FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Friedberg, JW Neuberg, D Kim, H Miyata, S McCauley, M Fisher, DC Takvorian, T Canellos, GP AF Friedberg, JW Neuberg, D Kim, H Miyata, S McCauley, M Fisher, DC Takvorian, T Canellos, GP TI Gemcitabine added to doxorubicin, bleomycin, and vinblastine for the treatment of de novo Hodgkin disease SO CANCER LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol DE gemcitabine; Hodgkin disease; pneumonitis; bleomycin ID PULMONARY TOXICITY; CELL TRANSPLANTATION; RADIATION-THERAPY; FOLLOW-UP; TRIAL; ABVD; CHEMOTHERAPY; LYMPHOMA; REGIMEN; BEACOPP AB BACKGROUND. Gemcitabine is an effective treatment for recurrent Hodgkin disease (HD), with relatively minimal associated toxicity. The authors conducted a trial substituting this drug for dacarbazine in the standard regimen to form ABVG (doxorubicin, bleomycin, vinblastine, gemcitabine) for patients with newly diagnosed, high-risk HD. METHODS. Twelve patients (median age, 34 years) with advanced-stage de novo HD were enrolled. Standard doses of doxorubicin, bleomycin, and vinblastine were given for six cycles. Cohorts of three patients were enrolled and the dose of gemcitabine was escalated to identify the maximally tolerated dose in this combination. RESULTS. The maximally tolerated dose of gemcitabine was determined to be 800 mg/m(2) in this combination. Five patients developed clinically significant pulmonary toxicity. Three required hospitalization during the final two cycles of treatment. pneumonitis could not be predicted with serial diffusion capacity for carbon monoxide (DECO) evaluations, and reversed after discontinuation of bleomycin in three patients and steroid therapy in two patients. All 12 patients are alive to date, and 4 patients have experienced disease progression. CONCLUSIONS. The bleomycin/gemcitabine combination should not be pursued for de novo HD due to significant pulmonary toxicity. (C) 2003 American Cancer Society. C1 Univ Rochester, James P Wilmont Canc Ctr, Rochester, NY USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA USA. RP Friedberg, JW (reprint author), 601 Elmwood Ave,POB 704, Rochester, NY 14642 USA. NR 27 TC 34 Z9 34 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 2003 VL 98 IS 5 BP 978 EP 982 DI 10.1002/cncr.11582 PG 5 WC Oncology SC Oncology GA 714RV UT WOS:000184928000014 PM 12942565 ER PT J AU Silver, DP AF Silver, DP TI HIN-1 and the nosology of breast cancer SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE medullary; BRCA1; basal; breast cancer ID GENE; CARCINOMA; BRCA1; METHYLATION; MUTATIONS; TUMORS C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Silver, DP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Smith Bldg,Rm 808,1 Jimmy Fund Way, Boston, MA 02115 USA. EM Daniel_Silver@DFCI.Harvard.Edu NR 18 TC 1 Z9 1 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD SEP-OCT PY 2003 VL 2 IS 5 BP 564 EP 565 PG 2 WC Oncology SC Oncology GA 751PN UT WOS:000187076300019 PM 14614328 ER PT J AU Forbes, NS Munn, LL Fukumura, D Jain, RK AF Forbes, NS Munn, LL Fukumura, D Jain, RK TI Sparse initial entrapment of systemically injected Salmonella typhimurium leads to heterogeneous accumulation within tumors SO CANCER RESEARCH LA English DT Article ID COMPLETE GENOME SEQUENCE; IN-VIVO; PROTEIN DELIVERY; BACTERIA; THERAPY; ANGIOGENESIS; VECTORS; AGENT; MICE AB Blood-borne therapeutics, which rely on diffusion and convection for delivery, often do not accumulate in effective concentrations distant from vasculature and are therefore unable to eradicate all cells within a tumor. Motile bacteria have the potential to overcome the diffusion and pressure gradients that prevent passive materials from penetrating into poorly perfused regions of tumors. Here, we test several proposed mechanisms of Salmonella typhimurium accumulation in tumors, including: (a) entrapment in the chaotic vasculature of tumors; (b) attraction to specific tumor microenvironments; and (c) preferential replication within specific microenvironments. After systemic injection of S. typhimurium into tumor-bearing mice, we used intravital microscopy and histological techniques to quantify their interaction with tumor vasculature. Immediately after injection, few S. typhimurium (<4 in 10,000) adhered to tumor vasculature; most remained passively suspended in the blood. Despite this low initial adhesion, similar to10,000-fold more S. typhimurium accumulated in tumors than any other organ I week after the injection, thus demonstrating their specificity. However, within the tumors, we found that most bacteria were located in necrotic tissue as large colonies far (750 mum) from functional vasculature. Together, these results suggest that S. typhimurium has limited ability to adhere to tumor vasculature and migrate within tumors and only survives in tissue that becomes necrotic. Although S. typhimurium is a promising delivery vehicle because of its tumor specificity, increasing its intra-tumoral motility should improve its therapeutic effectiveness. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, EL Steele Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, EL Steele Lab, Cox 7, Boston, MA 02114 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NCI NIH HHS [P01-CA-80124, T32-CA-73479] NR 20 TC 79 Z9 81 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2003 VL 63 IS 17 BP 5188 EP 5193 PG 6 WC Oncology SC Oncology GA 722XD UT WOS:000185402600003 PM 14500342 ER PT J AU O'Hagan, RC Brennan, CW Strahs, A Zhang, XG Kannan, K Donovan, M Cauwels, C Sharpless, NE Wong, WH Chin, L AF O'Hagan, RC Brennan, CW Strahs, A Zhang, XG Kannan, K Donovan, M Cauwels, C Sharpless, NE Wong, WH Chin, L TI Array comparative genome hybridization for tumor classification and gene discovery in mouse models of malignant melanoma SO CANCER RESEARCH LA English DT Article ID CYTOGENETIC ABNORMALITIES; EXPRESSION PROFILES; BREAST CARCINOMAS; CANCER; AMPLIFICATIONS; PATTERNS; ONCOGENE; IDENTIFICATION; MICROARRAYS; SUBCLASSES AB Chromosomal numerical aberrations (CNAs), particularly regional amplifications and deletions, are a hallmark of solid tumor genomes. These genomic alterations carry the potential to convey etiologic and clinical significance by virtue of their clonality within a tumor cell population, their distinctive patterns in relation to tumor staging, and their recurrence across different tumor types. In this study, we showed that array-based comparative genomic hybridization (CGH) analysis of genome-wide CNAs can classify tumors on the basis of differing etiologies and provide mechanistic insights to specific biological processes. In a RAS-induced p19(Arf-/-) mouse model that experienced accelerated melanoma formation after UV exposure, array-CGH analysis was effective in distinguishing phenotypically identical melanomas that differed solely by previous UV exposure. Moreover, classification by array-CGH identified key CNAs unique to each class, including amplification of cyclin-dependent kinase 6 in UV-treated cohort, a finding consistent with our recent report that UVB targets components of the p16(INK4a)-cyclin-dependent kinase-RB pathway in melanoma genesis (K. Kannan, et aL, Proc. Natl. Acad. Sci. USA, 21: 2003). These results are the first to establish the utility of array-CGH as a means of etiology-based tumor classification in genetically defined cancer-prone models. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Canc Genom Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Tsing Hua Univ, Dept Automat, Beijing 100084, Peoples R China. Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. RP Chin, L (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St M413, Boston, MA 02115 USA. OI Brennan, Cameron/0000-0003-4064-8891 FU NCI NIH HHS [U01 CA84313, P20 CA96470] NR 31 TC 30 Z9 31 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2003 VL 63 IS 17 BP 5352 EP 5356 PG 5 WC Oncology SC Oncology GA 722XD UT WOS:000185402600028 PM 14500367 ER PT J AU Sattler, M Pride, YB Ma, P Gramlich, JL Chu, SC Quinnan, LA Shirazian, S Liang, CX Podar, K Christensen, JG Salgia, R AF Sattler, M Pride, YB Ma, P Gramlich, JL Chu, SC Quinnan, LA Shirazian, S Liang, CX Podar, K Christensen, JG Salgia, R TI A novel small molecule met inhibitor induces apoptosis in cells transformed by the oncogenic TPR-MET tyrosine kinase SO CANCER RESEARCH LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; FORKHEAD TRANSCRIPTION FACTOR; FACTOR-RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; PROTEIN-KINASE; C-MET; MEDIATED TRANSFORMATION; HUMAN GLIOBLASTOMA; GASTRIC-CARCINOMA; INVASIVE GROWTH AB The Met receptor tyrosine kinase has been shown to be overexpressed or mutated in a variety of solid tumors and has, therefore, been identified as a good candidate for molecularly targeted therapy. Activation of the Met tyrosine kinase by the TPR gene was originally described in vitro through carcinogen-induced rearrangement. The TPR-MET fusion protein contains constitutively elevated Met tyrosine kinase activity and constitutes an ideal model to study the transforming activity of the Met kinase. We found, when introduced into an interleukin 3-dependent cell line, TPR-MET induces factor independence and constitutive tyrosine phosphorylation of several cellular proteins. One major tyrosine phosphorylated protein was identified as the TPR-MET oncoprotein itself. Inhibition of the Met kinase activity by the novel small molecule drug SU11274 [(3Z)-N-(3-chlorophenyl)-3-({3,5-dimethyl-4-[(4-methylpiperazin-1-yl)carbonyl]-1H-pyrrol-2-yl}methylene)-N-methyl-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide] led to time- and dose-dependent reduced cell growth. The inhibitor did not affect other tyrosine kinase oncoproteins, including BCR-ABL, TEL-JAK2, TEL-PDGFbetaR, or