of steady-state pharmacokinetic variables for both PKC412 and 5-FU were comparable to single agent studies. Conclusions: The recommended phase II dose of PKC412 is 150 mg/day when combined with a continuous infusion of 200 mg/m(2)/day 5-FU. The dose limiting toxicity was grade 2 emesis and stomatitis and the regimen showed indications of activity. There was no evidence of a pharmacokinetic interaction between the two drugs. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Novartis Pharmaceut, E Hanover, NJ USA. RP Eder, JP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Gossman Bldg,G550B,44 Binney St, Boston, MA 02115 USA. EM jeder@partners.org NR 32 TC 17 Z9 20 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD APR PY 2004 VL 22 IS 2 BP 139 EP 150 DI 10.1023/B:DRUG.0000011790.31292.ef PG 12 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 762WX UT WOS:000188006100004 PM 14739662 ER PT J AU Razzaque, MS Foster, CS Ahmed, AR AF Razzaque, MS Foster, CS Ahmed, AR TI Role of macrophage migration inhibitory factor in conjunctival pathology in ocular cicatricial pemphigoid SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID DELAYED-TYPE HYPERSENSITIVITY; SHOCK-PROTEIN 47; COLLAGEN-BINDING HEAT-SHOCK-PROTEIN-47; RAT CRESCENTIC GLOMERULONEPHRITIS; NECROSIS-FACTOR-ALPHA; FACTOR MIF; IGA NEPHROPATHY; TRANSFORMING GROWTH-FACTOR-BETA-1; INTRAVENOUS IMMUNOGLOBULIN; MOLECULAR EVENTS AB PURPOSE. Macrophage migration inhibitory factor (MIF) is a pleiotropic, proinflammatory cytokine that mediates various immunoinflammatory processes. Ocular cicatricial pemphigoid (OCP) is an autoimmune disease in which affected conjunctivae show features of an immunoinflammatory disease. In this study, the role of MIF in the pathogenesis of OCP was examined. METHODS. The expression of MIF in conjunctival tissues of patients with OCP (n = 10) and normal subjects (n = 5) was studied by quantitative real-time PCR and immunohistochemistry. The production of MIF by conjunctival fibroblasts of normal control subjects and patients with OCP was determined, by using quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA). In addition, the effects of interleukin (IL)-1, tumor necrosis factor (TNF)-alpha, and transforming growth factor (TGF)-beta1 on the induction of MIF by conjunctival fibroblasts were studied by quantitative real-time PCR. To determine the relationship between conjunctival expression of MIF and accumulation of macrophages, in patients with OCP, a correlation study was performed. RESULTS. An increased conjunctival expression of MIF was detected in patients with OCP, both at the mRNA (by real-time PCR) and protein level (by immunohistochemistry), compared with normal control patients. The expression of MIF was detected in the epithelial cells and occasionally in the stromal cells in control conjunctival tissues, by immunohistochemistry. In contrast, a statistically significant increase (P < 0.0001) in the expression of MIF was detected in the stromal cells of conjunctival tissues obtained from patients with OCP (control: 4.89 +/- 0.5; OCP: 19.82 +/- 1.34). By quantitative real-time PCR, compared with control conjunctiva, an increase in the expression of MIF was detected in the conjunctiva obtained from patients with OCP. A similar increase in the expression of MIF was also detected in conjunctival fibroblasts of patients with OCP, compared with control fibroblasts, by quantitative real-time PCR. A significantly increased (P < 0.001) level of MIF was also detected in supernatant collected from conjunctival fibroblasts of patients with OCP (186 +/- 5.4), compared with supernatant collected from control fibroblasts (9.3 +/- 7.6). Moreover, IL-1, TNF-alpha, and TGF-beta1, known factors involved in the pathogenesis of OCP, were found to induce the expression of MIF by conjunctival fibroblasts. A statistically significant correlation (P < 0.0001, r(2) = 0.4465) was observed between the expression of MIF and accumulation of CD68-positive macrophages in conjunctiva of patients with OCP. CONCLUSIONS. This study demonstrated an increased conjunctival expression of MIF in patients with OCP. MIF may be actively involved in the pathogenesis of OCP, possibly regulating the inflammatory events of the disease process. C1 Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Immunol & Uveitis Serv, Boston, MA USA. RP Razzaque, MS (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA. EM razzaque_ahmed@hms.harvard.edu FU NEI NIH HHS [EY14228] NR 44 TC 16 Z9 16 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 IS 4 BP 1174 EP 1181 DI 10.1167/iovs.03-1138 PG 8 WC Ophthalmology SC Ophthalmology GA 806GK UT WOS:000220422200020 PM 15037585 ER PT J AU Acharya, N Henderson, B Ciolino, J Cremers, S AF Acharya, N Henderson, B Ciolino, J Cremers, S TI Retrospective study of outcomes after phacoemulsification cataract extraction and sulcus intraocular lens implantation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 335 BP U167 EP U167 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338000310 ER PT J AU Adam, SM Dryja, TP Berson, EL AF Adam, SM Dryja, TP Berson, EL TI A screen for mutations of the IMPGI gene in patients with retinitis pigmentosa SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degererat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2445 BP U940 EP U940 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002376 ER PT J AU Ahmad, O Hirose, T AF Ahmad, O Hirose, T TI Retinal detachment with macular hole in infants with retinopathy of prematurity SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Schepens Retina Associates, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 4031 BP U356 EP U356 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338201225 ER PT J AU Ahmed, AR Razzaque, MS Daoud, YJ Rashid, KA Foster, CS AF Ahmed, AR Razzaque, MS Daoud, YJ Rashid, KA Foster, CS TI Effects of IL-13 on fibroblasts isolated from conjunctivae of control and cicatricial pemphigoid SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 1498 BP U567 EP U567 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338001452 ER PT J AU Ahmed, M Androudi, S Kump, L Foster, CS AF Ahmed, M Androudi, S Kump, L Foster, CS TI Pars-plana vitrectomy and phacoemulsification surgery and as a combined procedure to restore visual acuity in patients with chronic uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Uveitis Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2678 BP U984 EP U984 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002612 ER PT J AU Ambati, J Anand, A Sakurai, E Fernandez, S Rollins, BJ Kuziel, WA Lynn, BC Ambati, BK AF Ambati, J Anand, A Sakurai, E Fernandez, S Rollins, BJ Kuziel, WA Lynn, BC Ambati, BK TI An animal model of atrophic and neovascular age-related macular degeneration in Ccl2(-/-) or Ccr2(-/-) mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Univ Kentucky, Lexington, KY USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, Inst Mol & Cellular Biol, Austin, TX 78712 USA. Med Coll Georgia, Augusta, GA 30912 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 3388 BP U122 EP U122 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338200586 ER PT J AU Andreoli, CM Hussels, IEM Xhu, D Mukai, S AF Andreoli, CM Hussels, IEM Xhu, D Mukai, S TI Histopathology and electron microscopy of a 16-week-gestation retina carrying the Norrie mutation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2502 BP U950 EP U950 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002436 ER PT J AU Androudi, SN Baehring, J Longtine, JJ Sklar, J Foster, CS Hochberg, FH AF Androudi, SN Baehring, J Longtine, JJ Sklar, J Foster, CS Hochberg, FH TI IgH gene rearrangement analysis in ocular lymphoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Brain Tumor Ctr, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 1227 BP U519 EP U519 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338001190 ER PT J AU Arie-Weintrob, YB Berson, EL Dryja, TP AF Arie-Weintrob, YB Berson, EL Dryja, TP TI Meta-analysis of histopathologic-genotype correlations in human retinal degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cogan Eye Pathol Lab, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 5087 BP U574 EP U574 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338202260 ER PT J AU Barabino, S Rolando, M Dana, R AF Barabino, S Rolando, M Dana, R TI Environmental control for dry eye mouse models SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Univ Genoa, Dept Neurosci Ophthalmol & Genet, Genoa, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 72 BP U119 EP U119 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338000046 ER PT J AU Brauner, SC Chen, TC Chang, MA Pasquale, LR Grosskreutz, CL AF Brauner, SC Chen, TC Chang, MA Pasquale, LR Grosskreutz, CL TI Glaucoma during pregnancy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 5568 BP U677 EP U677 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338202743 ER PT J AU Bula, DV Iliaki, A Gragoudas, E Miller, JW Arroyo, J AF Bula, DV Iliaki, A Gragoudas, E Miller, JW Arroyo, J TI Pigment epithelium-derived factor, angiopoietin-1 and VEGF expression in human choroidal neovascular membranes treated with photodynamic therapy. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Angiogenesis & Laser Lab, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 1787 BP U718 EP U718 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338001745 ER PT J AU Burns, SA Zhou, Y Lin, CP Bifano, TG Veilleux, I Webb, RH AF Burns, SA Zhou, Y Lin, CP Bifano, TG Veilleux, I Webb, RH TI Retinal imaging and wavefront sensing in mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Eye Res Inst, Boston, MA 02114 USA. Boston Univ, Photon Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. HMS, Boston, MA USA. Boston Univ, Boston, MA 02215 USA. RI Bifano, Thomas/E-6412-2013; Burns, Stephen/D-9259-2011 OI Bifano, Thomas/0000-0003-4952-2515; Burns, Stephen/0000-0001-5348-035X NR 0 TC 2 Z9 2 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2787 BP U1003 EP U1003 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002718 ER PT J AU Bursell, S Della Vecchia, KM Clermont, AC Takahashi, J Sundell, CL Luchoomun, J Qiu, FH Kunsch, C Aiello, LP AF Bursell, S Della Vecchia, KM Clermont, AC Takahashi, J Sundell, CL Luchoomun, J Qiu, FH Kunsch, C Aiello, LP TI Early diabetes-induced retinal vascular abnormalities are ameliorated by the antioxidant AGIX-4207 in diabetic rats SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Atherogen Inc, Alpharetta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 3207 BP U84 EP U84 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338200408 ER PT J AU Cabrita, FVL AF Cabrita, FVL TI Frequency of other autoimmune disorders in patients with Ocular Cicatricial Pemphigoid SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2712 BP U990 EP U990 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002645 ER PT J AU Chang, JH Javier, JA Chang, GY Oliveira, HB Jarade, EF Yu, A Albe, E Azar, DT AF Chang, JH Javier, JA Chang, GY Oliveira, HB Jarade, EF Yu, A Albe, E Azar, DT TI Functional characterization of the MMP-derived endostatin-spanning degradation products of type XVIII collagen SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 4813 BP U525 EP U525 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338201985 ER PT J AU Chen, L Cursiefen, C Maruyama, K Jackson, D Zhang, Q Streilein, JW Dana, R AF Chen, L Cursiefen, C Maruyama, K Jackson, D Zhang, Q Streilein, JW Dana, R TI Novel expression and characterization of lymphatic vessel endothelial hyaluronate receptor (LYVE-1) by ocular surface cells. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Inst Mol Med Oxford, MRC, Human Immunol Unit, Oxford, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 618 BP U307 EP U307 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338000593 ER PT J AU Chen, LJ Rajagopal, R Kuo, JC Azar, DT AF Chen, LJ Rajagopal, R Kuo, JC Azar, DT TI Cataract development following phakic intraocular lens surgery SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Schepens Eye Res Inst, Boston, MA USA. Taipei Municipal Ho Ping Hosp, Taipei, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 3754 BP U304 EP U304 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338200948 ER PT J AU Chen, TC Cense, B Park, BH Pierce, MC de Boer, JF AF Chen, TC Cense, B Park, BH Pierce, MC de Boer, JF TI Polarization sensitive optical coherence tomography measurement of thickness and birefringence of healthy retinal nerve fiber layer tissue SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Eye & Ear Infirm, Glaucoma Serv, Boston, MA USA. Massachusetts Gen Hosp, Wellman Ctr, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 3350 BP U114 EP U114 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338200553 ER PT J AU Chiu, CS Waheed, NK Vavvas, D AF Chiu, CS Waheed, NK Vavvas, D TI Perceived factors which influence the quality ofophthalmic surgical education: attributes of surgical educators and residency programs, and expectations of trainees SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 1406 BP U552 EP U552 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338001368 ER PT J AU Choi, JY Sandberg, MA Ling, CA Berson, EL AF Choi, JY Sandberg, MA Ling, CA Berson, EL TI Natural course of ocular function in pigmented paravenous retinochoroidal atrophy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 5118 BP U580 EP U580 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338202291 ER PT J AU Chow, SP Cavallerano, J Katalinic, P Hock, K Tolson, A Kirby, R Aiello, LM Aiello, LP Bursell, S AF Chow, SP Cavallerano, J Katalinic, P Hock, K Tolson, A Kirby, R Aiello, LM Aiello, LP Bursell, S TI Comparison of nonmydriatic digital retinal imaging with dilated clinical eye exam for detecting non-diabetes-related pathology in diabetic patients SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic, Australia. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 4120 BP U370 EP U370 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338201314 ER PT J AU Ciolino, JB Cremers, SL Henderson, BA AF Ciolino, JB Cremers, SL Henderson, BA TI Axial length as a factor in the complication rate in cataract surgery performed by residents SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 282 BP U158 EP U158 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338000258 ER PT J AU Clermont, AC Yasuda, Y Takahara, N Takahashi, J Kern, T Bursell, SE Aiello, LP King, GL AF Clermont, AC Yasuda, Y Takahara, N Takahashi, J Kern, T Bursell, SE Aiello, LP King, GL TI Overexpression of protein kinase C beta 2 in mouse vasculature induces retinal abnormalities characteristic of diabetic retinopathy without diabetes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. Shiga Univ Med Sci, Shiga, Japan. Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 1094 BP U404 EP U404 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338001068 ER PT J AU Cogan, SF Plante, TD Ehrlich, J Shire, DB Roach, K Wyatt, JL Rizzo, JF AF Cogan, SF Plante, TD Ehrlich, J Shire, DB Roach, K Wyatt, JL Rizzo, JF TI Charge-injection coatings for flexible electrode arrays used in retinal prostheses SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 EIC Labs, Norwood, MA 02062 USA. Cornell Nanofabricat Lab, Ithaca, NY USA. MIT, Cambridge, MA 02139 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 4227 BP U403 EP U403 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338201420 ER PT J AU Cohen, CS Challa, P Herndon, LW Pericak-Vance, M Abramson, K Hauser, M Wiggs, J Allingham, RR AF Cohen, CS Challa, P Herndon, LW Pericak-Vance, M Abramson, K Hauser, M Wiggs, J Allingham, RR TI Prevalence of optineurin mutations in adults with primary open angle glaucoma in Ghana, West Africa SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Duke Univ, Sch Med, Durham, NC USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 4627 BP U483 EP U483 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338201800 ER PT J AU Coney, JM Brathwaite, CE Doria, A Jager, R Timothy, N Aiello, LP King, GL AF Coney, JM Brathwaite, CE Doria, A Jager, R Timothy, N Aiello, LP King, GL TI Evaluation of insulin dependent diabetic patients with more than fifty years of diabetes. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 4119 BP U370 EP U370 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338201311 ER PT J AU D'Amico, DJ Bird, AC AF D'Amico, DJ Bird, AC TI VEGF inhibition study in ocular neovascularization-1 (VISION-1): Safety evaluation from the pivotal Macugen (TM) (Pegaptanib sodium) clinical trials SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. Moorfields Eye Hosp, London, England. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2363 BP U924 EP U924 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002294 ER PT J AU Dahlman, CH Barnes, SD Ma, JJ Grosskreutz, CL Pasquale, LR Chen, TC Rubin, PA AF Dahlman, CH Barnes, SD Ma, JJ Grosskreutz, CL Pasquale, LR Chen, TC Rubin, PA TI Diverting aqueous humor to distant sites in severe glaucoma - An update SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 920 BP U362 EP U362 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338000895 ER PT J AU Damico, FM Gragoudas, ES Young, LHY AF Damico, FM Gragoudas, ES Young, LHY TI Destruction of experimental choroidal melanoma: effects of trans-scleral Nd : YLF laser at 1047 nm vs. PDT using Visudyne SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 4631 BP U484 EP U484 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338201805 ER PT J AU Daoud, YJ Sami, N Leiko, E Androudi, S Foster, CS Ahmed, AR AF Daoud, YJ Sami, N Leiko, E Androudi, S Foster, CS Ahmed, AR TI Effectiveness of intravenous immunoglobulin therapy in patients with ocular cicatricial pemphigoid- long-term follow-up study SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. New England Baptist Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2714 BP U991 EP U991 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002649 ER PT J AU de Boer, JF Cense, B Nassif, N White, BR Park, BH Pierce, MC Tearney, GJ Bouma, BE Chen, TC AF de Boer, JF Cense, B Nassif, N White, BR Park, BH Pierce, MC Tearney, GJ Bouma, BE Chen, TC TI Ultra-high speed and ultra-high resolution optical coherence tomography and optical Doppler tomography SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Wellman Ctr, MGH, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 1139 BP U414 EP U414 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338001105 ER PT J AU DeAngelis, MM Chen, JA Kim, I Ott, J Miller, JW Dryja, TP AF DeAngelis, MM Chen, JA Kim, I Ott, J Miller, JW Dryja, TP TI Distribution of APOE alleles among patients with neovascular age-related macular degeneration and their unaffected siblings SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Serv,Dept Ophthalmol, Boston, MA USA. Rockefeller Univ, Lab Stat Genet, New York, NY USA. RI DeAngelis, e/J-7863-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 3730 BP U201 EP U201 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338200924 ER PT J AU Delaney, CM Perlman, JI Sothern, R Murray, D Thira, J Ryan, M Shirazi, P Nemchausky, BA Kanabrocki, EL AF Delaney, CM Perlman, JI Sothern, R Murray, D Thira, J Ryan, M Shirazi, P Nemchausky, BA Kanabrocki, EL TI Circadian, and overall relationships between intraocular pressure, blood pressure, heart rate and nitric oxide in men SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Loyola Univ, Maywood, IL 60153 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Univ Minnesota, Minneapolis, MN USA. Oxis Int, Res, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 5031 BP U564 EP U564 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338202206 ER PT J AU Dell, S Poulaki, V Mitsiades, N Kociok, N Joussen, AM AF Dell, S Poulaki, V Mitsiades, N Kociok, N Joussen, AM TI Intensive insulin therapy-induced vascular leakage and leukostasis in diabetes are decreased by anti-IGF SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Univ Cologne, Ctr Ophthalmol, Cologne, Germany. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 4111 BP U369 EP U369 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338201304 ER PT J AU Dobberfuhl, A Huang, W Filippopoulos, T Grosskreutz, CL AF Dobberfuhl, A Huang, W Filippopoulos, T Grosskreutz, CL TI Elevation in Hsp27 and the corresponding increase in procaspase 9 protein levels following induction of experimental glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Howe Lab Ophthalmol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2173 BP U789 EP U789 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002132 ER PT J AU Filippopoulos, T Matsubara, A Huang, W Ahmed, E Dobberfuhl, A Miller, JW Grosskreutz, CL AF Filippopoulos, T Matsubara, A Huang, W Ahmed, E Dobberfuhl, A Miller, JW Grosskreutz, CL TI Comparison of two non-invasive tonometers for the measurement of Intraocular Pressure (IOP) in the Mouse SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Mass Eye & Ear Infirm, Glaucoma Serv, Howe Lab, Boston, MA USA. Harvard Univ, Mass Eye & Ear Infirm, Angiogesis Lab, Retina Serv, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2169 BP U788 EP U788 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002127 ER PT J AU Friedman, E Rigas, IK Makar, M AF Friedman, E Rigas, IK Makar, M TI The roles of statins and hypertensives in the pathogenesis and management of AMD SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 3127 BP U70 EP U70 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338200330 ER PT J AU Gatinel, D Malet, J Azar, DT Hoang-Xuan, T AF Gatinel, D Malet, J Azar, DT Hoang-Xuan, T TI Theoretical effects on corneal wavefront analysis of corneal asphericity change after excimer laser hyperopic surgery. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Fdn Adolphe De Rothschild, Paris, France. Univ Paris 06, Inst Stat, F-75252 Paris 05, France. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 164 BP U136 EP U136 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338000137 ER PT J AU Goldstein, LE Hartley, D Liang, J Muffat, J Rehrmann, M Ericsson, M Thurston, G Marcus, M Bush, A Chylack, L AF Goldstein, LE Hartley, D Liang, J Muffat, J Rehrmann, M Ericsson, M Thurston, G Marcus, M Bush, A Chylack, L TI Alzheimer's disease B-amyloid (A beta) in the lens: Interactions with alphaB-crystallin, small heat shock proteins, and redox-active metal. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA. RI Muffat, Julien/P-2298-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 3507 BP U156 EP U156 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338200705 ER PT J AU Gragoudas, ES AF Gragoudas, ES TI VEGF inhibition study in ocular neovascularization-1 (VISION-1): Efficacy results from phase II/III Macugen (TM) (Pegaptanib sodium) clinical trials SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Retina Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2364 BP U924 EP U924 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002297 ER PT J AU Gulati, G Latina, M AF Gulati, G Latina, M TI Outcomes of repeat selective laser trabeculoplasty in open angle glaucoma cases on medications SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Tufts Univ, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 5582 BP U679 EP U679 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338202756 ER PT J AU Hafezi-Moghadam, A Thomas, KL Wagner, DD AF Hafezi-Moghadam, A Thomas, KL Wagner, DD TI Loss of barrier function in senescent vessels due to constitutive inflammation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 443 BP U189 EP U189 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338000417 ER PT J AU Hauser, MA Graham, FL Allingham, RR LaRocgue-Abramson, K Santiago, CM DelBono, E Olson, L Haines, JL Wiggs, JL Pericak-Vance, MA AF Hauser, MA Graham, FL Allingham, RR LaRocgue-Abramson, K Santiago, CM DelBono, E Olson, L Haines, JL Wiggs, JL Pericak-Vance, MA TI Evidence for linkage but not association to the GABRB3 region of chromosome 15 in a subset of primary open angle glaucoma (POAG) families. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Duke Univ, Durham, NC 27706 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Vanderbilt Univ, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 4394 BP U436 EP U436 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338201586 ER PT J AU Hoki, SL Zhao, L Pasquale, LR AF Hoki, SL Zhao, L Pasquale, LR TI The GON 10.9 Project: long-term visual prognosis of patients with advanced glaucomatous optic neuropathy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 5560 BP U675 EP U675 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338202733 ER PT J AU Hong, D Pawlyk, B Adamian, M Li, T AF Hong, D Pawlyk, B Adamian, M Li, T TI A single abbreviated ORF15 variant appears sufficient to reconstitute RPGR function in viva SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Berman Gund Lab Study Retianl Degenerat, Massachusetts Eye & Ear Infirm, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 3617 BP U180 EP U180 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338200811 ER PT J AU Hong, JE Rubin, PD AF Hong, JE Rubin, PD TI Sports-related orbital fractures SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 5593 BP U681 EP U681 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338202765 ER PT J AU Huang, E Gregory, M Marshak-Rothstein, A Mukai, S Ksander, BR AF Huang, E Gregory, M Marshak-Rothstein, A Mukai, S Ksander, BR TI Intratumor injection of membrane Fas Ligand vesicles triggers innate immunity SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Schepens Eye Res Inst, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 593 BP U303 EP U303 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338000566 ER PT J AU Huang, W Dobberfuhl, A Ingelsson, M Filippopoulos, T Grosskreutz, CL AF Huang, W Dobberfuhl, A Ingelsson, M Filippopoulos, T Grosskreutz, CL TI Detection of gene expression changes of caspase 8 and Thy1 in rat retinal ganglion cells after optic nerve crush using laser capture microdissection (LCM) with real-time PCR SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Howe Lab, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Lab, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2160 BP U787 EP U787 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002122 ER PT J AU Iaccheri, B Fiore, T Androudi, S Papadaki, T Loewenstein, JI Miller, JW Young, LH AF Iaccheri, B Fiore, T Androudi, S Papadaki, T Loewenstein, JI Miller, JW Young, LH TI Acute posterior multifocal placoid pigment epitheliopathy (APMPPE): final outcome and visual prognosis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2692 BP U987 EP U987 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002626 ER PT J AU Iliaki, E Poulaki, V Bula, DV Paulus, YM Mitsiades, N Ahmed, E Hafezi-Moghadam, A Gragoudas, ES Miller, JW AF Iliaki, E Poulaki, V Bula, DV Paulus, YM Mitsiades, N Ahmed, E Hafezi-Moghadam, A Gragoudas, ES Miller, JW TI Inhibition of very late antigen-4 (VLA-4) prevents endotoxin-induced uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Angiogenesis & Laser Labs, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 575 BP U212 EP U212 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338000549 ER PT J AU Jager, RD Timothy, N Coney, J Keenan, HA Arrigg, P Aiello, LP AF Jager, RD Timothy, N Coney, J Keenan, HA Arrigg, P Aiello, LP TI Endophthalmitis as a complication of intravitreal injection: A systemic review. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2001 BP U758 EP U758 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338001963 ER PT J AU Jansen, A Varoga, D Woon, CW Podolsky, D Barker, N Paulsen, F AF Jansen, A Varoga, D Woon, CW Podolsky, D Barker, N Paulsen, F TI Restitution of wounded cornea by TFF-peptides SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Univ Kiel, Inst Anat, D-2300 Kiel, Germany. GI Co, Framingham, MA USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 1413 BP U554 EP U554 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338001374 ER PT J AU Jarade, EF Oliveira, H Javier, J Chang, JH Azar, DT AF Jarade, EF Oliveira, H Javier, J Chang, JH Azar, DT TI In vivo quantification of corneal lesions sizes using improved image analysis software SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 146 BP U133 EP U133 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338000120 ER PT J AU Javier, JD Lee, JB Azar, DT AF Javier, JD Lee, JB Azar, DT TI Effect of the epithelial flap on scar and collagen formation after laser subepithelial kermomileusis (LASEK) on leghorn chick SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Schepens Eye Res Inst, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 1428 BP U556 EP U556 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338001390 ER PT J AU Jensen, RJ Ziv, OR Rizzo, JF AF Jensen, RJ Ziv, OR Rizzo, JF TI Activation of rabbit retinal ganglion cells with large diameter electrodes: Effects of pulse duration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Boston VA Med Ctr, Ctr Innovat Visual Rehabil, Boston, MA USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 4191 BP U382 EP U382 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338201383 ER PT J AU Jirawuthiworavong, GV Morales, SA Shimazaki, K Heckenlively, JR Seigel, GM Gordon, LK AF Jirawuthiworavong, GV Morales, SA Shimazaki, K Heckenlively, JR Seigel, GM Gordon, LK TI A flow cytometric assay for the detection of pro-apoptotic antiretinal antibodies in human serum SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Univ Calif Los Angeles, Jules Stein Eye Inst, David Geffen Sch Med, Los Angeles, CA 90024 USA. SUNY Coll Buffalo, Buffalo, NY USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2684 BP U986 EP U986 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002619 ER PT J AU Joussen, AM Poulaki, V Fauser, S Kociok, N Mitsiades, N AF Joussen, AM Poulaki, V Fauser, S Kociok, N Mitsiades, N TI Aspirin and COX-2 inhibition reduce diabetic endothelial cell death via a Fas-FasL dependent mechanism. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Res Lab, Boston, MA 02115 USA. Ctr Ophthalmol, Dept Vitreretinal Surg, Cologne, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 1095 BP U404 EP U404 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338001071 ER PT J AU Kalayoglu, MV Bula, D Arroyo, J Gragoudas, ES D'Amico, D Miller, JW AF Kalayoglu, MV Bula, D Arroyo, J Gragoudas, ES D'Amico, D Miller, JW TI Chlamydia pneumoniae is identified in human choroidal neovascular membranes secondary to age-related macular degeneration and induces vascular endothelial growth factor in vitro SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Angiogenesis Lab, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 3128 BP U71 EP U71 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338200331 ER PT J AU Karcich, KJ Buck, A Wyatt, J Shire, D Gingerich, MD Scholz, C Rizzo, J AF Karcich, KJ Buck, A Wyatt, J Shire, D Gingerich, MD Scholz, C Rizzo, J TI A system for leakage testing of flexible electronic components SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Boston VA Med Ctr, Ctr Innovat Visual Rehabil, Boston, MA USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. Cornell Univ, Cornell NanoScale Facil, Ithaca, NY 14853 USA. Univ Alabama, Dept Chem, Huntsville, AL 35899 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 4183 BP U381 EP U381 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338201376 ER PT J AU Kim, EC Letko, E Foster, CS AF Kim, EC Letko, E Foster, CS TI A retrospective review of infliximab for ocular inflammation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2669 BP U983 EP U983 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002602 ER PT J AU Kiss, S Letko, E Foster, C AF Kiss, S Letko, E Foster, C TI Long-term follow-up of patients with birdshot retinochoroidopathy treated with corticosteroid-sparing systemic immunosuppressive therapy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2666 BP U982 EP U982 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002600 ER PT J AU Koo, L Hatton, MP Rubin, PAD AF Koo, L Hatton, MP Rubin, PAD TI Quantification of enophthalmos SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 54 BP U116 EP U116 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338000028 ER PT J AU Krohne, TU Kociok, N Gavranic, C Fauser, S Poulaki, V Kirhhof, B Joussen, AM AF Krohne, TU Kociok, N Gavranic, C Fauser, S Poulaki, V Kirhhof, B Joussen, AM TI Local TNF-alpha inhibition prevents blood-ocular barrier changes and intraocular leakage in endotoxin-induced uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Univ Cologne, Ctr Ophthalmol, D-50931 Cologne, Germany. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RI Krohne, Tim/D-1497-2013 OI Krohne, Tim/0000-0003-2280-925X NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 578 BP U212 EP U212 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338000553 ER PT J AU Lane, A Colbert, AM Rego, AM Dryja, TP DeAngelis, MM Miller, JW AF Lane, A Colbert, AM Rego, AM Dryja, TP DeAngelis, MM Miller, JW TI Stalin use and risk of neovascular age-related macular degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Retina Serv, Dept Ophthalmol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ocular Mol Genet Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RI DeAngelis, e/J-7863-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 3043 BP U56 EP U56 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338200247 ER PT J AU Lee, RH Ng, PS Faull, KF AF Lee, RH Ng, PS Faull, KF TI In vivo phosphorylation at the serine-8 residue affects the conformation and the phosphorylation characterstics of phosducin. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 VA Greater LA Healthcare Syst, Mol Neurobiol Lab, Sepulveda, CA USA. Univ Calif Los Angeles, Dept Chem & Biochem, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 1279 BP U529 EP U529 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338001239 ER PT J AU Letko, E Papaliodis, G Christen, W Foster, S Ahmed, R AF Letko, E Papaliodis, G Christen, W Foster, S Ahmed, R TI Ocular cicatricial pemphigoid and relative risk for cancer. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2713 BP U991 EP U991 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002646 ER PT J AU Lin, B Wang, S Masland, RH AF Lin, B Wang, S Masland, RH TI Retinal ganglion cell type, size and spacing can be maintained independent of homotypic dendritic contacts SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 5330 BP U633 EP U633 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338202501 ER PT J AU Lin, CP Alt, C Pierce, M Wang, N DeBoer, J Burns, SA Webb, RH AF Lin, CP Alt, C Pierce, M Wang, N DeBoer, J Burns, SA Webb, RH TI Mouse eye parameters by optical coherence tomography (OCT) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Schepens Eye Res Inst, Boston, MA USA. RI Burns, Stephen/D-9259-2011 OI Burns, Stephen/0000-0001-5348-035X NR 0 TC 3 Z9 3 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2786 BP U1003 EP U1003 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002720 ER PT J AU Lindblad, AS Clemons, TE Seddon, JM Friberg, TR Klein, R Klein, BEK Bressler, SB AF Lindblad, AS Clemons, TE Seddon, JM Friberg, TR Klein, R Klein, BEK Bressler, SB CA AREDS Res Grp TI Estimated rates of progression to advanced AMD and vision loss by baseline maculopathy status: Results from the age-related eye disease study SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 EMMES Corp, Rockville, MD USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. Wilmer Eye Inst, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 3054 BP U58 EP U58 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338200256 ER PT J AU Mareninov, S Gordon, LK AF Mareninov, S Gordon, LK TI Age-dependent survival of retinal ganglion cells in vitro SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 5377 BP U642 EP U642 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338202550 ER PT J AU Matsubara, A Husain, D Connolly, E Michaud, N Gragoudas, ES Miller, JW AF Matsubara, A Husain, D Connolly, E Michaud, N Gragoudas, ES Miller, JW TI Investigating the effect of ciliary body photodyanmic therapy in mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Angiogenesis Lab, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Laser Lab,Retina Serv, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 990 BP U375 EP U375 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338000964 ER PT J AU Melson, MR Grabowski, EF Rizzo, JF Butler, WE Mukai, S AF Melson, MR Grabowski, EF Rizzo, JF Butler, WE Mukai, S TI Papilledema and benign intracranial hypertension in two children with intraocular retinoblastoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 3555 BP U168 EP U168 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338200751 ER PT J AU Meniconi, ME Razzaque, MS Androudi, S Ahmed, AR Foster, CS AF Meniconi, ME Razzaque, MS Androudi, S Ahmed, AR Foster, CS TI Cytokeratin 14 in ocular cicatricial pemphigoid and chronic cicatrizing conjunctivitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. Jules Gonin Univ Hosp, Lausanne, Switzerland. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 1488 BP U567 EP U567 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338001451 ER PT J AU Mocan, M Azar, NF Azar, DT AF Mocan, M Azar, NF Azar, DT TI Comparison of conjunctival autografting to amniotic membrane transplantation for the repair of clinically significant conjunctival dehiscence associated with strabismus surgery. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Pediat Ophthalmol & Strabismus, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Cornea & Refract Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2553 BP U960 EP U960 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002484 ER PT J AU Montezuma, SR Loewenstein, J Scholz, C Rizzo, JF AF Montezuma, SR Loewenstein, J Scholz, C Rizzo, JF TI Biocompatibility of subretinal materials in Yucatan pigs SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Univ Alabama, Huntsville, AL 35899 USA. Ctr Innovat Visual Rehabil, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 4169 BP U379 EP U379 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338201363 ER PT J AU Nishiguchi, K Sandberg, MA Kooijman, AC Martemyanov, KA Pott, JWR Hagstrom, SA Arshavsky, VY Berson, EL Dryja, TP AF Nishiguchi, K Sandberg, MA Kooijman, AC Martemyanov, KA Pott, JWR Hagstrom, SA Arshavsky, VY Berson, EL Dryja, TP TI Defects in RGS9 or its anchor protein R9AP in patients with bradyopsia, a novel form of retinal dysfunction SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Univ Groningen Hosp, Dept Ophthalmol, Groningen, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 1020 BP U382 EP U382 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338000995 ER PT J AU Pasquale, LR Feke, GT Menke, MN Kuperwaser, M McMeel, JW AF Pasquale, LR Feke, GT Menke, MN Kuperwaser, M McMeel, JW TI Effect of brimonidine versus latanoprost on the maintenance of retinal blood flow homeostasis during postural change in normal tension glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Schepens Retina Assoc Fdn, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 1178 BP U509 EP U509 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338001138 ER PT J AU Poulaki, V Iliaki, E Mitsiades, N Mitsiades, CS Mantas, YP Bula, D Gragoudas, ES Miller, JW AF Poulaki, V Iliaki, E Mitsiades, N Mitsiades, CS Mantas, YP Bula, D Gragoudas, ES Miller, JW TI Geldanamycin treatment reduces the inflammatory changes in the LPS-induced uveitis rat model SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 3444 BP U138 EP U138 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338200642 ER PT J AU Pungpapong, K Rubin, PAD Dartt, DA Shatos, MA AF Pungpapong, K Rubin, PAD Dartt, DA Shatos, MA TI Growth of human conjunctival cells on various support membranes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 1498 BP U568 EP U568 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338001459 ER PT J AU Raman, B Bursell, ES Wilson, M Nemeth, SC Soliz, P AF Raman, B Bursell, ES Wilson, M Nemeth, SC Soliz, P TI A computer-based retinal photo screening system for screening diabetic retinopathy using morphology and genetic algorithms SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Kestrel Corp, Div Biomed, Albuquerque, NM USA. Joslin Diabet Ctr, Joslin Vis Network, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 4125 BP U371 EP U371 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338201317 ER PT J AU Razzaque, MS Daoud, YJ Rashid, KA Foster, CS Ahmed, AR AF Razzaque, MS Daoud, YJ Rashid, KA Foster, CS Ahmed, AR TI Molecular mechanism that determines the macrophage population in ocular cicatricial pemphigoid SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 1484 BP U566 EP U566 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338001446 ER PT J AU Redd, HS Loewenstein, JI Lane, A Shen, L AF Redd, HS Loewenstein, JI Lane, A Shen, L TI Peripapillary choroidal neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 3077 BP U62 EP U62 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338200279 ER PT J AU Rigas, IK Makar, M Lane, AM Friedman, E AF Rigas, IK Makar, M Lane, AM Friedman, E TI Choroidal vascular resistance in age-related macular degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 3130 BP U68 EP U68 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338200313 ER PT J AU Rivolta, C Berson, EL Dryja, TP AF Rivolta, C Berson, EL Dryja, TP TI Search for mutations in the peropsin gene, an RPE-specific rhodopsin homolog, in patients with inherited retinal degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2447 BP U941 EP U941 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002380 ER PT J AU Rizzo, JF Wyatt, JL Loewenstein, J Montezuma, S Shire, DB Theogarajan, L Kelly, SK AF Rizzo, JF Wyatt, JL Loewenstein, J Montezuma, S Shire, DB Theogarajan, L Kelly, SK TI Development of a wireless, ab externo retinal prosthesis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Boston VA Med Ctr, Ctr Innovat Visual Rehabil, Boston, MA USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 3399 BP U126 EP U126 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338200596 ER PT J AU Rook, SL Yamagata, M Gundel, R White, M King, GL Aiello, LP AF Rook, SL Yamagata, M Gundel, R White, M King, GL Aiello, LP TI Vitreous but not plasma concentrations of Bactericidal/Permeability-Increasing Protein (BPI) may be associated with quiescent proliferative diabetic retinopathy. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Vasc Biol Lab, Boston, MA USA. Beetham Eye Inst, Boston, MA USA. Joslin Diabet Ctr, Boston, MA USA. Xoma US LLC, Preclin Res, Berkeley, CA USA. Xoma US LLC, Analyt Biol, Berkeley, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 4122 BP U371 EP U371 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338201318 ER PT J AU Rosenblatt, MI Yeh, SI Chang, JH Azar, DT AF Rosenblatt, MI Yeh, SI Chang, JH Azar, DT TI Gene transfer of matrix melloproteinase-7 (MMP-7) to corneal cell lines SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Schepens Eye Res Inst, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 4821 BP U526 EP U526 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338201992 ER PT J AU Sakurai, E Baffi, JZ Ambati, BK Kuziel, WA Rollins, BJ Ambati, J AF Sakurai, E Baffi, JZ Ambati, BK Kuziel, WA Rollins, BJ Ambati, J TI Targeted disruption of macrophage recruitment chemokines and chemokine receptors inhibits choroidal neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Univ Kentucky, Dept Ophthalmol & Visual Sci, Lexington, KY USA. Med Coll Georgia, Dept Ophthalmol, Augusta, GA 30912 USA. Univ Texas, Austin, TX 78712 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2227 BP U804 EP U804 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002187 ER PT J AU SanGiovanni, JP Chew, EY Ferris, FL Kurinij, N Sperduto, RD Lindblad, AS Seddon, J Klein, BEK Friberg, TR AF SanGiovanni, JP Chew, EY Ferris, FL Kurinij, N Sperduto, RD Lindblad, AS Seddon, J Klein, BEK Friberg, TR CA AREDS Res Grp TI Dietary carotenoids and risk for age-related macular degeneration in the Age-Related Eye Disease Study (AREDS) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 NEI, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA. NEI, Div Extramural Res, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. Univ Pittsburgh, Pittsburgh, PA USA. RI SanGiovanni, John Paul/A-7605-2008 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2242 BP U806 EP U806 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002197 ER PT J AU Santangelo, SL Yen, CH Chong, S Seddon, JM AF Santangelo, SL Yen, CH Chong, S Seddon, JM TI A discordant sib-pair linkage analysis of age-related macular degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psych & Neurodev Genet Unit, Charlestown, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2300 BP U910 EP U910 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002243 ER PT J AU Sena, DRF Pasquale, LR Allinghan, RR Hauser, MA Pericak-Vance, MA DelBono, EA Haines, JL Wiggs, JL AF Sena, DRF Pasquale, LR Allinghan, RR Hauser, MA Pericak-Vance, MA DelBono, EA Haines, JL Wiggs, JL TI Evaluation of NOS3 polymorphisms in patients with primary open angle glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. Duke Univ, Sch Med, Ctr Human Genet, Durham, NC 27706 USA. Vanderbilt Univ, Sch Med, Program Human Genet, Nashville, TN 37212 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 4391 BP U436 EP U436 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338201587 ER PT J AU Seyedahmadi, BJ Berson, EL Dryja, T AF Seyedahmadi, BJ Berson, EL Dryja, T TI USH3A mutations in patients with a prior diagnosis of Usher syndrome type 1, Usher syndrome type II, and nonsyndromic recessive retinitis pigmentosa SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 4726 BP U509 EP U509 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338201898 ER PT J AU Shah, HA Rizzo, JF Montezuma, SR AF Shah, HA Rizzo, JF Montezuma, SR TI In vivo electrical stimulation of healthy rabbit retina: Effect of stimulus duration and electrical field orientation. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. VA Med Ctr, Ctr Innovat Visual Rehabil, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 4179 BP U380 EP U380 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338201371 ER PT J AU Shimmura, S Miyashita, H Konomi, K Taguchi, T Kobayashi, H Tanaka, J Shimazaki, J Tsubota, K AF Shimmura, S Miyashita, H Konomi, K Taguchi, T Kobayashi, H Tanaka, J Shimazaki, J Tsubota, K TI Microkeratome-assisted posterior keratoplasty using infant donor cornea tissue SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Schepens Eye Res Inst, Boston, MA USA. RI Shimmura, Shigeto/J-4678-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 2901 BP U30 EP U30 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338200105 ER PT J AU Sobrin, L Young, TA Sharma, A Nakazawa, T Grosskreutz, CL Zacks, DN Miller, JW AF Sobrin, L Young, TA Sharma, A Nakazawa, T Grosskreutz, CL Zacks, DN Miller, JW TI Pigment epithelial-derived factor (PEDF) inhibits apoptosis in a rat model of retinal detachment SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Glaucoma Serv, Boston, MA 02114 USA. Univ Michigan, Kellogg Eye Ctr, Retina Serv, Ann Arbor, MI 48109 USA. RI Zacks, David/I-4394-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2064 BP U769 EP U769 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002026 ER PT J AU Sproule, M Forooghian, F O'Connor, P Gordon, L Jirawuthiworavong, G Wastall, C AF Sproule, M Forooghian, F O'Connor, P Gordon, L Jirawuthiworavong, G Wastall, C TI Autoimmune retinopathy in multiple sclerosis: A pilot study SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Univ Toronto, Toronto, ON, Canada. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 1592 BP U585 EP U585 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338001555 ER PT J AU Sun, JK Montezuma, SR Loewenstein, J Rizzo, JF AF Sun, JK Montezuma, SR Loewenstein, J Rizzo, JF TI Progress toward a minimally invasive, ab externo technique for subretinal prosthetic implantation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. VA Ctr Innovat Visual Rehabil, Boston, MA USA. MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 4190 BP U382 EP U382 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338201385 ER PT J AU Theogarajan, LS Jensen, RJ Rizzo, JF AF Theogarajan, LS Jensen, RJ Rizzo, JF TI Stimulation of rabbit retinal ganglion cells by altering K+ ion gradients: Dose-response curve SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 MIT, Cambridge, MA 02139 USA. Boston VA Med Ctr, Ctr Innovat Visual Rehabil, Boston, MA USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 4215 BP U401 EP U401 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338201408 ER PT J AU Timothy, NH Clermont, AC Della Vecchia, KM King, GL Aiello, LP Bursell, SE AF Timothy, NH Clermont, AC Della Vecchia, KM King, GL Aiello, LP Bursell, SE TI d-alpha-Tocopherol reduces diabetes-induced retinal vascular leakage and ERG abnormalities in the rat SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 1099 BP U404 EP U404 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338001073 ER PT J AU Tullis, SD Rizzo, JF Wall, C Balkwill, MD AF Tullis, SD Rizzo, JF Wall, C Balkwill, MD TI Optokinetic Nystagmus (OKN) as a measure of visual function in severely blind patients SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Jenks Vestibular Lab, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 4171 BP U379 EP U379 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338201364 ER PT J AU Ufret, R Yu, SY Christoforidis, J D'Amico, DJ AF Ufret, R Yu, SY Christoforidis, J D'Amico, DJ TI Evaluation of a polyethylene glycol (PEG)-derived glue as a potential bioadhesive for vitreoretinal applications. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 1 Z9 2 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2054 BP U767 EP U767 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002015 ER PT J AU Waheed, NK Chu, TG Mukai, S AF Waheed, NK Chu, TG Mukai, S TI Visudyne photodynamic therapy in subfoveal neovascular membranes related to Best's disease and combined hamartoma of the retina and the retinal pigment epithelium. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Retina Vitreous Assoc Med Grp, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 3185 BP U81 EP U81 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338200388 ER PT J AU Wen, Y Feng, J Sachs, G AF Wen, Y Feng, J Sachs, G TI Expression of LEP503 gene in early development of mouse lens SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Univ Calif Los Angeles, Membrane Biol Lab, VA Greater Los Angeles Hlth Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2642 BP U977 EP U977 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002573 ER PT J AU Wiggs, JL Allingham, RR Auguste, J Olsen, L LaRocque-Abramson, K Hauser, MA Del Bono, EA Graham, FL Pericak-Vance, MA Haines, JL AF Wiggs, JL Allingham, RR Auguste, J Olsen, L LaRocque-Abramson, K Hauser, MA Del Bono, EA Graham, FL Pericak-Vance, MA Haines, JL TI Genomic screen for adult-onset primary open angle glaucoma: Follow-up studies suggest loci on 14q11 and 15q. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. Ctr Human Genet, Durham, NC USA. Duke Univ, Sch Med, Durham, NC USA. Vanderbilt Univ, Sch Med, Program Human Genet, Nashville, TN 37212 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 4392 BP U436 EP U436 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338201585 ER PT J AU Yamauchi, Y Enzmann, V Franco, LM Jackson, D Naber, J Rizzo, JF Ziv, OR Kaplan, HJ AF Yamauchi, Y Enzmann, V Franco, LM Jackson, D Naber, J Rizzo, JF Ziv, OR Kaplan, HJ TI The retinal prosthesis - The stimulation threshold is lower with a subretinal microelectrode array SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Kentucky Lions Eye Ctr, Louisville, KY USA. Univ Louisville, Speed Sch Engn, Louisville, KY 40292 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. VA Med Ctr, Ctr Innovat Visual Reh, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 4222 BP U402 EP U402 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338201417 ER PT J AU Yang, R Fekete, A Roth, SI Stock, EL AF Yang, R Fekete, A Roth, SI Stock, EL TI The influence of the basement membrane on formation of the corneal epithelium after stem cell transplant SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Med Coll Wisconsin, Inst Eye, Milwaukee, WI 53226 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 57 BP U116 EP U116 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338000032 ER PT J AU Yates, PA Holub, AD McLaughlin, T Sejnowski, TJ O'Leary, DD AF Yates, PA Holub, AD McLaughlin, T Sejnowski, TJ O'Leary, DD TI Modeling the molecular control of retinotopic map development and refinement SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Salk Inst Biol Studies, Computat Neurobiol Lab, La Jolla, CA USA. Salk Inst Biol Studies, Mol Neurobiol Lab, La Jolla, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 5308 BP U629 EP U629 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338202479 ER PT J AU Young, TA Nakazawa, T Sobrin, L Sharma, A Grosskreutz, CL Gragoudas, ES Miller, JW AF Young, TA Nakazawa, T Sobrin, L Sharma, A Grosskreutz, CL Gragoudas, ES Miller, JW TI Modulation of apoptosis following combination PEDF and photodynamic therapy for choroidal neovascularization in the rat model SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 2231 BP U804 EP U804 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338002189 ER PT J AU Yu, SY Viola, F Damico, FM D'Amico, DJ AF Yu, SY Viola, F Damico, FM D'Amico, DJ TI Retinal toxicity of intravitreal triamcinolone acetonide; a morphologic study SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 1930 BP U745 EP U745 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338001892 ER PT J AU Zhao, T Ahmed, M El-Shabrawi, Y Christen, W Baltatzis, S Foster, CS AF Zhao, T Ahmed, M El-Shabrawi, Y Christen, W Baltatzis, S Foster, CS TI Interleukin-1 (IL-1) and interleukin-1 receptor antagonist (IL-lra) in patients with uveitis. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Immunol Lab, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, Boston, MA USA. Univ Athens, Athens, Greece. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 1 MA 559 BP U209 EP U209 PG 1 WC Ophthalmology SC Ophthalmology GA 846TA UT WOS:000223338000532 ER PT J AU Ziv, OR Jensen, RJ Rizzo, JF AF Ziv, OR Jensen, RJ Rizzo, JF TI In vitro activation of retinal cells: Estimating location of stimulated cell by using a mathematical model SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 VA Med Ctr, Ctr Innovat Visual Rehabil, Boston, MA USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2004 VL 45 SU 2 MA 4198 BP U383 EP U383 PG 1 WC Ophthalmology SC Ophthalmology GA 846TC UT WOS:000223338201392 ER PT J AU Harlow, BL Cohen, LS Otto, MW Spiegelman, D Cramer, DW AF Harlow, BL Cohen, LS Otto, MW Spiegelman, D Cramer, DW TI Early life menstrual characteristics and pregnancy experiences among women with and without major depression: the Harvard study of moods and cycles SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE major depression; menstruation; pregnancy; risk factors ID RECALL BIAS; DISORDERS; PREVALENCE; RISK; MENOPAUSE; ABORTION; SYMPTOMS AB Background: Other than premenstrual dysphoria, few studies have examined the extent to which basic characteristics of the menstrual cycle and the occurrence of other reproductive landmarks impact on the risk of major depression. Methods: From a population-based sample of 4161 premenopausal women 36-45 years of age, we identified 332 women who met DSM criteria for past or current major depression and a sample of 644 women with no such history. In person interviews included a detailed assessment of menstrual cycle characteristics from age at menarche through study enrollment as well as other reproductive landmarks. Results: Risk of depression increased significantly with decreasing age at menarche (P<0.001). The risk of depression was also higher in women with heavier menstrual flow and cycle irregularity during the first 5 years of menstruation. Women with a history Of Multiple abortions were 2-3-times more likely to develop major depression (95% CI 1.6-4.1). Increasing months of breastfeeding was associated with a decreased risk of depression after adjustment for education, marital status, and number of livebirths (P-value, test of trend =0.012). This association was largely confined to depression during the postpartum period. Limitations: Menstrual and pregnancy history exposures were self-reported and retrospectively assessed. However. women with and without a HISTORY of depression were subject to similar recall requirements that likely resulted in an underestimate of most risk estimates. Conclusions: Clinicians involved in routine obstetrical and gynecological care of women need to recognize that menstrual and pregnancy history events may serve as potential markers for subsequent psychiatric sequelae. (C) 2003 Elsevier B.V. All rights reserved. C1 Brigham & Womens Hosp, Ob Gyn Epidemiol Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Perinatal Psychiat Clin Res Program, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Harlow, BL (reprint author), Brigham & Womens Hosp, Ob Gyn Epidemiol Ctr, 221 Longwood Ave, Boston, MA 02115 USA. EM bharlow@rics.bwh.harvard.edu FU NIMH NIH HHS [R01-MH-50013] NR 37 TC 45 Z9 48 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD APR PY 2004 VL 79 IS 1-3 BP 167 EP 176 DI 10.1016/S0165-0327(02)00459-7 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 806BM UT WOS:000220409400017 PM 15023491 ER PT J AU Yildiz, A Sachs, GS AF Yildiz, A Sachs, GS TI Characteristics of rapid cycling bipolar-I patients in a bipolar speciality clinic SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article; Proceedings Paper CT 7th World Congress of Biological Psychiatry CY JUL 01-06, 2001 CL BERLIN, GERMANY DE rapid cycling; age of onset; gender ID AFFECTIVE-DISORDER; CIRCADIAN-RHYTHMS; DEMOGRAPHICS; ILLNESS; HAMSTER; WOMEN; MEN AB Objective: To investigate the characteristics of patients with rapid cycling bipolar illness. Method: The charts of bipolar patients treated at the Massachusetts General Hospital Bipolar Clinic were reviewed for age of the first affective episode, demographics and history of rapid cycling. Results: Data from 223 bipolar-I-II patients, of whom 11.7% were bipolar-II, were obtained, and only the data from 197 bipolar-I patients were analyzed. Forty-three percent of them had a positive history of rapid cycling. Rapid cycling was more common in women, with rapid cycling females having an earlier age of onset than non-rapid cycling bipolar-I females. No such association was found in bipolar-I males. In addition, with respect to current age, rapid cyclers were younger than non-rapid cyclers in bipolar-I females. No association was found for duration of illness. Conclusions: Women with bipolar-I illness have an increased probability of rapid cycling, which may still be increased in those with an early onset. Therefore, biological factors, such as sex and age onset, appear to be relevant to the physiology of rapid cycling. The retrospective design and the selected population of bipolar-I patients from an academic tertiary-referral center may limit the generalizability of our results. (C) 2002 Elsevier B.V. All rights reserved. C1 Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Program, Boston, MA 02115 USA. RP Yildiz, A (reprint author), Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. EM agul_yildiz@hotmail.com NR 21 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD APR PY 2004 VL 79 IS 1-3 BP 247 EP 251 DI 10.1016/S0165-0327(02)00350-6 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 806BM UT WOS:000220409400028 PM 15023502 ER PT J AU Perlis, RH Smoller, JW Fava, M Rosenbaum, JF Nierenberg, AA Sachs, GS AF Perlis, RH Smoller, JW Fava, M Rosenbaum, JF Nierenberg, AA Sachs, GS TI The prevalence and clinical correlates of anger attacks during depressive episodes in bipolar disorder - Presented at the 42nd annual meeting of the NIMH New Clinical Drug Evaluation Unit, Boca Raton, FL, 2002. SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE bipolar disorder; depression; anger attacks; phenomenology ID UNIPOLAR DEPRESSION; MIXED STATES; BORDERLINE PERSONALITY; FLUOXETINE TREATMENT; OUTPATIENTS; QUESTIONNAIRE; SPECTRUM; SYMPTOM AB Background: Anger attacks, characterized by sudden episodes of intense anger with autonomic arousal, have been described in patients with major depressive disorder (MDD). This study compared the prevalence and clinical significance of anger attacks in unipolar versus bipolar depression. Methods: Using the questionnaire of Fava et al. [Psychopharmacol. Bull. 27(3) (1991) 275-279], we assessed rates of anger attacks among outpatients with MDD (n = 50) or bipolar disorder (BPD) (n = 29) who were currently in a pure depressive episode. Results: Anger attacks were significantly more common among bipolar (62%) than unipolar (26%) depressed individuals. In a multiple logistic regression, the presence of anger attacks emerged as a significant predictor of bipolarity. Limitations: This preliminary finding should be confirmed in a larger sample. Conclusions: These results suggest that anger attacks may be a common feature of bipolar depression. (C) 2003 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM rperlis@partners.org NR 27 TC 52 Z9 53 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD APR PY 2004 VL 79 IS 1-3 BP 291 EP 295 DI 10.1016/S0165-0327(02)00451-2 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 806BM UT WOS:000220409400036 PM 15023510 ER PT J AU Nascimento, ALTO Ko, AI Martins, EAL Monteiro-Vitorello, CB Ho, PL Haake, DA Verjovski-Almeida, S Hartskeerl, RA Marques, MV Oliveira, MC Menck, CFM Leite, LCC Carrer, H Coutinho, LL Degrave, WM Dellagostin, OA El-Dorry, H Ferro, ES Ferro, MIT Furlan, LR Gamberini, M Giglioti, EA Goes-Neto, A Goldman, GH Goldman, MHS Harakava, R Jeronimo, SMB Junqueira-de-Azevedo, ILM Kimura, ET Kuramae, EE Lemos, EGM Lemos, MVF Marino, CL Nunes, LR de Oliveira, RC Pereira, GG Reis, MS Schriefer, A Siqueira, WJ Sommer, P Tsai, SM Simpson, AJG Ferro, JA Camargo, LEA Kitajima, JP Setubal, JC Van Sluys, MA AF Nascimento, ALTO Ko, AI Martins, EAL Monteiro-Vitorello, CB Ho, PL Haake, DA Verjovski-Almeida, S Hartskeerl, RA Marques, MV Oliveira, MC Menck, CFM Leite, LCC Carrer, H Coutinho, LL Degrave, WM Dellagostin, OA El-Dorry, H Ferro, ES Ferro, MIT Furlan, LR Gamberini, M Giglioti, EA Goes-Neto, A Goldman, GH Goldman, MHS Harakava, R Jeronimo, SMB Junqueira-de-Azevedo, ILM Kimura, ET Kuramae, EE Lemos, EGM Lemos, MVF Marino, CL Nunes, LR de Oliveira, RC Pereira, GG Reis, MS Schriefer, A Siqueira, WJ Sommer, P Tsai, SM Simpson, AJG Ferro, JA Camargo, LEA Kitajima, JP Setubal, JC Van Sluys, MA TI Comparative genomics of two Leptospira interrogans serovars reveals novel insights into physiology and pathogenesis SO JOURNAL OF BACTERIOLOGY LA English DT Article ID PSEUDOMONAS-AERUGINOSA; TREPONEMA-PALLIDUM; ESCHERICHIA-COLI; MOLECULAR CHARACTERIZATION; SUPEROXIDE REDUCTASE; NUCLEOTIDE-SEQUENCE; SYPHILIS SPIROCHETE; XYLELLA-FASTIDIOSA; PROTEIN; IDENTIFICATION AB Leptospira species colonize a significant proportion of rodent populations worldwide and produce life-threatening infections in accidental hosts, including humans. Complete genome sequencing of Leptospira interrogans serovar Copenhageni and comparative analysis with the available Leptospira interrogans serovar Lai genome reveal that despite overall genetic similarity there are significant structural differences, including a large chromosomal inversion and extensive variation in the number and distribution of insertion sequence elements. Genome sequence analysis elucidates many of the novel aspects of leptospiral physiology relating to energy metabolism, oxygen tolerance, two-component signal transduction systems, and mechanisms of pathogenesis. A broad array of transcriptional regulation proteins and two new families of afimbrial adhesins which contribute to host tissue colonization in the early steps of infection were identified. Differences in genes involved in the biosynthesis of lipopolysaccharide 0 side chains between the Copenhageni and Lai serovars were identified, offering an important starting point for the elucidation of the organism's complex polysaccharide surface antigens. Differences in adhesins and in lipopolysaccharide might be associated with the adaptation of serovars Copenhageni and Lai to different animal hosts. Hundreds of genes encoding surface-exposed lipoproteins and transmembrane outer membrane proteins were identified as candidates for development of vaccines for the prevention of leptospirosis. C1 Univ Sao Paulo, Ctr Biotechnol, Inst Butantan, BR-05503900 Sao Paulo, SP, Brazil. Univ Sao Paulo, Inst Quim, Sao Paulo, Brazil. Univ Sao Paulo, Inst Ciencias Biomed, BR-05508 Sao Paulo, Brazil. Univ Sao Paulo, Inst Biociencias, Sao Paulo, Brazil. Univ Sao Paulo, Inst Biol, Sao Paulo, Brazil. Univ Sao Paulo, Piracicaba, Brazil. Univ Estadual Paulista, Fac Ciencias Agrarias & Vet, Jaboticabal, Brazil. Univ Fed Sao Carlos, Ctr Ciencias Agrarias, Araras, Brazil. Fac Ciencias Farmaceut, Ribeirao Preto, Brazil. Fac Filosofia Ciencias & Letras, Ribeirao Preto, Brazil. Univ Sao Paulo, BR-14049 Ribeirao Preto, Brazil. Univ Mogi Cruzes, Fac Ciencias Agron, Mogi Cruzes, Brazil. Univ Mogi Cruzes, Inst Biociencias, Mogi Cruzes, Brazil. Univ Estadual Paulista, Botucatu, SP, Brazil. Univ Mogi Cruzes, Nucleo Integrado Biotecnol, Mogi Das Cruzes, Brazil. Univ Estadual Paulista, Dept Genet & Evolucao, Campinas, SP, Brazil. Univ Estadual Paulista, Inst Computacao, Campinas, SP, Brazil. Univ Estadual Paulista, Inst Agron Campinas, Campinas, SP, Brazil. Univ Estadual Paulista, Ctr Biol Mol & Engn Genet, Campinas, SP, Brazil. Univ Fed Bahia, Serv Immunol, BR-41170290 Salvador, BA, Brazil. UEFS, LAPEM, Dept Ciencias Biol, Feira De Santana, BA, Brazil. Inst Oswaldo Cruz, Dept Bioquim & Biol Mol, BR-20001 Rio De Janeiro, Brazil. Univ Fed Pelotas, Ctr Biotechnol, Pelotas, Brazil. Univ Fed Rio Grande Norte, Ctr Biociencias, BR-59072970 Natal, RN, Brazil. Cornell Univ, Weill Med Coll, Div Int Med & Infect Dis, New York, NY USA. Ludwig Inst Canc Res, New York, NY USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. Koninklin Inst Tropen, Royal Trop Inst, KIT Biomed Res, Amsterdam, Netherlands. RP Nascimento, ALTO (reprint author), Univ Sao Paulo, Ctr Biotechnol, Inst Butantan, Avenida Vital Brazil 1500, BR-05503900 Sao Paulo, SP, Brazil. EM tabet@usp.br RI Degrave, Wim/B-4162-2009; Dellagostin, Odir/C-2331-2009; Menck, Carlos/G-6321-2011; Junqueira-de-Azevedo, Inacio/H-5239-2011; Setubal, Joao/C-7305-2012; Coutinho, Luiz/C-8455-2012; Leite, Luciana/D-1353-2012; FERRO, MARIA INES/D-3634-2012; Verjovski-Almeida, Sergio/E-4082-2012; LEMOS, ELIANA/A-3604-2008; Oliveira, Mariana /G-2512-2012; Van Sluys, Marie-Anne/A-8483-2012; Carrer, Helaine/C-3159-2012; Nascimento, Ana Lucia/E-8488-2012; Camargo, Luis Eduardo/C-2735-2012; Ferro, Jesus/C-8251-2013; Goes-Neto, Aristoteles/A-6955-2013; Kimura, Edna/D-7334-2012; Harakava, Ricardo/C-4471-2012; Reis, Marcelo/K-4075-2012; Goldman, Gustavo/F-1848-2013; Marino, Celso/L-2448-2013; Nunes, Luiz/M-4804-2013; Jeronimo, Selma/M-8672-2014; Ferro, Emer/D-3908-2012; Tsai, Siu /C-2793-2012; Ko, Albert/P-2343-2015; Ho, Paulo/P-8267-2015; Goldman, Maria Helena /D-1424-2012; Kuramae, Eiko/F-4738-2012; Monteiro-Vitorello, Claudia/F-2436-2012; Marques, Marilis/C-3085-2013; Costa de Oliveira, Regina/A-4571-2017; IB/USP, Botanica/Q-7627-2016; Martins, Elizabeth/B-7135-2015; OI Dellagostin, Odir/0000-0003-2803-4088; Setubal, Joao/0000-0001-9174-2816; Verjovski-Almeida, Sergio/0000-0002-6356-2401; Oliveira, Mariana /0000-0001-8495-2962; Van Sluys, Marie-Anne/0000-0002-6506-2734; Carrer, Helaine/0000-0002-9329-1841; Nascimento, Ana Lucia/0000-0003-4851-0870; Camargo, Luis Eduardo/0000-0002-5650-5695; Ferro, Jesus/0000-0002-3966-1303; Goes-Neto, Aristoteles/0000-0002-7692-6243; Kimura, Edna/0000-0001-8403-4459; Harakava, Ricardo/0000-0003-1431-2665; Reis, Marcelo/0000-0002-3754-9115; Nunes, Luiz/0000-0001-9619-269X; Ferro, Emer/0000-0003-1651-9192; Tsai, Siu /0000-0002-3733-6312; Ho, Paulo/0000-0003-3652-241X; Goldman, Maria Helena /0000-0002-6786-9320; Kuramae, Eiko/0000-0001-6701-8668; Monteiro-Vitorello, Claudia/0000-0002-1238-9354; Costa de Oliveira, Regina/0000-0002-2446-5510; IB/USP, Botanica/0000-0002-4192-3747; Martins, Elizabeth/0000-0002-2333-9379; Menck, Carlos FM/0000-0003-1941-0694 FU NIAID NIH HHS [R01 AI034431-07, R01 AI034431] NR 52 TC 248 Z9 636 U1 4 U2 30 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 2004 VL 186 IS 7 BP 2164 EP 2172 DI 10.1128/JB.186.7.2164-2172.2004 PG 9 WC Microbiology SC Microbiology GA 805JS UT WOS:000220363200029 PM 15028702 ER PT J AU White, AR Barnham, KJ Huang, X Voltakis, I Beyreuther, K Masters, CL Cherny, RA Bush, AI Cappai, R AF White, AR Barnham, KJ Huang, X Voltakis, I Beyreuther, K Masters, CL Cherny, RA Bush, AI Cappai, R TI Iron inhibits neurotoxicity induced by trace copper and biological reductants SO JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY LA English DT Article DE Alzheimer's disease; homocysteine; neurodegeneration; oxidative stress; transition metals ID AMYLOID PRECURSOR PROTEIN; PRIMARY NEURONAL CULTURES; ALZHEIMER A-BETA; OXIDATIVE STRESS; NEURODEGENERATIVE DISEASE; PARKINSONS-DISEASE; HYDROGEN-PEROXIDE; TRANSGENIC MICE; IN-VIVO; BRAIN AB The extracellular microenvironment of the brain contains numerous biological redox agents, including ascorbate, glutathione, cysteine and homocysteine. During ischemia/reperfusion, aging or neurological disease, extracellular levels of reductants can increase dramatically owing to dysregulated homeostasis. The extracellular concentrations of transition metals such as copper and iron are also substantially elevated during aging and in some neurodegenerative disorders. Increases in the extracellular redox capacity can potentially generate neurotoxic free radicals from reduction of Cu(II) or Fe(III), resulting in neuronal cell death. To investigate this in vitro, the effects of extracellular reductants (ascorbate, glutathione, cysteine, homocysteine or methionine) on primary cortical neurons was examined. All redox agents except methionine induced widespread neuronal oxidative stress and subsequent cell death at concentrations occurring in normal conditions or during neurological insults. This neurotoxicity was totally dependent on trace Cu (greater than or equal to0.4 muM) already present in the culture medium and did not require addition of exogenous Cu. Toxicity involved generation of Cu(I) and H2O2, while other trace metals did not induce toxicity. Surprisingly, administration of Fe(II) or Fe(III) (greater than or equal to2.5 muM) completely abrogated reductant-mediated neurotoxicity. The potent protective activity of Fe correlated with Fe inhibiting reductant-mediated Cu(I) and H2O2 generation in cell-free assays and reduced cellular Cu uptake by neurons. This demonstrates a novel role for Fe in blocking Cu-mediated neurotoxicity in a high reducing environment. A possible pathogenic consequence for these phenomena was demonstrated by abrogation of Fe neuroprotection after pre-exposure of cultures to the Alzheimer's amyloid beta peptide (Abeta). The loss of Fe neuroprotection against reductant toxicity was greater after treatment with human Abeta1-42 than with human Abeta1-40 or rodent Abeta1-42, consistent with the central role of Abeta1-42 in Alzheimer's disease. These findings have important implications for trace biometal interactions and free radical-mediated damage during neurodegenerative illnesses such as Alzheimer's disease and old-age dementia. C1 Univ Melbourne, Dept Pathol, Carlton, Vic 3010, Australia. Univ Melbourne, Ctr Neurosci, Carlton, Vic 3010, Australia. Mental Hlth Res Inst, Parkville, Vic 3052, Australia. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Unit, Charlestown, MA 02129 USA. Univ Heidelberg, Ctr Mol Biol, D-69120 Heidelberg, Germany. RP White, AR (reprint author), Univ Melbourne, Dept Pathol, Carlton, Vic 3010, Australia. EM arwhite@unimelb-edu.au RI Cappai, Roberto/B-3347-2010; Bush, Ashley/A-1186-2007; White, Anthony/P-5596-2016; OI Cappai, Roberto/0000-0002-9505-8496; Bush, Ashley/0000-0001-8259-9069; White, Anthony/0000-0003-1802-9891; Volitakis, Irene/0000-0003-0766-817X FU NIMH NIH HHS [5 K01 MH02001] NR 50 TC 34 Z9 35 U1 0 U2 7 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0949-8257 J9 J BIOL INORG CHEM JI J. Biol. Inorg. Chem. PD APR PY 2004 VL 9 IS 3 BP 269 EP 280 DI 10.1007/s00775-004-0521-8 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 812TN UT WOS:000220861900003 PM 14758525 ER PT J AU Li, GA Wuerz, TH DeFrate, LE AF Li, GA Wuerz, TH DeFrate, LE TI Feasibility of using orthogonal fluoroscopic images to measure in vivo joint kinematics SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article ID TOTAL KNEE ARTHROPLASTY AB Accurately determining in vivo knee kinematics is still a challenge in biomedical engineering. This paper presents an imaging technique using two orthogonal images to measure 6 degree-of-freedom (DOF) knee kinematics during weight-bearing flexion. Using this technique, orthogonal images of the knee were captured using a 3-D fluoroscope at different flexion angles during weight-bearing flexion. The two orthogonal images uniquely characterized the knee Position at the specific flexion angle. A virtual fluoroscope was then created in solid modeling software and was used to reproduce the relative positions of the orthogonal images and X-ray sources of the 3-D fluoroscope during the actual imaging procedure. Two virtual cameras in the software were used to represent the X-ray sources. The 3-D computer model of the knee was then introduced into the virtual fluoroscope and was projected onto the orthogonal images by the two virtual cameras. By matching the projections of the knee model to the orthogonal images of the knee obtained during weight-bearing flexion, the knee kinematics in 6 DOF were determined. Using regularly shaped objects with known positions and orientations, this technique was shown to have an accuracy, of 0.1 mm and 0.1 deg in determining the positions and orientations of the objects, respectively. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, GA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, 55 Fruit St,GRL 1215, Boston, MA 02114 USA. EM gli1@partners.org NR 17 TC 96 Z9 101 U1 0 U2 15 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD APR PY 2004 VL 126 IS 2 BP 314 EP 318 DI 10.1115/1.1691448 PG 5 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 819XN UT WOS:000221349700024 PM 15179865 ER PT J AU Bhattacharyya, T Vrahas, MS AF Bhattacharyya, T Vrahas, MS TI The medical-legal aspects of compartment syndrome SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID MALPRACTICE CLAIMS AB Background: Management of compartment syndrome in the modern era involves not only avoiding the sequelae of a missed diagnosis but also minimizing the risk of a malpractice claim. Little information is available on the legal aspects of compartment syndrome. Methods: Twenty-three years of records on closed malpractice claims involving compartment syndrome were reviewed. The data were abstracted from medical records and were analyzed to determine the factors associated with a successful defense. Results: Nineteen closed claims, involving sixteen patients and encompassing a total liability of $3.8 million, were found in the data for malpractice claims closed between 1980 and 2003. Ten claims were resolved in favor of the physician. The average time to closure was 5.5 years. All three claims that went to trial resulted in a verdict for the physician. Evidence of poor physician-patient communication was found in six cases, all of which resulted in an indemnity payment (p < 0.01). Increasing time from the onset of symptoms to the fasciotomy was linearly associated with an increased indemnity payment (p < 0.05). A fasciotomy performed within eight hours after the first presentation of symptoms was uniformly associated with a successful defense. Conclusions: While malpractice claims involving compartment syndrome were uncommon, they resulted in a high rate and amount of indemnity payments. Early fasciotomy not only improves patient outcome but is also associated with decreased indemnity risk. C1 Massachusetts Gen Hosp, Partners Orthopaed Trauma Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bhattacharyya, T (reprint author), Massachusetts Gen Hosp, Partners Orthopaed Trauma Serv, WAC 525,15 Parkman St, Boston, MA 02114 USA. EM tbhattacharyya@partners.org NR 16 TC 44 Z9 45 U1 0 U2 2 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 APR PY 2004 VL 86A IS 4 BP 864 EP 868 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 810FR UT WOS:000220690700028 PM 15069156 ER PT J AU Kacena, MA Shivdasani, RA Wilson, K Xi, Y Troiano, N Nazarian, A Gundberg, CM Bouxsein, ML Lorenzo, JA Horowitz, MC AF Kacena, MA Shivdasani, RA Wilson, K Xi, Y Troiano, N Nazarian, A Gundberg, CM Bouxsein, ML Lorenzo, JA Horowitz, MC TI Megakaryocyte-osteoblast interaction revealed in mice deficient in transcription factors GATA-1 and NF-E2 SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE bone phenotype; anabolic; proliferation; thrombocytopenia; megakaryocytosis ID OSTEOCLASTOGENESIS-INHIBITORY FACTOR; INCREASED BONE-FORMATION; GROWTH-FACTOR-BETA; MYELOPROLIFERATIVE DISORDERS; OSTEOPROTEGERIN LIGAND; HEMATOPOIETIC-CELLS; PARATHYROID-HORMONE; RAT BONE; IN-VITRO; THROMBOPOIETIN AB Mice deficient in GATA-1 or NF-E2 have a 200-300% increase in bone volume and formation parameters. Osteoblasts and osteoclasts generated in vitro from mutant and control animals were similar in number and function. Osteoblast proliferation increased up to 6-fold when cultured with megakaryocytes. A megakaryocyte-osteoblast interaction plays a role in the increased bone formation in these mice. Introduction: GATA-1 and NF-E2 are transcription factors required for the differentiation of megakaryocytes. Mice deficient in these factors have phenotypes characterized by markedly increased numbers of immature megakaryocytes, a concomitant drastic reduction of platelets, and a striking increased bone mass. The similar bone phenotype in both animal models led us to explore the interaction between osteoblasts and megakaryocytes. Materials and Methods: Histomorphometry, muCT, and serum and urine biochemistries were used to assess the bone phenotype in these mice. Wildtype and mutant osteoblasts were examined for differences in proliferation, alkaline phosphatase activity, and osteocalcin secretion. In vitro osteoclast numbers and resorption were measured. Because mutant osteoblasts and osteoclasts were similar to control cells, and because of the similar bone phenotype, we explored the interaction between cells of the osteoblast lineage and megakaryocytes. Results: A marked 2- to 3-fold increase in trabecular bone volume and bone formation indices were observed in these mice. A 20- to 150-fold increase in trabecular bone volume was measured for the entire femoral medullary canal. The increased bone mass phenotype in these animals was not caused by osteoclast defects, because osteoclast number and function were not compromised in vitro or in vivo. In contrast, in vivo osteoblast number and bone formation parameters were significantly elevated. When wildtype or mutant osteoblasts were cultured with megakaryocytes from GATA-1- or NF-E2-deficient mice, osteoblast proliferation increased over 3- to 6-fold by a mechanism that required cell-to-cell contact. Conclusions: These observations show an interaction between megakaryocytes and osteoblasts, which results in osteoblast proliferation and increased bone mass, and may represent heretofore unrecognized anabolic pathways in bone. C1 Yale Univ, Sch Med, Dept Orthopaed & Rehabil, New Haven, CT 06520 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Orthoped Surg, Boston, MA 02115 USA. Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. RP Horowitz, MC (reprint author), Yale Univ, Sch Med, Dept Orthopaed & Rehabil, Box 208071, New Haven, CT 06520 USA. EM mark.horowitz@yale.edu FU NIAMS NIH HHS [AR47342, AR38933, AR46032] NR 57 TC 69 Z9 71 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD APR PY 2004 VL 19 IS 4 BP 652 EP 660 DI 10.1359/JBMR.0301254 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 804ZD UT WOS:000220335700017 PM 15005853 ER PT J AU Massie, BM Krol, WF Ammon, SE Armstrong, PW Cleland, JG Collins, JF Ezekowitz, M Jafri, SM O'Connor, CM Packer, M Schulman, KA Warren, S AF Massie, BM Krol, WF Ammon, SE Armstrong, PW Cleland, JG Collins, JF Ezekowitz, M Jafri, SM O'Connor, CM Packer, M Schulman, KA Warren, S TI The warfarin and Antiplatelet Therapy in Heart Failure Trial (WATCH): Rationale, design, and baseline patient characteristics SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE heart failure; clinical trial; anticoagulation; antiplatelet therapy; warfarin; aspirin; clopidogrel ID LEFT-VENTRICULAR DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; CONVERTING-ENZYME-INHIBITORS; DILATED CARDIOMYOPATHY; THROMBOEMBOLIC EVENTS; SYSTOLIC DYSFUNCTION; COHORT ANALYSIS; ACE-INHIBITORS; DOUBLE-BLIND; ASPIRIN AB Background: The role of anticoagulation in patients with chronic heart failure has long been an area of interest and controversy. Traditionally the goal of anticoagulation has been to prevent embolic events, but recent trials also demonstrated that oral anticoagulation also prevents vascular events in patients with prior myocardial infarction, who constitute the majority of heart failure patients. Although antiplatelet agents also reduce postinfarction vascular events, few data are available in heart failure patients, and some evidence suggests that aspirin may also have the potential to worsen heart failure morbidity and mortality, possibly by interfering with the effects of angiotensin-converting enzyme inhibitors. Methods and Results: The Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial was undertaken to determine the optimal antithrombotic agent for heart failure patients. WATCH was a prospective-randomized trial in which symptomatic heart failure patients in sinus rhythm with ejection fractions less than or equal to35% taking angiotensin-converting enzyme inhibitors (unless not tolerated) and diuretics were randomized to open-label warfarin (target International Normalized Ratio 2.5-3.0) or double-blind antiplatelet therapy with aspirin 162 mg or clopidogrel 75 mg. Two primary comparisons were specified: anticoagulation with warfarin versus antiplatelet therapy with aspirin and antiplatelet therapy with clopidogrel versus antiplatelet therapy with aspirin. The primary outcome is the composite of death from all causes, nonfatal myocardial infarction, and nonfatal stroke analyzed as time to first event using the intent-to-treat approach. The secondary endpoint was the broader composite of death from all causes, nonfatal myocardial infarction, non-fatal stroke, and hospitalizations for worsening heart failure, unstable angina pectoris, and systemic or pulmonary artery embolic events. Additional prespecified analyses include heart failure events, coronary events, and resource utilization. Conclusions: Although the trial was designed to enter 4500 patients, it was terminated 18 months prematurely in June 2003 by the VA Cooperative Study Program because of poor enrollment with a resulting reduction of its power to achieve its original objective. This manuscript describes the study rationale, protocol design, and the baseline characteristics of the 1587 patients who were entered into the study. The WATCH trial will help define the optimal approach to antithrombotic therapy in the contemporary management of patients with chronic heart failure resulting from left ventricular systolic dysfunction. C1 San Francisco VAMC, Div Cardiol, San Francisco, CA 94121 USA. RP Massie, BM (reprint author), San Francisco VAMC, Div Cardiol, 111C,4150 Clement St, San Francisco, CA 94121 USA. OI Cleland, John/0000-0002-1471-7016 NR 51 TC 54 Z9 57 U1 1 U2 5 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD APR PY 2004 VL 10 IS 2 BP 101 EP 112 DI 10.1016/j.cardfail.2004.02.006 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 816ZK UT WOS:000221147600002 PM 15101020 ER PT J AU Mansour, M Holmvang, G Sosnovik, D Migrino, R Abbara, S Ruskin, J Keane, D AF Mansour, M Holmvang, G Sosnovik, D Migrino, R Abbara, S Ruskin, J Keane, D TI Assessment of pulmonary vein anatomic variability by magnetic resonance imaging: Implications for catheter ablation techniques for atrial fibrillation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; pulmonary; vein isolation; magnetic resonance imaging; catheter ablation ID ISOLATED SHEEP HEART; RADIOFREQUENCY ABLATION; ANGIOGRAPHY AB PV Anatomy by MRA. Introduction: Pulmonary vein (PV) isolation for atrial fibrillation (AF) currently is performed using either an ostial or an extra-ostial approach. The objective of this study was to analyze by three-dimensional (3D) magnetic resonance angiography (MRA) the anatomy of the PVs in order to detect structural variability that would impact the choice of ablation approach. Methods and Results: Three-dimensional MRA was performed in 105 patients undergoing PV isolation. The ostial diameter, branching pattern, and PV angulation were analyzed. Fifty-nine(56%) patients had the typical pattern of 4 PVs with 4 separate ostia, 30 (29%) patients had an additional PV, and 18 (17%) patients had a left common PV trunk. In two patients, there were three right-sided veins and a common left-sided trunk, giving rise to four ostia: three on the right and one on the left. Two different populations of right middle PVs were noted: one where the additional vein projected anteriorly to drain the right middle lobe and one posterior to drain the superior portion of the right lower lobe. The average intrapatient variability in PV diameter was 7.9 +/- 4.2 mm. The PV ostium was <10 mm in 26 (25%) patients and >25 mm in 15 (14%) patients. The first branch originated 6.7 +/- 2.3 mm from the ostium. The left superior, right superior, right inferior, and left interior PVs were found to enter the left atrium at the following angles: 32 +/- 13degrees,131 +/- 11degrees,206 +/- 16degrees, and 329 +/- 14degrees, respectively. Forty-nine patients (47%) had at least one funnel shaped PV. Conclusion: This largest PV imaging study to date demonstrates that MRA is a valuable tool that allows detection of marked intrapatient and interpatient anatomic variability of the PVs. These findings suggest that, at least in some patients, circumferential extra-ostial left atrial encirclement of the PVs may be preferable to ostial PV isolation. These findings also may have significant implications on the future development of coil- and balloon-based catheter ablation designs for AF ablation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Cardiac Arrhythmia Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 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 24 TC 106 Z9 106 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 APR PY 2004 VL 15 IS 4 BP 387 EP 393 DI 10.1046/j.1540-8167.2004.03515.x PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 813SM UT WOS:000220926800001 PM 15089984 ER PT J AU Plesnila, N Zhu, CL Culmsee, C Groger, M Moskowitz, MA Blomgren, K AF Plesnila, N Zhu, CL Culmsee, C Groger, M Moskowitz, MA Blomgren, K TI Nuclear translocation of apoptosis-inducing factor after focal cerebral ischemia SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE focal cerebral ischemia; stroke; apoptosis; programmed cell death; apoptosis-inducing factor; caspases; caspase-independent ID NEURONAL CELL-DEATH; CYTOCHROME-C; CASPASE-3 ACTIVATION; CYCLOSPORINE-A; FACTOR AIF; POLY(ADP-RIBOSE) POLYMERASE; CALCIUM HOMEOSTASIS; EXPERIMENTAL STROKE; DNA FRAGMENTATION; HYPOXIA-ISCHEMIA AB Signaling cascades associated with apoptosis contribute to cell death after focal cerebral ischemia. Cytochrome c release from mitochondria and the Subsequent activation of caspases 9 and 3 are critical steps. Recently, a novel mitochondrial protein, apoptosis-inducing factor (AIF), has been implicated in caspase-independent programmed cell death following its translocation to the nucleus. We, therefore. addressed the question whether AIF also plays a role in cell death after focal cerebral ischemia. We detected AIF relocation from mitochondria to nucleus in primary cultured rat neurons 4 and 8 hours after 4 hours of oxygen/glucose deprivation. In ischemic mouse brain, AIF was detected within the nucleus I hour after reperfusion after 45 minutes occlusion of the middle cerebral artery. AIF translocation preceded cell death, Occurred before or at the time when cytochrome c was released from mitochondria, and was evident within cells showing apoptosis-related DNA fragmentation. From these findings, we infer that AIF may be involved in neuronal cell death after focal cerebral ischemia and that caspase-independent signaling pathways downstream of mitochondria may play a role in apoptotic-like cell death after experimental stroke. C1 Univ Munich, Inst Chirurg Forsch, Lab Expt Neurosurg, D-81366 Munich, Germany. Gothenburg Univ, Dept Physiol, Perinatal Ctr, S-41124 Gothenburg, Sweden. Zhengzhou Univ, Affiliated Hosp 3, Dept Pediat, Zhengzhou 450052, Peoples R China. Univ Munich, Dept Pharm, Lab Biotechnol & Pharmaceut Biol, D-80539 Munich, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. Gothenburg Univ, Queen Silvia Childrens Hosp, Dept Pediat, S-41124 Gothenburg, Sweden. RP Plesnila, N (reprint author), Univ Munich, Inst Chirurg Forsch, Lab Expt Neurosurg, Marchioninistr 15, D-81366 Munich, Germany. EM plesnila@icf.med.uni-muenchen.de RI Moskowitz, Michael/D-9916-2011; OI Blomgren, Klas/0000-0002-0476-7271 NR 48 TC 131 Z9 140 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD APR PY 2004 VL 24 IS 4 BP 458 EP 466 DI 10.1097/01.WCB.0000113454.95821.91 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 810TX UT WOS:000220727700011 PM 15087715 ER PT J AU Van Do, N Mino, L Merriam, GR LeMar, H Case, HS Palinkas, LA Reedy, K Reed, HL AF Van Do, N Mino, L Merriam, GR LeMar, H Case, HS Palinkas, LA Reedy, K Reed, HL TI Elevation in serum thyroglobulin during prolonged antarctic residence: Effect of thyroxine supplement in the polar 3,5,3 '-triiodothyronine syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 83rd Annual Meeting of the Endocrine-Society CY JUN 20-23, 2001 CL DENVER, CO SP Endocrine Soc ID RECOMBINANT HUMAN THYROTROPIN; THYROID-CARCINOMA; CLINICAL-PRACTICE; PITUITARY; KINETICS AB Extended Antarctic residence (AR) is associated with an increase in serum TSH, a decrease in free T(4), and an increase in T(3) production and clearance. It is not clear whether these adaptations reflect changes in clearance alone or whether intrinsic thyroidal synthetic activity also changes. Thyroglobulin (Tg) secretion is an independent marker of intrinsic thyroid activity whose kinetics are independent of those of T(3) and T(4). In this study we examined changes in Tg levels in healthy subjects before and during AR and their responses to thyroid supplementation to help determine whether alterations in thyroid activity, and not just kinetics of clearance, underlie the changes seen with the polar T(3) syndrome. In cohort 1, we compared measurements of TSH and Tg in 12 subjects before deployment and monthly for 11 months during AR. In cohort 2, we compared the same measurements in 12 subjects monthly for 11 months of AR. Subjects were randomized to receive either placebo or levothyroxine in cohort 1 for 7 months and in cohort 2 for 11 months. Tg increased over baseline during the first 4 months of AR by 17.0+/-4.6% and after 7 more months by 31.7+/-4.3% over baseline in the placebo group of both cohorts ( P<0.0002). When L-T(4) was taken, Tg returned to a value not different from baseline (4.5 +/- 3.9%). The percent changes from baseline in serum TSH and Tg during AR were highly correlated (P<0.00003) in the placebo group for both cohorts. The rise in Tg with TSH and the reduction in Tg with L-T(4) provide evidence of target tissue response to TSH and further confirm the TSH rise as physiologically significant. The results also suggest that the adaptive changes in thyroid hormone economy with AR reflect TSH-dependent changes in thyroid synthetic activity, which may help explain a portion of the increases in T(3) production found with AR. C1 Madigan Army Med Ctr, Internal Med Serv, Tacoma, WA 98431 USA. New Mexico Resonance, Albuquerque, NM USA. Vet Affairs Puget Sound Hlth Care Syst, Tacoma, WA 98493 USA. Univ Washington, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. William Beaumont Army Med Ctr, Endocrine Serv, El Paso, TX 79920 USA. McDaniel Coll, Dept Exercise Sci & Phys Educ, Westminster, MD 21157 USA. Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. US FDA, Rockville, MD 20857 USA. Multicare Med Grp, Tacoma, WA 98415 USA. RP Van Do, N (reprint author), Stanford Med Informat, Sch Med, Off Bldg,X-215,251 Campus Dr, Stanford, CA 94305 USA. EM nhan.do@us.army.mil NR 23 TC 2 Z9 3 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 APR PY 2004 VL 89 IS 4 BP 1529 EP 1533 DI 10.1210/jc.2003-031747 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 810OV UT WOS:000220714500004 PM 15070908 ER PT J AU Misra, M Miller, KK Herzog, DB Ramaswamy, K Aggarwal, A Almazan, C Neubauer, G Breu, J Klibanski, A AF Misra, M Miller, KK Herzog, DB Ramaswamy, K Aggarwal, A Almazan, C Neubauer, G Breu, J Klibanski, A TI Growth hormone and ghrelin responses to an oral glucose load in adolescent girls with anorexia nervosa and controls SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 85th Annual Meeting of the Endocrine-Society CY JUN 19-22, 2003 CL PHILADELPHIA, PA SP Endocrine Soc ID GH SECRETION; INTRAVENOUS GLUCOSE; TOLERANCE TEST; PLASMA-LEVELS; WOMEN; PYRIDOSTIGMINE; SUPPRESSION; DIAGNOSIS; CORTISOL; CHILDREN AB Anorexia nervosa (AN) is associated with high levels of GH and low levels of IGF-I suggestive of a nutritionally acquired lack of GH action or GH resistance. The suppression of GH levels after administration of inhibitors of GH secretion such as oral glucose is the definitive test to distinguish normal from pathological states of GH excess, such as acromegaly. However, suppression of GH by glucose has not been well characterized in states of adaptive GH excess, such as AN, especially in a younger adolescent population with relatively higher GH levels, compared with adults. In this study, we investigated GH suppression after a 100-g oral glucose load over a 1-h period in 19 adolescent girls with AN and 20 healthy controls of similar chronologic and bone age. We also compared nocturnal GH secretion characteristics by deconvolutional analysis in both groups to determine differences in secretory patterns between adolescents whose GH values suppressed vs. those whose values did not after oral glucose. Fasting levels of ghrelin, a GH secretagogue, and suppression of ghrelin with oral glucose were also determined to assess whether GH suppression or nonsuppression could be related to ghrelin values at respective time points. At 0 min (0')of the oral glucose tolerance test, girls with AN had significantly lower levels of glucose (P=0.009) and higher levels of GH (P=0.04) than controls. Nadir GH values were higher in AN than in controls (2.0+/-1.8 vs. 0.5+/-0.5 ng/ml, P=0.001). Only 31.6% of girls with AN suppressed their GH values to 1 ng/ml or less vs. 85.0% of healthy adolescents (P=0.0005). All healthy controls had nadir postglucose GH values of 2 ng/ml or less. Nadir GH concentrations during the oral glucose tolerance test correlated directly with all measures of GH secretion [basal (r=0.37, P=0.02), pulsatile (r=0.56, P=0.0002), and total (r=0.57, P=0.0002)]. Adolescent girls who did not suppress their GH values to 1 ng/ml or less had significantly higher levels of ghrelin at 0', 30', and 60' (P=0.02, 0.004, and 0.008), significantly higher GH at 0' (P=0.001), and higher nocturnal basal (P=0.002), pulsatile (P=0.05), and total GH secretion (P=0.03) than those who did suppress below this level. Ghrelin values were higher in AN than in controls at each time point (P=0.02, 0.0002, and 0.01 at 0', 30', and 60') but did not predict GH values at these time points. Adolescent girls with AN fail to adequately suppress their GH values after a 100-g oral glucose load. This lack of suppression may be related to the higher GH secretion seen in adolescents with this disorder. In contrast, all healthy adolescents suppress their GH values to 2 ng/ml or less but not 1 ng/ml or less after a glucose load. Although ghrelin values are higher in AN than in controls, we could not demonstrate a relationship between ghrelin and GH values. The inability of healthy girls to uniformly suppress GH levels to 1 ng/ml or less, a normal level defined for adults, may be related to higher GH secretion in the pubertal years, compared with adult life. Further studies are needed to define GH suppression in an adolescent population. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Eating Disorders Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp Children, Pediat Endocrinet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Core Lab, Gen Clin Res Ctr, Boston, MA 02114 USA. MIT, Core Lab, Gen Clin Res Ctr, Cambridge, MA 02142 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457B,55 Fruit St, Boston, MA 02114 USA. EM aklibanski@partners.org FU NCRR NIH HHS [M01-RR-01066]; NIDDK NIH HHS [DK07703, 1R01 DK062249] NR 41 TC 65 Z9 68 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 APR PY 2004 VL 89 IS 4 BP 1605 EP 1612 DI 10.1210/jc.2003-031861 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 810OV UT WOS:000220714500015 PM 15070919 ER PT J AU McLaughlin, T Abbasi, F Lamendola, C Frayo, RS Cummings, DE AF McLaughlin, T Abbasi, F Lamendola, C Frayo, RS Cummings, DE TI Plasma ghrelin concentrations are decreased in insulin-resistant obese adults relative to equally obese insulin-sensitive controls SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MEDIATED GLUCOSE DISPOSAL; POLYCYSTIC-OVARY-SYNDROME; PRADER-WILLI-SYNDROME; BODY-WEIGHT GAIN; CIRCULATING GHRELIN; FOOD-INTAKE; ACYLATED PEPTIDE; LOWER RATES; HUMANS; SECRETION AB Ghrelin, an orexigenic hormone that may play a role in body weight regulation, is reduced in states of obesity. Because obesity is associated with insulin resistance and compensatory hyperinsulinemia, we determined whether these metabolic characteristics were independently associated with suppressed ghrelin concentrations. To investigate this hypothesis, using steady-state plasma glucose concentrations, we identified 20 insulin-resistant (IR) and 20 insulin-sensitive (IS) individuals who were equally obese. The mean body mass indexes were 32.5+/-0.4 and 32.0+/-0.4 kg/m(2) for the IR and IS groups, respectively. Fasting insulin concentrations were 19.5 and 7.4 muU/ml (P<0.001), respectively. Ghrelin concentrations were suppressed in the IR group (252 +/- 19 pg/ml) relative to the IS group (412 +/- 35 pg/ml; P<0.001). Ghrelin correlated inversely with both insulin resistance (r=-0.64; P<0.001) and fasting insulin concentration (r=-0.58; P<0.001). Multivariate analysis confirmed that both insulin resistance and hyperinsulinemia independently predicted low ghrelin concentrations. Our results demonstrate that in obese individuals, insulin resistance and hyperinsulinemia are inversely associated with ghrelin concentrations. Thus, insulin resistance or related metabolic abnormalities may constitute part of a feedback mechanism by which body weight is regulated in humans. C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol, Seattle, WA 98108 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Cummings, DE (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol, 1660 S Columbian Way,S-111 Endo, Seattle, WA 98108 USA. EM davidec@u.washington.edu FU NCRR NIH HHS [RR-000070-40, RR-16071-01]; NIDDK NIH HHS [R01-DK-61516] NR 46 TC 176 Z9 192 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2004 VL 89 IS 4 BP 1630 EP 1635 DI 10.1210/jc.2003-031572 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 810OV UT WOS:000220714500018 PM 15070922 ER PT J AU Wahlstrom, JT Fowler, MJ Nicholson, WE Kovacs, WJ AF Wahlstrom, JT Fowler, MJ Nicholson, WE Kovacs, WJ TI A novel mutation in the preprovasopressin gene identified in a kindred with autosomal dominant neurohypophyseal diabetes insipidus SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MUTANT VASOPRESSIN PRECURSORS; REGULATED SECRETORY PATHWAY; SINGLE-BASE SUBSTITUTION; NEUROPHYSIN-II; ENDOPLASMIC-RETICULUM; SIGNAL PEPTIDE; CODING REGION; PROHORMONE; TRAFFICKING AB Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is a defect in free water conservation caused by mutations in the single gene that encodes both vasopressin (VP) and its binding protein, neurophysin II (NP II). Most of the human mutations in this gene have been in the portion encoding the NP molecule; the resultant abnormal gene products are believed to cause cellular toxicity as improperly folded precursor molecules accumulate in the endoplasmic reticulum. We identified a new American kindred with ADNDI and found a novel mutation in the VP molecule. A 78-yr-old man was noted to have hypotonic polyuria and plasma hyperosmolarity; the urinary concentration defect was reversed by administration of VP. His symptomatology dated to childhood, and his family history was consistent with autosomal transmission of the polyuric syndrome, with affected members in three generations, including several females. Affected individuals were found to be heterozygous for a 3-bp deletion in exon 1 of arginine VP (AVP)-NP II, predicting a deletion of phenylalanine 3 (known to be critical for receptor binding) in the VP nonapeptide. Neuro 2A cells stably transfected with the mutant AVP-NP construct showed increased rates of apoptosis as assessed by flow cytometric methods. These observations support the concept that cellular toxicity of abnormal AVP-NP gene products underlies the development of ADNDI, and the data further demonstrate that mutations affecting the AVP moiety can result in initiation of these pathological processes. C1 Vanderbilt Univ, Sch Med, Div Endocrinol Diabet & Metab, Nashville, TN 37232 USA. Tennessee Valley Healthcare Syst, US Dept Vet Affairs, Nashville, TN 37212 USA. RP Kovacs, WJ (reprint author), Vanderbilt Univ, Sch Med, Div Endocrinol Diabet & Metab, Room 715 Preston Res Bldg, Nashville, TN 37232 USA. EM william.kovacs@vanderbilt.edu OI Kovacs, William/0000-0002-3940-2109 FU NIDDK NIH HHS [P60 DK020593] NR 19 TC 16 Z9 16 U1 1 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 APR PY 2004 VL 89 IS 4 BP 1963 EP 1968 DI 10.1210/jc.2003-031542 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 810OV UT WOS:000220714500066 PM 15070970 ER PT J AU Niquet, J Wasterlain, CG AF Niquet, J Wasterlain, CG TI Bim, Bad, and Bax: a deadly combination in epileptic seizures SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID APOPTOSIS-INDUCING FACTOR; INDUCED NEURONAL DEATH; CELL-DEATH; ACTIVATION; HIPPOCAMPUS; PROTEINS; CLEAVAGE; PATHWAYS; BRAIN AB Several Bcl-2 family members, including Bim, may contribute to programmed cell death by inducing mitochondrial cytochrome c release, which activates caspase-9 and then caspase-3, the "executioner" of the cell. In this issue of the JCI, Shinoda and collaborators show the key role of Bim in epileptic seizure-induced neuronal injury and identify the contribution of transcription factors responsible for seizure-induced Bim upregulation (see the related article beginning on page 1059). C1 Vet Affairs Greater Los Angeles Healthcare Syst, Epilepsy Res Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90024 USA. RP Niquet, J (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Epilepsy Res Lab, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jniquet@ucla.edu NR 17 TC 24 Z9 36 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2004 VL 113 IS 7 BP 960 EP 962 DI 10.1172/JCI200421478 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 809QR UT WOS:000220651700007 PM 15057301 ER PT J AU Steere, AC Coburn, J Glickstein, L AF Steere, AC Coburn, J Glickstein, L TI The emergence of Lyme disease SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID SPIROCHETE BORRELIA-BURGDORFERI; SURFACE PROTEIN-A; HUMAN GRANULOCYTIC EHRLICHIOSIS; CONFIRMED ERYTHEMA MIGRANS; NEW-YORK-STATE; ANTIBIOTIC-TREATMENT; IXODES-SCAPULARIS; PROTECTIVE IMMUNITY; ANTIBODY-RESPONSE; BINDING-PROTEIN AB Since its identification nearly 30 years ago, Lyme disease has continued to spread, and there have been increasing numbers of cases in the northeastern and north central US. The Lyme disease agent, Borrelia burgdorferi, causes infection by migration through tissues, adhesion to host cells, and evasion of immune clearance. Both innate and adaptive immune responses, especially macrophage- and antibody-mediated killing, are required for optimal control of the infection and spirochetal eradication. Ecological conditions favorable to the disease, and the challenge of prevention, predict that Lyme disease will be a continuing public health concern. C1 Harvard Univ, Sch Med,Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Tufts Univ, Sch Med, Tufts New England Med Ctr, Div Geog & Med & Infect Dis, Boston, MA 02111 USA. RP Steere, AC (reprint author), Harvard Univ, Sch Med,Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, 55 Fruit St,CNY 149-8301, Boston, MA 02114 USA. EM asteere@partners.org FU NIAMS NIH HHS [AR20358, R01 AR020358]; ODCDC CDC HHS [CCU110291] NR 100 TC 426 Z9 455 U1 8 U2 70 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 APR PY 2004 VL 113 IS 8 BP 1093 EP 1101 DI 10.1172/JCI200421681 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 820CU UT WOS:000221365100005 PM 15085185 ER PT J AU Panoutsakopoulou, V Huster, KM McCarty, N Feinberg, E Wang, RJ Wucherpfennig, KW Cantor, H AF Panoutsakopoulou, V Huster, KM McCarty, N Feinberg, E Wang, RJ Wucherpfennig, KW Cantor, H TI Suppression of autoimmune disease after vaccination with autoreactive T cells that express Qa-1 peptide complexes SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MYELIN-BASIC-PROTEIN; IMMUNOREGULATORY CIRCUITS; ENCEPHALOMYELITIS EAE; FEEDBACK INHIBITION; MULTIPLE-SCLEROSIS; VIRAL-INFECTION; HELPER CELLS; LINE CELLS; CD8 CELLS; RECEPTOR AB The ability of autoreactive T cells to provoke autoimmune disease is well documented. The finding that immunization with attenuated autoreactive T cells (T cell vaccination, or TCV) can induce T cell-dependent inhibition of autoimmune responses has opened the possibility that regulatory T cells may be harnessed to inhibit autoimmune disease. Progress in the clinical application of TCV, however, has been slow, in part because the underlying mechanism has remained clouded in uncertainty. We have investigated the molecular basis of TCV-induced disease resistance in two murine models of autoimmunity: herpes simplex virus-1 (KOS strain)-induced herpes stromal keratitis and murine autoimmune diabetes in non-obese diabetic (NOD) mice. We find that the therapeutic effects of TCV depend on activation of suppressive CD8 cells that specifically recognize Qa-1-bound peptides expressed by autoreactive CD4 cells. We clarify the molecular interaction between Qa-1 and self peptides that generates biologically active ligands capable of both inducing suppressive CD8 cells and targeting them to autoreactive CD4 cells. These studies suggest that vaccination with peptide-pulsed cells bearing the human equivalent of murine Qa-1 (HLA-E) may represent a convenient and effective clinical approach to cellular therapy of autoimmune disease. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Cantor, H (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, SM 722,44 Binney St, Boston, MA 02115 USA. EM Harvey_Cantor@dfci.harvard.edu OI Panoutsakopoulou, Vily/0000-0002-1569-1508 FU NIAID NIH HHS [AI13600, AI37562, AI48125, R01 AI013600, R01 AI037562, R01 AI048125] NR 47 TC 47 Z9 49 U1 0 U2 1 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 APR PY 2004 VL 113 IS 8 BP 1218 EP 1224 DI 10.1172/JCI200420772 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 820CU UT WOS:000221365100021 PM 15085201 ER PT J AU Langer, CJ Stephenson, P Thor, A Vangel, M Johnson, DH AF Langer, CJ Stephenson, P Thor, A Vangel, M Johnson, DH TI Trastuzumab in the treatment of advanced non-small-cell lung cancer: Is there a role? Focus on eastern cooperative oncology group study 2598 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MONOCLONAL-ANTIBODY; EXPRESSION; HER-2/NEU; CARCINOMAS; SURVIVAL; RECEPTOR; P185NEU; GROWTH; TRIAL; PLUS AB Purpose Multiple non-small-cell lung cancer (NSCLC) cell lines and 20% to 50% of pathologic specimens express HER-2/neu, the target of trastuzumab, and HER-2/neu expression has proven to be an independent, unfavorable prognostic factor in resected patients with NSCLC. Trastuzumab, in vitro, has demonstrated growth-inhibiting synergy with platinating agents, and additivity with paclitaxel. The Eastern Cooperative Oncology Group therefore launched a phase II study evaluating combination carboplatin, paclitaxel, and trastuzumab in patients with advanced NSCLC. Materials and Methods Eligibility stipulated the following: measurable tumor, HER-2/neu positivity (1+ to 3+ by Herceptest [Dako Corp, Carpinteria, CA], confirmed by central review), Eastern Cooperative Oncology Group PS 0 to 1, adequate marrow, hepatic and renal function, and left ventricular ejection fraction 45%. Patients received paclitaxel 225 mg/m(2)/3 hours, and carboplatin (area under the curve, 6) every 3 weeks, and trastuzumab 4 mg/kg intravenously on day 1, then 2 mg/kg weekly for less than or equal to1 year. Results Between August 1999 and May 2000, 139 patients were screened; seven specimens (5%) were indeterminate. Fifty patients (36%) were HER-2/neu negative, 38 (27%) were HER-2/neu 1+, 31 (22%) were 2+, and 13 (9%) were 3+. Fifty-six patients were enrolled; 53 were eligible (22 [42%] were 1+, 23 (43%) were 2+, and eight (115%) were 3+). Thirteen (24.5%) of 52 assessable patients (95% Cl, 13.8 to 38.3) responded. The incidence of grade greater than or equal to3 neutropenia and thrombocytopenia was 57% (34%) and 16% (2%), respectively. Asymptomatic grade less than or equal to2 reduction in left ventricular ejection fraction occurred in 7%. Other nonhematologic toxicities, including nausea, fatigue, arthralgias, and peripheral sensory neuropathy, were mild to moderate and matched those expected with carboplatin and paclitaxel alone. Eighteen patients (35%) received maintenance trastuzumab. Median progression-free survival was 3.3 months; median survival was 10.1 months, and 1-year survival rate was 42%. Conclusion Combination paclitaxel, carboplatin, and trastuzumab is feasible. Toxicity appears no worse than cytotoxic therapy alone. Overall survival is similar to historical data using carboplatin and paclitaxel alone. However, patients with 3+ HER-2/neu expression did well in contrast to historical data suggesting potential benefit for trastuzumab in this rare subset of NSCLC. Critical assessment of trastuzumab's role in advanced NSCLC will require phase III trials. (C) 2004 by American Society of Clinical Oncology. C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Vanderbilt Ingram Canc Ctr, Div Hematol & Oncol, Nashville, TN USA. RP Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. EM CJ_Langer@fccc.edu RI Johnson, David/A-7437-2009 NR 30 TC 102 Z9 108 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2004 VL 22 IS 7 BP 1180 EP 1187 DI 10.1200/JCO.2004.04.105 PG 8 WC Oncology SC Oncology GA 808DQ UT WOS:000220550200004 PM 14981103 ER PT J AU Saltz, LB Meropol, NJ Loehrer, PJ Needle, MN Kopit, J Mayer, RJ AF Saltz, LB Meropol, NJ Loehrer, PJ Needle, MN Kopit, J Mayer, RJ TI Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor 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 MONOCLONAL-ANTIBODIES; ANTITUMOR-ACTIVITY; CHIMERIC ANTIBODY; FLUOROURACIL; IRINOTECAN; LEUCOVORIN; COMBINATION; C225; OXALIPLATIN; XENOGRAFTS AB Purpose To evaluate the antitumor activity and toxicity of single-agent cetuximab in patients with chemotherapy-refractory colorectal cancer whose tumors express the epidermal growth factor receptor. Patients and Methods Phase II, open-label clinical trial. Patients were required to have EGFr expression demonstrated on formalin-fixed paraffin-embedded tumor tissue by immunohistochemical staining before study participation. Patients were required to have received irinotecan, either alone or in a combination regimen, and to have demonstrated clinical failure on this regimen before study entry. Cetuximab was administered weekly by intravenous infusion. The first dose of 400 mg/m(2) was given during the course of 2 hours. Subsequent weekly treatments were given at a dose of 250 mg/m(2) during the course of 1 hour. Results Fifty-seven eligible patients were treated. All were assessable for toxicity and response. The most commonly encountered grade 3 to 4 adverse events, regardless of relationship to study drug, were an acne-like skin rash, predominantly on the face and upper torso (86% with any grade; 18% with grade 3), and a composite of asthenia, fatigue, malaise, or lethargy (56% with any grade, 9% with grade 3). Two patients (3.5%) experienced grade 3 allergic reactions requiring discontinuation of study treatment. A third patient experienced a grade 3 allergic reaction that resolved, and the patient continued on the study. Neither diarrhea nor neutropenia were dose limiting in any of the 57 patients treated. Five patients (9%; 95% Cl, 3% to 19%) achieved a partial response. Twenty-one additional patients had stable disease or minor responses. The median survival in these previously treated patients with chemotherapy-refractory colorectal cancer is 6.4 months. Conclusion Cetuximab on this once-weekly schedule has modest activity and is well-tolerated as a single agent in patients with chemotherapy-refractory colorectal cancer whose tumors express the epidermal growth factor receptor. Further studies of cetuximab will evaluate the use of cetuximab in conjunction with first-line and adjuvant treatments for this disease. (C) 2004 by American Society of Clinical Oncology. C1 Mem Sloan Kettering Canc Ctr, Gastrointestinal Oncol Serv, Dept Med, New York, NY 10021 USA. Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. Indiana Univ, Ctr Canc, Indianapolis, IN USA. Walther Canc Inst, Indianapolis, IN USA. Imclone Syst Inc, Somerville, NJ USA. Bristol Myers Squibb Inc, Wallingford, CT USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. RP Saltz, LB (reprint author), Mem Sloan Kettering Canc Ctr, Gastrointestinal Oncol Serv, Dept Med, 1275 York Ave, New York, NY 10021 USA. EM Saltzl@mskcc.org OI Saltz, Leonard/0000-0001-8353-4670 NR 37 TC 1187 Z9 1252 U1 1 U2 30 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2004 VL 22 IS 7 BP 1201 EP 1208 DI 10.1200/JCO.2004.10.182 PG 8 WC Oncology SC Oncology GA 808DQ UT WOS:000220550200007 PM 14993230 ER PT J AU Tallman, MS Kim, HT Paietta, E Bennett, JM Dewald, G Cassileth, PA Wiernik, PH Rowe, JM AF Tallman, MS Kim, HT Paietta, E Bennett, JM Dewald, G Cassileth, PA Wiernik, PH Rowe, JM TI Acute monocytic leukemia (French-American-British classification M5) does not have a worse prognosis than other subtypes of acute myeloid leukemia: A report from the Eastern Cooperative Oncology Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Hematology CY DEC 07-11, 2001 CL ORLANDO, FL SP Amer Soc Hematol ID ACUTE MONOBLASTIC LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA; MLL GENE; DE-NOVO; BIOLOGICAL CHARACTERISTICS; DEOXYADENOSINE ANALOGS; POOR-PROGNOSIS; TRANSLOCATION; CHEMOTHERAPY AB Purpose Acute monocytic leukemia is a distinct subtype of acute myeloid leukemia (AML) with characteristic biologic and clinical features. This study was designed to compare the outcome of patients with M5 to that of other subtypes of AML, and to identify differences in M5a and M5b. Patients and Methods We reviewed all patients with AML M5 entered in three clinical trials for newly diagnosed AML conducted by the Eastern Cooperative Cincology Group between 1989 and 1998. Eighty-one patients, 21 with M5a and 60 with M5b, were identified. Results The complete remission rate was 62% for all patients with M5; 52% for patients with M5a and 65% for patients with M5b (P=.3), and 60% for the 1,122 patients with non-M5 AML entered on the same clinical trials (P=.8 for M5 v non-M5). The 3-year disease-free survival was 26% for all M5 patients; 18% for M5a and 28% for M5b (P=.31), and 33% for non-M5 patients (P=.13 for M5 v non-M5). The 3-year overall survival was 31% for all M5 patients; 33% for M5a and 30% for M5b (P=.65), and 30% for non-M5 (P=.74 for M5 v non-M5). The karyotypes of patients with AML M5 were heterogeneous. CD11b was the only leukemic cell antigen expressed differently in M5a (53%) compared to M5b (77%) to a significant degree (P=.02). Conclusion AML MS represents an immunologically heterogeneous population similar to non-M5 AML with a prognosis that is not dependent on morphology. The disease-free survival and overall survival of patients with M5a, M5b, and non-M5 appear not to differ with currently available therapy. (C) 2004 by American Society of Clinical Oncology. C1 Northwestern Univ, Feinberg Sch Med, Dept Med,Div Hematol Oncol, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. New York Med Coll, Our Lady Mercy Canc Ctr, Bronx, NY USA. Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. Mayo Clin, Rochester, MN USA. Univ Miami, Ctr Comprehens Canc, Miami, FL USA. Technion Israel Inst Technol, Rambam Med Ctr, Haifa, Israel. Eastern Cooperat Oncol Grp, Brookline, MA USA. RP Tallman, MS (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Med,Div Hematol Oncol, Robert H Lurie Comprehens Canc Ctr, 676 N St Clair St,Suite 850, Chicago, IL 60611 USA. EM m-tallman@northwestern.edu NR 70 TC 40 Z9 46 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2004 VL 22 IS 7 BP 1276 EP 1286 DI 10.1200/JCO.2004.08.060 PG 11 WC Oncology SC Oncology GA 808DQ UT WOS:000220550200017 PM 14970186 ER PT J AU Miller, AL Hall, CS Buchanan, RW Buckley, PF Chiles, JA Conley, RR Crismon, ML Ereshefsky, L Essock, SM Finnerty, M Marder, SR Miller, DD McEvoy, JP Rush, AJ Saeed, SA Schooler, NR Shon, SP Stroup, S Tarin-Godoy, B AF Miller, AL Hall, CS Buchanan, RW Buckley, PF Chiles, JA Conley, RR Crismon, ML Ereshefsky, L Essock, SM Finnerty, M Marder, SR Miller, DD McEvoy, JP Rush, AJ Saeed, SA Schooler, NR Shon, SP Stroup, S Tarin-Godoy, B TI The Texas Medication Algorithm Project antipsychotic algorithm for schizophrenia: 2003 update SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID TREATMENT-RESISTANT SCHIZOPHRENIA; MAJOR DEPRESSIVE DISORDER; SCHIZOAFFECTIVE DISORDER; DOUBLE-BLIND; ATYPICAL ANTIPSYCHOTICS; CLOZAPINE AUGMENTATION; CONTROLLED-TRIALS; PHASE-3 TMAP-3; ARIPIPRAZOLE; PLACEBO AB Background: The Texas Medication Algorithm Project (TMAP) has been a public-academic collaboration in which guidelines for medication treatment of schizophrenia, bipolar disorder, and major depressive disorder were used in selected public outpatient clinics in Texas. Subsequently, these algorithms were implemented throughout Texas and are being used in other states. Guidelines require updating when significant new evidence emerges; the antipsychotic algorithm for schizophrenia was last updated in 1999. This article reports the recommendations developed in 2002 and 2003 by a group of experts, clinicians, and administrators. Method: A conference in January 2002 began the update process. Before the conference, experts in the pharmacologic treatment of schizophrenia, clinicians, and administrators reviewed literature topics and prepared presentations. Topics included ziprasidone's inclusion in the algorithm, the number of antipsychotics tried before clozapine, and the role of first generation antipsychotics. Data were rated according to Agency for Healthcare Research and Quality criteria. After discussing the presentations, conference attendees arrived at consensus recommendations. Consideration of aripiprazole's inclusion was subsequently handled by electronic communications. Results: The antipsychotic algorithm for schizophrenia was updated to include ziprasidone and aripiprazole among the first-line agents. Relative to the prior algorithm, the number of stages before clozapine was reduced. First generation antipsychotics were included but not as first-line choices. For patients refusing or not responding to clozapine and clozapine augmentation, preference was given to trying monotherapy with another antipsychotic before resorting to antipsychotic combinations. Conclusion: Consensus on algorithm revisions was achieved, but only further well-controlled research will answer many key questions about sequence and type of medication treatments of schizophrenia. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. El Paso Community Mental Hlth & Mental Retardat C, El Paso, TX USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. Hillside Hosp, Long Isl Jewish Med Ctr, Long Isl City, NY USA. Univ Illinois, Coll Med, Dept Psychiat & Behav Sci, Peoria, IL 61656 USA. Univ Texas, SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75235 USA. Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. Univ Iowa, Coll Med, Dept Psychiat, Iowa City, IA 52242 USA. W Los Angeles VA Hlth Care Ctr, Los Angeles, CA USA. New York Off State Mental Hlth, Albany, NY USA. Vet Adm, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. Mt Sinai Sch Med, New York, NY USA. Texas Dept Mental Hlth & Mental Retardat Unit, Austin, TX USA. Univ Texas, Coll Pharm, Austin, TX 78712 USA. Univ Washington, Sch Med, Dept Psychiat, Seattle, WA USA. Med Coll Georgia, Dept Psychiat, Augusta, GA 30912 USA. Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. San Antonio State Hosp, San Antonio, TX USA. RP Miller, AL (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, 7703 Floyd Curl Dr,MC 7792, San Antonio, TX 78229 USA. EM millera@uthscsa.edu RI Stroup, Thomas/F-9188-2014; OI Stroup, Thomas/0000-0002-3123-0672; Rush, Augustus/0000-0003-2004-2382 NR 74 TC 122 Z9 128 U1 2 U2 8 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 APR PY 2004 VL 65 IS 4 BP 500 EP 508 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 831JL UT WOS:000222190600008 PM 15119912 ER PT J AU Fava, M Mallinckrodt, CH Detke, MJ Watkin, JG Wohlreich, MM AF Fava, M Mallinckrodt, CH Detke, MJ Watkin, JG Wohlreich, MM TI The effect of duloxetine on painful physical symptoms in depressed patients: Do improvements in these symptoms result in higher remission rates? SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SOMATIC SYMPTOMS; PRIMARY-CARE; MAJOR DEPRESSION; SCALE; PREVALENCE; DISORDERS; SEROTONIN; ANXIETY; TRIAL; QUESTIONNAIRE AB Background: Depression is a chronic disease consisting of emotional/psychological and physical symptoms. Emotional symptoms have been shown to respond to currently available antidepressants; however, physical symptoms may not be as responsive. It was hypothesized that resolution of both psychological and physical symptoms of depression would predict a higher percentage of patients achieving remission. Method: Efficacy data were pooled from 2 identical, but independent, 9-week randomized, double-blind clinical trials of duloxetine 60 mg q.d. (N = 251) and placebo (N = 261). All patients met diagnostic criteria for DSM-IV major depressive disorder, which was confirmed by the Mini-International Neuropsychiatric Interview. Efficacy measures included the 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score, the HAM-D-17 Maier subscale, the Clinical Global Impressions-Severity of Illness (CGI-S) scale, the Patient Global Impression of Improvement (PGI-I) scale, the Somatic Symptom Inventory, the Quality of Life in Depression Scale, and Visual Analog Scales (VAS) for pain (overall pain, headaches, back pain, shoulder pain, interference with daily activities, and time in pain while awake). Results: Duloxetine-treated patients demonstrated significantly greater improvement in overall pain (p = .016), back pain (p = .002), and shoulder pain (p = .021) at week 9 compared with patients receiving placebo. When treatment effects were pooled over all visits, patients receiving duloxetine, 60 mg q.d., exhibited significantly greater improvement than placebo-treated patients in 5 of the 6 assessed VAS pain measures. Approximately 50% of the improvement in overall pain was independent of improvement in HAM-D-17 total score. Assuming the same level of improvement in core emotional symptoms of depression (Maier subscale), improvement in overall pain severity was associated with higher estimated probabilities of remission (p < .001). The week 9 means for VAS overall pain severity were 13.0 for remitters (last observed value for HAM-D-17 was less than or equal to 7) compared with 22.7 for nonremitters (p < .001), respectively, representing a greater than 3-fold improvement from baseline in remitters. The remission rate for pain responders (improvement in VAS overall pain from baseline to last observation greater than or equal to 50%) was twice that observed for pain nonresponders (36.2% vs. 17.8%, p < .001). Greater improvements in pain outcomes were associated with more favorable endpoint outcomes on the CGI-S and PGI-I scales. In addition, early favorable responses in VAS overall pain severity were associated with favorable endpoint outcomes. Conclusions: Treatment with duloxetine, 60 mg q.d., significantly reduced pain compared with placebo. Improvements in pain severity were attributable equally to the direct effect of duloxetine and to associated changes in depression severity. Improvement in painful physical symptoms was associated with higher remission rates even after accounting for improvement in core emotional symptoms. C1 Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. McLean Hosp, Belmont, MA 02178 USA. Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. RP Wohlreich, MM (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. EM mwmd@lilly.com NR 55 TC 139 Z9 144 U1 4 U2 10 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 APR PY 2004 VL 65 IS 4 BP 521 EP 530 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 831JL UT WOS:000222190600011 PM 15119915 ER PT J AU Papakostas, GI Petersen, TJ Iosifescu, DV Summergrad, P Sklarsky, KG Alpert, JE Nierenberg, AA Fava, M AF Papakostas, GI Petersen, TJ Iosifescu, DV Summergrad, P Sklarsky, KG Alpert, JE Nierenberg, AA Fava, M TI Somatic symptoms as predictors of time to onset of response to Fluoxetine in major depressive disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID COMPLAINTS; EFFICACY; SCALE; TRIAL; PAIN; CARE AB Objective: In the present study we assessed the relationship between somatic symptoms and the time to onset of clinical response to fluoxetine in patients with major depressive disorder (MDD). Method: 87 outpatients (mean age = 41.4 +/- 10.2 years; 59.8% women) with DSM-III-R MDD who had sustained acute response to fluoxetine completed the Symptom Questionnaire (SQ) at baseline. Onset of response was defined as a 30% decrease in the total score for the 17-item Hamilton Rating Scale for Depression that led to a 50% decrease by week 8. With the use of 2 separate multiple regressions, controlling for the severity of depression at baseline, we then assessed the relationship between the number of somatic symptoms as assessed by the SQ subscale for somatic symptoms (SQ-SS) and both the time to onset of clinical response and the time to clinical response. The study was conducted between November 1992 and January 1999. Results: A greater number of somatic symptoms at baseline predicted a greater amount of time to onset of clinical response to fluoxetine (p = .0233). The relationship between SQ-SS scores and time to response was not found to be statistically significant (p > .05). Conclusion: Somatic symptoms of depression were found to be associated with a delayed onset of antidepressant response to fluoxetine in MDD. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Depress Clin & Res Program, Boston, MA 02114 USA. RP Papakostas, GI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Depress Clin & Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R01 MH 48483-05] NR 20 TC 18 Z9 19 U1 2 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 2004 VL 65 IS 4 BP 543 EP 546 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 831JL UT WOS:000222190600014 PM 15119918 ER PT J AU Pande, AC Feltner, DE Jefferson, JW Davidson, JRT Pollack, M Stein, MB Lydiard, RB Futterer, R Robinson, P Slomkowski, M DuBoff, E Phelps, M Janney, CA Werth, JL AF Pande, AC Feltner, DE Jefferson, JW Davidson, JRT Pollack, M Stein, MB Lydiard, RB Futterer, R Robinson, P Slomkowski, M DuBoff, E Phelps, M Janney, CA Werth, JL TI Efficacy of the novel anxiolytic pregabalin in social anxiety disorder - A placebo-controlled, multicenter study SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID DOUBLE-BLIND; CONTROLLED TRIAL; RATING SCALE; SUBSTANCE-P; PHOBIA; GABAPENTIN; RELEASE; SLICES; CLONAZEPAM; INHIBITION AB Pregabalin is a novel compound in development for the treatment of anxiety disorders. The safety and efficacy of pregabalin for the treatment of social anxiety disorder was evaluated in a double-blind, multicenter clinical trial in which 135 patients were randomized to 10 weeks of double-blind treatment with either pregabalin 150 mg/d, pregabalin 600 mg/d, or placebo. The primary efficacy parameter was change from baseline to end point in the Liebowitz Social Anxiety Scale (LSAS) total score. Safety was assessed through clinical and laboratory monitoring, and recording spontaneously reported adverse events. Ninety-four patients (70%) completed the 11-week double-blind treatment phase. LSAS total score was significantly decreased by pregabalin 600 mg/d treatment compared with placebo (P = 0.024, analysis of covariance). Significant differences (P less than or equal to 0.05) between pregabalin 600 mg/d and placebo were seen on several secondary measures including the LSAS subscales of total fear, total avoidance, social fear, and social avoidance, and the Brief Social Phobia Scale fear subscale. Pregabalin 150 mg/d was not significantly better than placebo on any measures. Somnolence and dizziness were the most frequently occurring adverse events among patients receiving pregabalin 600 mg/d. In conclusion, pregabalin 600 mg/d was an effective and well-tolerated treatment of social anxiety disorder. C1 Pfizer Global Res & Dev, New London, CT 06320 USA. Madison Inst Med, Madison, WI USA. Duke Univ, Med Ctr, Dept Psychiat, Durham, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Med Univ S Carolina, Inst Psychiat, Charleston, SC 29425 USA. Dean Fdn Hlth, Res & Educ, Middleton, WI USA. Denver Ctr Med Res, Denver, CO USA. RP Pande, AC (reprint author), Pfizer Global Res & Dev, MS 6025,50 Pequot Ave, New London, CT 06320 USA. EM atul_pande@groton.pfizer.com NR 34 TC 131 Z9 136 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD APR PY 2004 VL 24 IS 2 BP 141 EP 149 DI 10.1097/01.jcp.0000117423.05703.e7 PG 9 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 804PK UT WOS:000220310400005 PM 15206660 ER PT J AU Spollen, JJ Wooten, RG Cargile, C Bartztokis, G AF Spollen, JJ Wooten, RG Cargile, C Bartztokis, G TI Prolactin levels and erectile function in patients treated with risperidone SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID CORPUS CAVERNOSUM PENIS; SEXUAL DYSFUNCTION; SCHIZOPHRENIC-PATIENTS; INTERNATIONAL INDEX; HYPERPROLACTINEMIA; OLANZAPINE; SCALE; MEN AB Treatment with risperidone is associated with prolactin (PRL) elevation, and PRL elevations are associated with erectile dysfunction (ED). We evaluated whether the PRL elevations caused by risperidone treatment of subjects with schizophrenia are associated with objective measures of erectile function. Subjects were hospitalized for 2 nights, and serum measurements of PRL, total testosterone, and free and weakly bound testosterone were performed in the morning and afternoon of each day. Risperidone levels, parent compound, and 9-hydroxy metabolite levels were drawn on the first day. Erectile function assessments, using the RigiScan, an instrument that measures nocturnal penile tumescence and rigidity, were performed on both nights. Consistent with previous reports, the correlation between total risperidone level and PRL was very high (r = 0.92, df = 12, P < 0.0001), but risperidone did not appear to affect either testosterone (r = 0.29, df = 5, P = 0.51) or free and weakly bound testosterone (r = -0.11, df = 10, P = 0.72). Contrary to expectations, PRL levels from the second night were positively correlated with erectile function (r = 0.68, df = 9, P = 0.022). Using objective measures, we were unable to confirm a detrimental association between PRL levels and male erectile function. These results are tentative given the small sample. C1 Cent Arkansas Vet Hlth Syst, N Little Rock, AR 72114 USA. Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. Greater Los Angeles Vet Hlth Syst, N Little Rock, VA USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. RP Spollen, JJ (reprint author), Cent Arkansas Vet Hlth Syst, 2200 Ft Roots Dr,116-F2, N Little Rock, AR 72114 USA. EM John.Spollen@med.va.gov NR 31 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD APR PY 2004 VL 24 IS 2 BP 161 EP 166 DI 10.1097/01.jcp.0000115664.45074.44 PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 804PK UT WOS:000220310400008 PM 15206663 ER PT J AU O'Farrell, TJ Murphy, CM Stephan, SH Fals-Stewart, W Murphy, M AF O'Farrell, TJ Murphy, CM Stephan, SH Fals-Stewart, W Murphy, M TI Partner violence before and after couples-based alcoholism treatment for male alcoholic patients: The role of treatment involvement and abstinence SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID RELAPSE PREVENTION SESSIONS; BEHAVIORAL MARITAL-THERAPY; TIMELINE FOLLOWBACK; DOMESTIC VIOLENCE; DRUG-ABUSE; AGGRESSION; CONFLICT; SCALES; RELIABILITY; DEPENDENCE AB This study examined partner violence before and after behavioral couples therapy (BCT) for 303 married or cohabiting male alcoholic patients and used a demographically matched nonalcoholic comparison sample. In the year before BCT, 60% of alcoholic patients had been violent toward their female partner, 5 times the comparison sample rate of 12%. In the 1st and 2nd year after BCT, violence decreased significantly from the year before BCT, and clinically significant violence reductions occurred for patients whose alcoholism was remitted after BCT. Structural equation modeling indicated that greater treatment involvement (attending BCT sessions and using BCT-targeted behaviors) was related to lower violence after BCT and that this association was mediated by reduced problem drinking and enhanced relationship functioning. C1 Harvard Univ, Sch Med, Families & Addict Program, VA Boston Healthcare Syst,Dept Psychiat,VAMC, Brockton, MA 02301 USA. Univ Maryland, Dept Psychol, Baltimore, MD 21201 USA. SUNY Buffalo, Res Inst Addict, Buffalo, NY 14260 USA. RP O'Farrell, TJ (reprint author), Harvard Univ, Sch Med, Families & Addict Program, VA Boston Healthcare Syst,Dept Psychiat,VAMC, 116B1,940 Belmont St, Brockton, MA 02301 USA. EM timothy_ofarrell@hms.harvard.edu FU NIAAA NIH HHS [AA10356, AA08637, AA10796, K02AA0234, R21AA12433] NR 54 TC 109 Z9 109 U1 1 U2 14 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD APR PY 2004 VL 72 IS 2 BP 202 EP 217 DI 10.1037/0022-006X.72.2.202 PG 16 WC Psychology, Clinical SC Psychology GA 806OE UT WOS:000220442400006 PM 15065955 ER PT J AU Taft, CT Murphy, CM Musser, PH Remington, NA AF Taft, CT Murphy, CM Musser, PH Remington, NA TI Personality, interpersonal, and motivational predictors of the working alliance in group cognitive-behavioral therapy for partner violent men SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID BATTERER PROGRAM PARTICIPANTS; CONSTRUCT-VALIDITY; INVENTORY; PSYCHOPATHY; CIRCUMPLEX; ATTENDANCE; VALIDATION; DISORDER; TYPOLOGY AB Recent studies have demonstrated that the working alliance predicts treatment outcome for partner violent men. This study examined the influence of personality and interpersonal characteristics, motivational readiness to change, and demographic factors on working alliance formation among a sample of men (N = 107) participating in a cognitive-behavioral group treatment program for partner violence. Motivational readiness to change was the strongest predictor of the working alliance. Psychopathic personality characteristics also emerged as a strong (negative) predictor of the working alliance. Lower levels of borderline personality characteristics and interpersonal problems, self-referred status, married status, and higher age and income predicted higher working alliance ratings. The results support recent clinical efforts to address motivational readiness in programs for partner violent men. C1 VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA 02130 USA. Boston Univ, Dept Psychiat, Sch Med, Boston, MA 02215 USA. Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21228 USA. RP Taft, CT (reprint author), VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, 116B-2,150 S Huntington Ave, Boston, MA 02130 USA. EM casey.taft@med.va.gov FU NIMH NIH HHS [1R03MH56373, 1F31MH12234] NR 46 TC 49 Z9 53 U1 1 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD APR PY 2004 VL 72 IS 2 BP 349 EP 354 DI 10.1037/0022-006X.72.2.349 PG 6 WC Psychology, Clinical SC Psychology GA 806OE UT WOS:000220442400018 PM 15065967 ER PT J AU Zembowicz, A Mastalerz, L Setkowicz, M Radziszewski, W Szczeklik, A AF Zembowicz, A Mastalerz, L Setkowicz, M Radziszewski, W Szczeklik, A TI Histological spectrum of cutaneous reactions to aspirin in chronic idiopathic urticaria SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID DRUG-REACTIONS; CLASSIFICATION AB Background: During a clinical trial, we obtained 16 biopsies of skin eruptions induced by aspirin in patients with chronic idiopathic urticaria (CIU). In this setting, aspirin triggers skin eruptions through a well-established non-immunological mechanism involving the inhibition of cyclooxygenase type I. This presented the rare opportunity to evaluate histological features of a series of skin eruptions induced by a drug acting through a defined mechanism in a controlled experimantal setting. Objective: Histological analysis of 16 biopsies of skin eruptions induced by oral aspirin challenge in patients with CIU. Design: Microscopic analysis of tissue sections. Patients: 16 patients with CIU. Results: Aspirin (up to 500 mg) induced a restricted range of histological responses with a classic pattern of urticarial tissue reaction occuring in the majority of (12 of 16) cases. Two biopsies showed an interstitial fibrohistiocytic (granuloma annulare-like) reaction pattern. One case showed only a sparse perivascular lymphocytic infiltrate, and paucicellular dermal mucinosis was observed in one case. Conclusions: Polymorphism of histological patterns induced by aspirin suggests that in addition to the drug-specific mechanisms triggering drug eruptions, individual factors also play a role in determining the ultimate histological phenotype of a drug response. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Jagiellonian Univ, Sch Med, Dept Med, Krakow, Poland. Merck Sharp & Dohme Idea, Warsaw, Poland. RP Zembowicz, A (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 820,55 Fruit St, Boston, MA 02114 USA. EM azembowicz@partners.org NR 20 TC 7 Z9 8 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 APR PY 2004 VL 31 IS 4 BP 323 EP 329 DI 10.1111/j.0303-6987.2004.0195.x PG 7 WC Dermatology; Pathology SC Dermatology; Pathology GA 801MC UT WOS:000220099000006 PM 15005690 ER PT J AU Thomsen, TW Brown, DFM Nadel, ES AF Thomsen, TW Brown, DFM Nadel, ES TI Blunt renal trauma SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID NONOPERATIVE TREATMENT; INJURY; MANAGEMENT; EXPERIENCE C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Affiliated Emergency Med Residency, Boston, MA USA. Mt Auburn Hosp, Dept Emergency Med, Cambridge, MA USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Bulfinch 105, Boston, MA 02114 USA. NR 13 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD APR PY 2004 VL 26 IS 3 BP 331 EP 337 DI 10.1016/j.jemermed.2003.12.012 PG 7 WC Emergency Medicine SC Emergency Medicine GA 805MN UT WOS:000220370500013 PM 15028334 ER PT J AU Chun, LB Liddicoat, RV AF Chun, LB Liddicoat, RV TI Altered mental status and an abdominal mass. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 34 EP 34 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800051 ER PT J AU Woo, HE Fung, CH AF Woo, HE Fung, CH TI Nontuberculous Mycobacterium as a cause of bursitis. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Univ Calif Los Angeles, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 64 EP 64 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800170 ER PT J AU Goroll, A Bass, EB Kuzma, M Defer, T AF Goroll, A Bass, EB Kuzma, M Defer, T TI Proposed competency prerequisites for entering the core clinical clerkships. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Drexel Univ, Philadelphia, PA 19104 USA. Washington Univ, St Louis, MO 63130 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 93 EP 94 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800298 ER PT J AU Green, AR Betancourt, JR Grainger-Monsen, M AF Green, AR Betancourt, JR Grainger-Monsen, M TI "Worlds apart": Using documentary films to teach cross-cultural health care. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Stanford Univ, Palo Alto, CA 94304 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 99 EP 99 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800322 ER PT J AU Lester, WT Grant, RW Chueh, HC AF Lester, WT Grant, RW Chueh, HC TI Guidelines vs. reality: Physician explanations for not adjusting cholesterol therapy. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 105 EP 105 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800345 ER PT J AU Shea, SJ Weinstock, RS Starren, J Teresi, J AF Shea, SJ Weinstock, RS Starren, J Teresi, J TI A randomized trial comparing telemedicine case management with usual care in older patients with diabetes mellitus. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Columbia Univ, New York, NY 10027 USA. SUNY Upstate Med Univ, Joslin Diabet Ctr, Syracuse, NY USA. Hebrew Home Aged, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 112 EP 112 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800375 ER PT J AU Shrank, WH Kravitz, R Ettner, S Glassman, PA Young, HN Asch, SM AF Shrank, WH Kravitz, R Ettner, S Glassman, PA Young, HN Asch, SM TI Are the incentives in incentive-based pharmaceutical benefit plans operating as intended? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90024 USA. Univ Calif Davis, Sacramento, CA 95817 USA. RAND Corp, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 120 EP 120 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800409 ER PT J AU Williams, E Kivlahan, D Saitz, R Merrill, J Bradley, K AF Williams, E Kivlahan, D Saitz, R Merrill, J Bradley, K TI Are primary care patients with at-risk drinking ready to change? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Univ Washington, Seattle, WA 98195 USA. Boston Univ, Boston, MA 02215 USA. VA Puget Sound, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 120 EP 120 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800407 ER PT J AU Ngo-Metzger, Q Massagli, M Clarridge, B Sorkin, D Phillips, RS AF Ngo-Metzger, Q Massagli, M Clarridge, B Sorkin, D Phillips, RS TI Asian Americans' health care experiences and ratings: Differences between Vietnamese and Chinese immigrants. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Univ Calif Irvine, Irvine, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Massachusetts, Boston, MA 02125 USA. Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 121 EP 121 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800411 ER PT J AU Lasser, KE Seger, DL Yu, T Fiskio, J Seger, AC Karson, AS Bates, DW AF Lasser, KE Seger, DL Yu, T Fiskio, J Seger, AC Karson, AS Bates, DW TI Assessing the frequency of failure to adhere to black-box warnings in outpatients. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Harvard Univ, Sch Med, Cambridge Hlth Alliance, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Partners Healthcare Syst, Wellesley, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 122 EP 122 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800415 ER PT J AU Morrill, JA Shrestha, M Grant, RW AF Morrill, JA Shrestha, M Grant, RW TI Barriers to the treatment of hepatitis C infection: Patient, provider, and system factors. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Massachusetts Gen Hosp, Revere Healthcare Ctr, Boston, MA 02114 USA. Partners Healthcare, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 125 EP 125 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800429 ER PT J AU Gurmankin, A Volpp, K AF Gurmankin, A Volpp, K TI Beliefs about smoking risks, intentions to quit and enrollment in a smoking cessation program. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Rutgers State Univ, New Brunswick, NJ 08903 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 126 EP 126 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800431 ER PT J AU Corson, K Gerrity, M Dobscha, S AF Corson, K Gerrity, M Dobscha, S TI Brief screens for depression and suicidality in primary care: Two items are better than one. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 127 EP 127 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800436 ER PT J AU Sussman, JB Jain, S Jha, AK Luck, J Peabody, JW AF Sussman, JB Jain, S Jha, AK Luck, J Peabody, JW TI Clinical vignettes to examine the effect of fatigue on quality of care. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 130 EP 131 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800451 ER PT J AU Bean-Mayberry, BA Chang, CH McNeil, MA Hayes, PM Scholle, SH AF Bean-Mayberry, BA Chang, CH McNeil, MA Hayes, PM Scholle, SH TI Comprehensive care for women veterans: Indicators of dual use of VA and non-VA providers. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. Natl Comm Qual Assurance, Washington, DC USA. VA Pittsburgh Healthcare Syst, VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 131 EP 131 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800455 ER PT J AU Lorenz, K Ryan, G Chan, K Morton, SC Shekelle, PG AF Lorenz, K Ryan, G Chan, K Morton, SC Shekelle, PG TI Comparing primary care clinician and physician managers uses and views' of evidence. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RAND Corp, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 131 EP 131 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800453 ER PT J AU Thorndike, AN Rigotti, NA Regan, S Swartz, S Pasternak, R Chang, Y Emmons, KM Singer, DE AF Thorndike, AN Rigotti, NA Regan, S Swartz, S Pasternak, R Chang, Y Emmons, KM Singer, DE TI Depression and relapse to smoking in patients hospitalized with acute cardiovascular disease. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Maine Med Ctr, Portland, ME 04102 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 135 EP 136 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800472 ER PT J AU Vargas, RB Mangione, CM Keesey, J Asch, S Schonlau, M Keeler, E AF Vargas, RB Mangione, CM Keesey, J Asch, S Schonlau, M Keeler, E TI Do collaborative quality improvement programs reduce cardiovascular risk for persons with diabetes? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA USA. W Los Angeles Vet Adm, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 142 EP 142 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800500 ER PT J AU Gopal, R Glasheen, JJ Miyoshi, TJ Prochazka, A AF Gopal, R Glasheen, JJ Miyoshi, TJ Prochazka, A TI Does personality hardiness protect against resident burnout? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Denver VAMC, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Denver VA, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 145 EP 145 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800511 ER PT J AU Grant, RW Wong, N Singer, DE AF Grant, RW Wong, N Singer, DE TI Does poor medication adherence predict increases in anti-hypertensive therapy? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 145 EP 145 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800512 ER PT J AU Ortiz, E Surks, M Daniels, G Sawin, C Col, N AF Ortiz, E Surks, M Daniels, G Sawin, C Col, N TI Evidence review: Diagnosis and management of subclinical thyroid disease. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 AHRQ, Rockville, MD USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Vet Adm, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 151 EP 151 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800537 ER PT J AU Stafford, RS O'Leary, KM Finkelstein, SN Weilburg, JB AF Stafford, RS O'Leary, KM Finkelstein, SN Weilburg, JB TI Health care costs before and after antidepressant initiation: Does adequate treatment reduce costs? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Stanford Prevent Res Ctr, Program Prevent Outcomes & Practices, Stanford, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 156 EP 156 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800557 ER PT J AU Hofer, TP Asch, S Hayward, RA Hogan, MM Rubenstein, LV Adams, JL Kerr, EM AF Hofer, TP Asch, S Hayward, RA Hogan, MM Rubenstein, LV Adams, JL Kerr, EM TI How many reviews do you need? Measuring the quality of care at clinic sites with implicit physician review. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Univ Michigan, Ann Arbor, MI 48109 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Ann Arbor VAMC Ctr Practice Management & Outcomes, Ann Arbor, MI USA. RAND Corp, Sepulveda, CA USA. RAND Corp, Santa Monica, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 160 EP 160 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800575 ER PT J AU Murff, H Syngal, S AF Murff, H Syngal, S TI Identification of individuals at high-risk for inherited colon or breast cancer syndromes in primary care: Implications of an inadequate family history assessment for early screening and genetic testing. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Tennessee Valley Healthcare Syst, Dept Vet Affairs, Nashville, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 161 EP 162 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800581 ER PT J AU Conroy, M Cook, N Buring, JE Lee, I AF Conroy, M Cook, N Buring, JE Lee, I TI Impact of past physical activity on current physical activity and risk of coronary heart disease. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 164 EP 164 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800591 ER PT J AU Friedman, J Vazirani, S Tillisch, J Wenger, NS AF Friedman, J Vazirani, S Tillisch, J Wenger, NS TI Improving medical resident fatigue may require more than work hour limits. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 166 EP 166 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800601 ER PT J AU Gerrity, MS Williams, JW Dobscha, SK Deveau, J Holsinger, T Gaynes, BN Moser, BK Dietrich, AJ AF Gerrity, MS Williams, JW Dobscha, SK Deveau, J Holsinger, T Gaynes, BN Moser, BK Dietrich, AJ TI Improving depression care: Systematic review of multifaceted interventions in primary care settings. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Portland VA Med Ctr, Portland, OR USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Dartmouth Coll Sch Med, Hanover, NH USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 0 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 166 EP 166 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800600 ER PT J AU Sherman, SE Takahashi, N Kalra, P Kuschner, W Canfield, J Gifford, E Kelly, J Finney, J AF Sherman, SE Takahashi, N Kalra, P Kuschner, W Canfield, J Gifford, E Kelly, J Finney, J TI Increasing referrals to telephone counseling for smoking cessation. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. VA Palo Alto Healthcare Syst, Palo Alto, CA USA. Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 167 EP 168 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800607 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 Intensity and quantity of physical activity and the risk of diabetes in women. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Boston VA Healthcare Syst, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 169 EP 169 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800613 ER PT J AU Long, JA Metlay, JP AF Long, JA Metlay, JP TI Meeting the mandate to care for low-income veterans. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 179 EP 180 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800659 ER PT J AU Liddicoat, RV Losina, E Kang, M Freedberg, KA Walensky, RP AF Liddicoat, RV Losina, E Kang, M Freedberg, KA Walensky, RP TI Missed opportunities: Refusers of routine HIV testing in an urgent care setting. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 181 EP 181 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800664 ER PT J AU Haidet, P Kroll, T Sharf, B AF Haidet, P Kroll, T Sharf, B TI Patients' illness narratives: The meaning of active participation in health decisions. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Baylor Coll Med, Houston VA Med Ctr, Houston, TX 77030 USA. Texas A&M Univ, College Stn, TX 77843 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 188 EP 188 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800696 ER PT J AU Chan, EC Barry, MJ Vernon, SW Ahn, CW AF Chan, EC Barry, MJ Vernon, SW Ahn, CW TI Physicians and their personal prostate cancer screening practices with prostate specific antigen. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Univ Texas, Sch Med, Div Gen Internal Med, Houston, TX USA. Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. Univ Texas, Sch Publ Hlth, Ctr Hlth Promot & Prevent, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 192 EP 192 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800711 ER PT J AU Takahashi, TA Binswanger, I Baernstein, A Merrill, JO Bradley, KA AF Takahashi, TA Binswanger, I Baernstein, A Merrill, JO Bradley, KA TI Predictors of hospitalization for injection drug users with soft tissue infections. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 195 EP 195 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800724 ER PT J AU Park, ER Betancourt, J Kim, M Maina, A Weissman, J AF Park, ER Betancourt, J Kim, M Maina, A Weissman, J TI Preparedness of resident physicians to deliver cross-cultural care: A qualitative study. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 196 EP 197 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800730 ER PT J AU Singhal, R Chan, AY Eidem, E AF Singhal, R Chan, AY Eidem, E TI Providing preventive health care to low income uninsured women using a community partnered mobile van program. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA USA. Los Angeles Cty Dept Hlth Serv, Data Collect & Anal Unit, Los Angeles, CA USA. Los Angeles Cty Dept Hlth Serv, Off Womens Hlth, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 200 EP 200 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800744 ER PT J AU Ibrahim, S Stone, R Han, X Khuri, S Henderson, W Kwoh, K AF Ibrahim, S Stone, R Han, X Khuri, S Henderson, W Kwoh, K TI Race/ethnicity-specific mortality and complication rates after knee replacement. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Vet Adm, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. VA Boston Healthcare Syst, W Roxbury, MA USA. Univ Colorado, Aurora, CO USA. NR 0 TC 0 Z9 0 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 APR PY 2004 VL 19 SU 1 BP 201 EP 202 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800752 ER PT J AU Rehman, SU Egan, BM Hutchison, FN AF Rehman, SU Egan, BM Hutchison, FN TI Racial differences in blood pressure control rates in the VA Medical Center. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Med Univ S, Ralph H Johnson VA Med Ctr, Mt Pleasant, MI USA. Med Univ S Carolina, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 202 EP 202 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800753 ER PT J AU Haidet, P O'Malley, K Cooper, LA Street, RL AF Haidet, P O'Malley, K Cooper, LA Street, RL TI Redefining concordance: Patients' perceptions of relational similarity. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Baylor Coll Med, Houston VA Med Ctr, Houston, TX 77030 USA. Pearson Educ Measurement, Austin, TX USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Texas A&M Univ, College Stn, TX 77843 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 204 EP 204 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800763 ER PT J AU Kast, D Prochazka, A Miyoshi, TJ Bublitz, C Oboler, SK Fryer, GE Anderson, RJ AF Kast, D Prochazka, A Miyoshi, TJ Bublitz, C Oboler, SK Fryer, GE Anderson, RJ TI The annual physical examination: Estimates from the National Ambulatory Medical Care Survey. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Denver VA, Denver, CO USA. Denver VAMC, Denver, CO USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 214 EP 214 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800806 ER PT J AU Mortensen, E Restrepo, M Anzueto, A Pugh, J AF Mortensen, E Restrepo, M Anzueto, A Pugh, J TI The association between statin and ACE inhibitor use and mortality for patients hospitalized with community-acquired pneumonia. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 215 EP 215 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800809 ER PT J AU Seshamani, M Volpp, KG AF Seshamani, M Volpp, KG TI The effect of cuts in Medicare reimbursement on quality of hospital care. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 APR PY 2004 VL 19 SU 1 BP 216 EP 217 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800816 ER PT J AU Volpp, KG Gurmankin, A Asch, DA Murphy, JJ Gomez, A Sox, HC Lerman, C AF Volpp, KG Gurmankin, A Asch, DA Murphy, JJ Gomez, A Sox, HC Lerman, C TI The effect of financial incentives on smoking cessation program attendance and completion. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Annals Internal Med, Philadelphia, PA USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 217 EP 217 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800819 ER PT J AU Thorndike, AN Rigotti, NA Regan, S Swartz, S Torres-Finnerty, N Pasternak, R Chang, Y Emmons, KM Singer, DE AF Thorndike, AN Rigotti, NA Regan, S Swartz, S Torres-Finnerty, N Pasternak, R Chang, Y Emmons, KM Singer, DE TI The efficacy and safety of bupropion SR in smokers hospitalized with acute cardiovascular disease: A randomized controlled trial. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Maine Med Ctr, Portland, ME 04102 USA. Boston Med Ctr, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 218 EP 219 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800825 ER PT J AU Mangrulkar, RS Lencoski, K Gerrity, M Hayward, RS Straus, S AF Mangrulkar, RS Lencoski, K Gerrity, M Hayward, RS Straus, S CA T SGIM EBM Task Force TI The impact of a series of workshops to improve evidence based clinical practice. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Univ Michigan, Ann Arbor, MI 48109 USA. SGIM, Washington, DC USA. Portland VA Med Ctr, Portland, OR USA. Univ Alberta, Edmonton, AB T6G 2M7, Canada. Univ Toronto, Toronto, ON, Canada. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 219 EP 219 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800829 ER PT J AU Sequist, TD Gandhi, TK Karson, AS Fiskio, J Sperling, M Bugbee, D Bates, DW AF Sequist, TD Gandhi, TK Karson, AS Fiskio, J Sperling, M Bugbee, D Bates, DW TI The impact of an electronic clinical reminder system on quality of care. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 APR PY 2004 VL 19 SU 1 BP 219 EP 220 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800830 ER PT J AU Garibaldi, KL Gibson, RW Reiss, J Villarreal, GB Haidet, P AF Garibaldi, KL Gibson, RW Reiss, J Villarreal, GB Haidet, P TI Transition from pediatric to adult healthcare: The experiences of young adults with spina bifida. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Baylor Coll Med, Houston, TX 77030 USA. Univ Florida, Gainesville, FL 32611 USA. Houston VA Med Ctr, Houston, TX USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 229 EP 229 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800869 ER PT J AU Diamant, AL Hays, RD Asch, S Dyer, I Gelberg, L AF Diamant, AL Hays, RD Asch, S Dyer, I Gelberg, L TI Unmet need for dental care in a publicly funded system of health care. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 Univ Calif Los Angeles, Los Angeles, CA 90024 USA. W Los Angeles Vet Adm, Los Angeles, CA USA. Los Angeles Cty Dept Hlth Serv, Los Angeles, CA USA. RI Hays, Ronald/D-5629-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 231 EP 231 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800878 ER PT J AU Fung, CH Woods, JN Asch, S Glassman, PA Doebbeling, BN AF Fung, CH Woods, JN Asch, S Glassman, PA Doebbeling, BN TI Variation in the use of computerized clinical reminders in an integrated national delivery system. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Iowa, Iowa City, IA 52242 USA. Indiana Univ Purdue Univ, Indianapolis, IN 46202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2004 VL 19 SU 1 BP 235 EP 235 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816RA UT WOS:000221125800895 ER PT J AU Liddicoat, RV Horton, NJ Urban, R Maier, E Christiansen, D Samet, JH AF Liddicoat, RV Horton, NJ Urban, R Maier, E Christiansen, D Samet, JH TI Assessing missed opportunities for HIV testing in medical settings SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE multiple informants; delay; HIV screening; AIDS; risk factors ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONGITUDINAL DATA-ANALYSIS; RISK BEHAVIORS; PRIMARY-CARE; INFECTION; ANTIBODY; TIME; AIDS; INDIVIDUALS; PREVENTION AB BACKGROUND: Many HIV-infected persons learn about their diagnosis years after initial infection. The extent to which missed opportunities for HIV testing occur in medical evaluations prior to one's HIV diagnosis is not known. DESIGN: We performed a 10-year retrospective chart review of patients seen at an HIV intake clinic between January 1994 and June 2001 who 1) tested positive for HIV during the 12 months prior to their presentation at the intake clinic and 2) had at least one encounter recorded in the medical record prior to their HIV-positive status. Data collection included demographics, clinical presentation, and whether HIV testing was recommended to the patient or addressed in any way in the clinical note. Prespecified triggers for physicians to recommend HIV testing, such as specific patient characteristics, symptoms, and physical findings, were recorded for each visit. Multivariable logistic regression was used to identify factors associated with missed opportunities for discussion of HIV testing. Generalized estimating equations were used to account for multiple visits per subject. RESULTS: Among the 221 patients meeting eligibility criteria, all had triggers for HIV testing found in an encounter note. Triggers were found in 50% (1,702/3,424) of these 221 patients' medical visits. The median number of visits per patient prior to HIV diagnosis to this single institution was 5; 40% of these visits were to either the emergency department or urgent care clinic. HIV was addressed in 27% of visits in which triggers were identified. The multivariable regression model indicated that patients were more likely to have testing addressed in urgent care clinic (39%), sexually transmitted disease clinic (78%), primary care clinics (32%), and during hospitalization (47%), compared to the emergency department (11%), obstetrics/gynecology (9%), and other specialty clinics (10%) (P < .0001). More recent clinical visits (1997-2001) were more likely to have HIV addressed than earlier visits (P < .0001). Women were offered testing less often than men (P = .07). CONCLUSIONS: Missed opportunities for addressing HIV testing remain unacceptably high when patients seek medical care in the period before their HIV diagnosis. Despite improvement in recent years, variation by site of care remained important. In particular, the emergency department merits consideration for increased resource commitment to facilitate HIV testing. In order to detect HIV infection prior to advanced immunosuppression, clinicians must become more aware of clinical triggers that suggest a patient's increased risk for this infection and lower the threshold at which HIV testing is recommended. C1 Boston Univ, Sch Med, Dept Med, Boston Med Ctr,Sect Gen Internal Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Med, Clin Addict Res & Educ Unit, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Med, Clin AIDS Program, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Social & Behav Sci, Boston, MA 02118 USA. Boston Univ, Sch Med, Data Coordinating Ctr, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. Smith Coll, Dept Math, Northampton, MA 01063 USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. RP Samet, JH (reprint author), Boston Univ, Sch Med, Dept Med, Boston Med Ctr,Sect Gen Internal Med, 91 E Concord St,Suite 200, Boston, MA 02118 USA. EM jsamet@bu.edu RI Horton, Nicholas/A-2493-2008; OI Horton, Nicholas/0000-0003-3332-4311 FU NCRR NIH HHS [M01 RR000533, M01-RR00533]; NIMH NIH HHS [R01-MH54693, R01 MH054693] NR 35 TC 111 Z9 117 U1 1 U2 6 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 APR PY 2004 VL 19 IS 4 BP 349 EP 356 DI 10.1111/j.1525-1497.2004.21251.x PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 808CC UT WOS:000220546200008 PM 15061744 ER PT J AU Shekelle, PG Morton, SC Jungvig, LK Udani, J Spar, M Tu, WL Suttorp, MJ Coulter, I Newberry, SJ Hardy, M AF Shekelle, PG Morton, SC Jungvig, LK Udani, J Spar, M Tu, WL Suttorp, MJ Coulter, I Newberry, SJ Hardy, M TI Effect of supplemental vitamin E for the prevention and treatment of cardiovascular disease SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review DE vitamin E; antioxidants; meta-analysis; systematic review; cardiovascular disease ID BETA-CAROTENE SUPPLEMENTS; PLACEBO-CONTROLLED TRIAL; CORONARY-HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED CONTROLLED TRIAL; ANTIOXIDANT VITAMINS; ALPHA-TOCOPHEROL; CLINICAL-TRIALS; ANGINA-PECTORIS; RISK AB OBJECTIVE: To evaluate and synthesize the evidence on the effect of supplements of vitamin E on the prevention and treatment of cardiovascular disease. DESIGN: Systematic review of placebo-controlled randomized controlled trials; meta-analysis where justified. MEASUREMENTS AND MAIN RESULTS: Eighty-four eligible trials were identified. For the outcomes of all-cause mortality, cardiovascular mortality, fatal or nonfatal myocardial infarction, and blood lipids, neither supplements of vitamin E alone nor vitamin E given with other agents yielded a statistically significant beneficial or adverse pooled relative risk (for example, pooled relative risk of vitamin E alone = 0.96 [95% confidence interval (CI), 0.84 to 1.10]; 0.97 [95% CI, 0.80 to 1.90]; and 0.72 [95% CI, 0.51 to 1.02] for all-cause mortality, cardiovascular mortality, and nonfatal myocardial infarction, respectively. CONCLUSIONS: There is good evidence that vitamin E supplementation does not beneficially or adversely affect cardiovascular outcomes. C1 RAND Corp, So Calif Evidence Based Practice Ctr, Santa Monica, CA 90407 USA. Northridge Hosp Integrat Med Program, Los Angeles, CA USA. Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Shekelle, PG (reprint author), RAND Corp, So Calif Evidence Based Practice Ctr, 1700 Main St,POB 2138, Santa Monica, CA 90407 USA. EM shekelle@rand.org NR 51 TC 85 Z9 86 U1 1 U2 4 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 APR PY 2004 VL 19 IS 4 BP 380 EP U49 PG 49 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 808CC UT WOS:000220546200012 PM 15061748 ER PT J AU Timm, J Lauer, GM Kim, AY Ouchi, K Gandhi, RT Chung, RT Walker, BD Allen, TM AF Timm, J Lauer, GM Kim, AY Ouchi, K Gandhi, RT Chung, RT Walker, BD Allen, TM TI Longitudinal full length sequencing reveals mutations consistent with selective immune pressures by CTL SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 39th Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 14-18, 2004 CL Berlin, GERMANY SP European Assoc Study Liver C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA USA. Massachusetts Gen Hosp, Dept Gastroenterol & Hepatol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2004 VL 40 SU 1 MA 418 BP 124 EP 124 DI 10.1016/S0168-8278(04)90418-7 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 814BS UT WOS:000220950800419 ER PT J AU Rodriguez-Torres, M Torriani, FJ Lissen, E Brau, N Sulkowski, M Sola, R Clotet, B Clumeck, N Cooper, D Dieterich, D AF Rodriguez-Torres, M Torriani, FJ Lissen, E Brau, N Sulkowski, M Sola, R Clotet, B Clumeck, N Cooper, D Dieterich, D TI Early prediction of sustained virological response (SVR) during treatment with peginterferon alfa-2a (40KD) (PEGASYS (R)) plus ribavirin (RBV) (COPEGUS (R)) in patients with HCV/HIV co-infection: Results from the AIDS PEGASYS ribavirin international co-infectio SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 39th Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 14-18, 2004 CL Berlin, GERMANY SP European Assoc Study Liver C1 Fdn Invest De Diego, Santurce, PR USA. Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. Virgen Del Rocio Univ Hosp, Seville, Spain. Bronx Vet Adm Med Ctr, Bronx, NY USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Rovira & Virgili Univ, Reus, Spain. Hosp Germans Trias & Pujol, Barcelona, Spain. CHU St Pierre, Brussels, Belgium. Univ New S Wales, Sydney, NSW, Australia. Mt Sinai Sch Med, New York, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2004 VL 40 SU 1 MA 507 BP 149 EP 149 DI 10.1016/S0168-8278(04)90507-7 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 814BS UT WOS:000220950800508 ER PT J AU Siebert, U Sroczynski, G Rossol, S Aidelsburger, P Conrads-Frank, A Wong, JB Wasem, J AF Siebert, U Sroczynski, G Rossol, S Aidelsburger, P Conrads-Frank, A Wong, JB Wasem, J TI Cost-effectiveness of peginterferon plus ribavirin in a real-world population of patients with chronic hepatitis C and associated comorbidities SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 39th Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 14-18, 2004 CL Berlin, GERMANY SP European Assoc Study Liver C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. Univ Munich, Bavarian Publ Hlth Res & Coordinating Ctr, Munich, Germany. Univ Mainz, Gen Hosp Ruesselsheim, Dept Internal Med, Russelsheim, Germany. Univ Duisburg Essen, Alfired Krupp Von Bohlen & Halbach Chair Med Mana, Essen, Germany. Tufts Univ, Sch Med, Tufts New England Med Ctr, Boston, MA 02111 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 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2004 VL 40 SU 1 MA 515 BP 152 EP 152 DI 10.1016/S0168-8278(04)90515-6 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 814BS UT WOS:000220950800516 ER PT J AU Yang, SX Haluska, FG AF Yang, SX Haluska, FG TI Treatment of melanoma with 5-fluorouracil or dacarbazine in vitro sensitizes cells to antigen-specific CTL lysis through perforin/granzyme- and Fas-mediated pathways SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOLYTIC T-LYMPHOCYTES; DRUG-INDUCED APOPTOSIS; APO-1/FAS RECEPTOR/LIGAND SYSTEM; TUMOR-INFILTRATING LYMPHOCYTES; LIGAND-INDUCED APOPTOSIS; HUMAN GENE MAGE-3; DENDRITIC CELLS; METASTATIC MELANOMA; DNA FRAGMENTATION; ANTICANCER DRUGS AB Several factors may influence sensitivity of melanoma cells to CTL lysis. One is the avidity of the CTL TCR. A second is that certain cytotoxic drugs have been reported to sensitize cancer cells to CTL lysis through Fas-mediated apoptosis. In this study, we examined whether antineoplastic agents 5-fluorouracil (5-FU) and dacarbazine (DTIC) sensitize melanoma cells to lysis of 6209 peptide-specific CTL. Our results show that CTL generated from PBMC are HLA-A2 restricted and gp100 specific. Treatment with 5-FU or DTIC sensitized melanoma cells to lysis of 6209-specific CTL. Most importantly, 5-FU- or DTIC-treated melanoma cells also became sensitive to low-avidity CTL, which per se are less cytolytic to melanomas. We sought to identify apoptotic pathways mediating this effect. The enhanced cytolysis was mediated through the perforin/granzyme pathway. Although 5-FU up-regulated FasR expression on melanoma cells, sensitization was not blocked by anti-Fas Ab, and the 6209-specific CTL was Fas ligand (FasL) negative. However, when 6209-specific CTL were stimulated to express FasL, FasL signaling also contributed to enhanced cytolysis. DTIC treatment, which did not increase FasR expression, also sensitized FasL-mediated killing induced by neutralizing anti-Fas Ab. For CD95L-positive 6209-specific CTL, the sensitization was primarily mediated through the perforin/ granzyme pathway regardless of up-regulation of FasR. The findings demonstrate that cytotoxic drug-mediated sensitization primes both perforin/granzyme and Fas-mediated killing by melanoma-specific CTL. Considering that most of autoreactive antitumor CTL are low avidity, the findings provide experimental basis for understanding cytotoxic and immunologic therapeutic synergy in melanoma. C1 Massachusetts Gen Hosp, Hematol Oncol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Haluska, FG (reprint author), Massachusetts Gen Hosp, Hematol Oncol Unit, Jackson Bldg,GRJ 1021,55 Fruit St, Boston, MA 02114 USA. EM haluska.frank@mgh.harvard.edu NR 62 TC 44 Z9 47 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 APR 1 PY 2004 VL 172 IS 7 BP 4599 EP 4608 PG 10 WC Immunology SC Immunology GA 829TO UT WOS:000222072900071 PM 15034078 ER PT J AU Weinberg, AN AF Weinberg, AN TI Infection of man with Bacterium tularense. Commentary SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID PNEUMONIC TULAREMIA; MARTHAS-VINEYARD; OUTBREAK C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Weinberg, AN (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Jackson 517,55 Fruit St,GRJ 5, Boston, MA 02114 USA. EM aweinberg1@partners.org NR 22 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 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2004 VL 189 IS 7 BP 1317 EP 1320 DI 10.1086/382546 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 805AC UT WOS:000220338200025 PM 15031803 ER PT J AU Keane, D Ruskin, J Norris, N Chapelon, PA Berube, D AF Keane, D Ruskin, J Norris, N Chapelon, PA Berube, D TI In vitro and in vivo evaluation of the thermal patterns and lesions of catheter ablation with a microwave monopole antenna SO JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY LA English DT Article DE microwave ablation; monopole antenna; thermal patterns; arrhythmias ID INFERIOR VENA-CAVA; ATRIAL-FIBRILLATION; RADIOFREQUENCY ABLATION; CONSECUTIVE PATIENTS; TISSUE; TEMPERATURE; MYOCARDIUM; FLUTTER; CONVERSION; IMPEDANCE AB Background: Radiofrequency (RF) catheter ablation is an effective treatment for supraventricular tachycardia. The effectiveness of the technique is at times limited by the small lesion size produced by RF energy delivery. Previous reports have indicated that microwave energy is capable of producing a larger volume of heated tissue than radiofrequency energy, raising the possibility that microwave energy may offer a potential alternative energy source to radiofrequency for the substrate ablation of certain arrhythmias such as ventricular tachycardia or atrial flutter. Methods: The present study evaluated the thermal profiles of a monopole microwave antenna delivering energy at 2.45 GHz frequency in a phantom tissue-equivalent material with dielectric and thermal properties similar to myocardium. In addition, microwave catheter ablations were performed in vivo in the ventricles of goats prior to the examination of the lesions. Results: The measured thermal profiles in the phantom revealed that the antenna is capable of producing heating to a temperature associated with myocardial necrosis to a controllable depth that can be more than 8 mm, while the endocardial temperature is maintained relatively low. The ablation volume is significantly reduced but is still effective when there is only a partial contact between the antenna and the tissue surface. In vivo studies on goat models confirmed that the monopole antenna can produce a deep transmural lesion in the left ventricle without causing coagulation or charring on the endocardial surface. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. AFx Inc, Fremont, CA 94538 USA. RP Keane, D (reprint author), St James Hosp, Cardiac Arrhythmia Serv, Dublin 8, Ireland. EM dkeane@stjames.ie NR 38 TC 8 Z9 11 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1383-875X J9 J INTERV CARD ELECTR JI J. Interv. Card. Electrophysiol. PD APR PY 2004 VL 10 IS 2 BP 111 EP 119 DI 10.1023/B:JICE.0000019264.14661.8e PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 801ZN UT WOS:000220133900002 PM 15014211 ER PT J AU O'Brien, KD Zhao, XQ Shavelle, DM Caulfield, MT Letterer, RA Kapadia, SR Probstfield, JL Otto, CM AF O'Brien, KD Zhao, XQ Shavelle, DM Caulfield, MT Letterer, RA Kapadia, SR Probstfield, JL Otto, CM TI Hemodynamic effects of the angiotensin-converting enzyme inhibitor, ramipril, in patients with mild to moderate aortic stenosis and preserved left ventricular function SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article DE aortic stenosis; angiotensin-converting enzyme; contraindications; hemodyamics ID SMOOTH-MUSCLE-CELLS; PRESSURE-OVERLOAD HYPERTROPHY; LOW-DENSITY-LIPOPROTEIN; DOPPLER ECHOCARDIOGRAPHY; GENE-EXPRESSION; HEART-FAILURE; EARLY LESION; VALVE; TRANSITION; ADULTS AB Background: Angiotensin-converting enzyme (ACE) inhibitor use is presumed to be contraindicated in patients with aortic stenosis (AS). We determined the hemodynamic effects of ACE inhibitors in patients with mild to moderate aortic stenosis (AS) and preserved left ventricular function. Methods: Thirteen elderly patients (mean [SD] age = 65 [17] years), with mild to moderate AS (aortic jet velocity 2.5-4.0 m/s), normal left ventricular and renal function, and no clinical coronary artery disease, were enrolled in a single-center, open-label trial comparing the hemodynamic effects at baseline and following titration of ramipril to a maximum dose of 7.5 mg twice daily. Patients were identified from echocardiography laboratory logs. Despite a presumed contraindication to ACE inhibitor use in AS patients, 30% (71 of 235) of patients otherwise meeting inclusion or exclusion criteria were excluded owing to current ACE inhibitor use. Patients were monitored with weekly clinic visits, biweekly laboratory tests, and monthly echocardiog rams. Results: There were no significant changes from baseline to week 8 in echocardiographic parameters, including mean (SD) aortic jet velocity [2.9 (0.4) vs 2.9 (9.4) m/s], calculated aortic transvalvular gradient [18 (6) vs 18 (6) mm Hg], or cardiac output [5.5 (1.2) vs 6.0 (2.1) L/min], or significant changes in blood pressure or heart rate. Early discontinuations were for asymptomatic low blood pressure (one patient) or a reversible creatinine increase of 0.3 mg/dL (one patient). Conclusions: Short-term treatment with up to 7.5 mg twice daily of ramipril was well tolerated in patients with mild to moderate AS and preserved left ventricular function. A surprisingly high proportion of patients with documented AS were already receiving ACE inhibitors. C1 Univ Washington, Div Cardiol, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Cleveland Clin, Dept Cardiol, Cleveland, OH 44106 USA. RP O'Brien, KD (reprint author), Univ Washington, Div Cardiol, Box 356422,1959 NE Pacific St, Seattle, WA 98195 USA. EM cardiac@u.washington.edu OI Otto, Catherine/0000-0002-0527-9392 FU NCRR NIH HHS [M01-RR-00037] NR 24 TC 55 Z9 55 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD APR PY 2004 VL 52 IS 3 BP 185 EP 191 DI 10.2310/6650.2004.03025 PG 7 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 830XG UT WOS:000222156900023 PM 15222408 ER PT J AU Kalra, MK Maher, MM Rizzo, S Kanarek, D Shephard, JAO AF Kalra, MK Maher, MM Rizzo, S Kanarek, D Shephard, JAO TI Radiation exposure from chest CT: Issues and strategies SO JOURNAL OF KOREAN MEDICAL SCIENCE LA English DT Review DE tomography x-ray computed; CT chest; radiation dosage ID HIGH-RESOLUTION CT; LOW-DOSE CT; FLUOROSCOPICALLY GUIDED PROCEDURES; NOISE-REDUCTION FILTERS; COMPUTED-TOMOGRAPHY; IMAGE QUALITY; TUBE CURRENT; PULMONARY METASTASES; PEDIATRIC-PATIENTS; MULTIDETECTOR CT AB Concerns have been raised over alleged overuse of CT scanning and inappropriate selection of scanning methods, all of which expose patients to unnecessary radiation. Thus, it is important to identify clinical situations in which techniques with lower radiation dose such as plain radiography or no radiation such as MRI and occasionally ultrasonography can be chosen over CT scanning. This article proposes the arguments for radiation dose reduction in CT scanning of the chest and discusses recommended practices and studies that address means of reducing radiation exposure associated with CT scanning of the chest. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pulm & Crit Care Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kalra, MK (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM mkalra@partners.org NR 69 TC 13 Z9 14 U1 0 U2 0 PU KOREAN ACAD MEDICAL SCIENCES PI SEOUL PA 302 75 DONG DU ICHON, DONG YONGSAN KU, SEOUL 140 031, SOUTH KOREA SN 1011-8934 J9 J KOREAN MED SCI JI J. Korean Med. Sci. PD APR PY 2004 VL 19 IS 2 BP 159 EP 166 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 814UB UT WOS:000220998500001 PM 15082885 ER PT J AU Ha, TS Duraisamy, S Faulkner, JL Kasinath, BS AF Ha, TS Duraisamy, S Faulkner, JL Kasinath, BS TI Regulation of glomerular endothelial cell proteoglycans by glucose SO JOURNAL OF KOREAN MEDICAL SCIENCE LA English DT Article DE diabetes mellitus; diabetic nephropathies; endothelium; heparan sulfate proteoglycan; kidney glomerulus; proteinuria ID HEPARAN-SULFATE PROTEOGLYCAN; BASEMENT-MEMBRANE; EPITHELIAL-CELLS; INCREASED PERMEABILITY; DIABETIC NEPHROPATHY; FILTRATION CHANGES; GENE-EXPRESSION; PROTEIN; GLYCOSAMINOGLYCANS; LOCALIZATION AB The presence of heparan sulfate proteoglycan (HSPG) in anionic sites in the lamina rara interna of glomerular basement membrane suggests that the proteoglycan may be deposited by the glomerular endothelial cells (G Endo). We have previously demonstrated that bovine GEndo in vitro synthesize perlecan, a species of glomerular basement membrane HSPG. In this study we examined whether high glucose medium regulates the GEndo metabolism of glycopeptides including perlecan. Metabolic labeling of glycoconjugates with S-35-SO4, sequential ion exchange and Sepharose CL-4B chromatography of labeled glycoconjugates, and northern analysis were performed. Incubation of GEndo for 8 to 14 weeks (but not for 1-2 weeks) in medium containing 30 mM glucose resulted in nearly 50% reduction in the synthesis of cell layer and medium (SO4)-S-35-labeled low anionic glycoproteins and proteoglycans, including that of basement membrane HSPG (K-av 0.42) compared to GEndo grown in 5 mM glucose medium; no changes in anionic charge density or hydrodynamic size of proteoglycans were noted. Northern analysis demonstrated that the mRNA abundance of perlecan was reduced by 47% in cells incubated with 30 mM glucose. Our data suggest that high glucose medium reduces the GEndo synthesis of perlecan by regulating its gene expression. Reduced synthesis of perlecan by GEndo may contribute to proteinuria seen in diabetic nephropathy. C1 Chungbuk Natl Univ, Coll Med, Dept Pediat, Chonju 361240, South Korea. Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, Dept Med, San Antonio, TX 78284 USA. RP Ha, TS (reprint author), Chungbuk Natl Univ, Coll Med, Dept Pediat, 48 Gaesin Dong, Chonju 361240, South Korea. EM tsha@med.chungbuk.ac.kr FU NIDDK NIH HHS [DK 33665, R37 DK033665, R01 DK077295, R01 DK033665] NR 34 TC 9 Z9 9 U1 0 U2 0 PU KOREAN ACAD MEDICAL SCIENCES PI SEOUL PA 302 75 DONG DU ICHON, DONG YONGSAN KU, SEOUL 140 031, SOUTH KOREA SN 1011-8934 J9 J KOREAN MED SCI JI J. Korean Med. Sci. PD APR PY 2004 VL 19 IS 2 BP 245 EP 252 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 814UB UT WOS:000220998500014 PM 15082898 ER PT J AU Bertram, L Parkinson, M Mullin, K Menon, R Blacker, D Tanzi, RE AF Bertram, L Parkinson, M Mullin, K Menon, R Blacker, D Tanzi, RE TI No association between a previously reported OLR1 3 ' UTR polymorphism and Alzheimer's disease in a large family sample SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID ALPHA-2-MACROGLOBULIN; LINKAGE; GENOME; ONSET; GENE; AGE C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Gerontol Res Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,MIND,Genet & Aging Res Unit, Charlestown, MA USA. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp East, Genet & Aging Res Unit, MIND, 114 16th St, Boston, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X NR 11 TC 7 Z9 8 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1468-6244 J9 J MED GENET JI J. Med. Genet. PD APR 1 PY 2004 VL 41 IS 4 BP 286 EP 288 DI 10.1136/jmg.2003.016980 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 808SP UT WOS:000220589100009 PM 15060104 ER PT J AU Balmana, J Stoffel, EM Emmons, KM Garber, JE Syngal, S AF Balmana, J Stoffel, EM Emmons, KM Garber, JE Syngal, S TI Comparison of motivations and concerns for genetic testing in hereditary colorectal and breast cancer syndromes SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID NONPOLYPOSIS COLON-CANCER; BRCA1 MUTATION CARRIERS; PROPHYLACTIC SURGERY; DECISION-ANALYSIS; OVARIAN-CANCER; PREVENTION STRATEGIES; LIFE EXPECTANCY; WOMEN; FAMILIES; RISK C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Div Gastroenterol, Boston, MA 02115 USA. RP Syngal, S (reprint author), Dana Farber Canc Inst, Smith 209,44 Binney St, Boston, MA 02115 USA. EM ssyngal@partners.org FU NCI NIH HHS [K07CA08453] NR 40 TC 13 Z9 13 U1 2 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1468-6244 J9 J MED GENET JI J. Med. Genet. PD APR 1 PY 2004 VL 41 IS 4 AR e44 DI 10.1136/jmg.2003.012526 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 808SP UT WOS:000220589100024 PM 15060120 ER PT J AU Yeung, A Chang, D Gresham, RL Nierenberg, AA Fava, M AF Yeung, A Chang, D Gresham, RL Nierenberg, AA Fava, M TI Illness beliefs of depressed Chinese American patients in primary care SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID HELP-SEEKING BEHAVIOR; MENTAL-HEALTH; INVENTORY AB This study investigated the illness beliefs of 40 depressed Chinese Americans in a primary care setting using the Exploratory Model Interview Catalogue (EMIC). Twenty-two depressed Chinese Americans (76%) complained of somatic symptoms; 4 (14%) reported psychological symptoms including irritability, rumination, and poor memory. No patients reported depressed mood spontaneously. Yet, 93% endorsed depressed mood when they filled out the CBDI. Twenty-one patients (72%) did not know the name of their illness or did not consider it a diagnosable medical illness, and five patients (17%) attributed their symptoms to pre-existing medical problems. Only three patients (10%) labeled their illness as psychiatric conditions. The patients generally sought help from general hospital (69%), lay help (62%), and alternative treatment (55%) but rarely from mental health professionals (3.5%) for their depressive symptoms. The results suggest that many Chinese Americans do not consider depressed mood a symptom to report to their physicians, and many are unfamiliar with depression as a treatable psychiatric disorder. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. S Cove Community Hlth Ctr, Boston, MA USA. Ohio Univ, Dept Psychol, Athens, OH 45701 USA. RP Yeung, A (reprint author), 50 Staniford St,Suite 401, Boston, MA 02114 USA. FU NIMH NIH HHS [5T32MH19126-10] NR 22 TC 46 Z9 46 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD APR PY 2004 VL 192 IS 4 BP 324 EP 327 DI 10.1097/01.nmd.0000120892.96624.00 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 810KB UT WOS:000220702100011 PM 15060408 ER PT J AU Huffman, JC Blais, MA Pirl, WF AF Huffman, JC Blais, MA Pirl, WF TI A comparison of clinician and patient concerns about antipsychotic side effects: A pilot study SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID SCHIZOPHRENIA; NEUROLEPTICS AB Antipsychotic medications are associated with a variety of side effects, including tardive dyskinesia, weight gain, new-onset diabetes, cognitive slowing, and akathisia. In this pilot study, 20 psychiatric inpatients taking antipsychotics, 15 psychiatric nurses, and 31 psychiatrists ranked the aversiveness of these five potential side effects. Psychiatrists, nurses, and patients had similar concerns about these side effects. However, patients ranked cognitive slowing as more aversive than did mental health clinicians, while nurses rated weight gain as more aversive than did patients or psychiatrists. Larger studies are needed to further investigate these findings. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,Warren 605, Boston, MA 02114 USA. EM jhuffman@partners.org NR 9 TC 5 Z9 5 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 APR PY 2004 VL 192 IS 4 BP 328 EP 330 DI 10.1097/01.nmd.0000120893.42644.13 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 810KB UT WOS:000220702100012 PM 15060409 ER PT J AU Wagle, M Grunewald, B Subburaju, S Barzaghi, C Le Guyader, S Chan, J Jesuthasan, S AF Wagle, M Grunewald, B Subburaju, S Barzaghi, C Le Guyader, S Chan, J Jesuthasan, S TI EphrinB2a in the zebrafish retinotectal system SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE ephrinB2; tectal neuron; stripe assay; mutant; neurogenic ID RECEPTOR TYROSINE KINASES; GANGLION-CELL AXONS; VISUAL-SYSTEM; IN-VIVO; EPH RECEPTORS; EXPRESSION; PROJECTION; LIGANDS; DIFFERENTIATION; NEUROGENESIS AB members of the Eph-B family of receptors tyrosine kinase and their transmembrane ligands have been implicated in dorsoventral patterning of the vertebrate retinotectal projection. In the zebrafish retinotectal system, however, ephrinB2a is expressed strongly in the posterior tectum, in tectal neurons that form physical contacts with retinal ganglion cell (RGC) axons. In the gnarled mutant, where tectal neurons form ectopically in the pretectum, RGC axons stall before entering the tectum, or else are misrouted or branch aberrantly in the tectal neuropil. Ectopic expression of ephrinB2a in the anterior midbrain of wild-type embryos, with the aid of baculovirus, also inhibits RGC axon entry into the tectum. In vitro, zebrafish RGC axons are repelled by stripes of purified ephrinB2a. It is proposed that ephrinB2a may signal a subpopulation of RGC axons that they have reached their target neurons in the tectum. (C) 2004 Wiley Periodicals, Inc. C1 Temasek Life Sci Lab, Singapore 117604, Singapore. Max Planck Inst Entwicklungsbiol, D-72076 Tubingen, Germany. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Jesuthasan, S (reprint author), Temasek Life Sci Lab, 1 Res Link, Singapore 117604, Singapore. EM suresh@tll.org.sg RI Jesuthasan, Suresh/B-7870-2016; OI Jesuthasan, Suresh/0000-0002-5733-6555 NR 27 TC 23 Z9 24 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD APR PY 2004 VL 59 IS 1 BP 57 EP 65 DI 10.1002/neu.10340 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 806MD UT WOS:000220437100007 PM 15007827 ER PT J AU Yates, PA Holub, AD McLaughlin, T Sejnowski, TJ O'Leary, DDM AF Yates, PA Holub, AD McLaughlin, T Sejnowski, TJ O'Leary, DDM TI Computational modeling of retinotopic map development to define contributions of EphA-ephrinA gradients, axon-axon interactions, and patterned activity SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE axon arborization; axon branching; axon competition; axon elimination; axon guidance; axon repellents; bidirectional signaling; ephrinA knockout mice; Isl2-EphA3 knockin mice; retinotectal projection; topographic mapping ID GANGLION-CELL AXONS; RECEPTOR TYROSINE KINASES; RETINOTECTAL PROJECTION; RETINAL AXONS; VISUAL-SYSTEM; IN-VIVO; GUIDANCE MOLECULE; RETINOCOLLICULAR PROJECTION; TRANSMEMBRANE LIGANDS; TOPOGRAPHIC ORDER AB The topographic projection of retinal ganglion cell (RGC) axons to mouse superior colliculus (SC) or chick optic tectum (OT) is formed in three phases: RGC axons overshoot their termination zone (TZ); they exhibit interstitial branching along the axon that is topographically biased for the correct location of their future TZ; and branches arborize preferentially at the TZ and the initial exuberant projection refines through axon and branch elimination to generate a precise retinotopic map. We present a computational model of map development that demonstrates that the countergradients of EphAs and ephrinAs in retina and the OT/SC and bidirectional repellent signaling between RGC axons and OT/SC cells are sufficient to direct an initial topographic bias in RGC axon branching. Our model also suggests that a proposed repellent action of EphAs/ephrinAs present on RGC branches and arbors added to that of EphAs/ephrinAs expressed by OT/SC cells is required to progressively restrict branching and arborization to topographically correct locations and eliminate axon overshoot Simulations show that this molecular framework alone can develop considerable topographic order and refinement, including axon elimination, a feature not programmed into the model. Generating a refined map with a condensed TZ as in vivo requires an additional parameter that enhances branch formation along an RGC axon near sites that it has a higher branch density, and resembles an assumed role for patterned neural activity. The same computational model generates the phenotypes reported in ephrinA deficient mice and Is12-EphA3 knockin mice. This modeling suggests that gradients of counter-repellents can establish a substantial degree of topographic order in the OT/SC, and that repellents present on RGC axon branches and arbors make a substantial contribution to map refinement However, competitive interactions between RGC axons that enhance the probability of continued local branching are required to generate precise retinotopy. (C) 2004 Wiley Periodicals, Inc. C1 Salk Inst Biol Studies, Mol Neurobiol Lab, La Jolla, CA 92037 USA. Salk Inst Biol Studies, Computat Neurobiol Lab, La Jolla, CA 92037 USA. RP O'Leary, DDM (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM doleary@salk.edu FU Howard Hughes Medical Institute; NEI NIH HHS [R01 EY007025, EY07025]; NIA NIH HHS [T32 AG00216, T32 AG000216] NR 68 TC 53 Z9 53 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD APR PY 2004 VL 59 IS 1 BP 95 EP 113 DI 10.1002/neu.10341 PG 19 WC Neurosciences SC Neurosciences & Neurology GA 806MD UT WOS:000220437100010 PM 15007830 ER PT J AU Conrad, C Vianna, C Schultz, C Thal, DR Ghebremedhin, E Lenz, J Braak, H Davies, P AF Conrad, C Vianna, C Schultz, C Thal, DR Ghebremedhin, E Lenz, J Braak, H Davies, P TI Molecular evolution and genetics of the Saitohin gene and tau haplotype in Alzheimer's disease and argyrophilic grain disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE apolipoprotein E; evolution; Saitohin; tau ID PROGRESSIVE SUPRANUCLEAR PALSY; FRONTOTEMPORAL DEMENTIA; Q7R POLYMORPHISM; APOLIPOPROTEIN-E; PARKINSONS-DISEASE; PROTEIN ISOFORMS; ASSOCIATION; MUTATION; GENOME; HUMANS AB A single nucleotide polymorphism that results in an amino acid change (Q7R) has been identified in the Saitohin (STH) gene and was initially found to be over-represented in the homozygous state in subjects with late-onset Alzheimer's disease (AD). More extensive studies provide limited support for the association with AD, but confirm an association of the Q allele with progressive supranuclear palsy and argyrophilic grain disease. A homologous sequence was found in the appropriate location of the rat and mouse tau genes, but there was no open reading frame allowing STH expression in these species, suggesting relatively recent evolution of this gene. In some non-human primates, the STH gene was identified, and this was found to differ from the human gene at two of 128 amino acids. All primates in which the STH gene was identified were homozygous for the R allele of STH, suggesting this is the ancestral allele. This observation was surprising, in that the Q allele is more common in human populations, and raises the possibility that natural selection has operated to favor individuals carrying this allele. The STH polymorphism is part of the tau gene haplotype, of which two major variants exist in human populations, the Q being part of the H1 haplotype and the R part of the H2 haplotype. More detailed studies confirm the H2 haplotype to be the ancestral tau gene. This situation is reminiscent of the evolution of the apolipoprotein (ApoE) gene, another locus that is potentially important for the risk of development of AD. C1 Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA. Univ Frankfurt, Dept Clin Neuroanat, D-6000 Frankfurt, Germany. Univ Bonn, Inst Neuropathol, D-5300 Bonn, Germany. Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10467 USA. RP Conrad, C (reprint author), Massachusetts Gen Hosp, Dept Neurol, 114 16th St MIND 2021, Charlestown, MA 02129 USA. EM cgconrad@partners.org NR 43 TC 28 Z9 30 U1 1 U2 3 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 APR PY 2004 VL 89 IS 1 BP 179 EP 188 DI 10.1046/j.1471-4159.2004.02320.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 805HG UT WOS:000220356800020 PM 15030402 ER PT J AU Arai, K Lee, SR van Leyen, K Kurose, H Lo, EH AF Arai, K Lee, SR van Leyen, K Kurose, H Lo, EH TI Involvement of ERK MAP kinase in endoplasmic reticulum stress in SH-SY5Y human neuroblastoma cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE apoptosis; brefeldin A; calcium; neuron; neuroprotection; thapsigargin ID ACTIVATED PROTEIN-KINASE; FOCAL CEREBRAL-ISCHEMIA; TRAUMATIC BRAIN INJURY; OXIDATIVE STRESS; NEURONAL DEGENERATION; DOWN-REGULATION; APOPTOSIS; DEATH; INHIBITION; MITOCHONDRIA AB Endoplasmic reticulum (ER) stress has increasingly come into focus as a factor contributing to neuronal injury. Although caspase-dependent mechanisms have been implicated in ER stress, the signaling pathways involved remain unclear. In this study, we examined the role of the extracellular signal-regulated kinase (ERK), a mitogen-activated protein (MAP) kinase pathway that is highly conserved in many systems for balancing cell survival and death. Prolonged treatment of the human neuroblastoma cell line SH-SY5Y with thapsigargin, an inducer of ER stress, increased cell death over 24-48 h, as measured by LDH release. Caspases were involved; increased levels of active caspase-3 and cleaved caspase substrate PARP were detected, and treatment with Z-VAD-FMK reduced thapsigargin-induced cytotoxicity. In contrast, inhibition of calpain was not protective, although calpain was activated following thapsigargin treatment. An early and transient phosphorylation of ERK1/2 occurred after thapsigargin-induced ER stress, and targeting this pathway with the MEK inhibitors U0126 or PD98059 significantly reduced cell death. Similar cytoprotection was obtained against brefeldin A, another ER stress agent. However, protection against ER stress via ERK inhibition was not accompanied by amelioration of caspase-3 activation, PARP cleavage, or DNA laddering. These data indicate that ERK may contribute to non-caspase-dependent pathways of injury after ER stress. C1 Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Charlestown, MA USA. Kyushu Univ, Dept Pharmacol & Toxicol, Fukuoka 812, Japan. RP Lo, EH (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, MGH E 149-2401, Charlestown, MA 02129 USA. EM Lo@helix.mgh.harvard.edu RI van Leyen, Klaus/C-9126-2013 FU NINDS NIH HHS [P01-NS10828, R01-NS37074, R01-NS38731, R01-NS40529] NR 50 TC 41 Z9 41 U1 0 U2 1 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 APR PY 2004 VL 89 IS 1 BP 232 EP 239 DI 10.1111/j.1471-4159.2004.02317.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 805HG UT WOS:000220356800025 PM 15030407 ER PT J AU Scholz, J Klingemann, I Moser, A AF Scholz, J Klingemann, I Moser, A TI Increased systemic levels of norsalsolinol derivatives are induced by levodopa treatment and do not represent biological markers of Parkinson's disease SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID N-METHYL-NORSALSOLINOL; BLOOD-BRAIN-BARRIER; DOPAMINERGIC NEUROTOXIN; CEREBROSPINAL-FLUID; S-SALSOLINOL; ISOQUINOLINE; N-METHYL(R)SALSOLINOL; METABOLITES; CSF AB Endogenously synthesised norsalsolinol derivatives are elevated in Parkinson's disease (PD) and have been considered potentially useful biological markers of the disease. However, little is known about the impact of dopaminergic drugs on the formation of these compounds. We prospectively examined the urine concentrations of norsalsolinol, N-methyl-norsal-solinol and salsolinol in 47 PD patients and 14 control subjects. Patients and control subjects were re-examined after approximately 1 year to assess long term changes. Norsalsolinol derivatives were low in controls and untreated patients with early PD. Increased urine concentrations of norsalsolinol derivatives were significantly associated with levodopa treatment. They were elevated more markedly in the urine of patients treated with high (>600 mg daily) doses of levodopa compared with patients receiving medium ( 300 600 mg) or low (, 300 mg) doses of the drug. There was no correlation with disease parameters such as the severity of motor disability or deficits in the cognitive performance. In the patient group, the concentrations of all three norsalsolinol derivatives declined over the period of investigation, however, they still remained elevated compared with the control group. We conclude that systemic levels of norsalsolinol derivatives in treated patients with PD are likely to derive from the metabolism of levodopa and cannot be regarded as intrinsic markers of the disease. The limited ability of norsalsolinol derivatives to pass the blood-brain barrier prevents an intracerebral accumulation of these possibly harmful compounds, which are biochemically similar to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Med Univ Lubeck, Dept Neurol, Neurochem Res Grp, Lubeck, Germany. RP Scholz, J (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, 149 13th St,Room 4309, Charlestown, MA 02129 USA. EM scholz.joachim@mgh.harvard.edu NR 20 TC 5 Z9 5 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD APR 1 PY 2004 VL 75 IS 4 BP 634 EP 636 DI 10.1136/jnnp.2003.010769 PG 3 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 803UD UT WOS:000220255100027 PM 15026514 ER PT J AU Griffin, WC Middaugh, LD Cook, JE Tyor, WR AF Griffin, WC Middaugh, LD Cook, JE Tyor, WR TI The severe combined immunodeficient (SCID) mouse model of human immunodeficiency virus encephalitis: Deficits in cognitive function SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE AIDS; animal model; dementia; HIV-associated dementia; HIV encephalitis; SCID ID AIDS DEMENTIA COMPLEX; TYPE-1 ENCEPHALITIS; HIV ENCEPHALITIS; MURINE MODEL; WATER-MAZE; MICE; MORRIS; MEMORY; NAVIGATION; RATS AB The severe combined immunodeficient (SCID) mouse model of human immunodeficiency virus (HIV) encephalitis exhibits many of the histopathological and pathophysiological features of human HIV-associated dementia (HAD). Although deficits that may resemble HAD in humans have been reported for HIV-infected SCID mice, the cognitive deficit aspect of the model has very limited empirical support. Here, the authors report that HIV-infected SCID mice display cognitive deficits on a task requiring the animal to learn and remember the spatial relationship of cues in its environment in order to locate a submerged platform in a Morris water maze. The cognitive deficits manifest as longer latencies to locate the platform on the last day of the maze acquisition period and during a retention test 8 days later. Control experiments indicated that the poor performance by HIV-infected mice in comparison to controls was not due to impaired motor function or swimming ability, impaired visual acuity, or increased susceptibility to fatigue. Thus, the increased times required for HIV-infected mice to locate the submerged platform during the acquisition and memory tests likely reflect a cognitive deficit, rather than sensorimotor or emotional abnormalities. These behavioral deficits are associated with significant increases in astrogliosis and microgliosis in the HIV-infected mice. The results of this study strengthen the SCID mouse model of HIV encephalitis by definitively establishing cognitive deficits for the model in addition to its previously reported neuropathological features. C1 Med Univ S Carolina, Ctr Drug & Alochol Programs, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Physiol & Neurosci, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. RP Tyor, WR (reprint author), Ralph H Johnson VAMC, Serv Neurol, 109 Bee St, Charleston, SC 29401 USA. EM william.tyor@med.va.gov FU NIDA NIH HHS [T32 DA07288-11, DA11870-04]; NIMH NIH HHS [MH62697-03] NR 20 TC 15 Z9 16 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD APR PY 2004 VL 10 IS 2 BP 109 EP 115 DI 10.1080/13550280490428333 PG 7 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 801WR UT WOS:000220126500004 PM 15204929 ER PT J AU Ponte, PR Kruger, N DeMarco, R Hanley, D Conlin, G AF Ponte, PR Kruger, N DeMarco, R Hanley, D Conlin, G TI Reshaping the practice environment - The importance of coherence SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID PATIENT MORTALITY; NURSING PRACTICE; HEALTH; CARE; HARDINESS; QUALITY; NURSES C1 BMT, Nursing & Clin Serv, Hematol Oncol, Boston, MA USA. Brigham & Womens Hosp, Patient Care Serv, Boston, MA 02115 USA. Boston Coll, William F Connell Sch Nursing, Boston, MA USA. Dana Farber Canc Inst, Patient Care Serv, Boston, MA 02115 USA. RP Ponte, PR (reprint author), Dana Farber Canc Inst, Nursing & Patient Care Serv, 44 Binney St, Boston, MA 02115 USA. EM pat_reid_ponte@dfci.harvard.edu NR 30 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD APR PY 2004 VL 34 IS 4 BP 173 EP 179 DI 10.1097/00005110-200404000-00004 PG 7 WC Nursing SC Nursing GA 814EB UT WOS:000220956900004 ER PT J AU Chen, ZY Rex, S Tseng, CC AF Chen, ZY Rex, S Tseng, CC TI Kruppel-like factor 4 is transactivated by butyrate in colon cancer cells SO JOURNAL OF NUTRITION LA English DT Article DE GKLF/KLF4; butyrate; histone acetylation; short chain fatty acids ID LARGE-BOWEL CANCER; DIETARY FIBER; GROWTH-INHIBITION; EPITHELIAL-CELLS; SODIUM-BUTYRATE; FATTY-ACIDS; EXPRESSION; GENE; PROMOTER; DIFFERENTIATION AB High-fiber diets decrease the incidence of colorectal cancers, and SCFA, derived from dietary fiber, are involved in the regulation of cell growth, differentiation, and apoptosis of the colonic epithelium. The mediators of these effects remain poorly defined. Kruppel-like factor-4 (KLF4/GKLF) is a zinc-finger transcription factor that exhibits some physiologic properties similar to those of SCFA in the colon. The present study was undertaken to examine the role of KLF4 in the butyrate-mediated effect in colon cancer HT-29 cells. Butyrate induced KLF4 mRNA expression and stimulated KLF4 promoter activity in a dose- and time-dependent manner in HT-29 cells. Similar effects were observed in SCFA possessing different carbon lengths (C3-C7), but not in branched isobutyric acid, indicating that the stimulatory properties of SCFA were related to fatty acid structure. Transfection studies using 5' deletion and mutant constructs of the KLF4 promoter demonstrated that the butyrate-responsive element was located at a putative stimulatory protein (Sp)1-binding site. Electrophoretic mobility shift assays using an oligonucleotide containing a consensus Sp1-binding element revealed a DNA-protein complex that was enhanced by butyrate treatment and supershifted by the Sp1 antiserum. Furthermore, the effects of butyrate on cell growth and KLF4 mRNA expression were the same as those of trichostatin A (TSA), a specific inhibitor of histone deacetylase (HDAC-1). Overexpression of HDAC1 significantly attenuated transcriptional activation of the KLF4 promoter by butyrate or TSA. These results suggest that KLF4 may function as one of the downstream effectors of butyrate that mediates its growth arrest effect in the colon. Moreover, transactivation of KLF4 by butyrate appears to be mediated through interaction with a Sp1-binding domain on the promoter and is also likely to involve histone acetylation. C1 VA Boston Healthcare Syst, Gastroenterol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Chen, ZY (reprint author), VA Boston Healthcare Syst, Gastroenterol Sect, Boston, MA 02118 USA. EM zhiyi.chen@bmc.org FU NCI NIH HHS [CA82593]; NIDDK NIH HHS [DK061376] NR 25 TC 37 Z9 45 U1 0 U2 6 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD APR PY 2004 VL 134 IS 4 BP 792 EP 798 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 810CF UT WOS:000220681700014 PM 15051827 ER PT J AU Troulis, MJ Williams, WB Kaban, LB AF Troulis, MJ Williams, WB Kaban, LB TI Endoscopic mandibular condylectomy and reconstruction: Early clinical results SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID ASSISTED OPEN TREATMENT; CONDYLAR FRACTURES; SINUS SURGERY; FOLLOW-UP; OSTEOTOMY; UNIT AB Purpose: The purpose of this study was to evaluate early outcomes in patients who underwent endoscopic condylectomy and costochondral graft reconstruction (CCG) of the ramus/condyle unit (RCU). Patients and Methods: A retrospective evaluation of 10 consecutive patients who underwent endoscopic condylectomy and CCG (n = 17 sides) for the treatment of idiopathic condylar resorption (n = 7), degenerative joint disease (n = 1), and malunion of a fractured condyle (n = 2) was completed. Patients were included who had 1) adequate documentation after endoscopic condylectomy and CCG reconstruction and 2) a minimum of 6-months follow-up. Patients with inadequate documentation or follow-up were excluded. The surgical technique included a 1.5-cm incision inferior to the mandibular angle. Blunt dissection was carried to the masseter muscle, which was incised using needle point electrocautery. An optical cavity was created for insertion of a Hopkins (Karl Storz, Culver City, CA) endoscope. The resection and reconstruction were carried out with endoscopic instrumentation. Preoperative (T0), postoperative (T1), and follow-up (T2) clinical examinations, lateral cephalograms, and panoramic radiographs were used to evaluate the outcomes. Results: In all 10 cases, condylectomy and CCG reconstruction (n = 17 sides) were successfully performed using the endoscopic approach. The mean follow-up period was 17 months (range, 8 to 38 months). All submandibular scars were aesthetic ally satisfactory, and there were no facial, inferior alveolar, or lingual nerve injuries. No other intraoperative or postoperative complications occurred. Postoperative RCU length, mandibular position, and correction of the occlusion were documented using lateral cephalometric and panoramic radiographs. Conclusion: The results of this study indicate that endoscopic condylectomy and CCG reconstruction produce satisfactory clinical outcomes without significant morbidity. Long-term follow-up studies are in progress. (C) 2004 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA USA. RP Troulis, MJ (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren Bldg 1201,55 Fruit St, Boston, MA 02114 USA. FU NIDCR NIH HHS [K23-DE 14070-02] NR 24 TC 23 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD APR PY 2004 VL 62 IS 4 BP 460 EP 465 DI 10.1016/i.ioms.2003.09.012 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 809NE UT WOS:000220642600013 PM 15085514 ER PT J AU Medoff, D AF Medoff, D TI Clinical personality assessment, 2nd edition SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Book Review ID PSYCHOLOGICAL TEST USAGE C1 Harvard Univ, Children & Law Program, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Suffolk Univ, Dept Educ & Human Serv, Boston, MA 02108 USA. RP Medoff, D (reprint author), Harvard Univ, Children & Law Program, Massachusetts Gen Hosp, Sch Med, 60 Staniford St, Boston, MA 02114 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD APR PY 2004 VL 82 IS 2 BP 241 EP 243 DI 10.1207/s15327752jpa8202_11 PG 3 WC Psychology, Clinical; Psychology, Social SC Psychology GA 806OQ UT WOS:000220443600011 ER PT J AU Martinez, V Wang, LX Rivier, J Grigoriadis, D Tache, Y AF Martinez, V Wang, LX Rivier, J Grigoriadis, D Tache, Y TI Central CRF, urocortins and stress increase colonic transit via CRF1 receptors while activation of CRF2 receptors delays gastric transit in mice SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; ANXIETY-LIKE BEHAVIOR; MOTOR FUNCTION; COMPETITIVE ANTAGONISTS; BINDING-PROTEIN; ACID SECRETION; HIGH-AFFINITY; RATS; FAMILY; ANTISAUVAGINE-30 AB Recently characterized selective agonists and developed antagonists for the corticotropin releasing factor (CRF) receptors are new tools to investigate stress-related functional changes. The influence of mammalian CRF and related peptides injected intracerebroventricularly (I.C.V.) on gastric and colonic motility, and the CRF receptor subtypes involved and their role in colonic response to stress were studied in conscious mice. The CRF1/CRF2 agonists rat urocortin 1 (rUcn 1) and rat/human CRF (r/h CRF), the preferential CRF1 agonist ovine CRF (oCRF), and the CRF2 agonist mouse (m) Ucn 2, injected I.C.V. inhibited gastric emptying and stimulated distal colonic motor function (bead transit and defecation) while oCRF(9-33) OH (devoid of CRF receptor affinity) showed neither effects. mUcn 2 injected peripherally had no colonic effect. The selective CRF2 antagonist astressin(2)-B (I.C.V.), at a 20:1 antagonist: agonist ratio, blocked I.C.V. r/hCRF and rUcn 1 induced inhibition of gastric transit and reduced that of mUcn 2, while the CRF1 antagonist NBI-35965 had no effect. By contrast, the colonic motor stimulation induced by I.C.V. r/hCRF and rUcn 1 and 1 h restraint stress were antagonized only by NBI-35965 while stimulation induced by mUcn 2 was equally blocked by both antagonists. None of the CRF antagonists injected I.C.V.. alone influenced gut transit. These data establish in mice that brain CRF1 receptors mediate the stimulation of colonic transit induced by central CRF, urocortins (1 and 2) and restraint stress, while CRF2 receptors mediate the inhibitory actions of these peptides on gastric transit. C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Dept Med,Digest Dis Div, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Ctr Neurovisceral Sci, Dept Med,Digest Dis Div, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Brain Res Inst, Los Angeles, CA 90073 USA. Salk Inst Biol Studies, Clayton Fdn, Labs Peptide Biol, La Jolla, CA 92037 USA. Neurocrine Biosci Inc, San Diego, CA 92121 USA. RP Tache, Y (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Dept Med,Digest Dis Div, Bldg 115,Rm 117,11301 Whilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@ucla.edu RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [DK-57238, DK-26741, DK-41301, DK33061, P01 DK026741, P30 DK041301, R01 DK033061, R01 DK057238, R37 DK033061] NR 44 TC 118 Z9 122 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD APR 1 PY 2004 VL 556 IS 1 BP 221 EP 234 DI 10.1113/jphysiol.2003.059659 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 813DJ UT WOS:000220887500017 PM 14755002 ER PT J AU Kim, EH Hoge, SG Lightner, AM Grady, EF Coelho, AM Kirkwood, KS AF Kim, EH Hoge, SG Lightner, AM Grady, EF Coelho, AM Kirkwood, KS TI Activation of nociceptive neurons in T9 and T10 in cerulein pancreatitis SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Association-for-Academic-Surgery CY NOV 07-09, 2002 CL BOSTON, MA SP Assoc Acad Surg DE cerulein; pancreatitis; Fos; nociception; spinal cord; pain ID C-FOS EXPRESSION; RAT SPINAL-CORD; SUBSTANCE-P; PROTEIN; MORPHINE; PAIN; RECEPTOR-2; STIMULI; COMPLEX; FIBERS AB Mechanisms of pain transduction in acute pancreatitis are poorly understood. Increased Fos expression in the spinal cord is a marker of activation of nociceptive neurons. We hypothesized that cerulein pancreatitis leads to increased Fos expression at T9 and T10, which receive sensory input from the pancreas. Rats were injected with cerulein (100 mug/kg, s.c.) or saline carrier (NS). Endpoints at 4, 6, and 10 h were serum amylase, myeloperoxidase activity (MPO), and spinal cord Fos expression (number of immunoreactive nuclei/section dorsal gray matter). Fos-like immunoreactivity (FLI) at T9-T10 was compared to internal controls (T6, T12). An average of 20 spinal cord histologic sections were evaluated per rat. Some animals were injected with the mu-opioid receptor agonist, buprenorphine (90 mug/kg, s.c.), 3 h after cerulein, and their end-points were measured at 6 h. Analysis of variance and t tests were used for statistical analysis. Results are means +/- SEM. As expected, cerulein induced edematous pancreatitis, with a 4-fold increase in serum amylase at 6 h [cer (n = 8): 14,000 +/- 1,300 U/ml versus NS (n = 10): 3,700 +/- 300, P < 0.005)] and a 2-fold increase in MPO activity (0.25 +/- 0.05) activity units/dry wt versus 0.13 +/- 0.02, P < 0.05). Cerulein induced nearly a 2-fold increase in FLI at T9 and T10 [n = 10 (cer) and n = 13 (NS): T9, 14 +/- 1.5 versus 7.8 +/- 0.88; T10, 15 +/- 1.7 versus 8.3 +/- 0.70; P < 0.05]. Peak effects of cerulein on FLI occurred at 6 h and were greatest at T9/T10 with relative sparing of T6/T12. T6/T12 expression was similar in experimental and control groups. Buprenorphine significantly reduced both serum amylase and FLI and T9/T10. Cerulein-induced acute pancreatitis in rat increases visceral nociceptive signaling at spinal cord levels T9 and T10, with a peak at 6 h. Blockade of this effect by the mu-opioid receptor agonist buprenorphine could occur either by direct activation of central opioid receptors and/or an anti-inflammatory mechanism. FLI is a useful tool for studying the pathophysiology of pain in experimental acute pancreatitis. (C) 2004 Elsevier Science (USA) All rights reserved. C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Physiol, San Francisco, CA USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Kirkwood, KS (reprint author), Univ Calif San Francisco, Dept Surg, 533 Parnassus Room U-372, San Francisco, CA 94143 USA. EM kirkwoodk@surgery.ucsf.edu FU NIDDK NIH HHS [T32 DK 07573-15, R01 DK 46285-05] NR 27 TC 14 Z9 14 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 APR PY 2004 VL 117 IS 2 BP 195 EP 201 DI 10.1016/S0022-4804(03)00123-9 PG 7 WC Surgery SC Surgery GA 808CW UT WOS:000220548200003 PM 15047123 ER PT J AU Sanchez-Carpintero, I Mihm, MC Mizeracki, A Waner, M North, PE AF Sanchez-Carpintero, I Mihm, MC Mizeracki, A Waner, M North, PE TI Epithelial and mesenchymal hamartomatous changes in a mature port-wine stain: Morphologic evidence for a multiple germ layer field defect SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article; Proceedings Paper CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, DC SP US & Canadian Acad Pathol ID PULSED DYE-LASER; BLOOD-VESSELS AB The port-wine stain (PWS) is a congenital cutaneous venulocapillary malformation of unknown pathogenesis. Many patients with facial PWS develop thickening with cobblestoning and nodularity during adult life. The histologic correlates of this maturational change are poorly documented and its mechanisms remain unclear. in this case study we present new histologic observations that may elucidate this phenomenon. An extensive PWS on the face of a 75-year-old man exhibited gross thickening with cobblestoning and nodularity. Histologic examination revealed not only the expected vascular abnormalities, but also a number of widely distributed epithelial, neural, and mesenchymal hamartomatous changes. Epithelial changes included epidermal nevus, sebaceous trichofolliculoma, and basaloid follicular hamartoma. Changes of connective tissue nevus, smooth-muscle hamartoma, neural hamartoma, and subcuticular hamartoma were also noted. The complex hamartomatous changes observed in the PWS of this patient involved multiple germ lines and were distributed in a widespread pattern. These changes not only offer an explanation for the skin thickening and nodularity of this patient, but also suggest a genetically determined, multilineage developmental field defect in the pathogenesis of this lesion. Further studies of other patients are necessary to understand the full implications of these findings in the late stage of PWS. C1 Arkansas Childrens Hosp, Dept Otolaryngol, Little Rock, AR 72202 USA. Arkansas Childrens Hosp, Dept Pathol, Little Rock, AR 72202 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Harvard Univ, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP North, PE (reprint author), Arkansas Childrens Hosp, Dept Otolaryngol, 800 Marshall St, Little Rock, AR 72202 USA. EM northpaulae@uams.edu NR 10 TC 23 Z9 27 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD APR PY 2004 VL 50 IS 4 BP 608 EP 612 DI 10.1016/j.jaad.2003.04.002 PG 5 WC Dermatology SC Dermatology GA 808CU UT WOS:000220548000012 PM 15034512 ER PT J AU Guzman, JS Sohn, L Harada, ND AF Guzman, JS Sohn, L Harada, ND TI Living alone and outpatient care use by older veterans SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Geriatrics-Society CY MAY 08-12, 2002 CL WASHINGTON, DC SP Amer Geriatr Soc DE veterans; elderly; outpatient; living alone ID HEALTH-SERVICES; EMERGENCY ROOM; SOCIAL SUPPORT; MARITAL-STATUS; HOSPITALIZATION; PHYSICIAN; ADULTS; PATTERNS AB In nonveteran older adults, living alone influences outpatient care use, but its importance in the veteran population has not been well studied. The aims of this study are to describe the use of outpatient care by older veterans who live alone versus those who live with others and determine whether living alone influences outpatient use by older veterans. The data come from the 2001 Veteran Identity Program Survey designed to measure Department of Veterans Affairs (VA) and non-VA outpatient care use. Univariate and bivariate analyses were conducted to examine distributional properties, associations, and subgroup differences in outpatient care use. Poisson regression was used to assess the role of living alone on outpatient care use, controlling for predisposing, other enabling, and need factors. Results found that older veterans who use the VA, whether they live alone or not, have similar numbers of VA outpatient visits. Older veterans who use VA and non-VA facilities and who live alone have greater total outpatient visits than those who live with others. Regression results indicate that living alone is a predictor of VA routine medical visits, VA prescription refill visits, and total VA and non-VA outpatient visits but does not influence VA emergency room visits. These findings suggest that living alone is associated with differences in outpatient care use by older veterans. It is important for the VA to understand this relationship with the aim of developing interventions to improve access, effectiveness, and efficiency of health services for older veterans. C1 VA Greater Los Angeles Healthcare Syst, WLA, Ctr Geriatr Res Educ & Clin, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Guzman, JS (reprint author), VA Greater Los Angeles Healthcare Syst, WLA, Ctr Geriatr Res Educ & Clin, 11301 Wilshire Blvd 11G, Los Angeles, CA 90073 USA. EM jenice.guzman@med.va.gov NR 27 TC 6 Z9 6 U1 1 U2 2 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 APR PY 2004 VL 52 IS 4 BP 617 EP 622 DI 10.1111/j.1532-5415.2004.52172.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 805GO UT WOS:000220355000021 PM 15066081 ER PT J AU Salerno, JA Cooley, SG AF Salerno, JA Cooley, SG TI Tribute to Marsha Goodwin-Beck, RN-C, MA, MSN SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Biographical-Item C1 NIA, NIH, Bethesda, MD 20892 USA. US Dept Vet Affairs, Geriatr Res & Evaluat Geriatr & Extended Care Str, Washington, DC USA. RP Salerno, JA (reprint author), NIA, NIH, Bldg 31,Rm 5C35,MSC 2292, Bethesda, MD 20892 USA. EM salernoj@nia.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2004 VL 52 IS 4 BP 623 EP 624 DI 10.1111/j.1532-5415.2004.52189.x PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 805GO UT WOS:000220355000022 ER PT J AU Brown, CJ Allman, RM AF Brown, CJ Allman, RM TI Predictors of regaining ambulatory ability at hospital discharge. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 17-21, 2004 CL Las Vegas, NV SP Amer Geriatr Soc C1 Birmingham VAMC, GRECC, Birmingham, AL USA. Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2004 VL 52 IS 4 SU S MA P360 BP S140 EP S140 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 813HV UT WOS:000220899100405 ER PT J AU Chiang, L MacLean, CH Reuben, DB Wenger, NS AF Chiang, L MacLean, CH Reuben, DB Wenger, NS TI Predictors of quality of care in vulnerable elders. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 17-21, 2004 CL Las Vegas, NV SP Amer Geriatr Soc C1 Univ Calif Los Angeles, Los Angeles, CA USA. Rand Hlth, Santa Monica, CA USA. Greater Los Angeles VA Med Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2004 VL 52 IS 4 SU S MA P247 BP S101 EP S101 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 813HV UT WOS:000220899100292 ER PT J AU Chun, AK Fernandez, H Evelyn, G AF Chun, AK Fernandez, H Evelyn, G TI Training geriatric fellows as teachers. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 17-21, 2004 CL Las Vegas, NV SP Amer Geriatr Soc C1 CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2004 VL 52 IS 4 SU S MA P352 BP S137 EP S137 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 813HV UT WOS:000220899100397 ER PT J AU Hefzy, HM Growdon, JH Yap, L AF Hefzy, HM Growdon, JH Yap, L TI A comparison of survival rates in patients with Alzheimer's disease, dementia with Lewy bodies, and Pick's disease: An examination of patient records at the Massachusetts General Hospital. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 17-21, 2004 CL Las Vegas, NV SP Amer Geriatr Soc C1 NE Ohio Univ, Coll Med, Rootstown, OH 44272 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2004 VL 52 IS 4 SU S MA P543 BP S203 EP S203 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 813HV UT WOS:000220899100588 ER PT J AU Kinosian, B Martingdale, M Ripley, B Stallard, E AF Kinosian, B Martingdale, M Ripley, B Stallard, E TI Geographic barriers to nursing home access among priority group IA veterans. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 17-21, 2004 CL Las Vegas, NV SP Amer Geriatr Soc C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Dept Vet Affairs, Washington, DC USA. Dept Vet Affairs, Gainesville, FL USA. Duke Univ, Durham, NC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 APR PY 2004 VL 52 IS 4 SU S MA P378 BP S146 EP S146 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 813HV UT WOS:000220899100423 ER PT J AU LoConte, M Mahoney, J Shea, T Przybelski, R Hansen, K AF LoConte, M Mahoney, J Shea, T Przybelski, R Hansen, K TI Fall frequency and baseline characteristics: How many falls does it take to be different? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 17-21, 2004 CL Las Vegas, NV SP Amer Geriatr Soc C1 Univ Wisconsin, Dept Geriatr, Madison, WI USA. Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, GRECC, Madison, WI 53792 USA. NR 0 TC 0 Z9 0 U1 0 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 APR PY 2004 VL 52 IS 4 SU S MA P70 BP S41 EP S41 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 813HV UT WOS:000220899100116 ER PT J AU Mader, SL Benton, N Ansari, Y Baird, C Harper, R Chapman, K Donius, M Jenkins, K Jackson, J Setka, D Medcraft, M AF Mader, SL Benton, N Ansari, Y Baird, C Harper, R Chapman, K Donius, M Jenkins, K Jackson, J Setka, D Medcraft, M TI Program @ Home: A VA program to deliver hospital care in the home. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 17-21, 2004 CL Las Vegas, NV SP Amer Geriatr Soc C1 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 APR PY 2004 VL 52 IS 4 SU S MA P533 BP S200 EP S200 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 813HV UT WOS:000220899100578 ER PT J AU Mader, SL Fuglee, K Allen, D Werner, L Wanlass, W Pagel, K Beliel, K McEuen, J Stephens, E Allison, N McWhorter, K Holtorf, S Vandling, J AF Mader, SL Fuglee, K Allen, D Werner, L Wanlass, W Pagel, K Beliel, K McEuen, J Stephens, E Allison, N McWhorter, K Holtorf, S Vandling, J TI Development of a protocol for capillary blood glucose (CBG) testing in nursing home and rehabilitation settings. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 17-21, 2004 CL Las Vegas, NV SP Amer Geriatr Soc C1 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 APR PY 2004 VL 52 IS 4 SU S MA P95 BP S49 EP S50 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 813HV UT WOS:000220899100141 ER PT J AU Markland, AD Wang, C Lee, S Gerety, MB Hazuda, HP AF Markland, AD Wang, C Lee, S Gerety, MB Hazuda, HP TI Ethnic differences and urinary incontinence in a cross-sectional analysis of older, community-based Mexican and European Americans. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 17-21, 2004 CL Las Vegas, NV SP Amer Geriatr Soc C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2004 VL 52 IS 4 SU S MA P332 BP S130 EP S131 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 813HV UT WOS:000220899100377 ER PT J AU McDonald, M Hertz, RP Stafkey, D Yu, H Peterson, N Sonali, SN AF McDonald, M Hertz, RP Stafkey, D Yu, H Peterson, N Sonali, SN TI Comparison of the Department of Veterans Affairs healthcare utilization among veterans with Alzheimers disease, other mental disorders, and the overall system user. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 17-21, 2004 CL Las Vegas, NV SP Amer Geriatr Soc C1 Pfizer Inc, US Outcomes Res, New York, NY USA. Pfizer Inc, Outcomes Res, Ann Arbor, MI USA. Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, Dept Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2004 VL 52 IS 4 SU S MA P508 BP S191 EP S191 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 813HV UT WOS:000220899100553 ER PT J AU Perkins, CH Bergstrom, N Garcia, AD AF Perkins, CH Bergstrom, N Garcia, AD TI Pressure ulcer knowledge in primary care residencies. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 17-21, 2004 CL Las Vegas, NV SP Amer Geriatr Soc C1 Baylor Coll Med, Houston VAMC, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, UT Houston Sch Nursing, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2004 VL 52 IS 4 SU S MA P479 BP S181 EP S181 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 813HV UT WOS:000220899100524 ER PT J AU Richter, HE Duxbury, AS Granieri, E Halli, A Redden, DT Goode, PS AF Richter, HE Duxbury, AS Granieri, E Halli, A Redden, DT Goode, PS TI Pelvic floor surgery in the older woman: Effect of enhanced preoperative evaluation on functional and general health outcomes. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 17-21, 2004 CL Las Vegas, NV SP Amer Geriatr Soc C1 Univ Alabama, Birmingham, AL USA. Bronx Vet Affairs Med Ctr, New York, NY USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 APR PY 2004 VL 52 IS 4 SU S MA P585 BP S217 EP S218 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 813HV UT WOS:000220899100630 ER PT J AU Salazar, JA Raji, MA Schindler, JB AF Salazar, JA Raji, MA Schindler, JB TI Defining accessibility barriers to health care among a geriatric population in an urban minority community. A qualitative study. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 17-21, 2004 CL Las Vegas, NV SP Amer Geriatr Soc C1 Houston VA Med Ctr, Houston, TX USA. Univ Texas, Dept Med, Galveston, TX 77555 USA. NR 0 TC 0 Z9 0 U1 0 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 APR PY 2004 VL 52 IS 4 SU S MA P244 BP S100 EP S100 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 813HV UT WOS:000220899100289 ER PT J AU Unwin, BK AF Unwin, BK TI Post traumatic stress disorder and the geriatrician. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 17-21, 2004 CL Las Vegas, NV SP Amer Geriatr Soc C1 Madigan Army Med Ctr, Vet Affairs Puget Sound Hlth Care Syst, Tacoma, WA 98431 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2004 VL 52 IS 4 SU S MA P306 BP S121 EP S122 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 813HV UT WOS:000220899100351 ER PT J AU Vance, DE Sims, RV Chatman, T Ball, KK AF Vance, DE Sims, RV Chatman, T Ball, KK TI Physiological and psychosocial predictors of speed of processing in older community-dwelling adults. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 17-21, 2004 CL Las Vegas, NV SP Amer Geriatr Soc C1 Birmingham VAMC, Birmingham, AL USA. Univ Alabama Birmingham, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2004 VL 52 IS 4 SU S MA P75 BP S43 EP S43 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 813HV UT WOS:000220899100121 ER PT J AU Vance, DE Sims, RV Chatman, T Ball, KK AF Vance, DE Sims, RV Chatman, T Ball, KK TI Medical and psychosocial predictors of falling and balance in community-dwelling older adults. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 17-21, 2004 CL Las Vegas, NV SP Amer Geriatr Soc C1 Birmingham VAMC, Birmingham, AL USA. Univ Alabama Birmingham, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2004 VL 52 IS 4 SU S MA P76 BP S43 EP S43 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 813HV UT WOS:000220899100122 ER PT J AU Webber, AP Harker, JO Martin, JL Josephson, KR Alessi, CA AF Webber, AP Harker, JO Martin, JL Josephson, KR Alessi, CA TI Predictors of outcome of post-acute rehabilitation in nursing homes. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 17-21, 2004 CL Las Vegas, NV SP Amer Geriatr Soc C1 VA Greater Los Angeles Healthcare Syst, Sepulveda GRECC, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2004 VL 52 IS 4 SU S MA P431 BP S164 EP S164 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 813HV UT WOS:000220899100476 ER PT J AU Wiesenfeld, LA AF Wiesenfeld, LA TI Grannyland: Using a board game to teach geriatric psychiatry. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 17-21, 2004 CL Las Vegas, NV SP Amer Geriatr Soc C1 Bronx Vet Adm Med Ctr, Bronx, NY USA. Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2004 VL 52 IS 4 SU S MA P200 BP S85 EP S85 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 813HV UT WOS:000220899100245 ER PT J AU Young, AJ Rodriguez, KL AF Young, AJ Rodriguez, KL TI External health locus of control and advance directives: A matched-pair analysis of VA patients and providers. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 17-21, 2004 CL Las Vegas, NV SP Amer Geriatr Soc C1 VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, CHERP, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 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 APR PY 2004 VL 52 IS 4 SU S MA P426 BP S162 EP S163 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 813HV UT WOS:000220899100471 ER PT J AU Mele, D Pasanisi, G Heimdal, A Cittanti, C Guardigli, G Levine, RA Sutherland, G Ferrari, R AF Mele, D Pasanisi, G Heimdal, A Cittanti, C Guardigli, G Levine, RA Sutherland, G Ferrari, R TI Improved recognition of dysfunctioning myocardial segments by longitudinal strain rate versus velocity in patients with myocardial infarction SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID EMISSION-COMPUTED-TOMOGRAPHY; ACUTELY ISCHEMIC-MYOCARDIUM; HUMAN LEFT-VENTRICLE; REGIONAL LEFT; DOPPLER-ECHOCARDIOGRAPHY; QUANTITATIVE ASSESSMENT; CORONARY ANGIOPLASTY; PERFUSION SPECT; WALL-MOTION; ULTRASOUND AB Doppler tissue imaging (DTI) can measure myocardial velocities but velocities alone cannot distinguish active from passive wall motion, whereas this is possible by strain rate (SR) imaging (SRI). We evaluated the accuracy of SRI for recognition of abnormal regional systolic function compared with DTI, B-mode echocardiography, and anatomic M-mode in 24 patients with myocardial infarction who underwent gated stress Tc 99m sestamibi scan. Sensitivity and specificity for recognition of infarct segments were 91% and 84% for visual SRI, 63% and 73% for visual DTI, 78% and 71% for B-mode echocardiography, and 87% and 77% for anatomic M-mode, respectively. Peak SRs correlated with wall-motion assessment by B-mode echocardiography better than peak velocities (P = .66 vs .10), with less overlap between groups. Therefore, SRI improves evaluation of regional wall motion compared with DTI and conventional ultrasound techniques in patients with myocardial infarction, mainly because it identifies segments that are moving passively but not shortening normally. C1 Univ Hosp Ferrara, Div Cardiol, Ferrara, Italy. Univ Hosp Ferrara, Inst Nucl Med, Ferrara, Italy. Massachusetts Gen Hosp, Noninvas Cardiac Lab, Boston, MA 02114 USA. Katholieke Univ Leuven, Louvain, Belgium. RP Mele, D (reprint author), Univ Ferrara, Azienda Osped, Div Cardiol, Corso Giovecca 203, I-44100 Ferrara, Italy. EM donatomele@libero.it NR 42 TC 17 Z9 26 U1 0 U2 0 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 APR PY 2004 VL 17 IS 4 BP 313 EP 321 DI 10.1016/j.echo.2003.12.018 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 809QL UT WOS:000220651100004 PM 15044863 ER PT J AU Bedard, M Greif, JL Buckley, TC AF Bedard, M Greif, JL Buckley, TC TI International publication trends in the traumatic stress literature SO JOURNAL OF TRAUMATIC STRESS LA English DT Article DE trauma; publication trends; authorship; international ID REPRESENTATION; AUTHORSHIP; JOURNALS AB This analysis looked at international publication trends in the field of trauma by examining first author affiliations of over 13,000 trauma publications from 1987 to 2001. Searches were conducted using the Published International Literature on Traumatic Stress (PILOTS) database to determine frequency of international contributions. A similar search of the Journal of Traumatic Stress (JTS) was also conducted. Although the majority of trauma research comes from investigators in North America, examining publication trends over time revealed that trauma research is becoming increasingly international in its representation. Results suggest that of the overall trauma literature, 36% of contributions come from authors outside North America. Likewise, among JTS publications over the first 14 years of circulation, 27% came from authors outside North America. More recent publication years reflect higher levels of international contributions for both sources. The majority of trauma research published over the 15-year span was in English. Implications for the field of traumatic stress research are discussed. C1 VA Boston Healthcare Syst, Natl Ctr PTSD 116B2, Boston, MA 02131 USA. Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Buckley, TC (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B2, 150 S Huntington Ave, Boston, MA 02131 USA. EM todd.buckley@med.va.gov NR 8 TC 13 Z9 14 U1 1 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD APR PY 2004 VL 17 IS 2 BP 97 EP 101 DI 10.1023/B:JOTS.0000022615.03388.78 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 808XZ UT WOS:000220603100002 PM 15141782 ER PT J AU Kutter, CJ Wolf, EJ McKeever, VM AF Kutter, CJ Wolf, EJ McKeever, VM TI Predictors of veterans' participation in cognitive-behavioral group treatment for PTSD SO JOURNAL OF TRAUMATIC STRESS LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Association-for-the-Advancement-of-Behavior-Therapy CY 2002 CL Reno, NV DE posttraumatic stress disorder; cognitive-behavioral treatment; mental health service utilization; veterans ID POSTTRAUMATIC-STRESS-DISORDER; EXPOSURE; SERVICES; THERAPY; ANXIETY; DROPOUT; HELP AB Increasingly effective treatments for posttraumatic stress disorder (PTSD) have led to dramatic improvements in the lives of many trauma survivors; however, a significant subgroup of individuals with PTSD avoids mental health treatment. Little is known about the features distinguishing those who participate in treatment from those who do not. We analyzed archival clinical data from 197 male veterans who were evaluated in a Veterans Affairs Medical Center PTSD clinic. We found greater PTSD severity associated with initial enrollment and continued participation in a PTSD group treatment program, and we noted few differences on other background and symptom measures. These preliminary findings suggest possible directions for future research in this area, which may have implications for enhancing service delivery to individuals with PTSD. C1 VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. VA Puget Sound Healthcare Syst, Seattle, WA USA. RP Kutter, CJ (reprint author), White River Junction VA Med & Reg Off Ctr, 215 N Main St, White River Jct, VT 05009 USA. EM catherine.kutter@med.va.gov OI Wolf, Erika/0000-0003-2666-2435 NR 29 TC 5 Z9 5 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD APR PY 2004 VL 17 IS 2 BP 157 EP 162 DI 10.1023/B:JOTS.0000022622.71244.0f PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 808XZ UT WOS:000220603100009 PM 15141789 ER PT J AU Buckley, TC Holohan, D Greif, JL Bedard, M Suvak, M AF Buckley, TC Holohan, D Greif, JL Bedard, M Suvak, M TI Twenty-four-hour ambulatory assessment of heart rate and blood pressure in chronic PTSD and non-PTSD veterans SO JOURNAL OF TRAUMATIC STRESS LA English DT Article DE PTSD; blood pressure; heart rate; ambulatory monitoring ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM COMBAT VETERANS; CARDIOVASCULAR ACTIVITY; HYPERTENSION; DISEASE; VARIABILITY; REACTIVITY; RESPONSES; PROJECT; TRAUMA AB This study examined 24-hr levels of ambulatory heart rate (HR) and blood pressure (BP) in 2 groups of male veterans: 19 with chronic posttraumatic stress disorder (PTSD) and 17 who never met criteria for PTSD. The relationships between diagnostic status, basal cardiovascular activity, and cardiovascular reactivity to stress were examined. Hierarchical linear modeling analyses revealed that the PTSD group had higher resting HR than the non-PTSD group. Moreover, the PTSD group showed greater BP reactivity during times of affective distress than the non-PTSD group. The health care implications of these findings are discussed, as are directions for future research. C1 VA Boston Healthcare Syst, Natl Ctr PTSD 116B2, Boston, MA 02131 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Buckley, TC (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B2, 150 S Huntington Ave, Boston, MA 02131 USA. EM todd.buckley@med.va.gov NR 41 TC 28 Z9 28 U1 0 U2 5 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD APR PY 2004 VL 17 IS 2 BP 163 EP 171 DI 10.1023/B:JOTS.0000022623.01190.f0 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 808XZ UT WOS:000220603100010 PM 15141790 ER PT J AU Nigri, GR Kossodo, S Waterman, P Fungaloi, P LaMuraglia, GM AF Nigri, GR Kossodo, S Waterman, P Fungaloi, P LaMuraglia, GM TI Free radical attenuation prevents thrombosis and enables photochemical inhibition of vein graft intimal hyperplasia SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID GROWTH-FACTOR-BETA; PHOTODYNAMIC THERAPY; MOTEXAFIN LUTETIUM; ISCHEMIA-REPERFUSION; INJURY; REDUCTION; DISEASE; PHOTOANGIOPLASTY; SUPPRESSION; NEUTROPHILS AB Objective: Photodynamic therapy (PDT) inhibits post-interventional stenosis in balloon-injured arteries, but causes thrombosis when applied to vein grafts. This may result from added free radicals produced during the hypoxiareperfusion injury of vein graft implantation. The purposes of this study were to determine whether a free radical scavenger could inhibit vein graft thrombosis, enabling PDT to inhibit intimal hyperplasia; and to investigate the role of neutrophils, also a source of radicals, in this setting. Methods. Jugular vein bypass grafts of the common carotid artery were performed in rats. PDT was administered in situ to the vein graft and artery in the presence or absence of deferoxamine (DFX), an OH- scavenger. Results: PDT alone induced thrombosis in all untreated vein grafts. DFX administration or inhibition of neutrophil adhesion to the graft prevented PDT-induced vein graft thrombosis. Moreover, DFX given together with PDT significantly decreased vein graft intimal hyperplasia (0.010 mm(2) +/- 0.005 mm(2); p < .002) as compared with DFX alone (0.113 mm(2) +/- 0.009 mm(2)) or untreated control animals (0.112 +/- 0.007 mm(2)). Conclusions: OH- radicals and neutrophils both have key roles in PDT-induced vein graft thrombosis. By inhibiting free radical production or neutrophil adhesion to the graft, adequate PDT can be administered for successful inhibition of vein graft intimal hyperplasia. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg,Gen Surg Serv, Boston, MA 02114 USA. RP LaMuraglia, GM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg,Gen Surg Serv, WACC 464,15 Parkman St, Boston, MA 02114 USA. NR 35 TC 8 Z9 11 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD APR PY 2004 VL 39 IS 4 BP 843 EP 849 DI 10.1016/j.jvs.2003.11.028 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 902WL UT WOS:000227387300029 PM 15071453 ER PT J AU Sachs, Z Sharpless, NE DePinho, RA Rosenberg, N AF Sachs, Z Sharpless, NE DePinho, RA Rosenberg, N TI p16(Ink4a) interferes with Abelson virus transformation by enhancing apoptosis SO JOURNAL OF VIROLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; B-CELL TRANSFORMATION; TUMOR-SUPPRESSOR; TYROSINE KINASE; BONE-MARROW; INK4A LOCUS; ABL ONCOGENES; CYCLE ARREST; LUNG-CANCER; GENE AB Pre-B-cell transformation by Abelson virus (Ab-MLV) is a multistep process in which primary transformants are stimulated to proliferate but subsequently undergo crisis, a period of erratic growth marked by high levels of apoptosis. Inactivation of the p53 tumor suppressor pathway is an important step in this process and can be accomplished by mutation of p53 or down-modulation of p19(Arf), a p53 regulatory protein. Consistent with these data, pre-B cells from either p53 or Ink4a/Arf null mice bypass crisis. However, the Ink4a/Arf locus encodes both p19(Arf) and a second tumor suppressor, p16(Ink4a), that blocks cell cycle progression by inhibiting Cdk4/6. To determine if p16(Ink4a) plays a role in Ab-MLV transformation, primary transformants derived from Arf(-/-) and p16(Ink4a-/-) mice were compared. A fraction of those derived from Arf(-/-) animals underwent crisis, and even though all p16(Ink4a-/-) primary transformants experienced crisis, these cells became established more readily than cells derived from +/+ mice. Analyses of Ink4a/Arf(-/-) cells infected with a virus that expresses both v-Abl and p16(Ink4a) revealed that p16(Ink4a) expression does not alter cell cycle profiles but does increase the level of apoptosis in primary transformants. These results indicate that both products of the Ink4a/Arf locus influence Ab-MLV transformation and reveal that in addition to its well-recognized effects on the cell cycle, p16(Ink4a) can suppress transformation by inducing apoptosis. C1 Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Dept Pathol, Boston, MA 02111 USA. Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Grad Program Immunol, Boston, MA 02111 USA. Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Med Sci Training Program, Boston, MA 02111 USA. Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Ctr, Boston, MA 02115 USA. RP Rosenberg, N (reprint author), Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Dept Pathol, Jaharis 808,150 Harrison Ave, Boston, MA 02111 USA. EM naomi.rosenberg@tufts.edu FU NCI NIH HHS [CA 33771, R01 CA033771] NR 57 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2004 VL 78 IS 7 BP 3304 EP 3311 DI 10.1128/JVI.78.7.3304-3311.2004 PG 8 WC Virology SC Virology GA 804IY UT WOS:000220293600011 PM 15016851 ER PT J AU Madani, N Perdigoto, AL Srinivasan, K Cox, JM Chruma, JJ LaLonde, J Head, M Smith, AB Sodroski, JG AF Madani, N Perdigoto, AL Srinivasan, K Cox, JM Chruma, JJ LaLonde, J Head, M Smith, AB Sodroski, JG TI Localized changes in the gp120 envelope glycoprotein confer resistance to human immunodeficiency virus entry inhibitors BMS-806 and #155 SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; CD4 RECEPTOR-BINDING; HIV-1 GP41; VARIABLE REGIONS; ATOMIC-STRUCTURE; TYPE-1; NEUTRALIZATION; RETROVIRUS; EPITOPES; AIDS AB BMS-806 and the related compound, #155, are novel inhibitors of human immunodeficiency virus type 1 (HIV-1) entry that bind the gp120 exterior envelope glycoprotein. BMS-806 and #155 block conformational changes in the HIV-1 envelope glycoproteins that are induced by binding to the host cell receptor, CD4. We tested a panel of HIV-1 envelope glycoprotein mutants and identified several that were resistant to the antiviral effects of BMS-806 and #155. In the CD4-bound conformation of gp120, the amino acid residues implicated in BMS-806 and #155 resistance line the "phenylalanine 43 cavity" and a water-filled channel that extends from this cavity to the inner domain. Structural considerations suggest a model in which BMS-806 and #155 bind gp120 prior to receptor binding and, upon CD4 binding, are accommodated in the Phe-43 cavity and adjacent channel. The integrity of the nearby V1/V2 variable loops and N-linked carbohydrates on the V1/V2 stem indirectly influences sensitivity to the drugs. A putative binding site for BMS-806 and #155 between the gp120 receptor-binding regions and the inner domain, which is thought to interact with the gp41 transmembrane envelope glycoprotein, helps to explain the mode of action of these drugs. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Div AIDS, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. GlaxoSmithKline, King Of Prussia, PA 19406 USA. RP Sodroski, JG (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Jimmy Fund Bldg,Rm 824,44 Binney St, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU NIAID NIH HHS [AI24755, AI39420, R01 AI039420, R37 AI024755]; NIGMS NIH HHS [P01 GM056550, P01-GM56550]; NINDS NIH HHS [F32 NS043260, F32 NS43260 M] NR 52 TC 90 Z9 94 U1 0 U2 6 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 APR PY 2004 VL 78 IS 7 BP 3742 EP 3752 DI 10.1128/JVI.78.7.3742-3752.2004 PG 11 WC Virology SC Virology GA 804IY UT WOS:000220293600054 PM 15016894 ER PT J AU Han, ES Wu, YM McCarter, R Nelson, JF Richardson, A Hilsenbeck, SG AF Han, ES Wu, YM McCarter, R Nelson, JF Richardson, A Hilsenbeck, SG TI Reproducibility, sources of variability, pooling, and sample size: Important considerations for the design of high-density oligonucleotide array experiments SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID PROBE LEVEL DATA; GENE-EXPRESSION; SACCHAROMYCES-CEREVISIAE; QUANTITATIVE HYBRIDIZATION; MICROARRAY EXPERIMENTS; MESSENGER-RNA; BREAST-CANCER; PROFILES; NORMALIZATION; PREDICTION AB We have undertaken a series of experiments to examine several issues that directly affect design of gene expression studies using Affymetrix GeneChip arrays: probe-level analysis, need for technical replication, relative contribution of various sources of variability, and utility of pooling RNA from different samples. Probe-level data were analyzed by Affymetrix MAS 5.0, and three model-based methods, PM-MM and PM-only models by dChip, and the RMA model by Bioconductor, with the latter two providing the best performance. We found that replicate chips of the same RNA have limited value in reducing total variability, and for relatively highly expressed genes in this biologically homogeneous animal model of aging, about 11% of total variation is due to day effects and the remainder is approximately equally split between sample and residual sources. We also found that pooling samples is neither advantageous nor detrimental. Finally we suggest a strategy for sample size calculations using formulas appropriate when coefficients of variation are known, target effects are expressed as fold changes, and data can be assumed to be approximately lognormally distributed. C1 Univ Tulsa, Dept Biol Sci, Tulsa, OK 74104 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Baylor Coll Med, Breast Ctr, Houston, TX 77030 USA. RP Han, ES (reprint author), Univ Tulsa, Dept Biol Sci, 600 S Coll Ave, Tulsa, OK 74104 USA. EM eun-han@utulsa.edu FU NCI NIH HHS [P01CA30195]; NIA NIH HHS [AG-14674-04S1, AG-00746] NR 37 TC 49 Z9 52 U1 0 U2 1 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 APR PY 2004 VL 59 IS 4 BP 306 EP 315 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 812JM UT WOS:000220835800002 PM 15071073 ER PT J AU Yang, H Shi, MJ Story, J Richardson, A Guo, ZM AF Yang, H Shi, MJ Story, J Richardson, A Guo, ZM TI Food restriction attenuates age-related increase in the sensitivity of endothelial cells to oxidized lipids SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID GENETICALLY OBESE RATS; LOW CALORIE DIET; NITRIC-OXIDE; ADHESION MOLECULE-1; LEUKOCYTE ADHESION; OXIDATIVE STRESS; ATHEROSCLEROSIS; EXPRESSION; HYPERTENSION; DYSFUNCTION AB Age-related endothelial dysfunction has been suggested to play a role in atherogenesis. Food restriction (FR) has been shown to retard the development of atherosclerosis. The goal of this report is to assess the effect of aging and FR on endothelial functions, including the release of endothelial nitric oxide (NO) and the adhesion of mononuclear cells (MNCs) to endothelial cells (ECs). ECs were obtained from the aorta of young mice fed ad libitum (Y-AL), old mice fed ad libitum (O-AL), or a food-restricted diet (O-FR). When compared with those obtained from Y-AL and O-FR mice, ECs obtained from O-AL mice decreased the basal level of NO release and increased the basal level of peroxynitrite, superoxide, and hydrogen peroxide. In addition, ECs obtained from O-AL elevated the response to CuSO4-oxidized low-density lipoprotein (oxLDL). For example, incubation with oxLDL reduced NO release approximately 52% in ECs obtained from O-AL mice. In contrast, the same dose of oxLDL reduced NO release only approximately 40% in ECs obtained from Y-AL and O-FR mice. Moreover, the level of oxLDL-induced adhesion of MNCs and oxLDL-induced expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 was markedly higher in ECs obtained from O-AL mice as compared with those obtained from Y-AL and O-FR mice. These results suggest that aging increases the sensitivity of ECs in response to oxLDL-reduced endothelial NO release and oxLDL-increased adhesion of MNCs to ECs. FR attenuates age-related increase in the sensitivity of ECs to oxLDL, which might be responsible, at least in part, for the antiatherogenic action of FR. C1 Meharry Med Coll, Dept Pathol Anat & Cell Biol, Nashville, TN 37208 USA. Meharry Med Coll, Dept Physiol, Nashville, TN 37208 USA. Meharry Med Coll, Dept Internal Med, Nashville, TN 37208 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. RP Guo, ZM (reprint author), Meharry Med Coll, Dept Pathol Anat & Cell Biol, Nashville, TN 37208 USA. EM zguo@mmc.edu FU NHLBI NIH HHS [R15 HL071525, HL71525]; NIA NIH HHS [P03-AG13319]; NIGMS NIH HHS [S06 GM008037, GM08037] NR 32 TC 20 Z9 20 U1 0 U2 0 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 APR PY 2004 VL 59 IS 4 BP 316 EP 323 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 812JM UT WOS:000220835800003 PM 15071074 ER PT J AU Barnes, DE Tager, IB Satariano, WA Yaffe, K AF Barnes, DE Tager, IB Satariano, WA Yaffe, K TI The relationship between literacy and cognition in well-educated elders SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article; Proceedings Paper CT 55th Annual Meeting of the American-Academy-of-Neurology CY APR 02-03, 2003 CL HONOLULU, HI SP Amer Acad Neurol ID ADULT READING TEST; NEUROPSYCHOLOGICAL TEST-PERFORMANCE; MINI-MENTAL-STATE; ALZHEIMERS-DISEASE; PREMORBID INTELLIGENCE; AFRICAN-AMERICAN; OLDER-ADULTS; DEMENTIA; ABILITY; COMMUNITY AB Background. Literacy is correlated with general intelligence and is often used to estimate premorbid intelligence in persons with dementia. However, little is known about the relationship between literacy and specific cognitive domains. Methods. Study participants were 664 community-living adults aged 65 years or older who were participating in a community-based study of health and function in Sonoma, California. Literacy was measured using the North American Adult Reading Test, which evaluates the ability to pronounce words with irregular spellings (such as indict). Cognitive function was assessed using a neuropsychological test battery that included the Mini-Mental State Examination and measures of attention and executive function (Trails B, Stroup, Digit Symbol), verbal learning and memory (California Verbal Learning Test), and verbal fluency (letter "s," animals). Results. The mean age of the participants was 76 years, 50% were women, 97% were white, and 92% had 12 or more years of education. A strong, linear association was observed between literacy and all cognitive measures (all p <.001). Results were similar after adjustment for age, sex, education, and health-related covariates and were consistent in subgroups of the study population (e.g., women vs men; English vs other native languages). Education was not associated with most cognitive measures after adjustment for literacy. Conclusions. Literacy is strongly associated with cognitive function across all cognitive domains in well-educated, elderly white persons. Future studies should determine whether interventions to improve lifetime literacy may help prevent cognitive deterioration with age. C1 Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif Berkeley, Dept Epidemiol, Berkeley, CA 94720 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. RP Barnes, DE (reprint author), San Francisco VA Med Ctr, 4150 Clement St,MC 181G, San Francisco, CA 94121 USA. FU NIA NIH HHS [K23-AG00888, T32-AG00212, R01-AG09389]; NIMH NIH HHS [F31 MH012665, F31 MH012665-02, F31-MH12665] NR 29 TC 31 Z9 34 U1 0 U2 3 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 APR PY 2004 VL 59 IS 4 BP 390 EP 395 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 812JM UT WOS:000220835800013 PM 15071084 ER PT J AU Knight, EL Verhave, JC Spiegelman, D Hillege, HL De Zeeuw, D Curhan, GC De Jong, PE AF Knight, EL Verhave, JC Spiegelman, D Hillege, HL De Zeeuw, D Curhan, GC De Jong, PE TI Factors influencing serum cystatin C levels other than renal function and the impact on renal function measurement SO KIDNEY INTERNATIONAL LA English DT Article DE serum creatinine; serum cystatin C; creatinine clearance; renal function measurement; PREVEND ID GLOMERULAR-FILTRATION-RATE; REACTIVE PROTEIN; CREATININE CLEARANCE; REFERENCE RANGES; MARKERS; ASSOCIATION; IMPAIRMENT; DISEASE; OBESITY; ADULTS AB Background. It is well known that serum creatinine may be used as a marker of renal function only if taking into account factors that influence creatinine production, such as age, gender, and weight. Serum cystatin C has been proposed as a potentially superior marker than serum creatinine, because serum cystatin C level is believed to be produced at a constant rate and not to be affected by such factors. However, there are limited data on factors that may influence serum cystatin C levels, and there are limited data comparing cystatin C-based estimates of renal function with creatinine-based estimates that adjust for such factors, especially in individuals with normal, or mildly reduced, renal function. Methods. This was a cross-sectional study of 8058 inhabitants of the city of Groningen, The Netherlands, 28 to 75 years of age. Serum cystatin C and serum creatinine levels were measured, and creatinine clearance was determined from the average of two separate 24-hour urine collections. We performed multivariate analyses to identify factors independently associated with serum cystatin C levels after adjusting for creatinine clearance. Then, partial Spearman correlations were obtained after adjusting for factors that may influence serum cystatin C and creatinine levels. We also compared the goodness-of-fit (R 2)of different multivariate linear regression models including serum cystatin C level and serum creatinine level for the outcome of creatinine clearance. Results. Older age, male gender, greater weight, greater height, current cigarette smoking, and higher serum C-reactive protein (CRP) levels were independently associated with higher serum cystatin C levels after adjusting for creatinine clearance. After adjusting for age, weight, and gender, the partial Spearman correlations between creatinine and, respectively, serum cystatin C level and serum creatinine level were 0.29 (P < 0.001) and -0.42 (P < 0.001), respectively. The R-2 values for serum cystatin C level and serum creatinine level adjusted for age, weight, and gender were 0.38 and 0.42, respectively. The addition of cigarette smoking and serum CRP levels did not improve the R-2 value for the multivariate serum cystatin C-based model. Conclusion. Serum cystatin C appears to be influenced by factors other than renal function alone. In addition, we found no evidence that multivariate serum cystatin C-based estimates of renal function are superior to multivariate serum creatinine-based estimates. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Renal Div,Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Renal Unit, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Med Ctr Groningen, Dept Clin Pharmacol, Dept Cardiol, Dept Internal Med,Div Nephrol, Groningen, Netherlands. RP De Jong, PE (reprint author), Univ Groningen Hosp, Dept Internal Med, Div Nephrol, Hanzepl 1, NL-9713 GZ Groningen, Netherlands. EM p.e.de.jong@int.azg.nl RI de Zeeuw, Dick/E-9080-2014; Verhave, Jacobien/F-6786-2016 OI de Zeeuw, Dick/0000-0003-3434-7777; FU NIDDK NIH HHS [DK52866, T32DK07791] NR 36 TC 491 Z9 529 U1 1 U2 13 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD APR PY 2004 VL 65 IS 4 BP 1416 EP 1421 DI 10.1111/j.1523-1755.2004.00517.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 802AF UT WOS:000220135700032 PM 15086483 ER PT J AU Butt, AA Aldridge, KE Sanders, CV AF Butt, AA Aldridge, KE Sanders, CV TI Infections related to the ingestion of seafood Part I: viral and bacterial infections SO LANCET INFECTIOUS DISEASES LA English DT Review ID NORWALK-LIKE VIRUS; OYSTERS CRASSOSTREA-VIRGINICA; VIBRIO-VULNIFICUS INFECTION; GULF-COAST OYSTERS; AEROMONAS-HYDROPHILA INFECTION; POLYMERASE-CHAIN-REACTION; BOTULINUM TYPE-E; UNITED-STATES; LISTERIA-MONOCYTOGENES; SHELLFISH CONSUMPTION AB Foodbome diseases cause an estimated 76 million illnesses in the USA each year. Seafood is implicated in 10-19% of these illnesses. A causative agent can be traced in about 44% of seafood-related outbreaks, viruses accounting for around half of these illnesses. Although viruses are the most common cause of seafood-related infections, most hospitalisations and deaths are due to bacterial agents. A wide variety of viruses, bacteria, and parasites have been implicated in seafood-related outbreaks, which are reported worldwide. The factor most commonly associated with infection is consumption of raw or undercooked seafood. People with underlying disorders, particularly liver disease, are more susceptible to infection. The first part of this two-part review summarises the general incidence of seafood-related infections and discusses the common viral and bacterial causes of these infections. For each agent, the microbiology, epidemiology, mode of transmission, and treatment are discussed. In the May issue of the journal we will discuss parasites associated with seafood consumption, the safety of seafood, and the measures put in place in the USA to increase its safety. C1 Univ Pittsburgh, Div Infect Dis, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15213 USA. Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. Louisiana State Univ, Hlth Sci Ctr, Dept Med, Infect Dis Sect, New Orleans, LA USA. RP Butt, AA (reprint author), Univ Pittsburgh, Div Infect Dis, VA Pittsburgh Healthcare Syst, 3601 5th Ave,Suite 3A,Falk Bldg, Pittsburgh, PA 15213 USA. EM butta@msx.dept-med.pitt.edu NR 153 TC 100 Z9 102 U1 0 U2 10 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1473-3099 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD APR PY 2004 VL 4 IS 4 BP 201 EP 212 DI 10.1016/S1473-3099(04)00969-7 PG 12 WC Infectious Diseases SC Infectious Diseases GA 809II UT WOS:000220630000021 PM 15050937 ER PT J AU Heerema, NA Harbott, J Galimberti, S Camitta, BM Gaynon, PS Janka-Schaub, G Kamps, W Basso, G Pui, CH Schrappe, M Auclerc, MF Carroll, AJ Conter, V Harrison, CJ Pullen, J Raimondi, SC Richards, S Riehm, H Sather, HN Shuster, JJ Silverman, LB Valsecchi, MG AF Heerema, NA Harbott, J Galimberti, S Camitta, BM Gaynon, PS Janka-Schaub, G Kamps, W Basso, G Pui, CH Schrappe, M Auclerc, MF Carroll, AJ Conter, V Harrison, CJ Pullen, J Raimondi, SC Richards, S Riehm, H Sather, HN Shuster, JJ Silverman, LB Valsecchi, MG CA ALL-BFM Grp AIEOP Grp DCLSG Grp FRALLE Grp CCG Grp DFCI Grp POG Grp St Jude Grp UKALL Grp TI Secondary cytogenetic aberrations in childhood Philadelphia chromosome positive acute lymphoblastic leukemia are nonrandom and may be associated with outcome SO LEUKEMIA LA English DT Article DE Philadelphia chromosome; secondary abnormalities; prognosis; childhood acute lymphoblastic leukemia ID CHILDRENS CANCER GROUP; TERM FOLLOW-UP; PEDIATRIC-ONCOLOGY-GROUP; CHRONIC MYELOID-LEUKEMIA; CLINICAL-SIGNIFICANCE; PROGNOSTIC-SIGNIFICANCE; POOR-PROGNOSIS; ADVERSE RISK; TRIALS; GENE AB Additional chromosomal aberrations occur frequently in Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) of childhood. The treatment outcome of these patients is heterogeneous. This study assessed whether such clinical heterogeneity could be partially explained by the presence and characteristics of additional chromosomal abnormalities. Cytogenetic descriptions were available for 249 of 326 children with Ph+ ALL, diagnosed and treated by 10 different study groups/large single institutions from 1986 to 1996. Secondary aberrations were present in 61% of the cases. Chromosomes 9, 22, 7, 14, and 8 were most frequently abnormal. Most (93%) karyotypes were unbalanced. Three main cytogenetic subgroups were identified: no secondary aberrations, gain of a second Ph and/or >50 chromosomes, or loss of chromosome 7, 7p, and/or 9p, while other secondary aberrations were grouped as combinations of gain and loss or others. Of the three main cytogenetic subgroups, the loss group had the worst event-free survival (P=0.124) and disease-free survival (P=0.013). However, statistical significance was not maintained when adjusted for other prognostic factors and treatment. Karyotypic analysis is valuable in subsets of patients identified by molecular screening, to assess the role of additional chromosomal abnormalities and their correlation with clinical heterogeneity, with possible therapeutic implications. C1 Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. Dept Hematol & Oncol, Oncogenet Lab, Giessen, Germany. Univ Milano Bicocca, Dept Clin Med Prevent & Biotechnol, Sect Med Stat, Milan, Italy. Midwest Childrens Canc Ctr, Milwaukee, WI USA. Childrens Hosp, Childrens Ctr Canc & Blood Dis, Los Angeles, CA 90027 USA. Childrens Univ Hosp, Dept Hematol & Oncol, Hamburg, Germany. Univ Groningen Hosp, Dept Pediat, Groningen, Netherlands. Univ Padua, Dipartimento Pediat, Lab Oncoematol, I-35128 Padua, Italy. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. MHH Childrens Hosp, Hannover, Germany. Hop St Louis, Paris, France. Univ Alabama Birmingham, Birmingham, AL USA. Univ Southampton, Canc Sci Div, Cytogenet Grp, Southampton SO9 5NH, Hants, England. Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. Univ Oxford, Clin Trial Serv Unit, Oxford OX1 2JD, England. Univ Oxford, Epidemiol Studies Unit, Oxford OX1 2JD, England. Childrens Oncol Grp, Arcadia, CA USA. Univ Florida, Dept Stat, Gainesville, FL 32611 USA. Childrens Oncol Grp Res Data Ctr, Gainesville, FL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Osped Bambini Brescia, Palermo, Italy. RP Heerema, NA (reprint author), Ohio State Univ, Dept Pathol, 167 Hamilton Hall,1645 Neil Ave, Columbus, OH 43210 USA. EM heerema-1@medctr.osu.edu RI Schrappe, Martin/A-8109-2010; galimberti, stefania/H-2594-2012; OI BASSO, GIUSEPPE/0000-0002-2634-9302 NR 52 TC 50 Z9 51 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD APR PY 2004 VL 18 IS 4 BP 693 EP 702 DI 10.1038/sj.leu.2403324 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 811VS UT WOS:000220800000005 PM 15044926 ER PT J AU Sekeres, MA Stone, RM Zahrieh, D Neuberg, D Morrison, V De Angelo, DJ Galinsky, I Lee, SJ AF Sekeres, MA Stone, RM Zahrieh, D Neuberg, D Morrison, V De Angelo, DJ Galinsky, I Lee, SJ TI Decision-making and quality of life in older adults with acute myeloid leukemia or advanced myelodysplastic syndrome SO LEUKEMIA LA English DT Article; Proceedings Paper CT Leukemia 2002 Meeting CY 2002 CL Miami, FL DE acute myeloid leukemia; quality of life; decision-making; older adults; outcome ID ACUTE MYELOGENOUS LEUKEMIA; HIGH-DOSE CYTARABINE; ACUTE NONLYMPHOCYTIC LEUKEMIA; COLONY-STIMULATING FACTOR; SOUTHWEST-ONCOLOGY-GROUP; REMISSION-INDUCTION CHEMOTHERAPY; STAGE BREAST-CANCER; FORM HEALTH SURVEY; ELDERLY-PATIENTS; FAB CLASSIFICATION AB Older patients with acute myeloid leukemia (AML) and advanced myelodysplastic syndrome (aMDS) must decide between receiving intensive induction chemotherapy (IC) or nonintensive chemotherapy/best supportive care (NIC). Little information exists about what factors influence treatment decisions and what quality of life (QOL) is associated with treatment choices. We prospectively examined 43 patients 60 years or older who were interviewed at diagnosis and periodically over 1 year. IC choice was associated with younger age (66 vs 76 years, P = 0.01) and AML diagnosis, but not with performance status, comorbidities, or QOL. In total, 63% of all patients reported not being offered other treatment options despite physician documentation of alternatives. Patient and physician estimates of cure differed significantly: 74% of patients estimated their chance of cure to be 50% or greater, yet for 89% of patients physician estimates of cure were 10% or less. IC patients experienced decreased QOL at 2 weeks, but rebounded to baseline and to NIC levels by 6 weeks. Initial QOL is not associated with treatment choice in older AML and aMDS patients. Regardless of treatment choice, patients report not being offered treatment options and overestimate their chances of cure. In IC patients, QOL decreases during hospitalization but rebounds after discharge. C1 Cleveland Clin Fdn, Dept Hematol & Med Oncol, Cleveland, OH 44195 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Minneapolis Vet Adm Med Ctr, Minneapolis, MN USA. RP Sekeres, MA (reprint author), Cleveland Clin Fdn, Dept Hematol & Med Oncol, Desk R35,9500 Euclid Ave, Cleveland, OH 44195 USA. EM sekerem@ccf.org NR 54 TC 93 Z9 93 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD APR PY 2004 VL 18 IS 4 BP 809 EP 816 DI 10.1038/sj.leu.2403289 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 811VS UT WOS:000220800000019 PM 14762444 ER PT J AU Deininger, MWN McGreevey, L Willis, S Bainbridge, TM Druker, BJ Heinrich, MC AF Deininger, MWN McGreevey, L Willis, S Bainbridge, TM Druker, BJ Heinrich, MC TI Detection of ABL kinase domain mutations with denaturing high-performance liquid chromatography SO LEUKEMIA LA English DT Article DE BCR-ABL; mutation; imatinib; resistance; CML ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; GASTROINTESTINAL STROMAL TUMORS; BCR-ABL; IMATINIB MESYLATE; CHRONIC-PHASE; CYTOGENETIC RESPONSES; CLINICAL RESISTANCE; BLAST CRISIS; STI571 AB Mutations of the ABL kinase domain (KD) are common in patients with chronic myelogenous leukemia (CML) who develop resistance to imatinib. We developed an RT-PCR-based denaturing high-performance liquid chromatography (D-HPLC) assay to detect mutations of the ABL KD. Validation experiments using mixtures of wild type and mutant amplicons showed that the D-HPLC assay could detect mutant transcripts when they represented at least 15% of the total, and was thus twice as sensitive as automated sequencing. When D-HPLC was applied to 30 cDNAs from patients with imatinib resistance that had previously been characterized for KD mutations by direct sequencing of BCR-ABL RT-PCR products, there was concordance in 97% of samples. Resequencing confirmed the original mutations in all cases. In addition, sequencing of individual clones detected a mutation in one sample that had been mutation-positive by D-HPLC but wild type by conventional sequencing. In serial samples from the same individuals, D-HPLC detected mutations as early as 260 days before hematological relapse. D-HPLC is suitable for routine clinical monitoring of CML patients for emergence of KD mutations and may be useful for optimizing therapy. Early detection of emerging mutant clones may aid in guiding decisions regarding alternative treatment options. C1 Oregon Hlth & Sci Univ, BMT Leukemia Ctr, Inst Canc, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Portland VA Med Ctr, Inst Canc, Portland, OR USA. Howard Hughes Med Inst, Portland, OR USA. RP Deininger, MWN (reprint author), Oregon Hlth & Sci Univ, BMT Leukemia Ctr, Inst Canc, 3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. EM deininge@ohsu.edu FU NCI NIH HHS [1R01 CA65823, K24 CA82445] NR 27 TC 51 Z9 53 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD APR PY 2004 VL 18 IS 4 BP 864 EP 871 DI 10.1038/sj.leu.2403307 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 811VS UT WOS:000220800000025 PM 14973502 ER PT J AU Lacasce, A Howard, O Li, S Fisher, D Weng, A Neuberg, D Shipp, M AF Lacasce, A Howard, O Li, S Fisher, D Weng, A Neuberg, D Shipp, M TI Modified Magrath regimens for adults with Burkitt and Burkitt-like lymphomas: Preserved efficacy with decreased toxicity SO LEUKEMIA & LYMPHOMA LA English DT Article DE Burkitt; lymphoma; treatment; adults ID NONCLEAVED-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; CHEMOTHERAPY REGIMEN; RANDOMIZED TRIAL; HIGH-INTENSITY; CHILDREN; LEUKEMIA; THERAPY; CANCER AB Burkitt and Burkitt- like lymphomas are rapidly growing tumors which require specialized therapy. Although intensive, multi- agent regimens have been effective in children, results are more variable in adults. Magrath et al. previously described a regimen that was highly effective in children and young adults. This phase II study of a modified Magrath regimen was designed to assess its efficacy in older adults and reduce treatment- related toxicity. Fourteen patients with Burkitt/ Burkitt- like lymphoma and median age of 47 years were stratified into two categories: low- risk ( normal LDH and a single focus of disease measuring less than 10 cm, 3 patients) and high risk ( all other, 11 patients). Low- risk patients received three cycles of modified CODOX- M ( cyclophosphamide, doxorubicin, adriamycin, vincristine with intrathecal methotrexate and cytarabine followed by high- dose systemic methotrexate, regimen A). High- risk patients received four alternating cycles of regimens A and B ( A- B- A- B). Regimen B consisted of ifosfamide, cytarabine, etoposide and intrathecal methotrexate ( IVAC). The modified treatment regimen was associated with no grade 3/ 4 neuropathy and only one episode of grade 3/ 4 mucositis. All patients completed protocol therapy and there were no treatment- related deaths. Twelve patients ( 86%, 90% CI: 61 - 97%) achieved a complete response; 1 patient achieved a PR and 1 patient died of progressive disease. Nine patients ( 64%) are alive and disease free at a median follow- up of 29 months. This modified Magrath regimen is effective and well- tolerated in a representative group of older adult patients. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Shipp, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. RI Weng, Andrew/I-5015-2014 NR 18 TC 47 Z9 51 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD APR PY 2004 VL 45 IS 4 BP 761 EP 767 DI 10.1080/1042819031000141301 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 754QC UT WOS:000187327900020 PM 15160953 ER PT J AU Gross, J AF Gross, J TI How tadpoles lose their tails: path to discovery of the first matrix metalloproteinase SO MATRIX BIOLOGY LA English DT Article DE matrix metalloprotemase; tadpoles; amphibian; regeneration ID CORNEAL COLLAGENASE PRODUCTION; NEWT TRITURUS-VIRIDESCENS; HUMAN SKIN COLLAGENASE; NEUTRAL SALT SOLUTIONS; CONNECTIVE-TISSUE; COLLAGENOLYTIC ACTIVITY; REGENERATING LIMB; ADULT NEWT; ENZYME; HYALURONIDASE C1 Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Gross, J (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Bldg 149,Rm 3006,13th St, Charlestown, MA 02129 USA. EM jerry.gross@cbrc2.mgh.harvard.edu NR 75 TC 13 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD APR PY 2004 VL 23 IS 1 BP 3 EP 13 DI 10.1016/j.mathbio.2004.01.003 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 828WT UT WOS:000222005100002 PM 15172033 ER PT J AU Shifren, JL AF Shifren, JL TI The role of androgens in female sexual dysfunction SO MAYO CLINIC PROCEEDINGS LA English DT Article ID SURGICALLY MENOPAUSAL WOMEN; DEHYDROEPIANDROSTERONE REPLACEMENT; TESTOSTERONE CONCENTRATION; POSTMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; DESIRE; OOPHORECTOMY; DEFICIENCY; ESTROGENS; PROFILES AB There are many treatment options for female sexual dysfunction (FSD), with the optimal therapy depending on the etiology of the problem. The cause of sexual dysfunction is multifactorial and may include psychological problems such as depression or anxiety disorders, conflict within the relationship, partner performance and technique, issues relating to prior abuse, medical illness, medications, fatigue, stress, or gynecological problems that make sexual activity uncomfortable. The role of low androgen concentrations in FSD is gaining increasing attention. Available therapeutic options include adjusting medications, counseling, treating depression or anxiety, reducing stress and fatigue, sex therapy, devices, estrogen therapy for genitourinary atrophy, and possibly vasoactive substances. Although no androgen therapies are currently approved by the Food and Drug Administration for FSD, they are being used in clinical practice, and early clinical trial results suggest that they may be both effective and safe in the treatment of FSD, specifically low libido. Androgen therapy should be considered primarily in women who have a physiological reason for reduced androgen concentrations, including aging, hypopituitarism, oophorectomy, or adrenal insufficiency. Products in use include oral methyltestosterone and dehydroepiandrosterone, topical testosterone ointment, and testosterone implants and injections. Products available for men, including skin patches and gels, are currently being studied at doses appropriate for women. Possible risks include hirsutism, acne, liver dysfunction, lowering of the voice, adverse lipid changes, virilization of a female fetus, and, as androgens are aromatized to estrogens, potentially the risks of estrogen therapy. C1 Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Menopaus Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Shifren, JL (reprint author), Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Menopaus Program, 55 Fruit St,VBK 113, Boston, MA 02114 USA. NR 24 TC 36 Z9 39 U1 0 U2 4 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD APR PY 2004 VL 79 IS 4 SU S BP S19 EP S24 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 808TO UT WOS:000220591600005 PM 15065634 ER PT J AU Calvi, LM Shin, HI Knight, MC Weber, JM Young, MF Giovannetti, A Schipani, E AF Calvi, LM Shin, HI Knight, MC Weber, JM Young, MF Giovannetti, A Schipani, E TI Constitutively active PTH/PTHrP receptor in odontoblasts alters odontoblast and ameloblast function and maturation SO MECHANISMS OF DEVELOPMENT LA English DT Article DE parathyroid hormone; PTH-related protein; PTH/PTHrP receptor; odontoblast; ameloblast; cytodifferentiation; Sonic Hedgehog ID HORMONE-RELATED-PROTEIN; ENDOCHONDRAL BONE-FORMATION; PARATHYROID-HORMONE; TOOTH DEVELOPMENT; TRANSGENIC MICE; OSTEOBLASTIC CELLS; DENTAL DEVELOPMENT; ENAMEL KNOT; MOUSE TOOTH; IN-VITRO AB Parathyroid hormone (PTH)-related protein (PTH-rP) is an important autocrine/paracrine attenuator of programmed cell differentiation whose expression is restricted to the epithelial layer in tooth development. The PTH/PTHrP receptor (PPR) mRNA in contrast is detected in the dental papilla, suggesting that PTHrP and the PPR may modulate epithelial-mesenchymal interactions. To explore the possible interactions, we studied the previously described transgenic mice in which a constitutively active PPR is targeted to osteoblastic cells. These transgenic mice have a vivid postnatal bone and tooth phenotype, with normal tooth eruption but abnormal, widened crowns. Transgene mRNA expression was first detected at birth in the dental papilla and, at 1 week postnatally, in odontoblasts. There was no transgene expression in ameloblasts or in other epithelial structures. Prenatally, transgenic molars and incisors revealed no remarkable change. By the age of 1 week, the dental papilla was widened, with disorganization of the odontoblastic layer and decreased dentin matrix. In addition, the number of cusps was abnormally increased, the ameloblastic layer disorganized, and enamel matrix decreased. Odontoblastic and, surprisingly, ameloblastic cytodifferentiation was impaired, as shown by in situ hybridization and electron microscopy. Interestingly, ameloblastic expression of Sonic Hedgehog, a major determinant of ameloblastic cytodifferentiation, was dramatically altered in the transgenic molars. These data suggest that odontoblastic activation of the PPR may play an important role in terminal odontoblastic and, indirectly, ameloblastic cytodifferentiation, and describe a useful model to study how this novel action of the PPR may modulate mesenchymal/epithelial interactions at later stages of tooth morphogenesis and development. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Rochester, Sch Med, Dept Med, Endocrine Unit, Rochester, NY USA. Kyungpook Natl Univ, Sch Dent, Dept Oral Pathol, Taegu 702701, South Korea. NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. RP Schipani, E (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 501 Wellman Bldg, Boston, MA 02114 USA. EM schipani@helix.mgh.harvard.edu OI Calvi, Laura Maria/0000-0001-6969-239X FU NIDDK NIH HHS [K08 DK064381-03, K08 DK64381, K08 DK064381] NR 46 TC 22 Z9 27 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD APR PY 2004 VL 121 IS 4 BP 397 EP 408 DI 10.1016/j.mod.2004.02.004 PG 12 WC Developmental Biology SC Developmental Biology GA 823AR UT WOS:000221582600008 PM 15110049 ER PT J AU Goonan, KJ Stoltz, PK AF Goonan, KJ Stoltz, PK TI Leadership and management principles for outcomes-oriented organizations SO MEDICAL CARE LA English DT Article DE outcomes research; Baldrige National Quality Program; leadership; organizational performance; Malcolm Baldrige ID TQM; QUALITY; CARE AB Outcomes and effectiveness research has provided a wealth of information about interventions that can improve patient experience and outcomes. The challenges facing healthcare leaders today highlight the need for new research on how leadership and management principles can enable healthcare providers and systems to deploy this knowledge swiftly and effectively. The Baldrige National Quality Program (BNQP) is an education and award program established by the U.S. Congress in 1987 that supports American businesses seeking to improve product and service quality, customer and workforce satisfaction, efficiency, financial results, and overall capacity to perform and respond to changing circumstances. Award recipients show a constellation of strengths that suggest that certain basic leadership and management practices are correlated with a fundamental ability to achieve desired results. This article describes characteristics of highly effective organizations based on a review of Baldrige Award recipients, focuses on the application of these characteristics to healthcare settings, illustrates their application with best practices from SSM Health Care, the first-ever healthcare recipient in 2002, and presents several priorities for outcomes and effectiveness research to inform healthcare leadership and administration. C1 Massachusetts Gen Hosp, Inst Hlth Policy, Ctr Hlth Syst Design & Evaluat, Boston, MA 02116 USA. Henry Ford Syst, Qual Support Serv, Detroit, MI USA. RP Goonan, KJ (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, Ctr Hlth Syst Design & Evaluat, 50 Staniford St, Boston, MA 02116 USA. EM kgoonan@partners.org NR 15 TC 3 Z9 3 U1 1 U2 6 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 APR PY 2004 VL 42 IS 4 SU S BP 31 EP 38 DI 10.1097/01.mlr.0000120782.03031.b4 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 808HH UT WOS:000220559700006 ER PT J AU Glassman, PA Tanielian, T Harris, K Suarez, A Bradley, M Atkinson, SW Davies, W Williams, T AF Glassman, PA Tanielian, T Harris, K Suarez, A Bradley, M Atkinson, SW Davies, W Williams, T TI Provider perceptions of pharmacy management - Lessons from the military health system SO MEDICAL CARE LA English DT Article DE survey research; pharmacy benefits; physician attitudes; pharmaceutical care; formulary decision-making AB Objective: The objective of this study was to contrast experiences and opinion of providers in military treatment facilities, where a single formulary is used, with those of community providers where multiple formularies and preferred lists are commonly encountered. Study Design: We conducted cross-sectional surveys. Setting: The study was conducted at military and community practices that serve military beneficiaries. Participants: We studied randomly selected clinicians, stratified by military treatment facility (MTF) size or number of military beneficiaries served. The final samples included 566 eligible MTF and 557 private clinicians, with 69% and 38% response rates, respectively. Outcome Measures: We wanted to determine experiences with and opinions of formularies and/or preferred lists and related policies. Results: Sixty-three percent of military providers were very familiar with formulary content and 60% with nonformulary request procedures; 67% thought their formulary was up-to-date and 84% felt Pharmacy & Therapeutics (P&T) committees were responsive to providers. In contrast, 23% of community providers felt very familiar with (multiple) formulary content and 10% with nonformulary request procedures. Only 15% perceived that formularies were current and 34% thought P&T committees were responsive to providers. Statistically significant differences remained after analysis of potential bias. Conclusions: Community providers were less aware and less satisfied with pharmacy benefits management policies than military providers, likely as a result of their daily interactions with multiple, unrelated pharmacy management systems. Addressing the problems expressed by community providers is imperative for pharmacy benefits managers. C1 VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA USA. RAND Corp, Arlington, VA USA. SAMHSA, Off Appl Studies, Rockville, MD USA. Brooke Army Med Ctr, Ft Sam Houston, TX 78234 USA. TRICARE Management Act, Pharm Program, Falls Church, VA USA. RP Glassman, PA (reprint author), VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med, 111G,W Los Angeles Campus,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Peter.Glassman@med.va.gov NR 14 TC 7 Z9 7 U1 2 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 APR PY 2004 VL 42 IS 4 BP 361 EP 366 DI 10.1097/01.mlr.0000118862.92043.9b PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 807BA UT WOS:000220475800009 PM 15076813 ER PT J AU Jasper, JD Nickerson, CAE Ubel, PA Asch, DA AF Jasper, JD Nickerson, CAE Ubel, PA Asch, DA TI Altruism incentives, and organ donation - Attitudes of the transplant community SO MEDICAL CARE LA English DT Article DE attitudes; decision-making; health policy; incentives; organ donation; survey research ID FINANCIAL INCENTIVES; PUBLIC-ATTITUDES; FUTURES MARKET; DONORS; POLICY; COMPENSATION; FAMILIES; PROPOSAL; CONSENT AB Objectives: This study investigated the attitudes of the transplant community toward the current policy of altruistic organ donation and 6 alternative policies offering incentives to the donor family. Methods: Two hundred forty-nine transplant surgeons, 143 transplant coordinators, and 134 critical-care nurses rated the moral appropriateness and success of the current policy of altruistic donation, rated the moral appropriateness of the alternative policies, judged whether donation would increase or decrease under each alternative policy, and decided whether each alternative policy,should be put into effect. Results: All 3 professions believed the current policy of altruistic organ donation to be morally appropriate and most of the alternative policies to be morally appropriate or morally neutral. All 3 professions believed the current policy to be at best only moderately successful and judged most or all of the alternative policies to be likely to increase donation. All 3 professions favored implementing a policy offering donor recognition; approximately one half of the surgeons and one half of the coordinators also advocated implementing a policy offering $1500 toward funeral expenses. In all 3 professions, respondents' decisions to implement the alternative policies were more frequently related to those policies' moral appropriateness than to their likelihood of increasing organ donation. Conclusions: Specific incentives varied in their acceptability to the transplant community Attitudes of the transplant community toward incentives were not in accord with published criticisms of incentives. C1 Univ Toledo, Dept Psychol, Toledo, OH 43606 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Dept Operat & Informat Management, Philadelphia, PA 19104 USA. RP Jasper, JD (reprint author), Univ Toledo, Dept Psychol, 2801 W Bancroft St, Toledo, OH 43606 USA. EM jjasper@utnet.utoledo.edu OI Asch, David/0000-0002-7970-286X NR 47 TC 18 Z9 20 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD APR PY 2004 VL 42 IS 4 BP 378 EP 386 DI 10.1097/01.mlr.0000118863.47574.0f PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 807BA UT WOS:000220475800011 PM 15076815 ER PT J AU Scarra, GB Testori, A Mihm, M AF Scarra, GB Testori, A Mihm, M TI What is new in melanoma research: genetics and epidemiology of melanoma in 2003? Review of a workshop held in Milan in May 2003 SO MELANOMA RESEARCH LA English DT Review DE detection; early diagnosis; epidermiology; melanoma prevention; pigmented lesions clinic; sun protection factor; sunscreens; ultraviolet radiation ID CDKN2A GERMLINE MUTATIONS; MALIGNANT-MELANOMA; ANATOMIC SITE; CANCER; FAMILIES; BREAST; TRENDS; RISK; PREVENTION; DELETION C1 Ist Tumori, Genoa, Italy. European Inst Oncol, Milan, Italy. Harvard Univ, Sch Med, Boston, MA USA. RP Mihm, M (reprint author), Massachusetts Gen Hosp, Dept Dermatopathol, Warren 827,55 Fruit St, Boston, MA 02114 USA. EM MMIHM@PARTNERS.ORG RI Bianchi Scarra, Giovanna/G-8933-2014 OI Bianchi Scarra, Giovanna/0000-0002-6127-1192 NR 26 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD APR PY 2004 VL 14 IS 2 BP 77 EP 84 DI 10.1097/01.cmr.0000124208.72344.dc PG 8 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA 817ED UT WOS:000221159900001 PM 15057035 ER PT J AU Vidalain, PO Boxem, M Ge, H Li, SM Vidal, M AF Vidalain, PO Boxem, M Ge, H Li, SM Vidal, M TI Increasing specificity in high-throughput yeast two-hybrid experiments SO METHODS LA English DT Article DE yeast; two-hybrid; false-positives; high-throughput; large-scale; genomics proteomics ID PROTEIN-PROTEIN INTERACTIONS; SACCHAROMYCES-CEREVISIAE; C-ELEGANS; INTERACTION MAP; MAPPING DATA; DNA; IDENTIFICATION; INTERACTOME; SYSTEM; GENES AB Since its inception, the yeast two-hybrid (Y2H) system has proven to be an efficient system to identify novel protein-protein interactions. However, Y2H screens are sometimes criticized for generating high rates of false-positives. Minimizing false-positive interactions is especially important in proteome wide high-throughput (HT) Y2H. Here, we Summarize various approaches that reduce false-positives in HT-Y2H projects. We evaluated the potential of examining putative positives after removing the prey encoding plasmid by negative selection. We found that this method reliably identifies false-positives caused by spontaneous conversion of baits into auto-activators and provides significant time-savings in HT screens. In addition, we present a method to eliminate an important source of false-positives: contaminating prey plasmids. Y2H interactors can be wrongly identified due to the presence of two or more different plasmids in the cells of a single yeast colony. Of these independent plasmids, only one encodes a genuine interactor. Contaminating plasmids are eliminated by extended culture of yeast cells under positive selection for the interaction, allowing the identification of the true interaction partner. (C) 2003 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Vidal, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM Marc-Vidal@dfci.harvard.edu RI Boxem, Mike/B-8857-2011 OI Boxem, Mike/0000-0003-3966-4173 FU NCI NIH HHS [7R33CA81568-02]; NHGRI NIH HHS [5R01HG01715-02] NR 35 TC 95 Z9 101 U1 3 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD APR PY 2004 VL 32 IS 4 BP 363 EP 370 DI 10.1016/j.ymeth.2003.10.00 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 804HB UT WOS:000220288700003 PM 15003598 ER PT J AU Chen, T Duncan, MJ AF Chen, T Duncan, MJ TI Gingipain adhesin domains mediate Porphyromonas gingivalis adherence to epithelial cells SO MICROBIAL PATHOGENESIS LA English DT Article DE Porphyromonas gingivalis; gingipain; adherence; epithelia ID NEISSERIA-GONORRHOEAE; FIMBRIAE; PROTEASE; HEMAGGLUTINATION; FIBROBLASTS; BINDING AB Porphyromonas gingivalis, a Gram-negative oral anaerobe, interacts with epithelium lining the gingival sulcus. Continuing our studies on the role of gingipain cysteine proteinases in P. gingivalis adherence to epithelial cells, we showed that antibody raised to the recombinant adhesin domain of arg-gingipain A blocked bacterial attachment, providing new additional evidence that P. gingivalis adherence to epithelial cells is mediated by gingipain adhesin peptides. (C) 2003 Elsevier Ltd. All rights reserved. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. RP Duncan, MJ (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. EM mduncan@forsyth.org FU NIDCR NIH HHS [R01 DE10510] NR 16 TC 44 Z9 45 U1 0 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD APR PY 2004 VL 36 IS 4 BP 205 EP 209 DI 10.1016/j.micpath.2003.12.001 PG 5 WC Immunology; Microbiology SC Immunology; Microbiology GA 804CC UT WOS:000220275800004 PM 15001226 ER PT J AU Rumbaut, RE Randhawa, JK Smith, CW Burns, AR AF Rumbaut, RE Randhawa, JK Smith, CW Burns, AR TI Mouse cremaster venules are predisposed to light/dye-induced thrombosis independent of wall shear rate, CD18, ICAM-1, or P-selectin SO MICROCIRCULATION LA English DT Article DE arterioles; microcirculation; phototoxicity; platelets ID HAMSTER-CHEEK POUCH; IN-VIVO; PLATELET-AGGREGATION; NITRIC-OXIDE; VESSELS; MUSCLE; MICE AB Objective: Microvascular adhesion of platelets to endothelium occurs in response to various inflammatory stimuli, and in venules is often accompanied by adherent leukocytes. In a light/dye injury model, platelet adhesion and thrombi occur preferentially in venules, though the reasons for this predisposition are unknown. The authors sought to determine whether lower wall shear rates or leukocyte endothelial interactions accounted for preferential platelet thrombi formation in venules relative to arterioles. Methods: A light/dye injury model of microvascular thrombosis was used in the mouse cremaster microcirculation. Results: In wild-type mice (n = 17), the time to form microvascular platelet aggregates was delayed in arterioles by 3.1-fold relative to venules (p < .0001). However, arterioles with spontaneously low wall shear rates, as well as arterioles manipulated to reduce wall shear rate to venous levels, still had delayed thrombosis as compared to venules. Similarly, in animals deficient in CD18, P-selectin, or ICAM-1, the time to form platelet thrombi in arterioles was >3.0-fold higher than in venules. Conclusions: Mouse cremaster venules are predisposed to light/dye-induced microvascular thrombosis. The data suggest that functional differences between arteriolar and venular endothelial cells ( independent of wall shear rate and of CD18, P-selectin, and ICAM-1) account for the venular predisposition to thrombosis. C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Houston VA Med Ctr, Med Care Line, Houston, TX USA. RP Rumbaut, RE (reprint author), Baylor Coll Med, CNRC Room 6005,1100 Bates St, Houston, TX 77030 USA. EM rrumbaut@bcm.tmc.edu FU NHLBI NIH HHS [HL-42550, R01 HL064721, HL-64721]; NIAID NIH HHS [AI-46773] NR 20 TC 28 Z9 28 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1073-9688 J9 MICROCIRCULATION JI Microcirculation PD APR-MAY PY 2004 VL 11 IS 3 BP 239 EP 247 DI 10.1080/10739680490425949 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 829XR UT WOS:000222085500003 PM 15280078 ER PT J AU McCully, KS AF McCully, KS TI Homocysteine, vitamins, and prevention of vascular disease SO MILITARY MEDICINE LA English DT Article ID PATHOLOGY AB Within the past four decades, the efforts of investigators worldwide have established the amino acid homocysteine as an important factor in arteriosclerosis and diseases of aging. After its discovery in 1932, homocysteine was demonstrated to be an important intermediate in the metabolism of amino acids. However, little was known about the broader biomedical significance of homocysteine until 1962, when children with mental retardation, accelerated growth, dislocated ocular lenses, and frequent vascular thrombosis were found to excrete homocysteine in the urine. My study of two patients with homocystinuria caused by different inherited enzymatic disorders in 1968 disclosed advanced widespread arteriosclerotic plaques in both cases. This discovery led to the conclusion that homocysteine causes vascular disease by a direct effect on the cells and tissues of the arteries. This interpretation suggests that homocysteine is important in the pathogenesis of arteriosclerosis in persons with hereditary, dietary, environmental, hormonal, metabolic, and other factors predisposing them to hyperhomocysteinemia. Within the past decade, many major clinical and epidemiological studies have proven that hyperhomocysteinemia is a potent independent risk factor for vascular disease. According to the homocysteine theory of arteriosclerosis, insufficient dietary intake of the B vitamins, folic acid and pyridoxine, caused by losses of these nutrients during processing of foods, leads to elevation of blood homocysteine and vascular disease in the general population. The dramatic decline in cardiovascular mortality since the 1960s in the United States is attributed to fortification of the food supply by synthetic pyridoxine and folic acid. The recent Swiss Heart Study showed that B vitamins slowed restenosis in patients with coronary arteriosclerosis treated with angioplasty. Currently, more than 20 prospective, worldwide, interventional trials involving at least 100,000 participants are examining whether lowering plasma homocysteine levels with supplemental B vitamins will prevent mortality and morbidity from arteriosclerotic vascular disease. C1 Vet Adm Med Ctr W Roxbury, Pathol & Lab Med Serv, W Roxbury, MA 02132 USA. VA Boston Healthcare Syst, Boston Area Consolidated Labs, Boston, MA USA. RP McCully, KS (reprint author), Vet Adm Med Ctr W Roxbury, Pathol & Lab Med Serv, 1400 Veterans Foreign Wars Pkway, W Roxbury, MA 02132 USA. NR 4 TC 9 Z9 12 U1 0 U2 0 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD APR PY 2004 VL 169 IS 4 BP 325 EP 329 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 019IT UT WOS:000235829500016 PM 15132238 ER PT J AU Gomez-del Arco, P Maki, K Georgopoulos, K AF Gomez-del Arco, P Maki, K Georgopoulos, K TI Phosphorylation controls Ikaros's ability to negatively regulate the G(1)-S transition SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-KINASE CK2; DNA-BINDING PROTEINS; CELL-CYCLE; LYMPHOCYTE DEVELOPMENT; TUMOR-SUPPRESSOR; GENE; COMPLEXES; PROLIFERATION; REPRESSION; EXPRESSION AB Ikaros is a key regulator of lymphocyte proliferative responses. Inactivating mutations in Ikaros cause antigen-mediated lymphocyte hyperproliferation and the rapid development of leukemia and lymphoma. Here we show that Ikaros's ability to negatively regulate the G(1)-S transition can be modulated by phosphorylation of a serine/threonine-rich conserved region (p1) in exon 8. Ikaros phosphorylation in p1 is induced during the G(1)-S transition. Mutations that prevent phosphorylation in p1 increase Ikaros's ability to impede cell cycle progression and its affinity for DNA. Casein kinase II, whose increased activity in lymphocytes leads to transformation, is a key player in Ikaros Ill phosphorylation. We thus propose that Ikaros's activity as a regulator of the G(1)-S transition is controlled by phosphorylation in response to signaling events that down-modulate its DNA binding activity. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. RP Georgopoulos, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. EM katia.georgopoulos@cbrc2.mgh.harvard.edu RI Gomez-del Arco, Pablo/L-2728-2013 OI Gomez-del Arco, Pablo/0000-0001-6748-7157 FU NIAID NIH HHS [R01-AI380342] NR 39 TC 56 Z9 57 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2004 VL 24 IS 7 BP 2797 EP 2807 DI 10.1128/MCB.24.7.2797-2807.2004 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 804YK UT WOS:000220333800019 PM 15024069 ER PT J AU Inada, A Hamamoto, Y Tsuura, Y Miyazaki, J Toyokuni, S Ihara, Y Nagai, K Yamada, Y Bonner-Weir, S Seino, Y AF Inada, A Hamamoto, Y Tsuura, Y Miyazaki, J Toyokuni, S Ihara, Y Nagai, K Yamada, Y Bonner-Weir, S Seino, Y TI Overexpression of inducible cyclic AMP early repressor inhibits transactivation of genes and cell proliferation in pancreatic beta cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR ATF; CAMP-RESPONSIVE ELEMENT; INSULIN MESSENGER-RNA; ISLET CELLS; RIN-5F CELLS; I GENE; C-JUN; EXPRESSION; CREB; BINDING AB Transcriptional control mediated by the cyclic AMP-responsive element (CRE) represents-an important mechanism of gene regulation. To test our hypothesis that increased inducible cyclic AMP early repressor (ICER) Igamma inhibits function of CRE-binding proteins and thus disrupts CRE-mediated transcription in pancreatic beta cells, we generated transgenic mice with beta-cell-directed expression of ICER Igamma, a powerful repressor that is greatly increased in diabetes. Three transgenic lines clearly show that increased ICER Igamma expression in beta cells results in early severe diabetes. From birth islets were severely disorganized with a significantly increased proportion of et cells throughout the islet. Diabetes results from the combined effects of impaired insulin expression and a decreased number of beta cells. The decrease in beta cells appears to result from impaired proliferation rather than from increased apoptosis after birth. Cyclin A gene expression is impaired by the strong inhibition of ICER; the suppression of cyclin A results in a substantially decreased proliferation of beta cells in the postnatal period. These results suggest that CRE and CRE-binding factors have an important role in pancreatic beta-cell physiology not only directly by regulation of gene trans-activation but also indirectly by regulation of beta-cell mass. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. Kyoto Univ, Grad Sch Med, Dept Diabet & Clin Nutr, Kyoto 6068507, Japan. Kyoto Univ, Grad Sch Med, Dept Pathol & Biol Dis, Kyoto 6068507, Japan. Kyoto Univ, Grad Sch Med, Dept Geriatr, Kyoto 6068507, Japan. Osaka Univ, Sch Med, Div Stem Cell Regulat Res G6, Suita, Osaka 5650871, Japan. RP Bonner-Weir, S (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM susan.bonner-weir@joslin.harvard.edu RI Toyokuni, Shinya/C-1358-2010; Miyazaki, Jun-ichi/N-1976-2015 OI Toyokuni, Shinya/0000-0002-5757-1109; Miyazaki, Jun-ichi/0000-0003-2475-589X NR 56 TC 51 Z9 52 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2004 VL 24 IS 7 BP 2831 EP 2841 DI 10.1128/MCB.24.7.2831-2841.2004 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 804YK UT WOS:000220333800022 PM 15024072 ER PT J AU Cao, WH Daniel, KW Robidoux, J Puigserver, P Medvedev, AV Bai, X Floering, LM Spiegelman, BM Collins, S AF Cao, WH Daniel, KW Robidoux, J Puigserver, P Medvedev, AV Bai, X Floering, LM Spiegelman, BM Collins, S TI p38 mitogen-activated protein kinase is the central regulator of cyclic AMP-dependent transcription of the brown fat uncoupling protein 1 gene SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PPAR-GAMMA COACTIVATOR-1; RECEPTOR-GAMMA; MAP KINASE; HEPATIC GLUCONEOGENESIS; ADAPTIVE THERMOGENESIS; ADIPOSE-TISSUE; SB 239063; EXPRESSION; INHIBITOR; DIFFERENTIATION AB It is well established that catecholamine-stimulated thermogenesis in brown fat requires P-adrenergic elevations in cyclic AMP (cAMP) to increase expression of the uncoupling protein 1 (UCP1) gene. However, little is known about the downstream components of the signaling cascade or the relevant transcription factor targets thereof. Here we demonstrate that cAMP- and protein kinase A-dependent activation of p38 mitogen-activated protein kinase (MAPK) in brown adipocytes is an indispensable step in the transcription of the UCP1 gene in mice. By phosphorylating activating transcription factor 2 (ATF-2) and peroxisome proliferator-ctivated receptor gamma (PPARgamma) coativator 1alpha(PGC-1alpha) members of two distinct nuclear factor families, p38 MAPK controls the expression of the UCP1 gene through their respective interactions with a cAMP response element and a PPAR response element that both reside within a critical enhancer motif of the UCP1 gene. Activation of ATF-2 by p38 MAPK additionally serves as the cAMP sensor that increases expression of the PGC-1alpha gene itself in brown adipose tissue. In conclusion, our findings illustrate that by orchestrating the activity of multiple transcription factors, p38 MAPK is a central mediator of the cAMP signaling mechanism of brown fat that promotes thermogenesis. C1 Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Behav Sci & Pharmacol, Durham, NC 27710 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02115 USA. RP Collins, S (reprint author), CIIT, Ctr Hlth Res, 6 Davis Dr,POB 12137, Res Triangle Pk, NC 27709 USA. EM scollins@ciit.org FU NIDDK NIH HHS [R01 DK053092, R01 DK054024, R01 DK054477, R01-DK54024, R01-DK54477] NR 45 TC 230 Z9 245 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2004 VL 24 IS 7 BP 3057 EP 3067 DI 10.1128/MCB.24.7.3057-3067.2004 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 804YK UT WOS:000220333800042 PM 15024092 ER PT J AU Tou, LQ Liu, Q Shivdasani, RA AF Tou, LQ Liu, Q Shivdasani, RA TI Regulation of mammalian epithelial differentiation and intestine development by class I histone deacetylases SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTIONAL REPRESSION; VALPROIC ACID; CAENORHABDITIS-ELEGANS; ORGAN-CULTURE; N-COR; ACETYLATION; EXPRESSION; CELLS; GUT; MYOD AB The biochemical mechanisms underlying epigenetic control of gene expression are increasingly well known. In contrast, the contributions of individual modifications toward activation of lineage-specific genes during vertebrate development are poorly understood. Class II histone deacetylases (HDACs), which show restricted tissue distribution, regulate muscle-specific gene expression, in part through interactions with myogenic transcription factors. We have combined gene expression profiling with manipulation of fetal mouse intestinal tissue to define roles for other regulatory factors. We found that in the developing mouse intestine class I HDACs are confined to the prospective epithelium and that their levels decline coincidently with activation of differentiation genes, suggesting a functional relationship between these events. Overexpression of wild-type but not of mutant HDACs 1 and 2 in fetal intestine explants reverses expression of certain maturation markers. HDAC inhibitors, including the selective class I antagonist valproic acid, activate the same genes prematurely and accelerate cytodifferentiation. Chromatin immunoprecipitation of freshly isolated organs reveals early HDAC2 occupancy at differentiation gene promoters and corresponding histone hypoacetylation that reverses as HDAC levels fall. Thus, modulation of endogenous class I HDAC levels represents a previously unappreciated mechanism to enable onset of tissue-restricted gene expression in a developing mammalian organ. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM ramesh_shivdasani@dfci.harvard.edu FU NIDDK NIH HHS [R01 DK061139, R01DK61139] NR 47 TC 71 Z9 72 U1 2 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2004 VL 24 IS 8 BP 3132 EP 3139 DI 10.1128/MCB.24.8.3132-3139.2004 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 810DQ UT WOS:000220685400007 PM 15060137 ER PT J AU Stickle, NH Chung, J Klco, JM Hill, RP Kaelin, WG Ohh, M AF Stickle, NH Chung, J Klco, JM Hill, RP Kaelin, WG Ohh, M TI PVHL modification by NEDD8 is required for fibronectin matrix assembly and suppression of tumor development SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HYPOXIA-INDUCIBLE FACTOR; HIPPEL-LINDAU PROTEIN; DIRECT BINDING; REGULATE HIF; BETA-DOMAIN; ELONGIN-B; UBIQUITYLATION; DISEASE; COMPLEX; ALPHA AB Functional inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene is the cause of the familial VHL disease and most sporadic renal clear-cell carcinomas (RCC). pVHL has been shown to play a role in the destruction of hypoxia-inducible factor alpha (HIF-alpha) subunits via ubiquitin-mediated proteolysis and in the regulation of fibronectin matrix assembly. Although most disease-causing pVHL mutations hinder the regulation of the HIF pathway, every disease-causing pVHL mutant tested to date has failed to promote the assembly of the fibronectin matrix, underscoring its potential importance in VHL disease. Here, we report that a ubiquitin-like molecule called NEDD8 covalently modifies pVHL. A nonneddylateable pVHL mutant, while retaining its ability to ubiquitylate HIF, failed to bind to and promote the assembly of the fibronectin matrix. Expression of the neddylation-defective pVHL in RCC cells, while restoring the regulation of HIF, failed to promote the differentiated morphology in a three-dimensional growth assay and was insufficient to suppress the formation of tumors in SCID mice. These results suggest that NEDD8 modification of pVHL plays an important role in fibronectin matrix assembly and that in the absence of such regulation, an intact HIF pathway is insufficient to prevent VHL-associated tumorigenesis. C1 Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, Canada. Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada. Washington Univ, Sch Med, St Louis, MO 63110 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Mol Oncol, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Ohh, M (reprint author), Univ Toronto, Dept Lab Med & Pathobiol, 1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada. EM michael.ohh@utoronto.ca OI Klco, Jeffery/0000-0003-2961-6960 NR 33 TC 107 Z9 108 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2004 VL 24 IS 8 BP 3251 EP 3261 DI 10.1128/MCB.24.8.3251-3261.2004 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 810DQ UT WOS:000220685400018 PM 15060148 ER PT J AU Derjuga, A Gourley, TS Holm, TM Heng, HHQ Shivdasani, RA Ahmed, R Andrews, NC Blank, V AF Derjuga, A Gourley, TS Holm, TM Heng, HHQ Shivdasani, RA Ahmed, R Andrews, NC Blank, V TI Complexity of CNC transcription factors as revealed by gene targeting of the Nrf3 locus SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ELEMENT-MEDIATED EXPRESSION; LEUCINE ZIPPER PROTEIN; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; IN-SITU HYBRIDIZATION; HEME OXYGENASE-1 GENE; FACTOR NF-E2; FUNCTIONAL-CHARACTERIZATION; INDUCIBLE EXPRESSION; EMBRYONIC LETHALITY; MOLECULAR-CLONING AB Cap'n'collar (CNC) family basic leucine zipper transcription factors play crucial roles in the regulation of mammalian gene expression and development. To determine the in vivo function of the CNC protein Nrf3 (NF-E2-related factor 3), we generated mice deficient in this transcription factor. We performed targeted disruption of two Nrf3 exons coding for CNC homology, basic DNA-binding, and leucine zipper dimerization domains. Nrf3 null mice developed normally and revealed no obvious phenotypic differences compared to wild-type animals. Nrf3(-/-) mice were fertile, and gross anatomy as well as behavior appeared normal. The mice showed normal age progression and did not show any apparent additional phenotype during their life span. We observed no differences in various blood parameters and chemistry values. We infected wild-type and Nrf(-/-) mice with acute lymphocytic choriomeningitis virus and found no differences in these animals with respect to their number of virus-specific CD8 and CD4 T cells as well as their B-lymphocyte response. To determine whether the mild phenotype of Nrf3 null animals is due to functional redundancy, we generated mice deficient in multiple CNC factors. Contrary to our expectations, an absence of Nrf3 does not seem to cause additional lethality in compound Nrf3(-/-)/Nrf2(-/-) and Nrf3(-/-)/p45(-/-) mice. We hypothesize that the role of Nrf3 in vivo may become apparent only after appropriate challenge to the mice. C1 McGill Univ, Dept Med, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada. Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Wayne State Univ, Sch Med, Detroit, MI 48202 USA. RP Blank, V (reprint author), McGill Univ, Dept Med, Lady Davis Inst Med Res, 3755 Cote St Catherine Rd, Montreal, PQ H3T 1E2, Canada. EM volker.blank@mcgill.ca OI Andrews, Nancy/0000-0003-0243-4462 FU NHLBI NIH HHS [HL51057, HL63143, R01 HL051057, R01 HL063143, R56 HL063143]; NIAID NIH HHS [N01AI30048, AI30048]; NICHD NIH HHS [NIHP30-HD 18655, P30 HD018655] NR 63 TC 44 Z9 50 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2004 VL 24 IS 8 BP 3286 EP 3294 DI 10.1128/MCB.24.8.3286-3294.2004 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 810DQ UT WOS:000220685400021 PM 15060151 ER PT J AU Molk, JN Schuyler, SC Liu, JY Evans, JG Salmon, ED Pellman, D Bloom, K AF Molk, JN Schuyler, SC Liu, JY Evans, JG Salmon, ED Pellman, D Bloom, K TI The differential roles of budding yeast Tem1p, Cdc15p, and Bub2p protein dynamics in mitotic exit SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID SACCHAROMYCES-CEREVISIAE; MICROTUBULE DYNAMICS; CELL-CYCLE; SPINDLE ORIENTATION; NUCLEAR MIGRATION; CHECKPOINT PATHWAY; LIVING CELLS; ANAPHASE; GENE; MECHANISM AB In the budding yeast Saccharomyces cerevisiae the mitotic spindle must be positioned along the mother-bud axis to activate the mitotic exit network (MEN) in anaphase. To examine MEN proteins during mitotic exit, we imaged the MEN activators Tem1p and Cdc15p and the MEN regulator Bub2p in vivo. Quantitative live cell fluorescence microscopy demonstrated the spindle pole body that segregated into the daughter cell (dSPB) signaled mitotic exit upon penetration into the bud. Activation of mitotic exit was associated with an increased abundance of Tem1p-GFP and the localization of Cdc15p-GFP on the dSPB. In contrast, Bub2p-GFP fluorescence intensity decreased in mid-to-late anaphase on the dSPB. Therefore, MEN protein localization fluctuates to switch from Bub2p inhibition of mitotic exit to Cdc15p activation of mitotic exit. The mechanism that elevates Temlp-GFP abundance in anaphase is specific to dSPB penetration into the bud and Dhc1p and Lte1p promote Tem1p-GFP localization. Finally, fluorescence recovery after photobleaching (FRAP) measurements revealed Tem1p-GFP is dynamic at the dSPB in late anaphase. These data suggest spindle pole penetration into the bud activates mitotic exit, resulting in Tem1p and Cdc15p persistence at the dSPB to initiate the MEN signal cascade. C1 Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. MIT, Whitehead Inst, Cambridge, MA 02142 USA. RP Bloom, K (reprint author), Univ N Carolina, Dept Biol, CB 3280, Chapel Hill, NC 27599 USA. EM kerry_bloom@unc.edu FU NIGMS NIH HHS [GM61345-01, GM-32238, GM-24364, R37 GM024364, R01 GM032238, R37 GM061345, R01 GM061345, R37 GM032238, R01 GM024364] NR 50 TC 64 Z9 66 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD APR PY 2004 VL 15 IS 4 BP 1519 EP 1532 DI 10.1091/mbc.E03.09.0708 PG 14 WC Cell Biology SC Cell Biology GA 806RK UT WOS:000220450800004 PM 14718561 ER PT J AU Fiebiger, E Hirsch, C Vyas, JM Gordon, E Ploegh, HL Tortorella, D AF Fiebiger, E Hirsch, C Vyas, JM Gordon, E Ploegh, HL Tortorella, D TI Dissection of the dislocation pathway for type I membrane proteins with a new small molecule inhibitor, eeyarestatin SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID RETICULUM (ER)-ASSOCIATED DEGRADATION; TO-CYTOSOL DISLOCATION; ENDOPLASMIC-RETICULUM; INTRACELLULAR-TRANSPORT; PROTEASOME INHIBITORS; ANTIGEN PRESENTATION; HEAVY-CHAINS; ER; UBIQUITIN; COMPLEX AB The mammalian endoplasmic reticulum (ER)-to-cytosol degradation pathway for disposal of misfolded proteins is an attractive target for therapeutic intervention in diseases that are characterized by impaired protein degradation. The ability to do so is hampered by the small number of specific inhibitors available and by our limited understanding of the individual steps involved in this pathway. Cells that express a class I major histocompatibility complex (MHC) heavy chain-enhanced green fluorescent protein (EGFP) fusion protein and the human cytomegalovirus protein US11, which catalyzes dislocation of the class I MHC EGFP reporter, show only little fluorescence. Treatment with proteasome inhibitors increases their fluorescence by stabilizing EGFP-tagged MHC class I molecules. We used this change in signal intensity as a readout to screen a chemical library of 16,320 compounds and identified two structurally related compounds (eeyarestatin I and II) that interfered with the degradation of both EGFP-heavy chain and its endogenous unmodified class I MHC heavy chain counterpart. Eeyarestatin I also inhibited degradation of a second misfolded type I membrane protein, T-cell receptor a. Both compounds stabilize these dislocation substrates in the ER membrane, without preventing proteasomal turnover of cytosolic substrates. The new inhibitors must therefore interfere with a step that precedes proteasomal degradation. The use of eeyarestatin I thus allows the definition of a new intermediate in dislocation. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA. RP Ploegh, HL (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM ploegh@hms.harvard.edu RI Vyas, Jatin/Q-1627-2016; OI Vyas, Jatin/0000-0002-9985-9565; Tortorella, Domenico/0000-0003-0961-3535 FU NIAID NIH HHS [5R37-AI33456, R37 AI033456] NR 47 TC 53 Z9 53 U1 0 U2 7 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD APR PY 2004 VL 15 IS 4 BP 1635 EP 1646 DI 10.1091/mbc.E03-07-0506 PG 12 WC Cell Biology SC Cell Biology GA 806RK UT WOS:000220450800014 PM 14767067 ER PT J AU Xia, Y Sidis, Y Schneyer, A AF Xia, Y Sidis, Y Schneyer, A TI Overexpression of follistatin-like 3 in gonads causes defects in gonadal development and function in transgenic mice SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; ACTIVIN-BINDING PROTEIN; INHIBIN-ALPHA; GRANULOSA-CELLS; SERTOLI-CELLS; BETA-A; GENE; PROLIFERATION; EXPRESSION; DISORDERS AB Activin has numerous biological activities including regulation of follicular development, spermatogenesis, and steroidogenesis within the gonads. Activities of activin are regulated by follistatin (FST), an activin binding protein, and perhaps follistatin-like 3 (FSTL3; also known as FLRG and FSRP). FSTL3 is a recently described member of the FST family having an overall structure and activity profile similar to that of FST, including binding and neutralization of activin. FSTL3 is most highly expressed in the placenta and testis, whereas FST is highest in the ovary and kidney, suggesting that FSTL3 has biological actions that do not entirely overlap those of FST. To investigate the role of local FSTL3 as a potential regulator of activin action in gonad development and function, we examined FSTL3 expression in the mouse testis. FSTL3 protein was localized to Leydig cells, spermatagonia, and mature spermatids in normal male mice. We then created transgenic mice using a human FSTL3 cDNA driven by the mouse alpha-inhibin promoter. Three of five transgenic founders were fertile and were bred to establish lines. In the highest expressing line 3, transgene expression was largely restricted to gonads, with pituitary, adrenal, brain, and uterine expression being substantially lower. Gonad weights, sperm counts, and fertility were significantly reduced in transgenic males, and reduced litter size was evident in line 3 females. Within the testis, highest transgene expression was observed in Sertoli cells, and although most tubules showed evidence of normal spermatogenic development, degenerating tubules devoid of germ cells and Leydig cell hyperplasia were also evident in every line 3 animal examined. Ovaries from line 3 females contained fewer antral follicles and more apparent follicular atresia. Although circulating human FSTL3 levels were undetectable, FSH and LH levels in adult transgenic mice were not significantly different from wild-type animals. However, testosterone levels were significantly increased at d 21 and significantly reduced at d 60 compared with wild-type males. These results suggest that FSTL3 is likely to be a local regulator of activin action in gonadal development and gametogenesis and, further, that activin appears to have important actions in gonadal development and function that are critical for normal reproduction. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Schneyer, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX-5, Boston, MA 02114 USA. EM Schneyer.alan@mgh.harvard.edu FU NICHD NIH HHS [R01 HD 38777] NR 37 TC 36 Z9 36 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD APR 1 PY 2004 VL 18 IS 4 BP 979 EP 994 DI 10.1210/me.2003-0364 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 806IG UT WOS:000220427000017 PM 14739256 ER PT J AU Boecker, W Bernecker, OY Wu, JC Zhu, XS Sawa, T Grazette, L Rosenzweig, A del Monte, F Schmidt, U Hajjar, RJ AF Boecker, Wolfgang Bernecker, Oliver Y. Wu, Joseph C. Zhu, Xinsheng Sawa, Tomohiro Grazette, Luanda Rosenzweig, Anthony del Monte, Federica Schmidt, Ulrich Hajjar, Roger J. TI Cardiac-Specific Gene Expression Facilitated by an Enhanced Myosin Light Chain Promoter SO MOLECULAR IMAGING LA English DT Article DE Gene therapy; cardiac promoters; adenovirus AB Background: Adenoviral gene transfer has been shown to be effective in cardiac myocytes in vitro and in vivo. A major limitation of myocardial gene therapy is the extracardiac transgene expression. Methods: To minimize extracardiac gene expression, we have constructed a tissue-specific promoter for cardiac gene transfer, namely, the 250-bp fragment of the myosin light chain-2v (MLC-2v) gene, which is known to be expressed in a tissue-specific manner in ventricular myocardium followed by a luciferase (luc) reporter gene (Ad. 4 x MLC250.Luc). Rat cardiomyocytes, liver and kidney cells were infected with Ad. 4 x MLC.Luc or control vectors. For in vivo testing, Ad. 4 x MLC250.Luc was injected into the myocardium or in the liver of rats. Kinetics of promoter activity were monitored over 8 days using a cooled CCD camera. Results: In vitro: By infecting hepatic versus cardiomyocyte cells, we found that the promoter specificity ratio (luc activity in cardiomyocytes per liver cells) was 20.4 versus 0.9 (Ad. 4 x MLC250.Luc vs. Ad.CMV). In vivo: Ad. 4 x MLC250.Luc significantly reduced luc activity in liver (38.4-fold), lung (16.1-fold), and kidney (21.8-fold) versus Ad.CMV (p = .01); whereas activity in the heart was only 3.8-fold decreased. The gene expression rate of cardiomyocytes versus hepatocytes was 7:1 (Ad. 4 x MLC.Luc) versus 1:1.4 (Ad.CMV.Luc). Discussion: This new vector may be useful to validate therapeutic approaches in animal disease models and offers the perspective for selective expression of therapeutic genes in the diseased heart. Mol Imaging (2004) 3, 69-75. C1 [Hajjar, Roger J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Zhu, Xinsheng; Schmidt, Ulrich; Hajjar, Roger J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Sawa, Tomohiro] Teikyo Univ, Sch Med, Tokyo, Japan. [Wu, Joseph C.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RP Hajjar, RJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St,CNY 4,Room 4215, Charlestown, MA 02129 USA. EM rhajjar@partners.org FU National Institutes of Health (U. S.) [HL 57623, HL 71763, HL73375, HL069842, HL 697782]; Older Americans Independence Center (U. S.); Max Kade Foundation, New York FX This work was supported in part by grants from the National Institutes of Health: HL 57623, HL 71763, HL73375, (R. J. H.); HL069842 (F. dM), HL 697782 (U. S.) and the Older Americans Independence Center (U. S.). O. Y. B. is supported by a grant from the Max Kade Foundation, New York. R. J. H. is a Paul Beeson scholar of the American Federation of Aging Research. NR 23 TC 26 Z9 27 U1 0 U2 1 PU B C DECKER INC PI HAMILTON PA 69 JOHN STREET SOUTH, STE 310, HAMILTON, ONTARIO L8N 2B9, CANADA SN 1535-3508 J9 MOL IMAGING JI Mol. Imaging PD APR PY 2004 VL 3 IS 2 BP 69 EP 75 DI 10.1162/1535350041464847 PG 7 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA V22PW UT WOS:000208288100001 PM 15296671 ER PT J AU Call, ME Wucherpfennig, KW AF Call, ME Wucherpfennig, KW TI Molecular mechanisms for the assembly of the T cell receptor-CD3 complex SO MOLECULAR IMMUNOLOGY LA English DT Review DE T cell rcceptor; transmembrane; CD3 ID PRE-GOLGI DEGRADATION; ANTIGEN RECEPTOR; ALPHA-BETA; PROTEIN TRANSLOCATION; CD3 COMPLEX; ENDOPLASMIC-RETICULUM; ERYTHROPOIETIN RECEPTOR; MULTIVALENT STRUCTURE; TRANSMEMBRANE DOMAIN; SUBUNIT INTERACTIONS AB The T cell receptor (TCR)-CD3 complex represents on of the most intricate membrane receptor structures since it is built from six distinct chains. This complexity led to a number of different proposals for the arrangement of the receptor subunits, its stoichiometry and the mechanisms responsible for receptor triggering. Early work had demonstrated that basic and acidic transmembrane (TM) residues were involved in the assembly but the molecular arrangement could not be deduced due to the complexity of the receptor. Using a novel method for the isolation of intact radiolabeled protein complexes, we demonstrated that the complex assembled in the ER contains only a single TCRalphabeta heterodimer and one copy of each of the CD3deltaepsilon, CD3gammaepsilon and zeta-zeta signaling dimers. Surprisingly, assembly of each of the three signaling dimers with TCR was dependent on one of the three basic TCR TM residues as well as both acidic residues located in the TM domains of the interacting signaling dimer. Each assembly step thus results in the formation of a three-helix interface in the membrane that involves one basic and two acidic TM residues, and this arrangement effectively shields these ionizable residues at protein-protein interfaces from the lipid. Since proteins whose TM domains have exposed ionizable residues are not stably integrated into the lipid bilayer, assembly based on shielding of ionizable residues permits full equilibration of the receptor into the lipid bilayer and prevents degradation. Assembly. export of intact receptor complexes and degradation of unassembled components thus rely on the same organizing principle. (C) 2004 Elsevier Ltd. All rights reserved. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,Dana 1410, Boston, MA 02115 USA. EM wucherpf@mberr.harvard.edu OI Call, Matthew/0000-0001-5846-6469 FU NIAID NIH HHS [R01 AI 054520, R01 AI054520] NR 61 TC 43 Z9 46 U1 2 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD APR PY 2004 VL 40 IS 18 BP 1295 EP 1305 DI 10.1016/j.molimm.2003.11.017 PG 11 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 811JY UT WOS:000220769400001 PM 15072848 ER PT J AU Heidenreich, KA Linseman, DA AF Heidenreich, KA Linseman, DA TI Myocyte enhancer factor-2 transcription factors in neuronal differentiation and survival SO MOLECULAR NEUROBIOLOGY LA English DT Article DE neuron; apoptosis; brain; MADS-box; protein kinases; calcium signaling; muscle; development ID ACTIVATED PROTEIN-KINASE; CEREBELLAR GRANULE NEURONS; II HISTONE DEACETYLASES; CENTRAL-NERVOUS-SYSTEM; DNA-BINDING ACTIVITY; MADS-BOX GENE; FACTOR MEF2C; CARDIAC-HYPERTROPHY; FACTOR 2C; MUSCLE DEVELOPMENT AB Myocyte enhancer factor-2 (MEF2) transcription factors regulate genes that control critical cellular processes including proliferation, differentiation, and survival. Although MEF2 proteins were first identified as transcription factors that bound A/T rich DNA sequences and controlled muscle-specific genes during myogenic development, it is now apparent that MEF2 transcription factors are also highly expressed in neurons and are critical determinants of neuronal differentiation and fate. Here we focus our discussion on the role of MEF2 proteins in nervous tissue and the regulation of these transcription factors by calcium and phosphorylation signaling pathways. C1 Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. RP Heidenreich, KA (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. EM Kim.Heidenreich@UCHSC.edu FU NINDS NIH HHS [NS38619-01A1] NR 64 TC 56 Z9 58 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0893-7648 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD APR PY 2004 VL 29 IS 2 BP 155 EP 165 DI 10.1385/MN:29:2:155 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 822KB UT WOS:000221537000005 PM 15126683 ER PT J AU Yeh, E Cunningham, M Arnold, H Chasse, D Monteith, T Ivaldi, G Hahn, WC Stukenberg, PT Shenolikar, S Uchida, T Counter, CM Nevins, JR Means, AR Sears, R AF Yeh, E Cunningham, M Arnold, H Chasse, D Monteith, T Ivaldi, G Hahn, WC Stukenberg, PT Shenolikar, S Uchida, T Counter, CM Nevins, JR Means, AR Sears, R TI A signalling pathway controlling c-Myc degradation that impacts oncogenic transformation of human cells SO NATURE CELL BIOLOGY LA English DT Article ID TRANSACTIVATION DOMAIN; PROTEIN STABILITY; PHOSPHORYLATION; PIN1; ELEMENTS; BINDING; MICE; GENE; DIFFERENTIATION; PROLIFERATION AB The stability of c-Myc is regulated by multiple Ras effector pathways. Phosphorylation at Ser 62 stabilizes c-Myc, whereas subsequent phosphorylation at Thr 58 is required for its degradation. Here we show that Ser 62 is dephosphorylated by protein phosphatase 2A (PP2A) before ubiquitination of c-Myc, and that PP2A activity is regulated by the Pin1 prolyl isomerase. Furthermore, the absence of Pin1 or inhibition of PP2A stabilizes c-Myc. A stable C-MyC(T58A) mutant that cannot bind Pin1 or be dephosphorylated by PP2A replaces SV40 small T antigen in human cell transformation and tumorigenesis assays. Therefore, small T antigen, which inactivates PP2A, exerts its oncogenic potential by preventing dephosphorylation of c-Myc, resulting in c-Myc stabilization. Thus, Ras-dependent signalling cascades ensure transient and self-limiting accumulation of c-Myc, disruption of which contributes to human cell oncogenesis. C1 Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97239 USA. Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Howard Hughes Med Inst, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Med Oncol & Med, Boston, MA 02115 USA. Univ Virginia, Sch Med, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. Tohoku Univ, Inst Dev Aging & Canc, Aoba Ku, Sendai, Miyagi 9808575, Japan. RP Sears, R (reprint author), Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97239 USA. EM searsr@ohsu.edu RI ivaldi, giovanni /R-1106-2016; OI ivaldi, giovanni /0000-0002-7280-5698; Stukenberg, Todd/0000-0002-6788-2111 FU NCI NIH HHS [CA 100855, CA 86957, CA-82845] NR 38 TC 430 Z9 441 U1 3 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD APR PY 2004 VL 6 IS 4 BP 308 EP 318 DI 10.1038/ncb1110 PG 11 WC Cell Biology SC Cell Biology GA 808SA UT WOS:000220587600012 PM 15048125 ER PT J AU Freedman, ML Reich, D Penney, KL McDonald, GJ Mignault, AA Patterson, N Gabriel, SB Topol, EJ Smoller, JW Pato, CN Pato, MT Petryshen, TYL Kolonel, LN Lander, ES Sklar, P Henderson, B Hirschhorn, JN Altshuler, D AF Freedman, ML Reich, D Penney, KL McDonald, GJ Mignault, AA Patterson, N Gabriel, SB Topol, EJ Smoller, JW Pato, CN Pato, MT Petryshen, TYL Kolonel, LN Lander, ES Sklar, P Henderson, B Hirschhorn, JN Altshuler, D TI Assessing the impact of population stratification on genetic association studies SO NATURE GENETICS LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; HUMAN GENOME; ADMIXED POPULATIONS; PROSTATE-CANCER; SUSCEPTIBILITY; ADMIXTURE; DISEASE; MAP AB Population stratification refers to differences in allele frequencies between cases and controls due to systematic differences in ancestry rather than association of genes with disease. It has been proposed that false positive associations due to stratification can be controlled by genotyping a few dozen unlinked genetic markers. To assess stratification empirically, we analyzed data from 11 case-control and case-cohort association studies. We did not detect statistically significant evidence for stratification but did observe that assessments based on a few dozen markers lack power to rule out moderate levels of stratification that could cause false positive associations in studies designed to detect modest genetic risk factors. After increasing the number of markers and samples in a case-cohort study ( the design most immune to stratification), we found that stratification was in fact present. Our results suggest that modest amounts of stratification can exist even in well designed studies. C1 Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Med & Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Charlestown, MA USA. Vet Adm, Syracuse, NY USA. SUNY Upstate Med Ctr, Ctr Psychiat & Mol Genet, Syracuse, NY USA. Univ Hawaii, Canc Etiol Program, Canc Res Ctr Hawaii, Honolulu, HI 96822 USA. MIT, Dept Biol, Cambridge, MA USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. RP Reich, D (reprint author), Broad Inst, Program Med & Populat Genet, 1 Kendall Sq,Bldg 300, Cambridge, MA 02139 USA. EM reich@receptor.med.harvard.edu RI Altshuler, David/A-4476-2009; OI Altshuler, David/0000-0002-7250-4107; Topol, Eric/0000-0002-1478-4729 NR 29 TC 485 Z9 495 U1 1 U2 26 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 2004 VL 36 IS 4 BP 388 EP 393 DI 10.1038/ng1333 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 809OY UT WOS:000220647200023 PM 15052270 ER PT J AU Cantor, H AF Cantor, H TI Reviving suppression? SO NATURE IMMUNOLOGY LA English DT Editorial Material ID REGULATORY T-CELLS; TOLL-LIKE RECEPTORS; MICE; VACCINATION; MOUSE; ENCEPHALOMYELITIS; IDENTIFICATION; THYMECTOMY; TOLERANCE; ANTIGEN C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Cantor, H (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM harvey_cantor@dfci.harvard.edu NR 28 TC 16 Z9 17 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD APR PY 2004 VL 5 IS 4 BP 347 EP 349 DI 10.1038/ni0404-347 PG 3 WC Immunology SC Immunology GA 807QL UT WOS:000220515900002 PM 15052259 ER PT J AU Benn, SC Brown, RH AF Benn, SC Brown, RH TI Putting the heat on ALS SO NATURE MEDICINE LA English DT Editorial Material ID AMYOTROPHIC-LATERAL-SCLEROSIS; BIMOCLOMOL ELEVATES HEAT-SHOCK-PROTEIN-70; SHOCK FACTOR-I; UP-REGULATION; CO-INDUCER; PROTEINS; RATS; DISEASE; DAMAGE AB An enhancer of the heat shock response alleviates symptoms of neurodegeneration and prolongs lifespan in a mouse model of amyotrophic lateral sclerosis-even when administered after onset (pages 402-405). C1 Massachusetts Gen Hosp, Day Lab Neuromuscular Res, Charlestown, MA 02129 USA. RP Benn, SC (reprint author), Massachusetts Gen Hosp, Day Lab Neuromuscular Res, Charlestown, MA 02129 USA. EM sbenn@partners.org; rhbrown@partners.org NR 15 TC 8 Z9 9 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2004 VL 10 IS 4 BP 345 EP 347 DI 10.1038/nm0404-345 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 808RU UT WOS:000220587000019 PM 15057226 ER PT J AU Bjorkbacka, H Kunjathoor, VV Moore, KJ Koehn, S Ordija, CM Lee, MA Means, T Halmen, K Luster, AD Golenbock, DT Freeman, MW AF Bjorkbacka, H Kunjathoor, VV Moore, KJ Koehn, S Ordija, CM Lee, MA Means, T Halmen, K Luster, AD Golenbock, DT Freeman, MW TI Reduced atherosclerosis in MyD88-null mice links elevated serum cholesterol levels to activation of innate immunity signaling pathways SO NATURE MEDICINE LA English DT Article ID TOLL-LIKE RECEPTOR-4; NF-KAPPA-B; DEFICIENT MICE; MURINE MODELS; MACROPHAGES; LESIONS; ATHEROGENESIS; LDL; TRANSDUCTION; EXPRESSION AB Atherosclerosis, the leading cause of death in developed countries, has been linked to hypercholesterolemia for decades. More recently, atherosclerotic lesion progression has been shown to depend on persistent, chronic inflammation in the artery wall(1). Although several studies have implicated infectious agents in this process, the role of infection in atherosclerosis remains controversial(2-4). Because the involvement of monocytes and macrophages in the pathogenesis of atherosclerosis is well established, we investigated the possibility that macrophage innate immunity signaling pathways normally activated by pathogens might also be activated in response to hyperlipidemia. We examined atherosclerotic lesion development in uninfected, hyperlipidemic mice lacking expression of either lipopolysaccharide (LPS) receptor CD14 or myeloid differentiation protein-88 (MyD88), which transduces cell signaling events downstream of the Toll-like receptors (TLRs), as well as receptors for interleukin-1 (IL-1) and IL-18. Whereas the MyD88-deficient mice evinced a marked reduction in early atherosclerosis, mice deficient in CD14 had no decrease in early lesion development. Inactivation of the MyD88 pathway led to a reduction in atherosclerosis through a decrease in macrophage recruitment to the artery wall that was associated with reduced chemokine levels. These findings link elevated serum lipid levels to a proinflammatory signaling cascade that is also engaged by microbial pathogens. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Worcester, MA 01655 USA. RP Freeman, MW (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. EM freeman@molbio.mgh.harvard.edu OI Moore, kathryn/0000-0003-2505-2547; Bjorkbacka, Harry/0000-0003-3918-0857 FU NCRR NIH HHS [RR14466]; NHLBI NIH HHS [HL45098, HL66678]; NIDDK NIH HHS [DK50305] NR 33 TC 402 Z9 429 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2004 VL 10 IS 4 BP 416 EP 421 DI 10.1038/nm1008 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 808RU UT WOS:000220587000035 PM 15034566 ER PT J AU Raskind, M AF Raskind, M TI Cognition in AD: Long-term treatment benefits SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 8th International Montreal-Springfield Symposium on Advances in Alzheimer Therapy CY APR 14-17, 2004 CL Montreal, CANADA C1 VA Puget Sound Healthcare Syst, Seattle, WA USA. EM murray.raskind@med.va.gov 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD APR PY 2004 VL 25 SU 1 MA 77 BP S22 EP S22 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 808SW UT WOS:000220589800078 ER PT J AU Tanzi, R AF Tanzi, R TI Genetic analyses of late-onset Alzheimer disease SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 8th International Montreal-Springfield Symposium on Advances in Alzheimer Therapy CY APR 14-17, 2004 CL Montreal, CANADA C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. EM tanzi@helix.mgh.harvard.edu 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD APR PY 2004 VL 25 SU 1 MA 89 BP S25 EP S25 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 808SW UT WOS:000220589800090 ER PT J AU Tache, Y Perdue, MH AF Tache, Y Perdue, MH TI Role of peripheral CRF signalling pathways in stress-related alterations of gut motility and mucosal function SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE astressin; chronic stress; colonic motility; corticotrophin-releasing factor (CRF); CRF receptors; enteric nervous system; gastric motility; intestinal permeability; urocortin ID CORTICOTROPIN-RELEASING-FACTOR; IRRITABLE-BOWEL-SYNDROME; GASTROINTESTINAL-TRACT; RECEPTOR SUBTYPE-1; CONSCIOUS RATS; MOTOR-ACTIVITY; UROCORTIN; HORMONE; EXPRESSION; ANTAGONIST AB Central corticotrophin releasing-factor (CRF) signalling pathways are involved in the endocrine, behavioural and visceral responses to stress. Recent studies indicate that peripheral CRF-related mechanisms also contribute to stress-induced changes in gut motility and intestinal mucosal function. Peripheral injection of CRF or urocortin inhibits gastric emptying and motility through interaction with CRF2 receptors and stimulates colonic transit, motility, Fos expression in myenteric neurones and defecation through activation of CRF1 receptors. With regard to intestinal epithelial cell function, intraperitoneal CRF increases ion secretion and mucosal permeability to macromolecules. The motility and mucosal changes induced by peripheral CRF mimic those induced by acute stress. In addition, CRF receptor antagonists given peripherally prevent acute restraint and water avoidance stress-induced delayed gastric emptying, stimulation of colonic motor function and mucosal permeability. Similarly, early trauma enhanced intestinal mucosal dysfunction to an acute stressor in adult rats and the response is prevented by peripheral injection of CRF antagonist. Chronic psychological stress results in reduced host defence and initiates intestinal inflammation through mast cell-dependent mechanisms. These findings provide convergent evidence that activation of peripheral CRF receptors and mast cells are important mechanisms involved in stress-related alterations of gut physiology. C1 McMaster Univ, Intestinal Dis Res Program, Dept Pathol & Mol Med, Hamilton, ON L6J 3X6, Canada. Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Ctr Neurovisceral Sci & Womens Hlth, W Los Angeles Vet Affairs Med Ctr, Dept Med,Div Digest Dis, Los Angeles, CA 90024 USA. RP Perdue, MH (reprint author), McMaster Univ, Intestinal Dis Res Program, Dept Pathol & Mol Med, HSC-3 N5C,1200 Main St W, Hamilton, ON L6J 3X6, Canada. EM perdue@mcmaster.ca NR 44 TC 142 Z9 146 U1 1 U2 11 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 APR PY 2004 VL 16 SU 1 BP 137 EP 142 DI 10.1111/j.1743-3150.2004.00490.x PG 6 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 810PA UT WOS:000220715000026 PM 15066020 ER PT J AU Marinkovic, K AF Marinkovic, K TI Spatiotemporal dynamics of word processing in the human cortex SO NEUROSCIENTIST LA English DT Review DE language; functional neuroimaging; N400; fMRI; ERP; MEG ID EVENT-RELATED FMRI; TEMPORAL-LOBE; PREFRONTAL CORTEX; SEMANTIC MEMORY; HUMAN BRAIN; LANGUAGE COMPREHENSION; CORTICAL ACTIVITY; FORM AREA; FACE; RECOGNITION AB Understanding language relies on concurrent activation of multiple areas within a distributed neural network. Hemodynamic measures (WRI and PET) indicate their location, and electromagnetic measures (magnetoencephalography and electroencephalography) reveal the timing of brain activity during language processing. Their combination can show the spatiotemporal characteristics (where and when) of the underlying neural network. Activity to written and spoken words starts in sensory-specific areas and progresses anteriorly via respective ventral ("what") processing streams toward the simultaneously active supramodal regions. The process of understanding a word in its current context peaks about 400 ms after word onset. It is carried out mainly through interactions of the temporal and inferior prefrontal areas on the left during word reading and bilateral temporo-prefrontal areas during speech processing. Neurophysiological evidence suggests that lexical access, semantic associations, and contextual integration may be simultaneous as the brain uses available information in a concurrent manner, with the final goal of rapidly comprehending verbal input. Because the same areas may participate in multiple stages of semantic or syntactic processing, it is crucial to consider both spatial and temporal aspects of their interactions to appreciate how the brain understands words. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. RP Marinkovic, K (reprint author), Martinos Ctr, 149-2301 13th St, Charlestown, MA 02129 USA. EM xenia@nmr.mgh.harvard.edu FU NIAAA NIH HHS [K01 AA013402, AA13402]; NIBIB NIH HHS [EB00307, R01 EB000307]; NINDS NIH HHS [R01 NS018741, NS18741] NR 71 TC 43 Z9 43 U1 4 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD APR PY 2004 VL 10 IS 2 BP 142 EP 152 DI 10.1177/1073858403261018 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 804TW UT WOS:000220322000013 PM 15070488 ER PT J AU Levitsky, LL AF Levitsky, LL TI Childhood immunizations and chronic illness SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID THIMEROSAL; AUTISM C1 Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Levitsky, LL (reprint author), Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. NR 6 TC 2 Z9 4 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 1 PY 2004 VL 350 IS 14 BP 1380 EP 1382 DI 10.1056/NEJMp048034 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 808IJ UT WOS:000220562500002 PM 15070785 ER PT J AU Burstein, HJ Polyak, K Wong, JS Lester, SC Kaelin, CM AF Burstein, HJ Polyak, K Wong, JS Lester, SC Kaelin, CM TI Medical progress - Ductal carcinoma in situ of the breast SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID SURGICAL ADJUVANT BREAST; LYMPH-NODE BIOPSY; RANDOMIZED CONTROLLED-TRIAL; TERM FOLLOW-UP; LOCAL RECURRENCE; INTRADUCTAL-CARCINOMA; RADIATION-THERAPY; CONSERVING THERAPY; GENE-EXPRESSION; RISK-FACTORS C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM hburstein@partners.org FU NCI NIH HHS [P50 CA089393-040004, CA89393, P50 CA089393, P50 CA089393-010004, P50 CA089393-020004, P50 CA089393-030004, P50 CA089393-050004, R01 CA094074, R01 CA094074-01A1, R01 CA094074-02, R01 CA094074-03, R01 CA94074] NR 108 TC 287 Z9 312 U1 0 U2 12 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 1 PY 2004 VL 350 IS 14 BP 1430 EP 1441 DI 10.1056/NEJMra031301 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 808IJ UT WOS:000220562500010 PM 15070793 ER PT J AU Cornia, PB Lipsky, BA Dhaliwal, G Saint, S AF Cornia, PB Lipsky, BA Dhaliwal, G Saint, S TI Red snapper or crab? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PHYSICAL-EXAMINATION; HISTORY; MESOTHELIOMA C1 Vet Affairs Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Calif San Francisco, Sch Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA 94143 USA. Ann Arbor Vet Affairs Med Ctr, Ann Arbor, MI USA. Univ Michigan Hlth Syst, Dept Internal Med, Ann Arbor, MI USA. Univ Michigan Hlth Syst, Patient Safety Enhancement Program, Ann Arbor, MI USA. RP Cornia, PB (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, 1660 S Columbian Way,S-111-GIMC, Seattle, WA 98108 USA. EM paul.cornia@med.va.gov OI Lipsky, Benjamin A./0000-0001-9886-5114 FU AHRQ HHS [P20-HS11540] NR 12 TC 2 Z9 2 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 1 PY 2004 VL 350 IS 14 BP 1443 EP 1448 DI 10.1056/NEJMcps032443 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 808IJ UT WOS:000220562500012 PM 15070795 ER PT J AU Russell, TV Crawford, MA Woodby, LL AF Russell, TV Crawford, MA Woodby, LL TI Measurements for active cigarette smoke exposure in prevalence and cessation studies: Why simply asking pregnant women isn't enough SO NICOTINE & TOBACCO RESEARCH LA English DT Review ID RANDOMIZED CONTROLLED TRIAL; LOW-BIRTH-WEIGHT; SELF-REPORTS; ANTISMOKING INTERVENTIONS; MATERNAL SMOKING; HEALTH-EDUCATION; CARE; PROGRAM; COTININE; THIOCYANATE AB Tobacco smoke exposure during and after pregnancy may cause maternal, fetal, and infant morbidity and mortality. The purpose of this review is to (a) describe existing methods of measuring active tobacco exposure among pregnant women and (b) illustrate the usefulness of these measures in validating self-reported smoking status among these women. Medline, PsycINFO, and Academic Search Elite were used to identify measures of cigarette smoking exposure, prevalence reports, cessation and validity studies, and research on deception about smoking during pregnancy. Review of the research on smoking cessation among pregnant women since 1966 revealed that 36% of studies (9 out of 25) located used only self-report to assess smoking status. The remaining 16 studies used either significant other reports or at least one type of biochemical test to confirm self-report. Deception rates were reported at baseline only, follow-up only, or both in 15 studies. Three federal agencies in the United States collect data on self-reported smoking during pregnancy. Smoking prevalence rates are inconsistent among these agencies. This article demonstrates that measuring smoking status during pregnancy via self-report alone leads to discrepancies in national prevalence rates, deceptions in clinical practice disclosure, and inconsistencies in research study results. Evaluation studies that confirm smoking status among pregnant women by biochemical methods provide more accurate prevalence rates and lead to the most effective behavioral interventions to achieve cessation. National statistics should carry a disclaimer indicating the likelihood of underestimation. Researchers and clinicians should be trained in best-practice, evidence-based behavioral methods to assess prenatal smoking status and to assist those who desire to quit. C1 Univ Alabama, Sch Med, Dept Family & Community Med, Div Res, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, GRECC, Birmingham, AL 35294 USA. RP Russell, TV (reprint author), Univ Alabama, Sch Med, Dept Family & Community Med, Div Res, 930 20th St S,CH 371, Birmingham, AL 35294 USA. EM trussell@fms.uab.edu NR 76 TC 73 Z9 75 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD APR PY 2004 VL 6 SU 2 BP S141 EP S151 DI 10.1080/14622200410001669141 PG 11 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 823UY UT WOS:000221640100005 PM 15203817 ER PT J AU Tritos, NA Segal-Lieberman, G Vezeridis, PS Maratos-Flier, E AF Tritos, NA Segal-Lieberman, G Vezeridis, PS Maratos-Flier, E TI Estradiol-induced anorexia is independent of leptin and melanin-concentrating hormone SO OBESITY RESEARCH LA English DT Article DE estradiol; anorexia; leptin; melanin-concentrating hormone; neuropeptide Y ID DEFICIENT ARKO MICE; FOOD-INTAKE; NEUROPEPTIDE-Y; OVARIECTOMIZED RATS; BODY-WEIGHT; CENTRAL IMPLANTS; ADIPOSE-TISSUE; KNOCKOUT MICE; FEMALE RATS; ESTROGEN AB Objective: Treatment of male rodents with estradiol (E-2) is associated with anorexia and weight loss by poorly understood mechanisms. We examined the role of the orexigenic hypothalamic peptide melanin-concentrating hormone (MCH) and the appetite-inhibiting, fat-derived hormone leptin in mediating E-2-induced anorexia. Research Methods and Procedures: We studied the effect of E-2 treatment (implantation of either E-2 pellet or matching placebo) in male C57B1/6J mice, as well as in a lean mouse model (MCH knockout mice) and an obese model (leptin-deficient ob/ob mice). We also studied the effect of E-2 treatment in the context of high-fat diet. Results: We confirmed E-2 dose-dependent anorexia in male wild type mice fed a normal chow diet. E-2 treatment was associated with a significant decrease in body fat, serum leptin levels, and arcuate hypothalamic proopiomelanocortin expression. E-2-implanted mice also showed increased hypothalamic neuropeptide Y and MCH expression. As MCH has been implicated in E-2-induced hypophagia, we performed E-2, pellet implantation in MCH knockout mice and observed hypophagia and weight loss, indicating that MCH is not an essential mediator of E-2-induced anorexia. E-2-implanted ob/ob mice also had hypophagia and weight loss, indicating that leptin is not essential for E-2-induced anorexia. High-fat diet significantly exacerbated the effect of E-2 treatment, leading to a 99.6% decrease in food intake at 48 hours and a 30% loss of body weight within 1 week. Discussion: The anorectic effects of E-2 were independent of MCH and leptin. Our results suggested that E-2 may have effects on nutrient preferences. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Maratos-Flier, E (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM terry.maratos-flier@joslin.harvard.edu FU NIDDK NIH HHS [P30 DK46200, 5R01DK53978, 5R01DK56113, P01DK56116] NR 48 TC 30 Z9 30 U1 1 U2 3 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD APR PY 2004 VL 12 IS 4 BP 716 EP 724 DI 10.1038/oby.2004.84 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 813XU UT WOS:000220940600020 PM 15090642 ER PT J AU Cohen, LS Soares, CN Kyster, AK Winnick, JA Heller, V AF Cohen, LS Soares, CN Kyster, AK Winnick, JA Heller, V TI Intermittent use of venlafaxine in the treatment of premenstrual dysphoric disorder SO OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 52nd Annual Clinical Meeting of the American-College-of-Obstetricians-and-Gynecologists CY MAY 01-05, 2004 CL Philadelphia, PA SP Amer Coll Obstet & Gynecologists C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2004 VL 103 IS 4 SU S BP 83S EP 84S PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 876BH UT WOS:000225470000187 ER PT J AU Soares, CN Caron, J Schaefer, K Rubens, R Gottlieb, RH AF Soares, CN Caron, J Schaefer, K Rubens, R Gottlieb, RH TI Six-month efficacy study of eszopiclone in perimenopausal and postmenopausal women with chronic insomnia SO OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 52nd Annual Clinical Meeting of the American-College-of-Obstetricians-and-Gynecologists CY MAY 01-05, 2004 CL Philadelphia, PA SP Amer Coll Obstet & Gynecologists C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2004 VL 103 IS 4 SU S BP 102S EP 102S PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 876BH UT WOS:000225470000230 ER PT J AU D'Amico, AV AF D'Amico, AV TI Patient selection for prostate brachytherapy: More myth than fact - The Merrick/Wallner/Butler article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID RADIATION-THERAPY; CANCER; CARCINOMA; RADIOTHERAPY; IRRADIATION; EXTENSION; TRIAL C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. RP D'Amico, AV (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. NR 11 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 APR PY 2004 VL 18 IS 4 BP 456 EP 457 PG 2 WC Oncology SC Oncology GA 052DG UT WOS:000238210700011 ER PT J AU Gohongi, T Todoroki, T Fukumura, D Jain, RK AF Gohongi, T Todoroki, T Fukumura, D Jain, RK TI Influence of the site of human gallbladder xenograft (Mz-ChA-1) on angiogenesis at the distant site SO ONCOLOGY REPORTS LA English DT Article DE orthotopic human gallbladder cancer xenograft; Mz-ChA-1; TGF beta 1; angiogenesis; tissue microcirculation ID RENAL-CELL-CARCINOMA; ORGAN ENVIRONMENT; GROWTH-FACTOR; METASTASIS; EXPRESSION; ADHESION AB We reported that orthotopic xenograft of human gallbladder cancer (Mz-ChA-2) produced a greater amount of endogenous angiogenic inhibitory factors, however, only TGFbeta1 suppressed angiogenesis and tumor growth at the distant site (intracranium). The aim of this study was to confirm the validity of our previous findings that the site of the primary tumor would influence the angiogenesis in the distant site in a different xenograft of human gallbladder cancer (Mz-ChA-1). The growth rates, histology of the ectopic (flank) and orthotopic (gallbladder) xenografts, the plasma level of TGFBI, micro-circulation and angiogenesis in the distant site (intracranium) were estimated by size-measurement, hematoxylin and eosin staining, ELISA, intravital fluorescence microscopic observation and cranial window gel assay for angiogenesis. All experiments were performed in severe combined immunodeficient (SCID) mice. Orthotopic tumors grew faster and were less necrotic than ectopic tumors. Angiogenesis, vessel diameters, vessel density and leukocyte-rolling count in the distant site were significantly decreased in orthotopic tumor-bearing mice compared to those in either ectopic or no tumor-bearing mice. The plasma level of TGFbeta1 was significantly elevated in mice bearing orthotopic tumor as compared with ectopic and no tumor-bearing mice. Angiogenesis at the distant site was inhibited by the orthotopic xenograft of Mz-ChA-1 by the greatest amount of TGFBI production. The results of the present study together with our previous study imply that the primary tumor microenvironment is conducive to the angiogenesis at a distant site by the production of the endogenous angiogenesis inhibitor TGFbeta1. C1 Univ Tsukuba, Grad Sch Comprehens Human Sci, Inst Clin Med, Dept Surg, Tsukuba, Ibaraki 3058575, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA. RP Todoroki, T (reprint author), Univ Tsukuba, Grad Sch Comprehens Human Sci, Inst Clin Med, Dept Surg, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575, Japan. EM todorov@md.tsukuba.ac.jp FU NCI NIH HHS [R35-CA56591] NR 11 TC 4 Z9 4 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD APR PY 2004 VL 11 IS 4 BP 803 EP 807 PG 5 WC Oncology SC Oncology GA 802OI UT WOS:000220172400011 PM 15010876 ER PT J AU Yelin, D Bouma, BE Tearney, GJ AF Yelin, D Bouma, BE Tearney, GJ TI Generating an adjustable three-dimensional dark focus SO OPTICS LETTERS LA English DT Article ID BEAMS AB Conditions for generating a dark focus surrounded by light in all three dimensions are presented. A simple technique for generating such a dark region is demonstrated experimentally. The method is compared with previous attempts at creating a three-dimensional dark focus. (C) 2004 Optical Society of America. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Yelin, D (reprint author), Harvard Univ, Sch Med, 55 Fruit St,BAR 703, Boston, MA 02114 USA. EM dyelin@partners.org NR 7 TC 37 Z9 44 U1 0 U2 1 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 APR 1 PY 2004 VL 29 IS 7 BP 661 EP 663 DI 10.1364/OL.29.000661 PG 3 WC Optics SC Optics GA 805JN UT WOS:000220362700001 PM 15072350 ER PT J AU Correia, FF Plummer, AR Paster, BJ Dewhirst, FE AF Correia, FF Plummer, AR Paster, BJ Dewhirst, FE TI Genome size of human oral Treponema species by pulsed-field gel electrophoresis SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE genome sizes; oral treponeme groups; pulsed-field gel electrophoresis ID SPIROCHETE; DIVERSITY; SEQUENCE AB The genome sizes of seven strains of oral treponemes were determined using pulsed-field gel electrophoresis (PFGE). These strains represent members from six of the currently known cultivable oral treponeme groups. The PFGE fragments were digitally recorded and then quantitated using GIMP v 1.2, an image manipulation program. The results show that the six oral treponeme genomes are comparable in size, ranging from approximately 2.2 to 2.5 Mbp. The genome sizes of these strains are 20-25% smaller than Treponema denticola strains, which have genome sizes of approximately 2.8-3.0 Mbp. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. RP Correia, FF (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. EM fcorreia@forsyth.org FU NIDCR NIH HHS [DE-10374] NR 7 TC 3 Z9 3 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 APR PY 2004 VL 19 IS 2 BP 129 EP 131 DI 10.1111/j.0902-0055.2004.00126.x PG 3 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA 773HK UT WOS:000188892400013 PM 14871355 ER PT J AU Resto, VA Deschler, DG AF Resto, VA Deschler, DG TI Sinonasal malignancies SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID SQUAMOUS-CELL CARCINOMA; NASAL CAVITY; UNDIFFERENTIATED CARCINOMA; PARANASAL SINUSES; NEUROENDOCRINE CARCINOMA; OLFACTORY NEUROBLASTOMA; AGGRESSIVE NEOPLASM; RADIATION-THERAPY; MAXILLARY SINUS; ESTHESIONEUROBLASTOMA AB Sinonasal malignancies are a relatively rare and diverse group of tumors, each with varying biology, treatment, and outcome. These lesions present a great challenge to the otolaryngologist-head and neck surgeon because of their insidious and aggressive presentation, which often precludes curative treatment. These lesions can present with stereotypical signs and symptoms of rhinosinusitis, thus making an early initial diagnosis difficult. New insights into these diseases have led to novel treatment approaches that continue to be evaluated. This article reviews the presentation, diagnosis, and current management of these difficult tumors. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Deschler, DG (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM Daniel_Deschler@meei.harvard.edu RI Resto, Vicente/D-9891-2014 NR 33 TC 12 Z9 12 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 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD APR PY 2004 VL 37 IS 2 BP 473 EP + DI 10.1016/S0030-6665(03)00159-2 PG 16 WC Otorhinolaryngology SC Otorhinolaryngology GA 814YO UT WOS:000221010200018 PM 15064075 ER PT J AU Lerner, MA Spencer, T AF Lerner, MA Spencer, T TI Analysis of growth in children with ADHD during long-term therapy with once-daily OROS (R) methylphenidate SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 04, 2004 CL San Francisco, CA SP Pediatr Acad Soc C1 Univ Calif Irvine, Irvine, CA 92717 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2004 VL 55 IS 4 SU S MA 5 BP 1A EP 1A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 808TJ UT WOS:000220591100022 ER PT J AU Balasubramanian, S Tan, P Kieran, MW Klement, G Jenkins, KJ AF Balasubramanian, S Tan, P Kieran, MW Klement, G Jenkins, KJ TI Small molecule inhibitors as potential agents for treatment of obliterative pulmonary vein stenosis SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 04, 2004 CL San Francisco, CA SP Pediatr Acad Soc C1 Dana Farber Canc Inst, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2004 VL 55 IS 4 SU S MA 229 BP 41A EP 41A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 808TJ UT WOS:000220591100246 ER PT J AU McKinney, RE Cruz, MLS Powell, C Hughes, M Oleske, JM Winter, H Elgie, C Pardue, L Wolf, D Ortiz-Pujols, S Calles, NR McNamara, J Moye, J AF McKinney, RE Cruz, MLS Powell, C Hughes, M Oleske, JM Winter, H Elgie, C Pardue, L Wolf, D Ortiz-Pujols, S Calles, NR McNamara, J Moye, J TI International formula-based nutritional intervention for infants born to HIV-infected women SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 04, 2004 CL San Francisco, CA SP Pediatr Acad Soc C1 Duke Univ, Med Ctr, Durham, NC 27706 USA. Hosp Servidores Estado, Rio De Janeiro, Brazil. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Frontier Sci Tech Res Fdn, Amherst, NY USA. NIAID, NIH, DHHS, Bethesda, MD 20892 USA. Ross Prod Div, Columbus, OH USA. Soc Sci Syst, Silver Spring, MD USA. Texas Childrens Hosp, Houston, TX 77030 USA. RI Oleske, James/C-1951-2016 OI Oleske, James/0000-0003-2305-5605 NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2004 VL 55 IS 4 SU S MA 16 BP XLIII EP XLIII PN 2 PG 1 WC Pediatrics SC Pediatrics GA 808TJ UT WOS:000220591100017 ER PT J AU Perrin, JM Fluet, C Kuhlthau, KA Anderson, B Wells, N Epstein, S Turnbull, N Allen, D Tobias, C AF Perrin, JM Fluet, C Kuhlthau, KA Anderson, B Wells, N Epstein, S Turnbull, N Allen, D Tobias, C TI Benefits for employees with children with ADHD SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 04, 2004 CL San Francisco, CA SP Pediatr Acad Soc C1 MassGen Hosp Children, MGH, Ctr Child & Adolescent Hlth Policy, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Family Voices, Boston, MA USA. New England SERVE, Boston, MA USA. Boston Univ, Sch Publ Hlth, Working Grp Hlth & Disabil, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2004 VL 55 IS 4 SU S MA 386 BP 68A EP 68A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 808TJ UT WOS:000220591100403 ER PT J AU Friedman, SL Choueiri, R Gilmore, D AF Friedman, SL Choueiri, R Gilmore, D TI Can we improve pediatric skilled nursing facility caregivers understanding of end of life care? SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 04, 2004 CL San Francisco, CA SP Pediatr Acad Soc C1 Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Massachusetts, Inst Community Inclus, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2004 VL 55 IS 4 SU S MA 459 BP 81A EP 81A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 808TJ UT WOS:000220591100476 ER PT J AU Belcher, HME Kraut, MA Slifer, KJ Cataldo, MD Stern, SS Sparks, BF Pulsifer, MB Butz, AM AF Belcher, HME Kraut, MA Slifer, KJ Cataldo, MD Stern, SS Sparks, BF Pulsifer, MB Butz, AM TI Children with in-utero drug exposure: Preliminary MRI findings SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 04, 2004 CL San Francisco, CA SP Pediatr Acad Soc C1 Kennedy Krieger Inst, Baltimore, MD USA. Johns Hopkins Sch Med, Dept Pediat, Baltimore, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Univ Washington, Seattle, WA 98195 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2004 VL 55 IS 4 SU S MA 463 BP 82A EP 82A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 808TJ UT WOS:000220591100480 ER PT J AU Hoffman, MT Faraone, SV AF Hoffman, MT Faraone, SV CA CONCERTA Study Grp TI Predicting drug holiday use in children with ADHD SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 04, 2004 CL San Francisco, CA SP Pediatr Acad Soc C1 Univ Buffalo, Study Grp, Sch Med & Biomed Sci, Buffalo, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2004 VL 55 IS 4 SU S MA 480 BP 85A EP 85A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 808TJ UT WOS:000220591100497 ER PT J AU Smaldone, A Arons, R Wilson, TA Weinger, K AF Smaldone, A Arons, R Wilson, TA Weinger, K TI Racial disparity and childhood ketoacidosis: A tale of two cities SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 04, 2004 CL San Francisco, CA SP Pediatr Acad Soc C1 Joslin Diabet Ctr, Behav Res, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2004 VL 55 IS 4 SU S MA 763 BP 135A EP 135A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 808TJ UT WOS:000220591100796 ER PT J AU Rhoads, DB Thomas, MK Wang, L Coffinier, C Eddu, G Yaniv, M Levitsky, LL AF Rhoads, DB Thomas, MK Wang, L Coffinier, C Eddu, G Yaniv, M Levitsky, LL TI Altered islet gene expression in mice with selective deletion of the HNF1 beta (MODY5) gene in beta cells SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 04, 2004 CL San Francisco, CA SP Pediatr Acad Soc C1 MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA USA. Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Inst Pasteur, Unite Virus Oncongenes, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2004 VL 55 IS 4 SU S MA 857 BP 152A EP 152A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 808TJ UT WOS:000220591100890 ER PT J AU Aye, T Toschi, E Gaudet, J Sharma, A Sgroi, D Bonner-Weir, S AF Aye, T Toschi, E Gaudet, J Sharma, A Sgroi, D Bonner-Weir, S TI Ductal origin of beta cells suggested by transient expression of markers in new beta cells SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 04, 2004 CL San Francisco, CA SP Pediatr Acad Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2004 VL 55 IS 4 SU S MA 861 BP 153A EP 153A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 808TJ UT WOS:000220591100894 ER PT J AU Bastepe, M Frohlich, LF Linglart, A Juppner, H AF Bastepe, M Frohlich, LF Linglart, A Juppner, H TI Paternally imprinted autosomal dominant form of pseudohypoparathyroidism type Ib (AD-PHP-Ib) is associated with a heterozygous 3-kb deletion upstream of GNAS SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 04, 2004 CL San Francisco, CA SP Pediatr Acad Soc C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp Children, Pediat Nephrol Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2004 VL 55 IS 4 SU S MA 903 BP 160A EP 160A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 808TJ UT WOS:000220591100935 ER PT J AU Mahmud, FH Linglart, A Bastepe, M Juppner, H Lteif, AN AF Mahmud, FH Linglart, A Bastepe, M Juppner, H Lteif, AN TI Familial pseudohypoparathyroidism type Ib presenting as "paroxysmal dyskinesia" SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 04, 2004 CL San Francisco, CA SP Pediatr Acad Soc C1 Mayo Clin, Rochester, MN USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2004 VL 55 IS 4 SU S MA 900 BP 160A EP 160A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 808TJ UT WOS:000220591100932 ER PT J AU Tanski, SE Winickoff, JP McMillen, RC Klein, JD Weitzman, M AF Tanski, SE Winickoff, JP McMillen, RC Klein, JD Weitzman, M TI The more parents smoke, the less likely they are to have rules limiting children's smoke exposure in homes and vehicles SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Societies/Society-for-Pediatric-Research CY MAY 03-06, 2003 CL SEATTLE, WA SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Cont Educ C1 Univ Rochester, AAP Ctr Child Hlth Res, Rochester, NY USA. Univ Rochester, Strong Childrens Res Ctr, Rochester, NY USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02115 USA. Mississippi State Univ, Social Sci Res Ctr, Starkville, MS USA. RI McMillen, Robert/A-9326-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2004 VL 55 IS 4 SU S MA 1199 BP 212A EP 212A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 808TJ UT WOS:000220591101248 ER PT J AU Witt, WP Niemeck, T Fortuna, L Kahn, R Winickoff, J Kuhlthau, K Pirraglia, PA Ferris, T AF Witt, WP Niemeck, T Fortuna, L Kahn, R Winickoff, J Kuhlthau, K Pirraglia, PA Ferris, T TI Factors related to children's seat belt use: The importance of maternal psychological distress and mothers' own lack of seat belt SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 03-06, 2003 CL SEATTLE, WA SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Continuing Educ C1 Northwestern Univ, Freinberg Sch Med, Chicago, IL 60611 USA. Harvard Univ, Sch Med, Cambridge Hlth Alliance, Somerville, MA USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Harvard Univ, Sch Med, MassGen Hosp Children, Boston, MA 02115 USA. Brown Univ, Sch Med, Rhode Isl Hosp, Providence, RI 02912 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2004 VL 55 IS 4 SU S MA 1387 BP 245A EP 245A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 808TJ UT WOS:000220591101436 ER PT J AU Ellis, JM Gura, KM Patterson, A Neufeld, EJ AF Ellis, JM Gura, KM Patterson, A Neufeld, EJ TI Development and validation of guidelines for Enoxaparin use in high risk pediatric patients SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 03-06, 2003 CL SEATTLE, WA SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Continuing Educ C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Sch Pharm, Dept Pharm Practice, Storrs, CT USA. Childrens Hosp, Dept Pharm, Boston, MA 02115 USA. Childrens Hosp, Dept Hematol, Boston, MA 02115 USA. RI Neufeld, Ellis/F-9331-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2004 VL 55 IS 4 SU S MA 1628 BP 286A EP 286A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 808TJ UT WOS:000220591101677 ER PT J AU Kushak, RI Nestoridi, E Lambert, JW Selig, MK Ingelfinger, JR Grabowski, EF AF Kushak, RI Nestoridi, E Lambert, JW Selig, MK Ingelfinger, JR Grabowski, EF TI Activated endothelial cells shed significant tissue factor activity, as both detached cells and microparticles, into surrounding medium SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 03-06, 2003 CL SEATTLE, WA SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Continuing Educ C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. MassGen Hosp Children, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2004 VL 55 IS 4 SU S MA 1633 BP 287A EP 287A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 808TJ UT WOS:000220591101682 ER PT J AU Leary, RJ Mackeigan, S Thornley, I Shimamura, A AF Leary, RJ Mackeigan, S Thornley, I Shimamura, A TI Intranuclear localization of the Shwachman-Diamond protein, SBDS: Functional implications SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 03-06, 2003 CL SEATTLE, WA SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Continuing Educ C1 Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2004 VL 55 IS 4 SU S MA 1673 BP 294A EP 294A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 808TJ UT WOS:000220591101722 ER PT J AU Sklar, C Mertens, A Mitby, P Whitton, J Stovall, M Mulder, J Green, D Nicholson, S Yasui, Y Robison, L AF Sklar, C Mertens, A Mitby, P Whitton, J Stovall, M Mulder, J Green, D Nicholson, S Yasui, Y Robison, L TI Premature menopause in survivors of childhood and adolescent cancer: Data from the childhood cancer survivor study (CCSS) SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 03-06, 2003 CL SEATTLE, WA SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Continuing Educ C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX USA. Univ Minnesota, Seattle, WA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2004 VL 55 IS 4 SU S MA 1686 BP 297A EP 297A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 808TJ UT WOS:000220591101735 ER PT J AU Claud, EC Walker, WA Cherayil, BJ AF Claud, EC Walker, WA Cherayil, BJ TI Developmental regulation of I kappa B expression in intestinal epithelium SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 04, 2004 CL San Francisco, CA SP Pediatr Acad Soc C1 Massachusetts Gen Hosp, Dev Gastroenterol Lab, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2004 VL 55 IS 4 SU S MA 2631 BP 464A EP 464A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 808TJ UT WOS:000220591102696 ER PT J AU Roberts, JD Bloch, DB Chiche, JD Kolpa, EM Bloch, KD AF Roberts, JD Bloch, DB Chiche, JD Kolpa, EM Bloch, KD TI PKG interacts with JD6, a novel ring finger protein expressed in the lung SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 04, 2004 CL San Francisco, CA SP Pediatr Acad Soc C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2004 VL 55 IS 4 SU S MA 3404 BP 600A EP 600A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 808TJ UT WOS:000220591103481 ER PT J AU McKinney, RE Cruz, MLS Powell, C Hughes, M Oleske, JM Winter, H Elgie, C Perdue, L Wolf, D Ortiz-Pujols, S Calles, NR McNamara, J Moye, J AF McKinney, RE Cruz, MLS Powell, C Hughes, M Oleske, JM Winter, H Elgie, C Perdue, L Wolf, D Ortiz-Pujols, S Calles, NR McNamara, J Moye, J TI International formula-based nutritional intervention for infants born to HIV-infected women SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 04, 2004 CL San Francisco, CA SP Pediatr Acad Soc C1 Duke Univ, Ctr Med, Durham, NC USA. Hosp Servidores Estado, Rio De Janeiro, Brazil. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Newark, Newark, NJ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Tech Res Fndn, Amherst, NY USA. DHHS, NIH, Bethesda, MD USA. Ross Prod Div, Columbus, OH USA. Soc Sci Syst, Silver Spring, MD USA. Texas Childrens Hosp, Houston, TX 77030 USA. NJCHD, DHHS, NIH, Bethesda, MD USA. RI Oleske, James/C-1951-2016 OI Oleske, James/0000-0003-2305-5605 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2004 VL 55 IS 4 SU S MA 16 BP ER43 EP ER43 PN 2 PG 1 WC Pediatrics SC Pediatrics GA 808TJ UT WOS:000220591102951 ER PT J AU Michelow, IC Olsen, K Lozano, J Rollins, NK Duffy, LB Ziegler, T Kauppila, J Leinonen, M McCracken, GH AF Michelow, IC Olsen, K Lozano, J Rollins, NK Duffy, LB Ziegler, T Kauppila, J Leinonen, M McCracken, GH TI Epidemiology and clinical characteristics of community-acquired pneumonia in hospitalized children SO PEDIATRICS LA English DT Article DE community-acquired pneumonia; child; epidemiology; diagnosis; etiology; hospitalized ID CHLAMYDIA-PNEUMONIAE; PNEUMOCOCCAL PNEUMONIA; ANTIMICROBIAL THERAPY; CHILDHOOD PNEUMONIA; ETIOLOGY; DIAGNOSIS; EFFICACY; SAFETY AB Objectives. The precise epidemiology of childhood pneumonia remains poorly defined. Accurate and prompt etiologic diagnosis is limited by inadequate clinical, radiologic, and laboratory diagnostic methods. The objective of this study was to determine as precisely as possible the epidemiology and morbidity of community-acquired pneumonia in hospitalized children. Methods. Consecutive immunocompetent children hospitalized with radiographically confirmed lower respiratory infections ( LRIs) were evaluated prospectively from January 1999 through March 2000. Positive blood or pleural fluid cultures or pneumolysin-based polymerase chain reaction assays, viral direct fluorescent antibody tests, or viral, mycoplasmal, or chlamydial serologic tests were considered indicative of infection by those organisms. Methods for diagnosis of pneumococcal pneumonia among study subjects were published by us previously. Selected clinical characteristics, indices of inflammation ( white blood cell and differential counts and procalcitonin values), and clinical outcome measures ( time to defervescence and duration of oxygen supplementation and hospitalization) were compared among groups of children. Results. One hundred fifty-four hospitalized children with LRIs were enrolled. Median age was 33 months ( range: 2 months to 17 years). A pathogen was identified in 79% of children. Typical respiratory bacteria were identified in 60% ( of which 73% were Streptococcus pneumoniae), viruses in 45%, Mycoplasma pneumoniae in 14%, Chlamydia pneumoniae in 9%, and mixed bacterial/ viral infections in 23%. Preschool-aged children had as many episodes of atypical bacterial LRIs as older children. Children with typical bacterial or mixed bacterial/ viral infections had the greatest inflammation and disease severity. Multivariate logistic-regression analyses revealed that high temperature (greater than or equal to38.4 degreesC) within 72 hours after admission (odds ratio: 2.2; 95% confidence interval: 1.4 - 3.5) and the presence of pleural effusion ( odds ratio: 6.6; 95% confidence interval: 2.1 - 21.2) were significantly associated with bacterial pneumonia. Conclusions. This study used an expanded diagnostic armamentarium to define the broad spectrum of pathogens that cause pneumonia in hospitalized children. The data confirm the importance of S pneumoniae and the frequent occurrence of bacterial and viral coinfections in children with pneumonia. These findings will facilitate age-appropriate antibiotic selection and future evaluation of the clinical effectiveness of the pneumococcal conjugate vaccine as well as other candidate vaccines. C1 Univ Texas, SW Med Ctr, Div Pediat Infect Dis, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Radiol, Dallas, TX 75235 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Natl Publ Hlth Inst, Helsinki, Finland. Natl Publ Hlth Inst, Oulu, Finland. Univ Oulu, Dept Med Microbiol, Oulu, Finland. RP Michelow, IC (reprint author), Massachusetts Gen Hosp, Dept Pediat Infect Dis, GRJ-1402,15 Parkman St, Boston, MA 02114 USA. EM imichelow@partners.org NR 29 TC 332 Z9 381 U1 1 U2 32 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 APR 1 PY 2004 VL 113 IS 4 BP 701 EP 707 DI 10.1542/peds.113.4.701 PG 7 WC Pediatrics SC Pediatrics GA 808RB UT WOS:000220585100001 PM 15060215 ER PT J AU Greene, AK Kieran, M Burrows, PE Mulliken, JB Kasser, J Fishman, SJ AF Greene, AK Kieran, M Burrows, PE Mulliken, JB Kasser, J Fishman, SJ TI Wilms tumor screening is unnecessary in Klippel-Trenaunay syndrome SO PEDIATRICS LA English DT Article DE Klippel-Trenaunay syndrome; Wilms tumor; screening ID MALFORMATION SYNDROMES; HEMIHYPERTROPHY; MANAGEMENT; FEATURES; PREVALENCE; CHILDREN AB Background. Children with hemihypertrophy are screened for Wilms tumor, because this condition is a risk factor for developing the neoplasm. Patients with Klippel-Trenaunay syndrome (KTS) are often considered potential candidates for Wilms tumor, because they have unilateral overgrowth of the lower limb. In our experience, however, an association between KTS and Wilms tumor has not been observed. Methods. To determine whether KTS and Wilms tumor are associated, we reviewed our institutional experience for patients with both diagnoses and searched the Klippel-Trenaunay literature for patients with Wilms tumor. The National Wilms Tumor Study Group database also was studied to identify patients with KTS. Two-sided exact binomial tests were used to evaluate whether patients with 1 condition had an increased risk for the other. Ninety-five percent confidence intervals for these 2 risks were compared with the general population risks of Wilms tumor ( 1 in 10 000) and KTS ( 1 in 47 313). Results. None of the 115 patients with KTS followed at our institution developed Wilms tumor. One case of Wilms tumor has been reported in 1363 patients with KTS in the literature, giving a confidence interval of (1/57 377) and (1/267). None of the 8614 patients in the National Wilms Tumor Study Group database had KTS, giving a confidence interval of ( 0, 1/2336). Because the risks of KTS and Wilms tumor in the population fall within these confidence intervals, one cannot conclude that the risks of KTS among Wilms tumor patients or Wilms tumor among KTS patients are any different from the corresponding risks in the general population. Conclusions. Patients with KTS are not at increased risk for developing Wilms tumor and thus should not undergo routine ultrasonographic screening. C1 Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Childrens Hosp, Vasc Anomalies Ctr, Boston, MA 02115 USA. Childrens Hosp, Dept Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Childrens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Fishman, SJ (reprint author), Childrens Hosp, Dept Surg, 300 Longwood Ave, Boston, MA 02115 USA. EM steven.fishman@childrens.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 NR 29 TC 11 Z9 11 U1 0 U2 0 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 APR 1 PY 2004 VL 113 IS 4 BP E326 EP E329 DI 10.1542/peds.113.4.e326 PG 4 WC Pediatrics SC Pediatrics GA 808RB UT WOS:000220585100049 PM 15060262 ER PT J AU Pekary, AE Sattin, A Meyerhoff, JL Chilingar, M AF Pekary, AE Sattin, A Meyerhoff, JL Chilingar, M TI Valproate modulates TRH receptor, TRH and TRH-like peptide levels in rat brain SO PEPTIDES LA English DT Article DE valproate; TRH-like peptides; TRH receptors; depression; cortex; limbic system ID THYROTROPIN-RELEASING-HORMONE; PITUITARY RECEPTORS; MOOD STABILIZERS; DISORDERS; GLUTAMATE; LITHIUM; ACID; PROTECTION; EXPRESSION; DEPRESSION AB We have tested our hypothesis that alterations in the levels of TRH receptors, and the synthesis and release of tripeptide TRH, and other neurotropic TRH-like peptides mediate some of the mood stabilizing effects of valproate (Valp). We have directly compared the effect of 1 week of feeding two major mood stabilizers, Valp and lithium chloride (LiCl) on TRH binding in limbic and extra-limbic regions of male WKY rats. Valp increased TRH receptor levels in nucleus accumbens and frontal cortex. Li increased TRH receptor binding in amygdala, posterior cortex and cerebellum. The acute, chronic and withdrawal effects of Valp on brain levels of TRH (pGlu-His-Pro-NH2, His-TRH) and five other TRH-like peptides, Glu-TRH, Val-TRH, Tyr-TRH, Leu-TRH and Phe-TRH were measured by combined HPLC and RIA. Acute treatment increased TRH and TRH-like peptide levels within most brain regions, most strikingly in pyriform cortex. The fold increases (in parentheses) were: Val-TRH (58), Phe-TRH (54), Tyr-TRH (25), TRH (9), Glu-TRH (4) and Leu-TRH (3). We conclude that the mood stabilizing effects of Valp may be due, at least in part, to its ability to alter TRH and TRH-like peptide, and TRH receptor levels in the limbic system and other brain regions implicated in mood regulation and behavior. (C) 2004 Elsevier Inc. All rights reserved. C1 W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Hlth Care Syst, Psychiat Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Inst Neuropsychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Inst Brain Res, Los Angeles, CA USA. Walter Reed Army Inst Res, Div Neurosci, Dept Neurochem, Washington, DC 20307 USA. RP Pekary, AE (reprint author), W Los Angeles Vet Affairs Med Ctr, Res Serv, 11301 Wilshire Blvd,Bldg 114,Rm 229, Los Angeles, CA 90073 USA. EM epekary@ucla.edu NR 48 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD APR PY 2004 VL 25 IS 4 BP 647 EP 658 DI 10.1016/j.peptides.2004.01.016 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 829IA UT WOS:000222039800015 PM 15165721 ER PT J AU Morton, GJ Mystkowski, P Matsumoto, AM Schwartz, MW AF Morton, GJ Mystkowski, P Matsumoto, AM Schwartz, MW TI Increased hypothalamic melanin concentrating hormone gene expression during energy restriction involves a melanocortin-independent, estrogen-sensitive mechanism SO PEPTIDES LA English DT Article DE melanin-concentrating hormone; agouti; melanocortins; estrogen; hypothalamus ID MESSENGER-RIBONUCLEIC-ACID; ARCUATE NUCLEUS; NEUROPEPTIDE-Y; WEIGHT-LOSS; OBESITY; NEURONS; MICE; RNA; SYSTEM; MOUSE AB Increased expression of melanin concentrating hormone (MCH), an orexigenic neuropeptide produced by neurons in the lateral hypothalamic area (LHA), is implicated in the effect of energy restriction to increase food intake. Since melanocortins inhibit Mch gene expression, this effect of energy restriction to increase Mch signaling may involve reduced hypothalamic melanocortin signaling. Consistent with this hypothesis, we detected increased hypothalamic Mch mRNA levels in agouti (A(y)) mice (by 102%; P < 0.05), a model of genetic obesity resulting from impaired melanocortin signaling, compared to wild-type controls. If reduced melanocortin signaling mediates the effect of energy restriction, hypothalamic Mch gene expression in AY mice should not be increased further by energy restriction, since melanocortin signaling is impaired in these animals regardless of nutritional state. We therefore investigated the effects of energy restriction on hypothalamic Mch gene expression in both A(y) mice and in wild-type mice with diet-induced obesity (DIO). Responses in these mice were compared to those induced by administration of 17beta-estradiol (E2) at a dose previously shown to reduce food intake and Mch expression in rats. In both A(y) and DIO mice, energy restriction increased hypothalamic Mch mRNA levels (P < 0.05 for each) via a mechanism that was fully blocked by E2. However, E2 did not lower levels of Mch mRNA below basal values in A(y) mice, whereas it did so in DIO mice. Thus, the effect of energy restriction to increase hypothalamic Mch gene expression involves an E2-sensitive mechanism that is not altered by impaired melanocortin signaling. By comparison, impaired melanocortin signaling increases hypothalamic Mch gene expression via a mechanism that is insensitive to E2. These findings suggest that while both energy restriction and reduced melanocortin signaling stimulate hypothalamic Mch gene expression, they do so via distinct mechanisms. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Washington, Harborview Med Ctr, Dept Med, Seattle, WA 98104 USA. VA Puget Sound Hlth Care Syst, Geriatr Res, Educ & Clin Ctr, Seattle, WA 98108 USA. RP Schwartz, MW (reprint author), Univ Washington, Harborview Med Ctr, Dept Med, 325 9th Ave,Box 359757, Seattle, WA 98104 USA. EM mschwart@u.washington.edu RI Schwartz, Michael/H-9950-2012 FU NIDDK NIH HHS [DK12829, DK52989]; NINDS NIH HHS [NS32273] NR 21 TC 28 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 0196-9781 J9 PEPTIDES JI Peptides PD APR PY 2004 VL 25 IS 4 BP 667 EP 674 DI 10.1016/j.peptides.2004.02.007 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 829IA UT WOS:000222039800017 PM 15165723 ER PT J AU Busti, AJ Murillo, JR Cryer, B AF Busti, AJ Murillo, JR Cryer, B TI Tegaserod-induced myocardial infarction: Case report and hypothesis SO PHARMACOTHERAPY LA English DT Article DE tegaserod; myocardial infarction; 5-HT; receptor agonist; migraine; triptans; cardiovascular adverse events; cardiovascular risk factors ID IRRITABLE-BOWEL-SYNDROME; SEROTONIN 5-HT4 RECEPTOR; CORONARY-ARTERIES; PARTIAL AGONIST; DOUBLE-BLIND; IN-VITRO; SUMATRIPTAN; 5-HYDROXYTRYPTAMINE; CONSTIPATION; TOLERABILITY AB Serotonin (5-hydroxytryptamine [5-HT])(1) receptor agonists, such as those used for treating migraine, can cause coronary artery contraction, coronary spasm, and even myocardial infarction. Tegaserod maleate is a relatively new 5-HT4 receptor agonist with moderate affinity for the 5-HT1 receptor. Currently, it is approved only for treatment of irritable bowel syndrome in women who have constipation as the primary symptom. However, it is also being administered as a promotility agent in patients with gastroparesis. Since tegaserod has affinity for the 5-HT1 receptor, it is plausible that tegaserod could cause the same types of cardiovascular adverse events seen with agents prescribed for management of migraine. We report the first case of a man who experienced a myocardial infarction after receiving only two 6-mg doses of tegaserod; we also provide a hypothesis regarding this event. When considering prescribing a drug with 5-HT1 receptor agonist activity, clinicians should review the patient's medical history specifically for the presence of underlying cardiovascular risk factors. C1 Texas Tech Univ, Hlth Sci Ctr, Dept Pharm Practice, Sch Pharm, Dallas, TX 75216 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Dallas Vet Affairs Med Ctr, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Med, Dallas, TX USA. RP Busti, AJ (reprint author), Texas Tech Univ, Hlth Sci Ctr, Dept Pharm Practice, Sch Pharm, Dallas Ft Worth Reg Campus,4500 S Lancaster Rd, Dallas, TX 75216 USA. EM anthony.busti@ttuhsc.edu NR 40 TC 39 Z9 39 U1 0 U2 1 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD APR PY 2004 VL 24 IS 4 BP 526 EP 531 DI 10.1592/phco.24.5.526.33351 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 809GG UT WOS:000220624600015 PM 15098809 ER PT J AU Fitzsimons, MG Gaudette, RR Hurford, WE AF Fitzsimons, MG Gaudette, RR Hurford, WE TI Critical rebound methemoglobinemia after methylene blue treatment: Case report SO PHARMACOTHERAPY LA English DT Article DE benzocaine; methylene blue; methemoglobin; methemoglobinemia ID PATIENT; FAILURE AB A 39-year-old man developed significant methemoglobinemia after receiving benzocaine spray; he was treated appropriately with intravenous methylene blue. The patient's methemoglobin levels decreased, but this was followed by a critical rebound phenomenon to levels frequently considered near fatal. After further treatment with methylene blue, the patient's methemoglobin levels returned to normal. Clinicians need to be aware that a decreasing level of methemoglobin does not necessarily indicate that a crisis has passed and that further monitoring and treatment may be indicated. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fitzsimons, MG (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM mfitzsimons@partners.org RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 16 TC 12 Z9 12 U1 0 U2 2 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 APR PY 2004 VL 24 IS 4 BP 538 EP 540 DI 10.1592/phco.24.5.538.33356 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 809GG UT WOS:000220624600017 PM 15098811 ER PT J AU Zhou, XD Pogue, BW Chen, B Hasan, T AF Zhou, XD Pogue, BW Chen, B Hasan, T TI Analysis of effective molecular diffusion rates for verteporfin in subcutaneous versus orthotopic dunning prostate tumors SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID PHOTODYNAMIC THERAPY; OXYGEN-TRANSPORT; COLORECTAL-CARCINOMA; NEOPLASTIC TISSUES; IMPLANTATION SITE; BLOOD-FLOW; IN-VITRO; MACROMOLECULES; MODEL; FLUID AB Photosensitizer biodistribution change inside tissue is one of the dominant factors in photodynamic therapy efficacy. In this study, the pharmacokinetics of a benzoporphyrin derivative (BPD), delivered in verteporfin for injection formulation, have been quantified in the rat Dunning prostate tumor MAT-LyLu model, using both subcutaneous and orthotopic sites. Blood plasma sampling indicated that BPD had a bi-exponential metabolic lifetime in vivo, with the two lifetimes being 9.6 min and 8.3 h. The spatial distributions in the tumor were quantified as a function of distance from the perfused blood vessels, using fluorescence histologic images of the tumor. A fluorescent vascular marker was used to obtain locations and shapes of perfused capillaries at a wavelength of emission different from that of BPD and to allow colocalized images to be acquired of vessel and BPD locations. Using the BPD fluorescence images obtained 15 min after intravenous administration, a forward finite-element solution to the diffusion equation was used to predict the drug distribution by matching the fluorescence intensity images observed microscopically. An inverse solver was used to minimize the root mean square error between the image of simulated diffusion and the experimental image, resulting in estimation of the diffusion coefficient of BPD in the tumor models. Effective diffusion coefficients were 0.88 and 1.59 muM(2)/S for the subcutaneous and orthotopically grown tumors, respectively, indicating that orthotopic tumors have significantly higher vascular extravasation rates as compared with subcutaneous tumors. This analysis supports the hypothesis that leakage rates of the photosensitizer vary considerably. Thus, although varying the time between injection and optical irradiation may be used to vary the targeting between vascular and less vascular areas, the precise time of treatment will depend on the nature of the permeability of the vasculature in the tissue being treated. C1 Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. Massachusetts Gen Hosp, Harvard Med Sch, Wellman Labs Photomed, Boston, MA 02114 USA. RP Pogue, BW (reprint author), Dartmouth Coll, Thayer Sch Engn, 8000 Cummings Hall, Hanover, NH 03755 USA. EM pogue@dartmouth.edu FU NCI NIH HHS [P01CA84203] NR 47 TC 22 Z9 24 U1 0 U2 2 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD APR PY 2004 VL 79 IS 4 BP 323 EP 331 DI 10.1562/MU-03-31.1 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 814ES UT WOS:000220958600004 PM 15137508 ER PT J AU Nandi, A Utamura, Y Kahn, CR Accili, D AF Nandi, A Utamura, Y Kahn, CR Accili, D TI Mouse models of insulin resistance SO PHYSIOLOGICAL REVIEWS LA English DT Review ID GROWTH-FACTOR-I; FORKHEAD TRANSCRIPTION FACTOR; DEPENDENT DIABETES-MELLITUS; PANCREATIC BETA-CELLS; HOMOZYGOUS NONSENSE MUTATION; RECEPTOR-RELATED RECEPTOR; PROTEIN-KINASE-B; RABSON-MENDENHALL-SYNDROME; MUSCLE GLYCOGEN-SYNTHESIS; MEDIATED GLUCOSE-UPTAKE AB Insulin resistance plays a key role in the pathogenesis of several human diseases, including diabetes, obesity, hypertension, and cardiovascular diseases. The predisposition to insulin resistance results from genetic and environmental factors. The search for gene variants that predispose to insulin resistance has been thwarted by its genetically heterogeneous pathogenesis. However, using techniques of targeted mutagenesis and transgenesis in rodents, investigators have developed mouse models to test critical hypotheses on the pathogenesis of insulin resistance. Moreover, experimental crosses among mutant mice have shed light onto the polygenic nature of the interactions underlying this complex metabolic condition. C1 Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Accili, D (reprint author), Berrie Res Pavil,1150 St Nicholas Ave, New York, NY 10032 USA. EM da230@columbia.edu NR 254 TC 144 Z9 156 U1 2 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 APR PY 2004 VL 84 IS 2 BP 623 EP 647 DI 10.1152/physrev.00032.2003 PG 25 WC Physiology SC Physiology GA 807RL UT WOS:000220518500008 PM 15044684 ER PT J AU Yaremchuk, MJ AF Yaremchuk, MJ TI Infracture technique for reduction malarplasty with a short preauricular incision - Discussion SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Yaremchuk, MJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM myaremchuk@partners.org NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD APR 1 PY 2004 VL 113 IS 4 BP 1262 EP 1263 DI 10.1097/01.PRS.0000110296.54327.F4 PG 2 WC Surgery SC Surgery GA 809DY UT WOS:000220618600022 ER PT J AU Weintraub, D AF Weintraub, D TI Diagnosing and treating depression in patients with Parkinson's disease SO PSYCHIATRIC ANNALS LA English DT Article ID QUALITY-OF-LIFE; MAJOR DEPRESSION; CONTROLLED TRIAL; RISK-FACTORS; FREQUENCY; SYMPTOMS; STIMULATION; PREVALENCE; DISORDERS; VALIDITY C1 Univ Penn, Parkinsons Dis Ctr, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Ctr, Philadelphia, PA USA. RP Weintraub, D (reprint author), 3535 Market St,Room 3003, Philadelphia, PA 19104 USA. NR 41 TC 7 Z9 8 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD APR PY 2004 VL 34 IS 4 BP 299 EP 304 PG 6 WC Psychiatry SC Psychiatry GA 811HN UT WOS:000220763100008 ER PT J AU Petersen, T Harley, R Papakostas, GI Montoya, HD Fava, M Alpert, JE AF Petersen, T Harley, R Papakostas, GI Montoya, HD Fava, M Alpert, JE TI Continuation cognitive-behavioural therapy maintains attributional style improvement in depressed patients responding acutely to fluoxetine SO PSYCHOLOGICAL MEDICINE LA English DT Article ID POSITIVE LIFE EVENTS; RESIDUAL SYMPTOMS; EXPLANATORY STYLE; MAJOR DEPRESSION; PREVENTION; DISORDER; RECOVERY; RELAPSE; MODEL; STABILITY AB Background. Little is known about how continuation and maintenance cognitive-behavioural therapy (CBT) influences important psychological constructs that may be associated with long-term outcome of major depressive disorder. The goal of this study was to examine whether CBT would help maintain attributional style changes experienced by patients during acute phase fluoxetine treatment. Method. Three hundred and ninety-one patients with major depressive disorder were enrolled in an open, fixed-dose 8 week fluoxetine trial. Remitters to this acute phase treatment (N=132) were randomized to receive either fixed-dose fluoxetine (meds only) or fixed-dose fluoxetine plus cognitive-behavioural therapy (CBT+meds) during a 6-month continuation treatment phase. The Attributional Style Questionnaire (ASQ) was completed by patients at three time points-acute phase baseline, continuation phase baseline and continuation phase endpoint. Analysis of covariance was used to compare continuation phase ASQ composite score changes between groups. Results. Patients in both treatment groups experienced significant gains in positive attributional style during the acute phase of treatment. Continuation phase ASQ composite change scores differed significantly between treatment groups, with the CBT + meds group maintaining acute phase positive attributional style changes, and the meds only group exhibiting a worsening of attributional style. The two treatment groups did not significantly differ in rates of relapse and final continuation phase visit HAMD-17 scores. Conclusions. In this sample, the addition of CBT to continuation psychopharmacological treatment was associated with maintenance of acute treatment phase attributional style gains. Further research is needed to evaluate the role of such gains in the long-term course of depressive illness. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Petersen, T (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM tpetersen@partners.org RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X NR 33 TC 18 Z9 20 U1 0 U2 2 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 APR PY 2004 VL 34 IS 3 BP 555 EP 561 DI 10.1017/S0033291703001028 PG 7 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 816ZD UT WOS:000221146900018 PM 15259840 ER PT J AU Cook, JW Spring, B McChargue, DE Borrelli, B Hitsman, B Niaura, R Keuthen, NJ Kristeller, J AF Cook, JW Spring, B McChargue, DE Borrelli, B Hitsman, B Niaura, R Keuthen, NJ Kristeller, J TI Influence of fluoxetine on positive and negative affect in a clinic-based smoking cessation trial SO PSYCHOPHARMACOLOGY LA English DT Article DE fluoxetine; smoking cessation; positive affect; negative affect ID CIGARETTE SMOKERS; DOPAMINE RELEASE; WITHDRAWAL; NICOTINE; DEPRESSION; FACILITATION; PERSONALITY; DEPENDENCE; INTERVIEW; BUPROPION AB Rationale: Fluoxetine improves affect in clinical syndromes such as depression and premenstrual dysphoric disorder. Little is known about fluoxetine's influence on mood changes after quitting smoking, which often resemble sub-clinical depression. Objectives: The present study, a re-analysis of previously published data (Niaura et al. 2002), examined fluoxetine's effect on changes in negative and positive affect following quitting smoking. Methods: Adult smokers (n=175) without clinically significant depression were randomized on a double-blind basis to receive fluoxetine hydrochloride (30 or 60 mg daily) or placebo for 10 weeks in combination with cognitive-behavioral therapy (CBT) for smoking cessation. We postulated that fluoxetine would beneficially influence post-cessation changes in positive and negative affect. Results: Mood change across treatment was analyzed using mixed linear modeling controlling for initial level of nicotine dependence, plasma fluoxetine metabolites, and change in cotinine (a nicotine metabolite) at each visit. Relative to placebo, those on 60 mg fluoxetine experienced an elevation in positive affect that increased across time [t(526)=2.50, P=0.01], and a reduction in negative affect that returned to baseline across time [t(524)=2.26, P=0.02]. There were no differences between 30 mg and placebo on changes in positive or negative affect. Conclusions: Results indicate that 60 mg of fluoxetine improves both positive and negative mood states after quitting smoking and that diminished positive affect may be an overlooked affective response to smoking cessation. C1 Dept Psychol, Chicago, IL 60607 USA. Miriam Hosp, Coro Ctr, Ctr Behav Med, Providence, RI 02903 USA. Miriam Hosp, Coro Ctr, Ctr Prevent Med, Providence, RI 02903 USA. Massachusetts Gen Hosp, OCD Clin, Charlestown, MA 02129 USA. Indiana State Univ, Dept Psychol, Terre Haute, IN 47809 USA. RP Spring, B (reprint author), Dept Psychol, 1007 W Harrison Ave, Chicago, IL 60607 USA. EM bspring@uic.edu OI Borrelli, Belinda/0000-0002-0859-796X FU NCCIH NIH HHS [R21 AT000416, R21AT00416-01]; NCI NIH HHS [P50 CA084719, P50 CA84719]; NHLBI NIH HHS [R01 HL063307, HL59348, HL63307]; NIDA NIH HHS [DA14144, F31 DA014144, K08 DA000467]; PHS HHS [R01 62165] NR 37 TC 28 Z9 28 U1 3 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD APR PY 2004 VL 173 IS 1-2 BP 153 EP 159 DI 10.1007/s00213-003-1711-8 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 814NQ UT WOS:000220981800020 PM 14727000 ER PT J AU Rowe, BH Edmonds, ML Spooner, CH Diner, B Camargo, CA AF Rowe, BH Edmonds, ML Spooner, CH Diner, B Camargo, CA TI Corticosteroid therapy for acute asthma SO RESPIRATORY MEDICINE LA English DT Review DE asthma; inhaled corticosteroids; relapse; admission ID EMERGENCY-DEPARTMENT; RANDOMIZED-TRIAL; GUIDELINES; METAANALYSIS; FLUTICASONE; PHYSICIANS; MANAGEMENT; PREDNISONE; DISCHARGE; RESPONSES AB Asthma is a chronic inflammatory disease, which is characterised by reversible airflow obstruction in response to a variety of stimuli. Exacerbations in response to airway irritants are part of the natural history of asthma, but often they also represent a failure in chronic treatment. Presentations to emergency departments and other acute care settings are common and frequently lead to hospitalisation and other complications. After treatment, however, most patients are discharged to the care of their primary care physician for further management. This review highlights the role of systemic and inhaled corticosteroids as mainstays of treatment in the acute and sub-acute phase of an exacerbation. These agents form the basis of most current clinical practice guidelines, yet their use is not universal. We will review the evidence for the use of these agents that arises from the Cochrane Collaboration of Systematic Reviews contained in the Cochrane Library. (C) 2004 Elsevier Ltd. All rights reserved. C1 Univ Alberta, Div Emergency Med, Walter Mackenzie Ctr, Edmonton, AB T6G 2B7, Canada. Capital Hlth Author, Edmonton, AB, Canada. Emory Univ Hosp, Dept Emergency Med, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. RP Rowe, BH (reprint author), Univ Alberta, Div Emergency Med, Walter Mackenzie Ctr, 1G1-43,8440-112 St, Edmonton, AB T6G 2B7, Canada. EM brian.rowe@ualberta.ca FU NHLBI NIH HHS [HL-63841] NR 38 TC 45 Z9 46 U1 0 U2 5 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD APR PY 2004 VL 98 IS 4 BP 275 EP 284 DI 10.1016/j.rmed.2003.11.016 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 809JN UT WOS:000220633100002 PM 15072167 ER PT J AU Davalos, DB Compagnon, N Heinlein, S Ross, RG AF Davalos, DB Compagnon, N Heinlein, S Ross, RG TI Neuropsychological deficits in children associated with increased familial risk for schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; genetic predisposition; neuropsychology; cognition; school-age children ID CHILDHOOD-ONSET SCHIZOPHRENIA; SHORT-TERM-MEMORY; WORKING-MEMORY; INDIVIDUAL-DIFFERENCES; EYE TRACKING; PSYCHIATRIC-DISORDERS; EMOTION RECOGNITION; PSYCHOTIC SYMPTOMS; INHIBITORY CONTROL; RELATIVES AB By studying neuropsychological performance in children genetically at-risk for schizophrenia, greater understanding may be obtained regarding the developmental processes of schizophrenia and associated cognitive weaknesses. A variety of cognitive deficits in genetically at-risk children have been reported. The present study was designed to examine cognitive tasks that have traditionally differentiated children genetically at-risk for schizophrenia (e.g. working memory) from normal children, while also assessing abilities that have received scant attention in this population. Aspects of emotional perception, verbal abilities, inhibition, visuo-spatial skills, and working memory were assessed in children of schizophrenic parents and normal children. Significant differences in performances were identified in at-risk children on measures of verbal skills, working memory and inhibition. Findings suggest that children genetically at-risk for developing schizophrenia exhibit neurocognitive weaknesses generally consistent with those noted in the literature. However, inhibition also appeared to be a cognitive process that significantly differentiated the groups. The possibility of a developmental expression of neurocognitive deficits is discussed. (C) 2003 Elsevier B.V. All rights reserved. C1 Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Denver VA Med Ctr, Denver, CO 80220 USA. RP Davalos, DB (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Psychiat, 4200 E 9th Ave,Campus Box C268-71, Denver, CO 80262 USA. EM deana.davalos@uchsc.edu FU NIMH NIH HHS [MH15442, MH56539] NR 67 TC 29 Z9 29 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 1 PY 2004 VL 67 IS 2-3 BP 123 EP 130 DI 10.1016/S0920-9964(03)00187-7 PG 8 WC Psychiatry SC Psychiatry GA 800CW UT WOS:000220007500002 PM 14984871 ER PT J AU Liu, HH Harker, JO Wong, AL MacLean, CH Bulpitt, KJ Mittman, BS FitzGerald, J Grossman, J Rubenstein, LZ Hahn, B Paulus, HE Kahn, KL AF Liu, HH Harker, JO Wong, AL MacLean, CH Bulpitt, KJ Mittman, BS FitzGerald, J Grossman, J Rubenstein, LZ Hahn, B Paulus, HE Kahn, KL TI Case finding for population-based studies of rheumatoid arthritis: Comparison of patient self-reported ACR criteria-based algorithms to physician-implicit review for diagnosis of rheumatoid arthritis SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Review DE rheumatoid arthritis; agreement; reliability; algorithm ID PREDICTION AB Objective: To evaluate the interrater reliability of rheumatologist diagnosis of rheumatoid arthritis (RA) and the concordance between rheumatologist and computer algorithms for assessing the accuracy of a diagnosis of RA. Methods: Self-reported data regarding symptoms and signs for a diagnosis of RA were considered by a panel of rheumatologists and by computer algorithms to assess the probability of a diagnosis of RA for 90 patients. The rheumatologists' review was validated through medical record. Results: The interrater reliability among rheumatologists regarding a diagnosis of RA was 84%; the chance-corrected agreement (kappa) was 0.66. Agreement between the rheumatologists' rating and the best-performing algorithm was 95%. Using rheumatologist's review as a standard, the sensitivity of the algorithm was 100%, specificity was 88%, and the positive predictive value was 91%. The validation of rheumatologist's review by medical record showed 81% sensitivity, 60% specificity, and 78% positive predictive value. Conclusion: Reliability of rheumatologists' assignment of a diagnosis of RA by using self-report data is good. Algorithms defining symptoms as either joint swelling or tenderness with symptom duration greater than or equal to4 weeks have a better agreement with rheumatologist's diagnosis than do ones relying on a longer symptom duration. Relevance: These findings have important implications for health services research and quality improvement interventions pertinent to case finding for RA through self-report data. C1 Univ Calif Los Angeles, Dept Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Div Rheumatol, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Olive View UCLA Med Ctr, Sylmar, CA 91342 USA. RAND Corp, Santa Monica, CA USA. RP Liu, HH (reprint author), Univ Calif Los Angeles, Dept Med, Div Gen Internal Med & Hlth Serv Res, 911 Broxton Plaza,Room 202,Box 951736, Los Angeles, CA 90095 USA. EM hhliu@ucla.edu FU NIAMS NIH HHS [P60 AR36834] NR 15 TC 8 Z9 8 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0049-0172 J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD APR PY 2004 VL 33 IS 5 BP 302 EP 310 DI 10.1053/S0049-0172(03)00166-5 PG 9 WC Rheumatology SC Rheumatology GA 813UU UT WOS:000220932800003 PM 15079761 ER PT J AU Munshi, NC AF Munshi, NC TI Recent advances in the management of multiple myeloma SO SEMINARS IN HEMATOLOGY LA English DT Article ID HIGH-DOSE THERAPY; THALIDOMIDE PLUS DEXAMETHASONE; OVERCOMES DRUG-RESISTANCE; MARROW STROMAL CELLS; ARSENIC TRIOXIDE; INHIBITS GROWTH; TRANSPLANTATION; SURVIVAL; CHEMOTHERAPY; COMBINATION C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston VA Med Ctr, Boston, MA 02215 USA. RP Munshi, NC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Room M557,44 Binney St, Boston, MA 02215 USA. FU NCI NIH HHS [P50CA100700]; PHS HHS [P01-78378] NR 37 TC 5 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 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD APR PY 2004 VL 41 IS 2 SU 4 BP 21 EP 26 DI 10.1053/j.seminhematol.2004.03.002 PG 6 WC Hematology SC Hematology GA 823GF UT WOS:000221597400004 PM 15190512 ER PT J AU Eber, S Lux, SE AF Eber, S Lux, SE TI Hereditary spherocytosis - Defects in proteins that connect the membrane skeleton to the lipid bilayer SO SEMINARS IN HEMATOLOGY LA English DT Review ID RENAL TUBULAR-ACIDOSIS; BAND-3 AE1 GENE; REFLECT SPECTRIN DEFICIENCIES; INCREASED OSMOTIC FRAGILITY; GLYCEROL LYSIS TEST; DE-NOVO MUTATIONS; BETA-SPECTRIN; AUTOSOMAL-DOMINANT; MESSENGER-RNA; RED-CELLS C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Eber, S (reprint author), Tech Univ Munich, Childrens Hosp, Koelner Pl 1, D-80804 Munich, Germany. EM stefan-eber@t.online.de FU NHLBI NIH HHS [P01 HL 32262]; NIDDK NIH HHS [R01 DK 34083] NR 125 TC 106 Z9 111 U1 0 U2 9 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 APR PY 2004 VL 41 IS 2 BP 118 EP 141 DI 10.1053/j.seminhematol.2004.01.002 PG 24 WC Hematology SC Hematology GA 815MB UT WOS:000221045300003 PM 15071790 ER PT J AU Stone, RM Gilliland, DG Klion, AD AF Stone, RM Gilliland, DG Klion, AD TI Platelet-derived growth factor receptor inhibition to treat idiopathic hypereosinophilic syndrome SO SEMINARS IN ONCOLOGY LA English DT Review ID IMATINIB MESYLATE; TYROSINE KINASE; MYELOPROLIFERATIVE VARIANT; BCR-ABL; C-KIT; THERAPY; CELLS; TRANSPLANTATION; MYELOFIBROSIS; CYCLOSPORINE C1 Dana Farber Canc Inst, Adult Leukemia Program, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Stone, RM (reprint author), Dana Farber Canc Inst, Adult Leukemia Program, 44 Binney St,Dana 840, Boston, MA 02115 USA. OI Klion, Amy/0000-0002-4986-5326 NR 36 TC 8 Z9 8 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2004 VL 31 IS 2 SU 6 BP 12 EP 17 DI 10.1053/j.seminoncol.2004.030.35 PG 6 WC Oncology SC Oncology GA 824NQ UT WOS:000221693700003 PM 15175999 ER PT J AU Enzinger, PC Mayer, RJ AF Enzinger, PC Mayer, RJ TI Gastrointestinal cancer in older patients SO SEMINARS IN ONCOLOGY LA English DT Review ID ADVANCED COLORECTAL-CANCER; ADJUVANT COMBINED RADIATION; RANDOMIZED CONTROLLED TRIAL; FATAL COLON-CANCER; ELDERLY-PATIENTS; PANCREATIC-CANCER; RECTAL-CANCER; ESOPHAGEAL CANCER; GASTRIC-CANCER; HEPATOCELLULAR-CARCINOMA C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Enzinger, PC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 136 TC 14 Z9 17 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2004 VL 31 IS 2 BP 206 EP 219 DI 10.1053/j.seminoncol.2003.12.031 PG 14 WC Oncology SC Oncology GA 813DA UT WOS:000220886600009 PM 15112151 ER PT J AU Matulonis, UA AF Matulonis, UA TI End of life issues in older patients SO SEMINARS IN ONCOLOGY LA English DT Review ID ILL HOSPITALIZED-PATIENTS; NURSING-HOME RESIDENTS; ADVANCE DIRECTIVES; ADVANCED CANCER; TERMINALLY-ILL; MAJOR DEPRESSION; TREATMENT PREFERENCES; PAIN MANAGEMENT; HOSPICE CARE; SUICIDE C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Matulonis, UA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 66 TC 10 Z9 11 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2004 VL 31 IS 2 BP 274 EP 281 DI 10.1053/j.seminoncol.2003.10.036 PG 8 WC Oncology SC Oncology GA 813DA UT WOS:000220886600014 PM 15112156 ER PT J AU Blackard, JT Mayer, KH AF Blackard, JT Mayer, KH TI HIV superinfection in the ERA of increased sexual risk-taking SO SEXUALLY TRANSMITTED DISEASES LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 SUPERINFECTION; ANTIRETROVIRAL THERAPY; PRIMARY INFECTION; DUAL INFECTION; HOMOSEXUAL MEN; SAN-FRANCISCO; BISEXUAL MEN; VIRAL LOAD; GAY AB Recent reports have documented increases in unprotected intercourse (UI) and sexually transmitted diseases (STDs) among men who have sex with men (MSM) and other at-risk populations. A further consequence of persons living with HIV engaging in unprotected intercourse or shared parenteral exposures with seroconcordant partners is HIV recombination and superinfection, possibly with a drug-resistant or more pathogenic virus. The epidemiologic, clinical, and therapeutic implications of recent case reports confirming superinfection in persons living with HIV, as well as research priorities aimed at providing a more thorough understanding of the consequences of unprotected sex among HIV-infected people, are explored here. C1 Fenway Community Hlth, Res & Evaluat Dept, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Brown Univ, Miriam Hosp, Providence, RI USA. RP Mayer, KH (reprint author), Fenway Community Hlth, Res & Evaluat Dept, 7 Haviland St, Boston, MA 02115 USA. EM Kenneth_Mayer@brown.edu NR 38 TC 28 Z9 29 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD APR PY 2004 VL 31 IS 4 BP 201 EP 204 DI 10.1097/01.OLQ.0000118082.45312.1F PG 4 WC Infectious Diseases SC Infectious Diseases GA 807ZF UT WOS:000220538700001 PM 15028931 ER PT J AU Weeratunge, CN Bolivar, HH Anstead, GM Lu, DH AF Weeratunge, CN Bolivar, HH Anstead, GM Lu, DH TI Primary esophageal lymphoma: A diagnostic challenge in acquired immunodeficiency syndrome - Two case reports and review SO SOUTHERN MEDICAL JOURNAL LA English DT Review DE acquired immunodeficiency syndrome; esophagus; lymphoma ID ACTIVE ANTIRETROVIRAL THERAPY; NON-HODGKINS-LYMPHOMA; AIDS; PATIENT; PROGNOSIS AB Although extranodal presentation occurs in the majority of cases of acquired immunodeficiency syndrome-associated non-Hodgkin lymphoma, the esophagus is only rarely affected. We discuss two patients with acquired immunodeficiency syndrome who presented with dysphagia and weight loss, who were found to have human immunodeficiency virus-associated primary esophageal lymphoma. Both patients died within a few weeks of diagnosis, reflecting the poor prognosis associated with this malignancy. Primary esophageal lymphoma should be considered in the differential diagnosis in a human immunodeficiency virus-seropositive patient presenting with dysphagia. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, Div Infect Dis, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Weeratunge, CN (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, Mail Code 7881,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM cnamalw@hotmail.com NR 21 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD APR PY 2004 VL 97 IS 4 BP 383 EP 387 DI 10.1097/01.SMJ.0000100120.49153.3F PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 831DC UT WOS:000222172200015 PM 15108833 ER PT J AU Lipsitz, SR Molenberghs, G Fitzmaurice, GM Ibrahim, JG AF Lipsitz, SR Molenberghs, G Fitzmaurice, GM Ibrahim, JG TI Protective estimator for linear regression with nonignorably missing Gaussian outcomes SO STATISTICAL MODELLING LA English DT Article DE EM-algorithm; method of moments; nonignorable missing data; ordinary least squares ID INCOMPLETE DATA; DATA MECHANISM; NONRESPONSE; VARIABLES; MODELS AB We propose a method for estimating the regression parameters in a linear regression model for Gaussian data when the outcome variable is missing for some subjects and missingness is thought to be nonignorable. Throughout, we assume that missingness is restricted to the outcome variable and that the covariates are fully observed. Although maximum likelihood estimation of the regression parameters is possible once joint models for the outcome variable and the nonignorable missing data mechanism have been specified, these models are fundamentally nonidentifiable unless unverifiable modeling assumptions are imposed. In this paper, rather than explicitly modeling the nonignorable missingness mechanism, we consider the use of a 'protective' estimator of the regression parameters (Brown, 1990). To implement the proposed method, it is necessary to assume that the outcome variable and one of the covariates have an approximate bivariate normal distribution, conditional on the remaining covariates. In addition, it is assumed that the missing data mechanism is conditionally independent of this covariate, given the outcome variable and the remaining covariates; the latter is referred to as the 'protective' assumption. A method of moments approach is used to obtain the protective estimator of the regression parameters; the jackknife (Quenouille, 1956) is used to estimate the variance. The method is illustrated using data on the persistence of maternal smoking from the Six Cities Study of the health effects of air pollution (Ware et al., 1984). The results of a simulation study are presented that examine the magnitude of any finite sample bias. C1 Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. Limburgs Univ Ctr, Ctr Stat, Diepenbeek, Belgium. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Biostat Sci, Boston, MA 02115 USA. RP Lipsitz, SR (reprint author), Med Univ S Carolina, Dept Biometry & Epidemiol, 135 Cannon St,Suite 303, Charleston, SC 29425 USA. EM lipsitzs@musc.edu NR 14 TC 3 Z9 3 U1 0 U2 0 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1471-082X J9 STAT MODEL JI Stat. Model. PD APR PY 2004 VL 4 IS 1 BP 3 EP 17 DI 10.1191/1471082X04st066oa PG 15 WC Statistics & Probability SC Mathematics GA 810CM UT WOS:000220682400001 ER PT J AU Kim, DE Schellingerhout, D Ishii, K Shah, K Weissleder, R AF Kim, DE Schellingerhout, D Ishii, K Shah, K Weissleder, R TI Imaging of stem cell recruitment to ischemic infarcts in a murine model SO STROKE LA English DT Article DE diagnostic imaging; infarction; luciferase; stem cells ID IN-VIVO TRACKING; MIGRATION; STROKE; RAT; EXPRESSION; REPORTER; RECOVERY; THERAPY; BRAIN AB Background and Purpose-Neural progenitor cells (NPC) have been reported to aid in the functional recovery from stroke and hold promise as a novel treatment for a variety of neurological diseases. There is a need for imaging tools to study the in vivo migratory behavior of these cells. Methods-C17.2 NPC, stably transfected with firefly luciferase, were serially imaged through intact skull and skin by bioluminescence imaging over 2 to 3 weeks in nu/nu mice with closed-vessel middle cerebral artery infarcts, followed by contralateral intraparenchymal or intraventricular injections of NPC. Results-NPC migrated to the site of infarct from the contraleral parenchyma, crossing the midline at 7 days. In control animals without infarcts, NPC remained at the site of administration. Intraventricular cell administration resulted in a wide distribution of cells, including the site of infarct. Within the infarct area, NPC colabeled with the neuronal marker NeuN and with astroglial marker glial fibrillary acidic protein. The time course and magnitude of NPC recruitment were longitudinally compared between the treatment groups. Conclusions-NPC recruitment to infarct can be assessed noninvasively by serial in vivo imaging. Images correlate well with histological cell distributions. NPC are recruited to infarcts with both parenchymal and cerebrospinal fluid administration, but higher initial photon counts suggest that cerebrospinal fluid administration is more efficient at early infarct seeding. C1 Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Charlestown Navy Yard, MA 02129 USA. RP Schellingerhout, D (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Room 5403,Bldg 149,13th St, Charlestown Navy Yard, MA 02129 USA. EM Dawid@helix.mgh.harvard.edu FU NCI NIH HHS [1R24CA92782-01, 2PO1CA6924605] NR 22 TC 94 Z9 104 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2004 VL 35 IS 4 BP 952 EP 957 DI 10.1161/01.STR.0000120308.21946.5D PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 806RG UT WOS:000220450400028 PM 14988578 ER PT J AU Erkinjuntti, T Roman, G Gauthier, S Feldman, H Rockwood, K AF Erkinjuntti, T Roman, G Gauthier, S Feldman, H Rockwood, K TI Emerging therapies for vascular dementia and vascular cognitive impairment SO STROKE LA English DT Article DE carbamates; cognitive disorders; dementia; galantamine; memantine; nimodipine; piperidines; vascular diseases; donepezil; rivastigmine ID SCANDINAVIAN MULTIINFARCT DEMENTIA; PLACEBO-CONTROLLED TRIAL; LIPID-LOWERING AGENTS; ACUTE ISCHEMIC-STROKE; ALZHEIMERS-DISEASE; CLINICAL-TRIALS; CEREBROVASCULAR-DISEASE; MIXED DEMENTIA; DOUBLE-BLIND; RISK-FACTORS AB Background-Cerebrovascular disease (CVD) and ischemic brain injury secondary to cardiovascular disease are common causes of dementia and cognitive decline in the elderly. CVD also contributes to cognitive loss in Alzheimer disease (AD). Summary-Progress in understanding vascular cognitive impairment (VCI) and vascular dementia (VaD) has resulted in promising symptomatic and preventive treatments. Cholinergic deficits in VaD due to ischemia of basal forebrain nuclei and cholinergic pathways can be treated with cholinesterase inhibitors used in AD. Controlled clinical trials with donepezil and galantamine in patients with VaD, as well as in patients with AD plus CVD, have demonstrated improvement in cognition, behavior, and activities of daily living. The N-methyl-D-aspartate receptor antagonist memantine stabilized progression of VaD compared with placebo. Primary and secondary stroke prevention, in particular with control of hypertension and hyperlipidemia, can decrease VaD incidence. Conclusions-From a public health viewpoint, recognition of VCI before the development of dementia and correction of vascular burden on the brain may lead to a global decrease of incident dementia. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. Univ Helsinki, Cent Hosp, Helsinki, Finland. A Murphy Vet Adm Hosp, San Antonio, TX USA. McGill Ctr Studies Aging, Alzheimers Dis Res Unit, Montreal, PQ, Canada. Univ British Columbia, Div Neurol, Vancouver, BC V5Z 1M9, Canada. Dalhousie Univ, Queen Elizabeth II Hlth Sci Ctr, Geriatr Med Res Unit, Halifax, NS, Canada. RP Roman, G (reprint author), Univ Texas, Hlth Sci Ctr, Mail Code 7883,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM romang@uthscsa.edu OI Feldman, Howard/0000-0002-9258-4538 NR 87 TC 109 Z9 133 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2004 VL 35 IS 4 BP 1010 EP 1017 DI 10.1161/01.STR.0000120731.88236.33 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 806RG UT WOS:000220450400038 PM 15001795 ER PT J AU Wekerle, T Sykes, M AF Wekerle, T Sykes, M TI Induction of tolerance SO SURGERY LA English DT Article ID DONOR-SPECIFIC TOLERANCE; MIXED HEMATOPOIETIC CHIMERISM; BONE-MARROW-TRANSPLANTATION; RENAL-ALLOGRAFT TOLERANCE; TOTAL-BODY IRRADIATION; VERSUS-HOST-DISEASE; LARGE-ANIMAL-MODEL; T-CELL DEPLETION; COSTIMULATORY BLOCKADE; ALLOGENEIC CHIMERISM C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Univ Vienna, Vienna Gen Hosp, Dept Surg, Div Transplantat, Vienna, Austria. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, MGH E Bldg 149-5102,13th St, Boston, MA 02129 USA. OI Wekerle, Thomas/0000-0001-5159-2796 FU NHLBI NIH HHS [HL 49915]; NIAID NIH HHS [AI 05558] NR 45 TC 12 Z9 12 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD APR PY 2004 VL 135 IS 4 BP 359 EP 364 DI 10.1016/j.surg.2003.10.010 PG 6 WC Surgery SC Surgery GA 808GF UT WOS:000220556900001 PM 15041958 ER PT J AU Rattner, DW AF Rattner, DW TI Invited commentary: "Radical retropubic prostatectomy frustrated by laparoscopic mesh herniorrhaphy" SO SURGERY LA English DT Editorial Material ID INGUINAL-HERNIA REPAIR; RANDOMIZED CONTROLLED-TRIAL C1 Massachusetts Gen Hosp, Div Gen Gastrointestinal Surg, Boston, MA 02114 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Div Gen Gastrointestinal Surg, 15 Parkham Rd,WACC 337, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD APR PY 2004 VL 135 IS 4 BP 454 EP 454 DI 10.1016/.j.surg.2004.12.008 PG 1 WC Surgery SC Surgery GA 808GF UT WOS:000220556900015 ER PT J AU Rubio, F Cooley, J Accurso, FJ Remold-O'Donnell, E AF Rubio, F Cooley, J Accurso, FJ Remold-O'Donnell, E TI Linkage of neutrophil serine proteases and decreased surfactant protein-A (SP-A) levels in inflammatory lung disease SO THORAX LA English DT Article ID CYSTIC-FIBROSIS SPUTUM; PULMONARY SURFACTANT; CATHEPSIN-G; HOST-DEFENSE; ELASTASE; BINDING; COLLECTINS; PROTEOLYSIS; RECOGNITION; INHIBITOR AB Background: In patients with cystic fibrosis (CF) neutrophils are recruited in excess to the airways yet pathogens are not cleared and the patients suffer from chronic infections. Recent studies have shown a deficiency in airway fluids from patients with CF and other inflammatory pulmonary conditions of surfactant protein A (SP-A), a pattern recognition molecule that facilitates uptake of microbes by macrophages and neutrophils. Methods: In vitro simulations were used to test the hypothesis that decreased SP-A levels in CF might be the result of degradation by neutrophil serine proteases. Results: Very low levels of the neutrophil granule serine proteases cathepsin G, elastase, and proteinase-3 rapidly degraded pure SP-A when tested in buffered saline. The order of potency was cathepsin G>elastase>proteinase-3. The addition of cathepsin G or elastase to normal bronchoalveolar lavage (BAL) fluid caused a dose dependent degradation of endogenous native SP-A. Cathepsin G and elastase were present in the BAL fluid from many patients with CF. Simple incubation of protease positive BAL fluid from patients with CF caused a time dependent degradation of added SP-A or, where present, endogenous SP-A. The degradation of SP-A by protease(s) in BAL fluid of patients with CF was abrogated by diisopropylfluorophosphate and monocyte/neutrophil elastase inhibitor. Conclusions: The findings strongly suggest that the neutrophil serine proteases cathepsin G and/or elastase and/or proteinase-3 contribute to degradation of SP-A and thereby diminish innate pulmonary antimicrobial defence. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res Inc, Boston, MA USA. Univ Colorado, Sch Med, Dept Pediat, Denver, CO USA. Childrens Hosp, Denver, CO 80218 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA USA. RP Remold-O'Donnell, E (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. EM remold@cbr.med.harvard.edu FU NCRR NIH HHS [RR00069]; NHLBI NIH HHS [R01 HL066548, HL66548] NR 36 TC 46 Z9 50 U1 0 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 J9 THORAX JI Thorax PD APR 1 PY 2004 VL 59 IS 4 BP 318 EP 323 DI 10.1136/thx.2003.014902 PG 6 WC Respiratory System SC Respiratory System GA 807CT UT WOS:000220480300011 PM 15047952 ER PT J AU Rosito, GA D'Agostino, RB Massaro, J Lipinska, L Mittleman, MA Sutherland, P Wilson, PWF Levy, D Muller, JE Tofler, GH AF Rosito, GA D'Agostino, RB Massaro, J Lipinska, L Mittleman, MA Sutherland, P Wilson, PWF Levy, D Muller, JE Tofler, GH TI Association between obesity and a prothrombotic state: the Framingham Offspring Study SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE obesity; thrombosis; cardiovascular disease ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; INSULIN-RESISTANCE SYNDROME; CARDIOVASCULAR RISK-FACTORS; CORONARY RISK; MYOCARDIAL-INFARCTION; HEMOSTATIC FACTORS; ENDOTHELIAL-CELLS; ANGINA-PECTORIS; HEART-DISEASE; BODY-WEIGHT AB Although obesity is associated with increased cardiovascular risk, the mechanism has not been fully explained. Since thrombosis is a critical component of cardiovascular disease, we examined the relationship between obesity and hemostatic factors. We studied 3230 subjects (55% females, mean age 54 years) without a history of cardiovascular disease in cycle 5 of the Framingham Offspring Study. Obesity was assessed by body mass index and waist-to-hip ratio. Fasting blood samples were obtained for fibrinogen, plasminogen activator inhibitor (PAI-I) antigen, tissue plasminogen activator (tPA) antigen, factor VII antigen, von Willebrand factor (VWF), and plasma viscosity. Body mass index was directly associated with fibrinogen, factor VII, PAI-I and tPA antigen in both men and women (p<0.001) and with VWF and viscosity in women. Similar associations were present between waist-to-hip ratio and the hemostatic factors. With minor exceptions for VWF and viscosity, all associations persisted after controlling for age, smoking, total and HDL cholesterol, triglycerides, glucose level, blood pressure, and use of antihypertensive medication. The association between increased body mass index and waist-to-hip ratio and prothrombotic factors and impaired fibrinolysis suggests that obesity is a risk factor whose effect is mediated in part by a prothrombotic state. C1 Royal N Shore Hosp, St Leonards, NSW 2065, Australia. Hosp Clin, Porto Alegre, RS, Brazil. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Inst Prevent Cardiovasc Dis, Boston, MA 02215 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Tofler, GH (reprint author), Royal N Shore Hosp, St Leonards, NSW 2065, Australia. EM gtofler@doh.health.nsw.gov.au FU NHLBI NIH HHS [R01-HL-48157] NR 36 TC 109 Z9 116 U1 0 U2 1 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 APR PY 2004 VL 91 IS 4 BP 683 EP 689 DI 10.1160/TH03-01-0014 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 813FS UT WOS:000220893600007 PM 15045128 ER PT J AU Murphy, MF Stearn, BE Dzik, WH AF Murphy, MF Stearn, BE Dzik, WH TI Current performance of patient sample collection in the UK SO TRANSFUSION MEDICINE LA English DT Article DE blood transfusion; errors; patient safety; sample collection; survey ID TRANSFUSION; BLOOD AB Collection of the patient sample for pretransfusion testing begins a complex chain of events in the transfusion process. Hospitals in England and North Wales were surveyed to compare local policies against recommendations of the British Committee for Standards in Haematology (BCSH). Hospitals also measured the frequency of rejected and miscollected samples [designated as wrong blood in tube (WBIT)]. 185 of 360 (51.4%) hospitals returned questionnaires and 182 of 185 (98%) hospitals reported that a policy for sample collection existed. Apart from frequent omission of the gender of the patient, there was 96% compliance with all mandatory identifiers of the BCSH guidelines. Practice allowing additions or changes to labelling on sample tubes and request forms varied. 3.2% (14114/445726) of samples submitted were rejected for various reasons, the most frequent being incomplete or missing information (49.5% of the total rejected samples). The corrected mean frequency for WBIT in the 27 hospitals with one or more observed WBIT was 1 in 1501 samples (95% CI: less than or equal to1129.09 to less than or equal to1872.91), and the median corrected frequency for WBIT was 1 in 1303 samples. This study has identified great variation in the policy and practice for sample collection for pretransfusion testing. Regular tracking of the rates of sample rejection and WBIT could be used to identify poor performance in individual hospitals requiring investigation and action. C1 John Radcliffe Hosp, Natl Blood Serv, Oxford OX3 9BQ, England. Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. RP Murphy, MF (reprint author), John Radcliffe Hosp, Natl Blood Serv, Oxford OX3 9BQ, England. EM mike.murphy@nbs.nhs.uk NR 10 TC 39 Z9 40 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0958-7578 J9 TRANSFUSION MED JI Transfus. Med. PD APR PY 2004 VL 14 IS 2 BP 113 EP 121 DI 10.1111/j.0958-7578.2004.0488.x PG 9 WC Hematology SC Hematology GA 816FF UT WOS:000221095100004 PM 15113376 ER PT J AU Kulig, KM Vacanti, JR AF Kulig, KM Vacanti, JR TI Hepatic tissue engineering SO TRANSPLANT IMMUNOLOGY LA English DT Article DE liver; tissue engineering; hepatocyte; microfabrication; bioreactors ID LIVER SUPPORT-SYSTEM; EPIDERMAL-GROWTH-FACTOR; ADULT-RAT HEPATOCYTES; BIOARTIFICIAL LIVER; EXTRACELLULAR-MATRIX; BILIRUBIN CONJUGATION; NONPARENCHYMAL CELLS; CLINICAL-EXPERIENCE; COCULTURE SYSTEMS; COMB POLYMERS AB Fulminant hepatic failure (FHF) attributes to rising medical cost and accounts for many deaths each year in the United States. Currently, the only solution is organ transplantation. Due to increasing donor organ shortage, many in need of transplantation continue to remain on the waiting list. Liver Assist Devices (LADs) are being used to temporarily sustain liver function and bridge the period between FHF and transplantation. Hepatic Tissue Engineering is a step toward alleviating the need for donor organs; yet many challenges must be overcome including scaffold choice, cell source and immunological barriers. Bioreactors have aided in hepatocyte survival and have proven to sustain viable cells for several weeks. Achieving the necessary functions required for hepatic replacement is aided by the incorporation of growth factors and mitogens many that now can be bound to the polymer scaffold and released in a timely manner. Utilizing concepts such as MicroElectroMechanical systems (MEMs) technology, our laboratory is able to mimic the natural vasculature of the liver and sustain functional and viable hepatocytes. Expanding and improving upon this platform, technology, advancements made will continue toward the development of a fully functioning and implantable liver. (C) 2004 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Vacanti, JR (reprint author), Massachusetts Gen Hosp, Warren 11,55 Fruit St, Boston, MA 02114 USA. EM jvacanti@partners.org NR 62 TC 91 Z9 108 U1 1 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0966-3274 J9 TRANSPL IMMUNOL JI Transpl. Immunol. PD APR PY 2004 VL 12 IS 3-4 BP 303 EP 310 DI 10.1016/j.trim.2003.12.005 PG 8 WC Immunology; Transplantation SC Immunology; Transplantation GA 827KC UT WOS:000221897300012 PM 15157923 ER PT J AU Kwon, M Scholey, JM AF Kwon, M Scholey, JM TI Spindle mechanics and dynamics during mitosis in Drosophila SO TRENDS IN CELL BIOLOGY LA English DT Review ID KINESIN-LIKE PROTEIN; MICROTUBULE-ASSOCIATED PROTEIN; METAPHASE CHROMOSOME ALIGNMENT; HISTONE H3 PHOSPHORYLATION; MITOTIC SPINDLE; CELL-DIVISION; AURORA-A; D-TACC; CYTOPLASMIC DYNEIN; SELF-ORGANIZATION AB Drosophila melanogaster is an excellent model for studying mitosis. Syncytial embryos are amenable to time-lapse imaging of hundreds of synchronously dividing spindles, allowing the quantitation of spindle and chromosome dynamics with unprecedented fidelity. Other Drosophila cell types, including neuroblasts, cultured cells, spermatocytes and oocytes, contain spindles that differ in their design, providing cells amenable to different types of experiments and allowing identification of common core mechanisms. The function of mitotic proteins can be studied using mutants, inhibitor microinjection and RNA interference (RNAi) to identify the full inventory of mitotic proteins encoded by the genome. Here, we review recent advances in understanding how ensembles of mitotic proteins coordinate spindle assembly and chromosome motion in this system. C1 Univ Calif Davis, Ctr Genet & Dev, Davis, CA 95616 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Calif Davis, Sect Mol & Cellular Biol, Davis, CA 95616 USA. RP Scholey, JM (reprint author), Univ Calif Davis, Ctr Genet & Dev, Davis, CA 95616 USA. EM jmscholey@ucdavis.edu FU NIGMS NIH HHS [GM-55507] NR 65 TC 35 Z9 39 U1 0 U2 7 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD APR PY 2004 VL 14 IS 4 BP 194 EP 205 DI 10.1016/j.tcb.2004.03.003 PG 12 WC Cell Biology SC Cell Biology GA 816TP UT WOS:000221132500007 PM 15066637 ER PT J AU Wierman, ME Pawlowski, JE Allen, MP Xu, M Linseman, DA Nielsen-Preiss, S AF Wierman, ME Pawlowski, JE Allen, MP Xu, M Linseman, DA Nielsen-Preiss, S TI Molecular mechanisms of gonadotropin-releasing hormone neuronal migration SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID RECEPTOR TYROSINE KINASE; SIGNAL-REGULATED KINASE; NEURAL CELL-ADHESION; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; LINKED KALLMANN-SYNDROME; PROTEIN-KINASE; HYPOTHALAMIC NEURONS; GENE-EXPRESSION; LHRH NEURONS; FACILITATES MIGRATION AB Gonadotropin-releasing hormone (GnRH) neurons originate in the nasal compartment, migrate along olfactory nerves to the cribriform plate and then diverge caudally to the forebrain to reach their final destination in the hypothalamus. Here, GnRH neurons are dispersed in a network that synchronously releases GnRH in a pulsatile manner to activate pituitary gonadotropin production. Gonadotropins in turn promote gametogenesis and steroidogenesis from the gonad, ensuring reproductive competence. Failure of GnRH neurons to migrate normally results in deficient activation of the reproductive axis and delayed or absent pubertal maturation. The exact mechanisms that direct GnRH neuronal migration are under active investigation. This article will review new information concerning factors regulating GnRH neuronal migration and the intracellular signaling pathways involved in this process. C1 Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Physiol & Biophys, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Denver VA Med Ctr, Res Serv, Denver, CO 80220 USA. RP Wierman, ME (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Med, B151 Endocrinol,4200 E 9th, Denver, CO 80262 USA. EM Margaret.Wierman@uchsc.edu NR 72 TC 45 Z9 47 U1 0 U2 1 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 APR PY 2004 VL 15 IS 3 BP 96 EP 102 DI 10.1016/j.tem.2004.02.003 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 813GR UT WOS:000220896100002 PM 15046737 ER PT J AU Duda, DG Fukumura, D Jain, RK AF Duda, DG Fukumura, D Jain, RK TI Role of eNOS in neovascularization: NO for endothelial progenitor cells SO TRENDS IN MOLECULAR MEDICINE LA English DT Article ID NITRIC-OXIDE SYNTHASE; HEMATOPOIETIC STEM-CELLS; BONE-MARROW; TUMOR ANGIOGENESIS; INHIBITION; VEGF; REVASCULARIZATION; PERMEABILITY; MOBILIZATION; INDUCTION AB Nitric oxide (NO) is a gaseous molecule with an astonishingly wide range of physiological and pathophysiological activities, including the regulation of vessel tone and angiogenesis in wound healing, inflammation, ischaemic cardiovascular diseases and malignant diseases. Recent data have revealed the predominant role of endothelial nitric oxide synthase (eNOS), an endothelial-cell-specific isoform of NO producing enzyme, in both angiogenesis (the development of new blood vessels derived from existing vessels) and vasculogenesis (blood vessel formation de novo from progenitor cells). In addition, successes in gene therapy, together with the recent development of an eNOS-specific inhibitor, suggest that the modulation of eNOS might be a potent new strategy for the control of pathological neovascularization. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, EL Steele Lab Tumor Biol, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, EL Steele Lab Tumor Biol, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM jain@steele.mgh.hatward.edu NR 27 TC 146 Z9 152 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD APR PY 2004 VL 10 IS 4 BP 143 EP 145 DI 10.1016/j.molmed.2004.02.001 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 816TM UT WOS:000221132200001 PM 15162796 ER PT J AU Ewen, ME Lamb, J AF Ewen, ME Lamb, J TI The activities of cyclin D1 that drive tumorigenesis SO TRENDS IN MOLECULAR MEDICINE LA English DT Article ID ESTROGEN-RECEPTOR; GENE-EXPRESSION; RETINOBLASTOMA PROTEIN; CELL-PROLIFERATION; RESTRICTION POINT; CDK INHIBITORS; BREAST-CANCER; TRANSCRIPTION FACTOR; KINASE-ACTIVITY; G(1) AB The proto-oncogene cyclin D1 has been implicated in the genesis of a large proportion of human tumors from diverse histological origins. It has long been assumed that the action of cyclin D1, as an activator of cdk4 and cdk6 and leading to progression through the G1 phase of the cell cycle, underlies its pathological activity. But, more recently, analyses of the patterns of gene expression in human cancer have revealed a previously unappreciated mechanism of action for cyclin D1, suggesting that both cdk-dependent and cdk-independent activities might contribute to tumorigenesis. The development of therapeutics designed to target the aberrant activity of cyclin D1 in human cancers will rely upon an intimate molecular understanding of these distinct mechanisms of actions and their relative importance. Here, we describe the known functions of the cyclin D1 oncogene and delineate the evidence that cdk-independent actions are important for cyclin D1-mediated oncogenesis. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. MIT, Howard Hughes Med Inst, Cambridge, MA 02141 USA. MIT, Broad Inst, Cambridge, MA 02141 USA. RP Ewen, ME (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM mark_ewen@dfci.harvard.edu FU NCI NIH HHS [P01CA80111] NR 52 TC 100 Z9 106 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD APR PY 2004 VL 10 IS 4 BP 158 EP 162 DI 10.1016/j.molmed.2004.02.005 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 816TM UT WOS:000221132200004 PM 15059606 ER PT J AU Cambien, B Wagner, DD AF Cambien, B Wagner, DD TI A new role in hemostasis for the adhesion receptor P-selectin SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID FIBRINOGEN-GAMMA-CHAIN; VON-WILLEBRAND-FACTOR; TISSUE FACTOR; IN-VIVO; VENOUS THROMBOSIS; DEFICIENT MICE; LEUKOCYTE MICROPARTICLES; GLYCOPROTEIN LIGAND-1; SOLUBLE FORM; MONOCLONAL-ANTIBODY AB The adhesion receptor P-selectin has long been known to support leukocyte rolling and emigration at sites of inflammation. Recently, P-selectin was also revealed to be a key molecule in hemostasis and thrombosis, mediating platelet rolling, generating procoagulant microparticles containing active tissue factor and enhancing fibrin deposition. Elevated levels of plasma P-selectin are indicative of thrombotic disorders and predictive of future cardiovascular events. Because the interaction between P-selectin and its receptor P-selectin glycoprotein ligand-1 (PSGL-1) represents an important mechanism by which P-selectin induces the formation of procoagulant microparticles and recruits the microparticles to thrombi, anti-thrombotic strategies are currently aimed at inhibiting this interaction. Recent developments also suggest that the procoagulant potential of P-selectin could be used to treat coagulation disorders such as hemophilia A. C1 Harvard Univ, Sch Med, Ctr Blood Res, Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Inst Biomed Res, Boston, MA 02115 USA. EM wagner@cbr.med.harvard.edu FU NHLBI NIH HHS [P01 HL056949, P01HL56949, R01 HL053756, R01HL53756, R37 HL041002, R37HL41002] NR 83 TC 81 Z9 84 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD APR PY 2004 VL 10 IS 4 BP 179 EP 186 DI 10.1016/j.molmed.2004.02.007 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 816TM UT WOS:000221132200007 PM 15059609 ER PT J AU Smith, MR AF Smith, MR TI Changes in fat and lean body mass during androgen-deprivation therapy for prostate cancer SO UROLOGY LA English DT Article ID QUALITY-OF-LIFE; TESTOSTERONE REPLACEMENT; RESISTANCE EXERCISE; CONTROLLED-TRIAL; MUSCLE SIZE; MEN; HYPOGONADISM; LEUPROLIDE; STRENGTH; DENSITY AB Objectives. To assess the effects of androgen deprivation therapy on body composition in men with nonmetastatic prostate cancer. Methods. In a multicenter study, men with Stage MO prostate cancer were prospectively evaluated during initial androgen deprivation therapy (gonaclotropin-releasing hormone agonist or bilateral orchiectomy). The main outcomes were changes in weight, percentage fat mass, and percentage lean mass from baseline to 12 months. Results. Seventy-nine subjects were assessed. Serum testosterone concentrations decreased by 79.7% 3.0% (P < 0.001). Weight increased by 1.8% +/- 0.5% (P < 0.001). The percentage fat mass increased by 11.0% +/- 1.7%, and the percentage lean mass decreased by 3.8% +/- 0.6% (P < 0.001 for each comparison). Conclusions. Androgen deprivation therapy increased weight and fat mass and decreased lean mass in men with nonmetastatic prostate cancer. (C) 2004 Elsevier Inc. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Cox 640,100 Blossom St, Boston, MA 02114 USA. NR 21 TC 126 Z9 128 U1 4 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD APR PY 2004 VL 63 IS 4 BP 742 EP 745 DI 10.1016/j.urology.2003.10.063 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 811RW UT WOS:000220790000030 PM 15072892 ER PT J AU Canzoniere, D Farioli-Vecchioli, S Conti, F Ciotti, MT Tata, AM Augusti-Tocco, G Mattei, E Lakshmana, MK Krizhanovsky, V Reeves, SA Giovannoni, R Castano, F Servadio, A Ben-Arie, N Tirone, F AF Canzoniere, D Farioli-Vecchioli, S Conti, F Ciotti, MT Tata, AM Augusti-Tocco, G Mattei, E Lakshmana, MK Krizhanovsky, V Reeves, SA Giovannoni, R Castano, F Servadio, A Ben-Arie, N Tirone, F TI Dual control of Neurogenesis by PC3 through cell cycle inhibition and induction of Math1 SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cyclin D1; Math1; NeuroD1; nestin; neuroepithelia; tet-on/off ID NERVE GROWTH-FACTOR; DEVELOPING CEREBELLAR CORTEX; EXTERNAL GRANULAR LAYER; NEURONAL DIFFERENTIATION; GENE-EXPRESSION; PURKINJE-CELLS; MOUSE CEREBELLUM; GENERATION CYCLE; MAMMALIAN-CELLS; MESSENGER-RNA AB Growing evidence indicates that cell cycle arrest and neurogenesis are highly coordinated and interactive processes, governed by cell cycle genes and neural transcription factors. The gene PC3 (Tis21/BTG2) is expressed in the neuroblast throughout the neural tube and inhibits cell cycle progression at the G(1) checkpoint by repressing cyclin D1 transcription. We generated inducible mouse models in which the expression of PC3 was upregulated in neuronal precursors of the neural tube and of the cerebellum. These mice exhibited a marked increase in the production of postmitotic neurons and impairment of cerebellar development. Cerebellar granule precursors of PC3 transgenic mice displayed inhibition of cyclin D1 expression and a strong increase in the expression of Math1, a transcription factor required for their differentiation. Furthermore, PC3, encoded by a recombinant adenovirus, also induced Math1 in postmitotic granule cells in vitro and stimulated the Math1 promoter activity. In contrast, PC3 expression was unaffected in the cerebellar primordium of Math1 null mice, suggesting that PC3 acts upstream to Math1. As a whole, our data suggest that cell cycle exit of cerebellar granule cell precursors and the onset of cerebellar neurogenesis are coordinated by PC3 through transcriptional control of cyclin D1 and Math1, respectively. C1 CNR, Ist Neurobiol & Med Mol, I-00156 Rome, Italy. CNR, Ist Biol & Patol Mol, I-00156 Rome, Italy. Univ Roma La Sapienza, Dipartimento Biol Cellulare & Sviluppo, I-00185 Rome, Italy. Hebrew Univ Jerusalem, Dept Cell & Anim Biol, IL-91904 Jerusalem, Israel. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat,Cent Nervous Sys, Charlestown, MA 02129 USA. Telethon Inst Genet & Med, I-00161 Rome, Italy. RP Tirone, F (reprint author), CNR, Ist Neurobiol & Med Mol, Viale Marx 15, I-00156 Rome, Italy. EM tirone@in.rm.cnr.it RI Giovannoni, Roberto/A-1413-2009; Ben-Arie, Nissim/K-4997-2012; OI Giovannoni, Roberto/0000-0002-7706-0672; Tirone, Felice/0000-0002-0980-4377; farioli vecchioli, stefano/0000-0001-7059-7779 FU Telethon [F.4] NR 66 TC 60 Z9 61 U1 0 U2 1 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 MAR 31 PY 2004 VL 24 IS 13 BP 3355 EP 3369 DI 10.1523/JNEUROSCI.3860-03.2004 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 808VK UT WOS:000220596400022 PM 15056715 ER PT J AU Friedlich, AL Lee, JY van Groen, T Cherny, RA Volitakis, I Cole, TB Palmiter, RD Koh, JY Bush, AI AF Friedlich, AL Lee, JY van Groen, T Cherny, RA Volitakis, I Cole, TB Palmiter, RD Koh, JY Bush, AI TI Neuronal zinc exchange with the blood vessel wall promotes cerebral amyloid angiopathy in an animal model of Alzheimer's disease SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Alzheimer; blood-brain; neuropathology; synapse; zinc; amyloid; cerebrovasculature; congophilic angiopathy ID HISTOCHEMICALLY-REACTIVE ZINC; SULFIDE SILVER METHOD; PRECURSOR PROTEIN; TRANSGENIC MICE; HIPPOCAMPAL SLICES; SYNAPTIC VESICLES; PLAQUE-FORMATION; BETA-PROTEIN; HEAVY-METALS; RAT AB Cerebral amyloid angiopathy (CAA) is common in Alzheimer's disease ( AD) and may contribute to dementia and cerebral hemorrhage. Parenchymal beta-amyloid deposition is dependent on the activity of zinc transporter 3 (ZnT3), a neocortical synaptic vesicle membrane protein that causes enrichment of exchangeable Zn2+ in the vesicle, which is externalized on neurotransmission. However, the contribution of zinc to vascular beta-amyloid deposition remains unclear. Here, we identify for the first time an exchangeable pool of Zn2+ in the cerebrovascular wall of normal mice. This histochemically reactive Zn2+ is enriched in CAA in a transgenic mouse model of AD (Tg2576), and a dramatic reduction of CAA occurs after targeted disruption of the Znt3 gene in these mice. Also, in Znt3 knock-out mice, the amount of exchangeable Zn2+ [detected by N-(6-methoxy-8-quinolyl)-p-carboxybenzoylsulphonamide (TFL-Zn)] in the perivascular space was significantly decreased in the neocortex but not in peripheral organs. ZnT3 was not detected in the cerebral vessel walls or in blood components of wild-type mice. Thus, synaptic ZnT3 activity may promote CAA by indirectly raising exchangeable Zn2+ concentrations in the perivascular spaces of the brain. C1 Massachusetts Gen Hosp, Genet & Aging Res Unit, Lab Oxidat Biol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA. Univ Ulsan, Coll Med, Natl Creat Res Initiat Ctr Study CNS Zinc, Seoul 138736, South Korea. Univ Kuopio, Dept Neurol & Neurosci, FIN-70211 Kuopio, Finland. Mental Hlth Res Inst Victoria, Parkville, Vic 3052, Australia. Univ Melbourne, Dept Pathol, Parkville, Vic 3010, Australia. Univ Washington, Dept Biochem, Howard Hughes Med Inst, Seattle, WA 98195 USA. RP Bush, AI (reprint author), Massachusetts Gen Hosp, Genet & Aging Res Unit, Lab Oxidat Biol, Bldg 114,16th St, Charlestown, MA 02129 USA. EM bush@helix.mgh.harvard.edu RI van Groen, Thomas/A-3150-2008; Koh, Jae-Young/C-9014-2011; Lee, Joo-Yong/F-4545-2014; Bush, Ashley/A-1186-2007; OI Koh, Jae-Young/0000-0002-4318-495X; Bush, Ashley/0000-0001-8259-9069; Volitakis, Irene/0000-0003-0766-817X FU NIA NIH HHS [5R01AG12686-09]; NINDS NIH HHS [F32NS10874] NR 51 TC 89 Z9 96 U1 0 U2 1 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 MAR 31 PY 2004 VL 24 IS 13 BP 3453 EP 3459 DI 10.1523/JNEUROSCI.0297-04.2004 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 808VK UT WOS:000220596400032 PM 15056725 ER PT J AU Tsomaia, N Shimizu, M Shimizu, N Gardella, TJ Mierke, DF AF Tsomaia, N Shimizu, M Shimizu, N Gardella, TJ Mierke, DF TI Cooperative interaction of arginine-19 and the N-terminal signaling domain in the affinity and potency of parathyroid hormone SO BIOCHEMISTRY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; RECEPTOR-BINDING DOMAINS; NMR-SPECTROSCOPY; PTH RECEPTOR; MOLECULAR CHARACTERIZATION; DISTANCE CONSTRAINTS; COUPLING-CONSTANTS; EXTRACELLULAR LOOP; CROSS-LINKING; AMINO-ACIDS AB Residue 19 of parathyroid hormone (PTH) plays a unique role in the interaction process with the PTH1 receptor. A Glu(19) --> Arg(19) substitution, based on the Arg(19) of the PTH-related protein (PTHrP), increases the binding affinity when incorporated into the N-terminus of PTH [i.e., PTH(1 - 20)] and has no effect when introduced into the C-terminus of PTH [i.e., PTH(15 - 31)]. To explore Arg19 and the midregion (residues 10 - 15), we designed the novel PTH scaffold peptide, PG5, which has the PTH(1 - 9) domain linked to the PTH(15 - 31) segment via a pentaglycine spacer. Substitution of Glu19 with Arg19 in PG5 resulted in a 9-fold increase in binding affinity. Additionally, the substitution enhanced stimulated cAMP formation in cells expressing PTH1-de1Nt, a PTH1 receptor construct lacking most of the N-terminus, confirming, that residue 19 is interacting with the juxtamembrane portion of PTH1. The binding and Signaling capacities of the PG5 analogues were diminished relative to those of PTH(1 - 34), indicating that the residue 10-14 region of PTH provides more than just a simple linker function. To probe this further, the structural consequences of the glycine linker and its interaction with PTH I were examined by circular dichroism, H-1 NMR, and extensive ligand/receptor molecular dynamics simulations. The structural data clearly illustrate the helix-stabilizing effect of Arg(19) substitution propagating N-terminally from position 19 to the pentaglycine linker. Overall, these studies suggest that an alpha-helix is the preferred conformation for the residue 15 - 20 region of PTH and that residues 10 - 14 are also required for full affinity and potency of the hormone. C1 Brown Univ, Dept Mol Pharmacol, Div Biol & Med, Providence, RI 02912 USA. Brown Univ, Dept Chem, Providence, RI 02912 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Mierke, DF (reprint author), Brown Univ, Dept Mol Pharmacol, Div Biol & Med, 171 Meeting St, Providence, RI 02912 USA. EM Dale_Mierke@Brown.edu FU NIDDK NIH HHS [DK-11794]; NIGMS NIH HHS [GM-82054] NR 47 TC 3 Z9 4 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 30 PY 2004 VL 43 IS 12 BP 3459 EP 3470 DI 10.1021/bi036127t PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 806OP UT WOS:000220443500017 PM 15035617 ER PT J AU Schmidt-Supprian, M Tian, J Grant, EP Pasparakis, M Maehr, R Ovaa, H Ploegh, HL Coyle, AJ Rajewsky, K AF Schmidt-Supprian, M Tian, J Grant, EP Pasparakis, M Maehr, R Ovaa, H Ploegh, HL Coyle, AJ Rajewsky, K TI Differential dependence of CD4(+)CD25(+) regulatory and natural killer-like T cells on signals leading to NF-kappa B activation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID V-ALPHA-14I NKT CELLS; LYMPHOCYTE-ACTIVATION; ANTIGEN PRESENTATION; THYMIC SELECTION; SELF-PEPTIDE; MICE; REQUIREMENT; HOMEOSTASIS; MAINTENANCE; MATURE AB Natural killer-like (NK) T, regulatory T (T-R) and memory type T cells display surface phenotypes reminiscent of activated T cells. Previously, we reported that the generation of T-R cells and, to a lesser extent, of memory type T cells, depends on IkappaB kinase 2. Here, we show that T cell-specific ablation of IkappaB kinase 2, in addition, completely precludes NKT cell development. T cell antigen receptor (TCR)-induced signals to activate NF-kappaB are essential for mature T cell activation, leading us to hypothesize that this pathway could play an important role in the generation of the antigen-driven T cell subsets comprising T-R, memory type T, and NKT cells. TCR-mediated NF-kappaB activation critically depends on Bcl10 and PKCtheta. By using mice deficient for these proteins, we demonstrate that the generation of T-R and, to a lesser extent, of memory type T cells, depends on Bcl10 and PKCtheta, and therefore, most likely on NF-kappaB activation initiated by TCR engagement. NKT cells, on the other hand, require PKCtheta for thymic development, whereas absence of Bcl10 leads primarily to the reduction of peripheral NKT cell numbers. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Millennium Pharmaceut Inc, Cambridge, MA 02139 USA. EMBL Mouse Biol Programme, I-00016 Monterotondo, Italy. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Rajewsky, K (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM rajewsky@cbr.med.harvard.edu RI Schmidt-Supprian, Marc/F-5893-2011; OI Schmidt-Supprian, Marc/0000-0002-8543-6166; Pasparakis, Manolis/0000-0002-9870-0966 FU NIAID NIH HHS [AI057947, R01 AI057947] NR 47 TC 167 Z9 171 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 30 PY 2004 VL 101 IS 13 BP 4566 EP 4571 DI 10.1073/pnas.0400885101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 809PN UT WOS:000220648700044 PM 15070758 ER PT J AU Halet, G Tunwell, R Parkinson, SJ Carroll, J AF Halet, G Tunwell, R Parkinson, SJ Carroll, J TI Conventional PKCs regulate the temporal pattern of Ca(2+) oscillations at fertilization in mouse eggs SO JOURNAL OF CELL BIOLOGY LA English DT Article DE calcium; PKC; oscillations; GFP; influx ID PROTEIN-KINASE-C; CAPACITATIVE CALCIUM-ENTRY; CORTICAL GRANULE EXOCYTOSIS; GREEN FLUORESCENT PROTEIN; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; MEIOTIC MATURATION; PHORBOL ESTER; LIVING CELLS; ACTIVATION; OOCYTES AB In mammalian eggs, sperm-induced Ca(2+) oscillations at fertilization are the primary trigger for egg activation and initiation of embryonic development. Identifying the downstream effectors that decode this unique Ca(2+) signal is essential to understand how the transition from egg to embryo is coordinated. Here, we investigated whether conventional PKCs (cPKCs) can decode Ca(2+) oscillations at fertilization. By monitoring the dynamics of GFP-labeled PKCalpha and PKCgamma in living mouse eggs, we demonstrate that cPKCs translocate to the egg membrane at fertilization following a pattern that is shaped by the amplitude, duration, and frequency of the Ca(2+) transients. In addition, we show that cPKC translocation is driven by the C2 domain when Ca(2+) concentration reaches 1-3 muM. Finally, we present evidence that one physiological function of activated cPKCs in fertilized eggs is to sustain long-lasting Ca(2+) oscillations, presumably via the regulation of store-operated Ca(2+) entry. C1 UCL, Dept Physiol, London WC1E 6BT, England. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Halet, G (reprint author), UCL, Dept Physiol, Gower St, London WC1E 6BT, England. EM g.halet@ucl.ac.uk; j.carroll@ucl.ac.uk RI halet, guillaume/C-7502-2009; OI Halet, Guillaume/0000-0002-6204-2105 NR 56 TC 53 Z9 53 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAR 29 PY 2004 VL 164 IS 7 BP 1033 EP 1044 DI 10.1083/jcb.200311023 PG 12 WC Cell Biology SC Cell Biology GA 808NP UT WOS:000220576100010 PM 15051735 ER PT J AU Sever, S AF Sever, S TI Role of dynamin-auxilin interactions in endocytosis. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 227th National Meeting of the American-Chemical Society CY MAR 28-APR 01, 2004 CL Anaheim, CA SP Amer Chem Soc C1 Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Biol Renal Unit, Program Membrane, Charlestown, MA 02129 USA. EM ssever@receptor.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 28 PY 2004 VL 227 MA 041-COLL BP U810 EP U810 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851AJ UT WOS:000223655602663 ER PT J AU Tung, CH AF Tung, CH TI Developing fluorescence probes for in vivo molecular imaging. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 227th ACS National Meeting CY MAR 28-APR 01, 2004 CL Anaheim, CA SP Amer Chem Soc C1 Harvard Med Sch, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. EM tung@helix.mgh.harvard.edu NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 28 PY 2004 VL 227 MA 257-ORGN BP U146 EP U146 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851AK UT WOS:000223655700766 ER PT J AU Doukas, AG Kollias, N AF Doukas, AG Kollias, N TI Transdermal drug delivery with a pressure wave SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE photomechanical waves; shock waves; stratum corneum barrier; stress waves; transdermal delivery ID INDUCED PHOTOACOUSTIC INJURY; GENERATED STRESS WAVES; INDUCED SHOCK-WAVES; STRATUM-CORNEUM; IN-VIVO; PERCUTANEOUS ABSORPTION; PHOTOMECHANICAL WAVES; SKIN PERMEABILITY; CELL-MEMBRANE; EXCIMER LASER AB Pressure waves, which are generated by intense laser radiation, can permeabilize the stratum corneum (SC) as well as the cell membrane. These pressure waves are compression waves and thus exclude biological effects induced by cavitation. Their amplitude is in the hundreds of atmospheres (bar) while the duration is in the range of nanoseconds to a few microseconds. The pressure waves interact with cells and tissue in ways that are probably different from those of ultrasound. Furthermore, the interactions of the pressure waves with tissue are specific and depend on their characteristics, such as peak pressure, rise time and duration. A single pressure wave is sufficient to permeabilize the SC and allow the transport of macromolecules into the epidermis and dermis. In addition, drugs delivered into the epidermis can enter the vasculature and produce a systemic effect. For example, insulin delivered by pressure waves resulted in reducing the blood glucose level over many hours. The application of pressure waves does not cause any pain or discomfort and the barrier function of the SC always recovers. (C) 2004 Elsevier B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. Johnson & Johnson Consumer & Personal Prod Worldw, Skillman, NJ 08558 USA. RP Doukas, AG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. EM adoukas@partners.org NR 86 TC 111 Z9 121 U1 7 U2 21 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD MAR 27 PY 2004 VL 56 IS 5 BP 559 EP 579 DI 10.1016/j.addr.2003.10.031 PG 21 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 807HO UT WOS:000220492800003 PM 15019746 ER PT J AU Ruvkun, G AF Ruvkun, G TI DNA approach to Mars SO NEW SCIENTIST LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Genet, Boston, MA 02114 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Genet, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU REED BUSINESS INFORMATION LTD PI SUTTON PA QUADRANT HOUSE THE QUADRANT, SUTTON SM2 5AS, SURREY, ENGLAND SN 0262-4079 J9 NEW SCI JI New Sci. PD MAR 27 PY 2004 VL 181 IS 2440 BP 19 EP 19 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 807LN UT WOS:000220503100017 ER PT J AU Cosimi, AB Sachs, DH AF Cosimi, AB Sachs, DH TI Mixed chimerism and transplantation tolerance SO TRANSPLANTATION LA English DT Article ID BONE-MARROW-TRANSPLANTATION; REFRACTORY HEMATOLOGIC MALIGNANCIES; NONLETHAL PREPARATIVE REGIMEN; STAGE RENAL-DISEASE; LARGE-ANIMAL-MODEL; LYMPHOHEMATOPOIETIC CHIMERISM; ALLOGRAFT TOLERANCE; CYNOMOLGUS MONKEYS; MINIATURE SWINE; MULTIPLE-MYELOMA AB Establishment of mixed hematopoietic chimerism carries with it the induction of transplantation tolerance to any other tissue or organ from the same donor. This strategy has been studied extensively for induction of tolerance in mice. During the past decade, we have extended the same strategy, with modifications, to cynomolgus monkeys and most recently to renal transplant patients. In this report we review the evolution of these studies from preclinical applications to our current clinical experience with two therapeutic protocols sponsored by the Immune Tolerance Network. The first of these studies is for patients with myeloma and end-stage renal disease with an HILA-matched sibling donor; the second for patients with end-stage renal disease and HILA-mismatched donors. Although it is still early in the course of these studies, the results to date are very encouraging. C1 Massachusetts Gen Hosp, Transplantat Unit, Gen Surg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Cosimi, AB (reprint author), Massachusetts Gen Hosp, Transplantat Unit, Gen Surg Serv, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-18646]; NIAID NIH HHS [AI-37692] NR 25 TC 70 Z9 79 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAR 27 PY 2004 VL 77 IS 6 BP 943 EP 946 DI 10.1097/01.TP.0000117779.23431.3F PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 806VD UT WOS:000220460500030 PM 15077044 ER PT J AU Smith, DE Walker, BD Cooper, DA Rosenberg, ES Kaldor, JA AF Smith, DE Walker, BD Cooper, DA Rosenberg, ES Kaldor, JA TI Is antiretroviral treatment of primary HIV infection clinically justified on the basis of current evidence? SO AIDS LA English DT Review DE HIV; antiretroviral therapy; acute; primary ID IMMUNODEFICIENCY-VIRUS TYPE-1; PLACEBO-CONTROLLED TRIAL; NUCLEOSIDE ANALOG THERAPY; DRUG-RESISTANT MUTANTS; VIRAL LOAD; RAPID PROGRESSION; IMMUNE-RESPONSES; T-LYMPHOCYTES; DOUBLE-BLIND; ZIDOVUDINE C1 Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Smith, DE (reprint author), Level 2,376 Victoria St,Darlinghurst, Sydney, NSW 2010, Australia. RI Kaldor, John /D-4545-2011 NR 64 TC 75 Z9 79 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 26 PY 2004 VL 18 IS 5 BP 709 EP 718 DI 10.1097/01.aids.0000111469.61782.12 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 816DO UT WOS:000221090800001 PM 15075505 ER PT J AU Pajvani, UB Hawkins, M Combs, TP Rajala, MW Doebber, T Berger, JP Wagner, JA Wu, M Knopps, A Xiang, AH Utzschneider, KM Kahn, SE Olefsky, JM Buchanan, TA Scherer, PE AF Pajvani, UB Hawkins, M Combs, TP Rajala, MW Doebber, T Berger, JP Wagner, JA Wu, M Knopps, A Xiang, AH Utzschneider, KM Kahn, SE Olefsky, JM Buchanan, TA Scherer, PE TI Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PPAR-GAMMA; GLUCOSE-PRODUCTION; DIABETES-MELLITUS; PROTEIN ACRP30; RESISTANCE; AGONISTS; OBESITY; TROGLITAZONE; ASSOCIATION; INDUCTION AB Adiponectin is an adipocyte-specific secretory protein that circulates in serum as a hexamer of relatively low molecular weight (LMW) and a larger multimeric structure of high molecular weight (HMW). Serum levels of the protein correlate with systemic insulin sensitivity. The full-length protein affects hepatic gluconeogenesis through improved insulin sensitivity, and a proteolytic fragment of adiponectin stimulates beta oxidation in muscle. Here, we show that the ratio, and not the absolute amounts, between these two oligomeric forms ( HMW to LMW) is critical in determining insulin sensitivity. We define a new index, SA, that can be calculated as the ratio of HMW/(HMW + LMW). db/db mice, despite similar total adiponectin levels, display decreased SA values compared with wild type littermates, as do type II diabetic patients compared with insulin-sensitive individuals. Furthermore, SA improves with peroxisome proliferator-activated receptor-gamma agonist treatment ( thiazolidinedione; TZD) in mice and humans. We demonstrate that changes in SA in a number of type 2 diabetic cohorts serve as a quantitative indicator of improvements in insulin sensitivity obtained during TZD treatment, whereas changes in total serum adiponectin levels do not correlate well at the individual level. Acute alterations in S-A (DeltaS(A)) are strongly correlated with improvements in hepatic insulin sensitivity and are less relevant as an indicator of improved muscle insulin sensitivity in response to TZD treatment, further underscoring the conclusions from previous clamp studies that suggested that the liver is the primary site of action for the full-length protein. These observations suggest that the HMW adiponectin complex is the active form of this protein, which we directly demonstrate in vivo by its ability to depress serum glucose levels in a dose-dependent manner. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Ctr Diabet Res & Training, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Med, Div Endocrinol, Bronx, NY 10461 USA. Merck Res Labs, Rahway, NJ 07065 USA. SGS Biopharma, B-12060 Antwerp, Belgium. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98108 USA. Univ Calif San Diego, Dept Endocrinol & Metab, La Jolla, CA 92093 USA. RP Scherer, PE (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM scherer@aecom.yu.edu OI Kahn, Steven/0000-0001-7307-9002 FU NIDDK NIH HHS [2R01 DK 46374, DK 02654, DK 17047]; NIGMS NIH HHS [T32 GM 07288] NR 29 TC 775 Z9 806 U1 4 U2 24 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 MAR 26 PY 2004 VL 279 IS 13 BP 12152 EP 12162 DI 10.1074/jbc.M311113200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 804YV UT WOS:000220334900021 PM 14699128 ER PT J AU Brunet, A Sweeney, LB Sturgill, JF Chua, KF Greer, PL Lin, YX Tran, H Ross, SE Mostoslavsky, R Cohen, HY Hu, LS Cheng, HL Jedrychowski, MP Gygi, SP Sinclair, DA Alt, FW Greenberg, ME AF Brunet, A Sweeney, LB Sturgill, JF Chua, KF Greer, PL Lin, YX Tran, H Ross, SE Mostoslavsky, R Cohen, HY Hu, LS Cheng, HL Jedrychowski, MP Gygi, SP Sinclair, DA Alt, FW Greenberg, ME TI Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase SO SCIENCE LA English DT Article ID PROMOTES CELL-SURVIVAL; LIFE-SPAN EXTENSION; PROTEIN-KINASE B; SACCHAROMYCES-CEREVISIAE; CAENORHABDITIS-ELEGANS; CALORIE RESTRICTION; P53; LONGEVITY; NAD; PATHWAY AB The Sir2 deacetylase modulates organismal life-span in various species. However, the molecular mechanisms by which Sir2 increases longevity are largely unknown. We show that in mammalian cells, the Sir2 homolog SIRT1 appears to control the cellular response to stress by regulating the FOXO family of Forkhead transcription factors, a family of proteins that function as sensors of the insulin signaling pathway and as regulators of organismal longevity. SIRT1 and the FOXO transcription factor FOXO3 formed a complex in cells in response to oxidative stress, and SIRT1 deacetylated FOXO3 in vitro and within cells. SIRT1 had a dual effect on FOXO3 function: SIRT1 increased FOXO3's ability to induce cell cycle arrest and resistance to oxidative stress but inhibited FOXO3's ability to induce cell death. Thus, one way in which members of the Sir2 family of proteins may increase organismal longevity is by tipping FOXO-dependent responses away from apoptosis and toward stress resistance. C1 Harvard Univ, Sch Med, Childrens Hosp, Div Neurosci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst,CBR,Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Greenberg, ME (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Neurosci, Boston, MA 02115 USA. EM michael.greenberg@childrens.harvard.edu OI Sinclair, David/0000-0002-9936-436X FU NICHD NIH HHS [NIHP30-HD18655]; NINDS NIH HHS [P01 NS35138-17] NR 28 TC 1718 Z9 1815 U1 20 U2 144 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 MAR 26 PY 2004 VL 303 IS 5666 BP 2011 EP 2015 DI 10.1126/science.1094637 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 806JI UT WOS:000220429800040 PM 14976264 ER PT J AU Fishman, JA Dey, BR Hasserjian, RP Amrein, P Harris, NL Weinstein, H AF Fishman, JA Dey, BR Hasserjian, RP Amrein, P Harris, NL Weinstein, H TI A man with acute myeloid leukemia and fever after chemotherapy - Acute myeloid leukemia with multilineage dysplasia after a myelodysplastic syndrome. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID GRANULOCYTOPENIC CANCER-PATIENTS; NEUTROPENIC PATIENTS; ANTIBIOTIC-THERAPY C1 Massachusetts Gen Hosp, Div Infect Dis, Transplant Infect Dis & Compromised Host Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Transplant Infect Dis & Compromised Host Program, Boston, MA 02114 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 25 PY 2004 VL 350 IS 13 BP 1339 EP 1347 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 805VN UT WOS:000220393900014 PM 15044646 ER PT J AU Stoecklin, G Stubbs, T Kedersha, N Wax, S Rigby, WFC Blackwell, TK Anderson, P AF Stoecklin, G Stubbs, T Kedersha, N Wax, S Rigby, WFC Blackwell, TK Anderson, P TI MK2-induced tristetraprolin: 14-3-3 complexes prevent stress granule association and ARE-mRNA decay SO EMBO JOURNAL LA English DT Article DE AU-rich element; MAPKAP kinase-2; mRNA turnover; TNF alpha; TTP ID ACTIVATED PROTEIN-KINASE; AU-RICH ELEMENTS; DEGRADATION PATHWAY; BINDING PROTEIN; IN-VIVO; PHOSPHORYLATION; TURNOVER; ALPHA; EXPRESSION; REGULATOR AB Stress granules (SGs) are dynamic cytoplasmic foci at which stalled translation initiation complexes accumulate in cells subjected to environmental stress. SG-associated proteins such as TIA-1, TIAR and HuR bind to AU-rich element (ARE) -containing mRNAs and control their translation and stability. Here we show that tristetraprolin (TTP), an ARE-binding protein that destabilizes ARE-mRNAs, is recruited to SGs that are assembled in response to FCCP-induced energy deprivation, but not arsenite-induced oxidative stress. Exclusion of TTP from arsenite-induced SGs is a consequence of MAPKAP kinase-2 (MK2)-induced phosphorylation at serines 52 and 178, which promotes the assembly of TTP:14-3-3 complexes. 14-3-3 binding excludes TTP from SGs and inhibits TTP-dependent degradation of ARE-containing transcripts. In activated RAW 264.7 macrophages, endogenous TTP:14-3-3 complexes bind to ARE-RNA. Our data reveal the mechanism by which the p38-MAPK/MK2 kinase cascade inhibits TTP-mediated degradation of ARE-containing transcripts and thereby contributes to lipopolysaccharide-induced TNFalpha expression. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA USA. Dartmouth Coll Sch Med, Dept Med, Lebanon, NH USA. Harvard Univ, Sch Med, Ctr Blood Res, Inst Biomed Res, Boston, MA 02115 USA. RP Brigham & Womens Hosp, Div Rheumatol & Immunol, Smith 652,1 Jimmy Fund Way, Boston, MA 02115 USA. EM panderson@rics.bwh.harvard.edu OI Stoecklin, Georg/0000-0001-9284-9834 FU NCI NIH HHS [CA-84418, R01 CA084418]; NIAID NIH HHS [AI-33600, AI-50167, R01 AI033600, R01 AI050167, R56 AI033600] NR 39 TC 303 Z9 318 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD MAR 24 PY 2004 VL 23 IS 6 BP 1313 EP 1324 DI 10.1038/sj.emboj.7600163 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 818QI UT WOS:000221259200010 PM 15014438 ER PT J AU Culi, J Springer, TA Mann, RS AF Culi, J Springer, TA Mann, RS TI Boca-dependent maturation of beta-propeller/EGF modules in low-density lipoprotein receptor proteins SO EMBO JOURNAL LA English DT Article DE beta-propeller; chaperone; EGF; LDLR; LRP ID ENDOPLASMIC-RETICULUM; QUALITY-CONTROL; GENE FAMILY; DROSOPHILA; CHAPERONES; COMPLEX; DOMAIN AB The extracellular portions of cell surface receptor proteins are often comprised of independently folding protein domains. As they are translated into the endoplasmic reticulum (ER), some of these domains require protein chaperones to assist in their folding. Members of the low-density lipoprotein receptor (LDLR) family require the chaperone called Boca in Drosophila or its ortholog, Mesoderm development, in the mouse. All LDLRs have at least one six-bladed beta-propeller domain, which is immediately followed by an epidermal growth factor (EGF) repeat. We show here that Boca is specifically required for the maturation of these beta-propeller/EGF modules through the secretory pathway, but is not required for other LDLR domains. Protein interaction data suggest that as LDLRs are translated into the ER, Boca binds to the P-propeller. Subsequently, once the EGF repeat is translated, the beta-propeller/EGF module achieves a more mature state that has lower affinity for Boca. We also show that Boca-dependent beta-propeller/EGF modules are found not only throughout the LDLR family but also in the precursor to the mammalian EGF ligand. C1 Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. Harvard Univ, Sch Med, Ctr Blood Res, Inst Biomed Res,Dept Pathol, Boston, MA 02115 USA. Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA. RP Mann, RS (reprint author), Columbia Univ, Dept Biochem & Mol Biophys, 701 W 168 St,HHSC 1108, New York, NY 10032 USA. EM rsm10@columbia.edu FU NIGMS NIH HHS [R01 GM054510, R01 GM058575] NR 29 TC 33 Z9 36 U1 0 U2 0 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 MAR 24 PY 2004 VL 23 IS 6 BP 1372 EP 1380 DI 10.1038/sj.emboj.7600132 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 818QI UT WOS:000221259200015 PM 15014448 ER PT J AU Chen, J McPherson, SA Zajac, A Hsu, HC Wu, Q Yang, P Zhou, JL Xu, X Mountz, JD AF Chen, J McPherson, SA Zajac, A Hsu, HC Wu, Q Yang, P Zhou, JL Xu, X Mountz, JD TI Quantification of E1Bp-specific CD8+ T lymphocytes in anti-adenoviral infection SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Univ Alabama, CFAR, Birmingham, AL 35294 USA. Birmingham VAMC, Birmingham, AL USA. NR 0 TC 0 Z9 0 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 MAR 24 PY 2004 VL 18 IS 5 SU S BP A803 EP A803 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470700212 ER PT J AU Cherayil, B Huang, FC Werne, A Li, Q Galyov, E Walker, A AF Cherayil, B Huang, FC Werne, A Li, Q Galyov, E Walker, A TI Interactions between TLR5- and SopE2-activated signals during Salmonella infection of epithelial cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Inst Anim Hlth, Compton, England. NR 0 TC 0 Z9 0 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 MAR 24 PY 2004 VL 18 IS 5 SU S BP A1157 EP A1157 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470701901 ER PT J AU Evgenov, OV Ichinose, F Falkowski, GE Bloch, KD Zapol, WM AF Evgenov, OV Ichinose, F Falkowski, GE Bloch, KD Zapol, WM TI Stimulation of soluble guanylate cyclase attenuates acute pulmonary hypertension and augments the pulmonary vasodilator response to inhaled nitric oxide SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 MAR 24 PY 2004 VL 18 IS 5 SU S BP A1056 EP A1056 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470701420 ER EF