TEL-ABL. The Met inhibitor induced G, cell cycle arrest and apoptosis with increased Annexin V staining and caspase 3 activity. The autophosphorylation of the Met kinase was reduced on sites that have been shown previously to be important for activation of pathways involved in cell growth and survival, especially the phosphatidylinositol-3'-kinase and the Ras pathway. In particular, we found that the inhibitor blocked phosphorylation of AKT, GSK-3gamma, and the pro-apoptotic transcription factor FKHR. The characterization of SU11274 as an effective inhibitor of Met tyrosine kinase activity illustrates the potential of targeting for Met therapeutic use in cancers associated with activated forms of this kinase. C1 Univ Chicago, Pritzker Sch Med, Dept Med, Chicago, IL 60637 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Sugen, San Francisco, CA 94080 USA. RP Salgia, R (reprint author), Univ Chicago, Pritzker Sch Med, Dept Med, 5841 S Maryland Ave,MC 2115,M255A, Chicago, IL 60637 USA. NR 51 TC 176 Z9 185 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2003 VL 63 IS 17 BP 5462 EP 5469 PG 8 WC Oncology SC Oncology GA 722XD UT WOS:000185402600043 PM 14500382 ER PT J AU Ikeda, T Sporn, M Honda, T Gribble, GW Kufe, D AF Ikeda, T Sporn, M Honda, T Gribble, GW Kufe, D TI The novel triterpenoid CDDO and its derivatives induce apoptosis by disruption of intracellular redox balance SO CANCER RESEARCH LA English DT Article ID ABL TYROSINE KINASE; 2-CYANO-3,12-DIOXOOLEANA-1,9-DIEN-28-OIC ACID CDDO; TUMOR-NECROSIS-FACTOR; INDUCED CELL-DEATH; CYTOCHROME-C; 2-CYANO-3,12-DIOXOOLEAN-1,9-DIEN-28-OIC ACID; MAMMALIAN THIOREDOXIN; SIGNAL-TRANSDUCTION; STRESS-RESPONSE; LEUKEMIA-CELLS AB The novel oleanane triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) induces apoptosis of human leukemia cells by activation of the extrinsic caspase-8 pathway. The mechanisms responsible for the proapoptotic effects of CDDO are unknown. The present studies demonstrate that CDDO activates the c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase in U-937 leukemia cells. The results also show that CDDO activates stress kinases by increasing levels of reactive oxygen species and decreasing intracellular glutathione (GSH) concentrations. Similar findings were obtained with the C-28 methyl ester (CDDO-Me) and C-28 imidazolide ester (CDDO-Im) derivatives. The results also demonstrate that CDDO-induced: (a) stimulation of Jun NH2-terminal kinase; (b) activation of caspase-8; (c) loss of mitochondrial transmembrane potential; (d) release of cytochrome c; and (e) cleavage of caspase-3 are blocked by pretreatment with the antioxidant N-acetyl-L-cysteine and GSH but not with cysteine. In concert with these results, CDDO-induced apoptosis is also abrogated by N-acetyl-L-cysteine and GSH. These findings demonstrate that CDDO and its derivatives disrupt intracellular redox balance and thereby induce apoptosis. C1 Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. Dartmouth Coll, Dept Chem, Hanover, NH 03755 USA. Dartmouth Coll Sch Med, Dept Pharmacol, Hanover, NH 03755 USA. RP Kufe, D (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA42802, CA78814] NR 47 TC 81 Z9 82 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2003 VL 63 IS 17 BP 5551 EP 5558 PG 8 WC Oncology SC Oncology GA 722XD UT WOS:000185402600055 PM 14500394 ER PT J AU Sasaki, H Ide, N Sendo, F Takeda, Y Adachi, M Fukai, I Fujii, Y AF Sasaki, H Ide, N Sendo, F Takeda, Y Adachi, M Fukai, I Fujii, Y TI Glycosylphosphatidyl inositol-anchored protein (GPI-80) gene expression is correlated with human thymoma stage SO CANCER SCIENCE LA English DT Article ID NEUTROPHIL ADHERENCE; TRANSCRIPTIONAL PROGRAM; HUMAN-LEUKOCYTES; CROSS-LINKING; MIGRATION; HYBRIDIZATION; THYMOCYTE; SURFACES; ADHESION; MOLECULE AB Thymoma is one of the most common solid tumors in the mediastinum. Because there is no typical cell line for human thymoma, the development and use of molecular-based therapy for thymoma will require detailed molecular-genetic analysis of patients' tissues. Recent reports showed that genetic aberrations in thymoma were most frequently seen in chromosome 6q regions. We investigated the use of oligonucleotide arrays to monitor in vivo expression levels of genes in chromosome 6 regions in early(stage I or II) and late- (stage IVa) stage thymoma tissues from patients. These in vivo gene expression profiles were verified by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) using LightCycler for 48 thymoma patients and sandwich ELISA for 33 thymoma patients. Using both methods, a candidate gene was identified which was overexpressed in stage IV thymoma. This was a known glycosylphosphatidyl inositol (GPI)-anchored protein (GPI-80), which is highly homologous with Vanin-1, a mouse thymus homing protein. Serum level of GPI-80 was confirmed to be elevated in stage IV thymoma compared with in stage I thymoma by using sandwich ELISA. The combined use of oligonucleotide microarray, real-time RT-PCR, and ELISA analyses provides a powerful new approach to elucidate the in vivo molecular events surrounding the development and progression of thymoma. C1 Natl Kinki Cent Hosp Chest Dis, Dept Surg, Sakai, Osaka 5918555, Japan. Nagoya City Univ, Sch Med, Dept Surg 2, Mizuho Ku, Nagoya, Aichi 4678601, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Yamagata Univ, Sch Med, Dept Immunol & Parasitol, Yamagata 9909585, Japan. Japan Immunores Labs Co Ltd, Takasaki, Gumma 3700021, Japan. RP Sasaki, H (reprint author), Natl Kinki Cent Hosp Chest Dis, Dept Surg, 1180 Nagasone Cho, Sakai, Osaka 5918555, Japan. NR 30 TC 9 Z9 10 U1 1 U2 1 PU JAPANESE CANCER ASSOC PI TOKYO PA C/O JAPANESE FOUNDATION CANCER RESEARCH,1-37-1, KAMI-IKEBUKURO, TOSHIMA-KU, TOKYO, 170-0012, JAPAN SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD SEP PY 2003 VL 94 IS 9 BP 809 EP 813 DI 10.1111/j.1349-7006.2003.tb01523.x PG 5 WC Oncology SC Oncology GA 727ER UT WOS:000185644700010 PM 12967480 ER PT J AU Chopra, V Marmur, JD Cavusoglu, E AF Chopra, V Marmur, JD Cavusoglu, E TI The role of clopidogrel in the management of patients with ischemic heart disease SO CARDIOVASCULAR DRUGS AND THERAPY LA English DT Review DE atherosclerosis; thrombosis; ischemic heart disease; clopidogrel; aspirin; thienopyridine ID ACUTE CORONARY SYNDROMES; IN-STENT RESTENOSIS; INTRACORONARY GAMMA-RADIATION; ST-SEGMENT ELEVATION; MYOCARDIAL-INFARCTION; ANTIPLATELET THERAPY; ARTERY DISEASE; INTRAVASCULAR ULTRASOUND; NEOINTIMAL PROLIFERATION; CARDIOVASCULAR-DISEASE AB Antiplatelet therapy plays a pivotal role in the treatment of patients across the entire spectrum of coronary artery disease. Platelets are believed to be integrally involved in both the development and progression of atherosclerotic heart disease, as well as in its acute thrombotic complications. While aspirin remains the traditional antiplatelet agent in patients with CAD, adverse vascular events continue to occur in patients on aspirin therapy. Clopidogrel is a relatively new antiplatelet agent and is currently one of the most widely prescribed drugs for the treatment of symptomatic coronary artery disease. As a member of the class of drugs known as the thienopyridines, clopidogrel irreversibly prevents platelet activation by blocking one of the three known adenosine 5'-diphosphate ( ADP) receptors on its surface. The findings of a number of seminal clinical trials have expanded the indications for the use of clopidogrel in patients with coronary artery disease. When used in conjunction with aspirin, these studies have demonstrated an incremental benefit of clopidogrel above and beyond that of aspirin alone. This article reviews the data supporting the use of clopidogrel in patients with atherosclerotic heart disease, and makes recommendations for its use based on the available evidence. C1 SUNY Hlth Sci Ctr, Dept Med, Div Cardiol, Brooklyn, NY 11203 USA. Bronx Vet Affairs Med Ctr, Dept Med, Bronx, NY USA. Mt Sinai Sch Med, New York, NY USA. RP Cavusoglu, E (reprint author), SUNY Hlth Sci Ctr, Dept Med, Div Cardiol, 450 Clarkson Ave, Brooklyn, NY 11203 USA. EM ecavusoglu@aol.com NR 54 TC 13 Z9 13 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-3206 J9 CARDIOVASC DRUG THER JI Cardiovasc. Drugs Ther. PD SEP-NOV PY 2003 VL 17 IS 5-6 BP 467 EP 477 DI 10.1023/B:CARD.0000015862.62649.c8 PG 11 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 773KJ UT WOS:000188922700010 PM 15107602 ER PT J AU Zolk, O Marx, M Jackel, E El-Armouche, A Eschenhagen, T AF Zolk, O Marx, M Jackel, E El-Armouche, A Eschenhagen, T TI beta-Adrenergic stimulation induces cardiac ankyrin repeat protein expression: involvement of protein kinase A and calmodulin-dependent kinase SO CARDIOVASCULAR RESEARCH LA English DT Article DE contractile function; gene expression; hypertrophy; signal transduction ID NUCLEAR DELTA(B) ISOFORM; HUMAN HEART-FAILURE; GENE-EXPRESSION; DILATED CARDIOMYOPATHY; HYPERTROPHY; ACTIVATION; MYOCYTES; CARP; MYOCARDIUM; BINDING AB Objective: The cardiac ankyrin repeat protein (CARP), a nuclear transcription co-factor that negatively regulates cardiac gene expression, is increased in human heart failure and in animal models of cardiac hypertrophy. The mechanism by which CARP expression is regulated and the consequences of CARP overexpression on cardiac contractility are unknown. Methods and results: Compared to vehicle treated controls, 4-day treatment of male Wistar rats with the beta-adrenoceptor agonist isoprenaline (2.4 mg/kg per day) induced hypertrophy and significantly increased CARP mRNA and CARP protein levels in left ventricles. The signalling pathways were investigated in more detail in isolated neonatal rat cardiomyocytes. Treatment of cells with isoprenaline (1 mumol/l) caused a significant increase in CARP mRNA and protein by similar to50%. Combined beta(1)- and beta(2)-adrenoceptor blockade, inhibition of protein kinase A (PKA; Rp-cAMPS, 100 mumol/l), and inhibition of calmodulin-dependent protein kinases (CaMK; KN-62, 10 mumol/l) completely reversed the effects of isoprenaline. To examine the consequences of CARP overexpression on contractile function, an adenovirus encoding human CARP as well as a control virus were constructed. Although the basal force of contraction was not different, contractile response to Ca2+ and isoprenaline was significantly diminished in engineered heart tissue infected with the recombinant adenovirus that carries the CARP gene (Ad.CARP). Conclusions: Our study provides the first evidence that overexpression of CARP, which is thought to act as a transcriptional co-repressor, may deteriorate contractile function of the heart tissue. Furthermore, P-adrenoceptor stimulation and activation of PKA and CaMK have been identified as mechanisms that induce expression of CARP in cardiomyocytes. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. C1 Univ Erlangen Nurnberg, Inst Expt & Klin Pharmakol & Toxikol, D-91054 Erlangen, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Hamburg, Krankenhaus Eppendorf, Inst Expt & Klin Pharmakol, D-2000 Hamburg, Germany. RP Zolk, O (reprint author), Univ Erlangen Nurnberg, Inst Expt & Klin Pharmakol & Toxikol, Fahrstr 17, D-91054 Erlangen, Germany. OI Zolk, Oliver/0000-0002-8220-3834 NR 30 TC 32 Z9 37 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD SEP 1 PY 2003 VL 59 IS 3 BP 563 EP 572 DI 10.1016/S0008-6363(03)00476-0 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 730EW UT WOS:000185817100007 PM 14499857 ER PT J AU Bolay, H Gursoy-Ozdemir, Y Qui, JH Bermpohl, D Wang, XY Rosenberg, G Lo, EH Moskowitz, MA AF Bolay, H Gursoy-Ozdemir, Y Qui, JH Bermpohl, D Wang, XY Rosenberg, G Lo, EH Moskowitz, MA TI Activation of ipsilateral pia-arachnoid cells and matrix metalloproteinases by cortical spreading depression in a migraine model SO CEPHALALGIA LA English DT Meeting Abstract CT 11th Congress of the International-Headache-Society CY SEP 12-16, 2003 CL ROME, ITALY SP Int Headache Soc C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Neuroprotect Res Lab, Charlestown, MA USA. Univ New Mexico, Dept Neurol, Albuquerque, NM 87131 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 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD SEP PY 2003 VL 23 IS 7 BP 647 EP 647 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 717XA UT WOS:000185115000287 ER PT J AU Thomson, CC Clark, S Camargo, CA AF Thomson, CC Clark, S Camargo, CA TI Body mass index and asthma severity among adults presenting to the emergency department SO CHEST LA English DT Article DE asthma; adult; body mass index; obesity; sex ID UNITED-STATES; US ADULTS; OBESITY; CHILDREN; WEIGHT; PREVALENCE; POPULATION; HEALTH; OVERWEIGHT; WOMEN AB Study objectives: Among adults presenting to the emergency department (ED) with acute asthma, we sought to determine the prevalence of obesity, and the relation of body mass index (BMI) to asthma severity in this high-risk population. Design: Multicenter, prospective cohort study. Setting: Twenty-six North American EDs. Participants: Five hundred seventy-two patients aged IS to 54 years presenting with acute asthma. Interventions: None. Measurements and results: A standardized interview assessed demographic characteristics, asthma history, and details of the current asthma exacerbation. Data on ED medical management and disposition were obtained by chart review. Three of four asthmatic patients were either overweight (BMI, 25 to 29.9; 30%) or obese (BMI, greater than or equal to 30; 44%). Normal weight/underweight, overweight, and obese patients did not differ on several markers of chronic asthma severity; obese subjects tended to rate symptoms more severely and to use more inhaled beta-agonists in the 6 h hours prior to ED presentation despite a significantly higher initial percentage of predicted peak expiratory flow (PEF) [44%, 45%, and 51%, respectively; p < 0.05]. The three BMI groups responded similarly to acute therapy in the ED, with all groups demonstrating reversible airway obstruction. The sex distribution by BMI group differed markedly (p < 0.001), with women less often overweight (40% vs 24%) and more often obese (30% vs 52%). Since women were more likely have a higher initial PEF (45% vs 53%, p < 0.001), we stratified by sex to further examine the relation of BMI to asthma severity. The observed BMI-asthma associations were due largely, but not entirely, to confounding by sex. Conclusions: Despite lingering concerns about the veracity of "asthma" among obese individuals, asthma exacerbations among obese and nonobese adults were remarkably similar. Potential differences (eg, in symptom perception, use of inhaled beta-agonists before ED presentation, initial PEF rate) were due, in large part, to confounding by sex. C1 Massachusetts Gen Hosp, Dept Emergency Med, EMNet Coordinating Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pulm & Crit Care, EMNet Coordinating Ctr, Boston, MA 02114 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, EMNet Coordinating Ctr, 55 Fruit St,Clin Bldg 397, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL 707427, HL 63841, HL 63253] NR 43 TC 80 Z9 88 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2003 VL 124 IS 3 BP 795 EP 802 DI 10.1378/chest.124.3.795 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 721XQ UT WOS:000185344100008 PM 12970000 ER PT J AU Boudreaux, ED Emond, SD Clark, S Cainargo, CA AF Boudreaux, ED Emond, SD Clark, S Cainargo, CA TI Acute asthma among adults presenting to the emergency department - The role of race/ethnicity and socioeconomic status SO CHEST LA English DT Article DE adults; asthma; ethnicity; quality of care; race; socioeconomic status ID BLACK-AND-WHITE; INNER-CITY CHILDREN; SMALL-AREA ANALYSIS; NEW-YORK-CITY; RISK-FACTORS; SELF-EFFICACY; PUERTO-RICAN; HOSPITALIZATION RATES; ETHNIC-DIFFERENCES; AFRICAN-AMERICANS AB Objectives: To investigate racial/ethnic differences in acute asthma among adults presenting to the emergency department (ED), and to determine whether observed differences are attributable to socioeconomic status (SES). Design: Prospective cohort studies performed during 1996 to 1998 by the Multicenter Airway Research Collaboration. Using a standardized protocol, researchers provided 24-h coverage for a median duration of 2 weeks per year. Adults with acute asthma were interviewed in the ED and by telephone 2 weeks after hospital discharge. Participants: Sixty-four North American EDs. Results: A total of 1,847 patients were enrolled into the study. Black and Hispanic asthma patients had a history of more hospitalizations than did whites (ever-hospitalized patients: black, 66%; Hispanic, 63%; white, 54%; p < 0.001; patients hospitalized in the past year: black, 31%; Hispanic, 33%; white, 25%; p < 0.05) and more frequent ED use (median use in past year: black, three visits; Hispanic, three visits; white, one visit; p < 0.001). The mean initial peak expiratory flow rate (PEFR) was lower in blacks and Hispanics (black, 47%; Hispanic, 47%; white, 52%; p < 0.001). For most factors, ED management did not differ based on race/ethnicity. After accounting for several confounding variables, blacks and Hispanics were twice as likely to be admitted to the hospital. Blacks and Hispanics also were more likely to report continued severe symptoms 2 weeks after hospital discharge (blacks, 24%; Hispanic, 31%; white, 19%; p < 0.01). After adjusting for sociodemographic factors, the race/ethnicity differences in initial PEFR and posthospital discharge symptoms were markedly reduced. Conclusion: Despite significant racial/ethnic differences in chronic asthma severity, initial PEFR at ED presentation, and posthospital discharge outcome, ED management during the index visit was fairly similar for all racial groups. SES appears to account for most of the observed acute asthma differences, although hospital admission rates were higher among black and Hispanic patients after adjustment for confounding factors. Despite asthma treatment advances, race/ethnicity-based deficiencies persist. Health-care providers and policymakers might specifically target the ED as a place to initiate interventions designed to reduce race-based disparities in health. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA. Santa Clara Univ, Ctr Med, Kaiser Permanente, Emergency Dept, Santa Clara, CA USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA. Channing Labs, Boston, MA USA. RP Boudreaux, ED (reprint author), Cooper Hosp Univ Med Ctr, Emergency Med Residency Program, Dept Emergency Med, 1 Cooper Pl, Camden, NJ 08103 USA. OI Boudreaux, Edwin/0000-0002-3223-6371 NR 67 TC 70 Z9 70 U1 1 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2003 VL 124 IS 3 BP 803 EP 812 DI 10.1378/chest.124.3.803 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 721XQ UT WOS:000185344100009 PM 12970001 ER PT J AU Kouba, DJ Kirsch, DG Mimouni, D Nousari, CH AF Kouba, DJ Kirsch, DG Mimouni, D Nousari, CH TI Wegener's granulomatosis with cardiac involvement masquerading as Lyme disease SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article DE Wegener's granulomatosis; Lyme disease; heart block; ANCA ID COMPLETE HEART-BLOCK; COMPLICATIONS; DIAGNOSIS AB Cardiac conduction disease is an infrequent complication of Wegener's granulomatosis (WG). We describe a case demonstrating an association between WG and complete atrioventricular dissociation. This manifestation was initially interpreted as Lyme disease based on these cardiac findings, arthritis, myalgias and positive Lyme serology. The clinical overlap between these disorders and the appropriate use of respective serologies is discussed. C1 Johns Hopkins Univ, Dept Dermatol, Baltimore, MD 21218 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Nousari, CH (reprint author), Cleveland Clin, Dept Dermatol, 2960 Cleveland Clin Blvd, Weston, FL 33331 USA. NR 15 TC 4 Z9 4 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD SEP-OCT PY 2003 VL 21 IS 5 BP 647 EP 649 PG 3 WC Rheumatology SC Rheumatology GA 728QG UT WOS:000185727400015 PM 14611118 ER PT J AU Tahir, SA Ren, CZ Timme, TL Gdor, Y Hoogeveen, R Morrisett, JD Frolov, A Ayala, G Wheeler, TM Thompson, TC AF Tahir, SA Ren, CZ Timme, TL Gdor, Y Hoogeveen, R Morrisett, JD Frolov, A Ayala, G Wheeler, TM Thompson, TC TI Development of an immunoassay for serum caveolin-1: A novel biomarker for prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID SURVIVAL/CLONAL GROWTH; RADICAL PROSTATECTOMY; CLINICAL STAGE; ANTIGEN; EXPRESSION; CELLS; METASTASIS AB Purpose: Caveolin-1 (cav-1), the major protein component of caveolae, plays an important role in multiple signaling pathways, molecular transport, and cellular proliferation and differentiation. The specific functions of cav-1/ caveolae are highly cell and context dependent. We have previously shown that cav-1 expression is increased in metastatic human prostate cancer and that cav-1 cellular protein expression is predictive of recurrence of the disease after radical prostatectomy. Recently, we reported that cav-1 is secreted by androgen-insensitive prostate cancer cells, and we detected, by Western blotting, cav-1 in the high-density lipoprotein, fraction of serum specimens from patients with prostate cancer. Experimental Design: Using rabbit polyclonal antibodies with specificity for cav-1, we developed a direct sandwich inummoassay for the determination of cav-1 in serum. A recombinant human cav-1 fusion protein was overexpressed and purified from 293 PE cells and used as a calibrator. Results: The assay was highly specific and had a minimum detection limit of 0.017 ng/ml (mean + 3 SD of zero calibrator) and measuring range of up to 200 ng/ml. Intra-assay coefficient of variation was 2.29-6.74% and inter-assay coefficient of variation was 2.81-6.43% over the serum concentration tested 0.04-31.89 ng/ml. The recovery limit of cav-1 by the assay was 89.55-100.28%. The median serum cav-1 level in 102 prostate cancer patients with clinically localized disease (0.463 ng/ml) was significantly higher than 81 healthy control men (0.324 ng/ml; P = 0.0446, Mann-Whitney test) or 107 men with benign prostatic hyperplasia (0.172 ng/ml; P = 0.0317, Mann-Whitney test). Conclusions: Our results indicate that serum cav-1 has the power to differentiate between prostate cancer and benign prostatic hyperplasia patients and the potential to be an important biomarker for prostate cancer. Additional studies to test the potential of serum cav-1 as a diagnostic and/or prognostic marker in prostate cancer are warranted. C1 Scott Dept Urol, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cell Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. RP Thompson, TC (reprint author), Scott Dept Urol, 6560 Fannin St,Suite 2100, Houston, TX 77030 USA. FU NCI NIH HHS [CA 50588, CA 68814] NR 22 TC 59 Z9 64 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2003 VL 9 IS 10 BP 3653 EP 3659 PN 1 PG 7 WC Oncology SC Oncology GA 725NB UT WOS:000185548300019 PM 14506154 ER PT J AU Inadomi, JM Sonnenberg, A AF Inadomi, John M. Sonnenberg, Amnon TI An evidence-based medicine approach to economic studies: assessing the cost-effectiveness of competing strategies for colorectal cancer screening SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article AB Cost-effectiveness analysis aims to quantitatively compare the expected outcomes of competing management strategies in environments with limited economic resources. A valid economic study models all relevant strategies from an appropriate perspective. The model must use costs that are accurately measured and strategies that have established clinical effectiveness, and appropriately integrate these data. The results should include the incremental cost-effectiveness ratio, which quantifies the resources required to achieve greater benefit with one strategy compared to another. A sensitivity analysis is required to determine whether uncertainty in assumptions alters the conclusions. Final interpretation of a cost-effectiveness analysis relies on whether costs and outcomes in the study can be realized in one's own health care environment. C1 [Inadomi, John M.] Vet Adm Ctr Practice Management & Outcomes Res, Ann Arbor, MI USA. [Inadomi, John M.] Univ Michigan, Dept Med, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Dept Med, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. RP Inadomi, JM (reprint author), VA Med Ctr, 111-D,2215 Fuller Rd, Ann Arbor, MI 48105 USA. EM jinadomi@umich.edu RI Inadomi, John/A-6221-2014 OI Inadomi, John/0000-0001-6776-8661 NR 44 TC 3 Z9 4 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD SEP PY 2003 VL 1 IS 5 BP 404 EP 413 DI 10.1053/S1542-3565(03)00181-2 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V19KK UT WOS:000208071100011 PM 15017661 ER PT J AU Pappas, PG Rex, JH Lee, J Hamill, RJ Larsen, RA Powderly, W Kauffman, CA Hyslop, N Mangino, JE Chapman, S Horowitz, HW Edwards, JE Dismukes, WE AF Pappas, PG Rex, JH Lee, J Hamill, RJ Larsen, RA Powderly, W Kauffman, CA Hyslop, N Mangino, JE Chapman, S Horowitz, HW Edwards, JE Dismukes, WE CA NIAID Mycoses Study Grp TI A prospective observational study of candidemia: Epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INTENSIVE-CARE UNIT; BLOOD-STREAM INFECTIONS; RISK-FACTORS; AMPHOTERICIN-B; PARAPSILOSIS FUNGEMIA; ACQUIRED CANDIDEMIA; CANCER-PATIENTS; ATTRIBUTABLE MORTALITY; NOSOCOMIAL CANDIDEMIA; RANDOMIZED TRIAL AB We conducted a prospective, multicenter observational study of adults (n = 1447) and children (n = 144) with candidemia at tertiary care centers in the United States in parallel with a candidemia treatment trial that included nonneutropenic adults. Candida albicans was the most common bloodstream isolate recovered from adults and children (45% vs. 49%) and was associated with high mortality (47% among adults vs. 29% among children). Three-month survival was better among children than among adults (76% vs. 54%; P < .001). Most children received amphotericin B as initial therapy, whereas most adults received fluconazole. In adults, Candida parapsilosis fungemia was associated with lower mortality than was non-parapsilosis candidemia (24% vs. 46%; P < .001). Mortality was similar among subjects with Candida glabrata or non-glabrata candidemia; mortality was also similar among subjects with C. glabrata candidemia who received fluconazole rather than other antifungal therapy. Subjects in the observational cohort had higher Acute Physiology and Chronic Health Evaluation II scores than did participants in the clinical trial (18.6 vs. 16.1), which suggests that the former subjects are more often excluded from therapeutic trials. C1 Univ Alabama, Div Infect Dis, Birmingham, AL 35294 USA. Univ Texas, Houston, TX USA. Houston Vet Affairs Med Ctr, Houston, TX USA. Washington Univ, St Louis, MO USA. Univ Michigan, Ann Arbor, MI 48109 USA. Ann Arbor Vet Affairs Med Ctr, Ann Arbor, MI USA. Tulane Univ, New Orleans, LA 70118 USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. New York Med Coll, Westchester Cty Med Ctr, Valhalla, NY 10595 USA. Univ Calif Los Angeles, Harbor Med Ctr, Los Angeles, CA 90024 USA. Univ So Calif, Los Angeles, CA USA. RP Pappas, PG (reprint author), Univ Alabama, Div Infect Dis, 1900 Univ Blvd,229 Tinsley Harrison Tower, Birmingham, AL 35294 USA. FU PHS HHS [N01-AL-65296] NR 52 TC 481 Z9 511 U1 4 U2 18 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2003 VL 37 IS 5 BP 634 EP 643 DI 10.1086/376906 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 715YK UT WOS:000185001900003 PM 12942393 ER PT J AU Grinspoon, S AF Grinspoon, S TI Mechanisms and strategies for insulin resistance in acquired immune deficiency syndrome SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HIV-INFECTED PATIENTS; IMMUNODEFICIENCY-VIRUS INFECTION; ACTIVE ANTIRETROVIRAL THERAPY; TISSUE-PLASMINOGEN ACTIVATOR; PROTEASE INHIBITOR THERAPY; FAT REDISTRIBUTION; METABOLIC ABNORMALITIES; DIABETES-MELLITUS; BODY-COMPOSITION; RISK-FACTORS AB Abnormalities of glucose regulation, including impaired glucose tolerance and insulin resistance, are often seen among human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy. Insulin resistance in this population may result from antiviral medication directly impairing glucose uptake in the muscle, effects of HIV per se, or indirect effects, such as fat redistribution. Insulin resistance may increase the risk of coronary heart disease among this population of patients, in part by inhibiting normal thrombolysis. The optimal treatment for insulin resistance and impaired glucose intolerance in HIV-infected patients is not known, but preliminary studies have suggested that metformin, an insulin sensitizing agent, improves insulin sensitivity, blood pressure, and waist circumference. Initial studies of thiazolidinediones also suggest the potential utility of such agents to improve insulin sensitivity, decrease hepatic steatosis, and increase subcutaneous fat. Further studies are needed to determine the optimal treatment strategy for insulin resistance in this population. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Nutr Metab, Boston, MA 02114 USA. RP Grinspoon, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Nutr Metab, L0N 207, Boston, MA 02114 USA. NR 35 TC 36 Z9 37 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2003 VL 37 SU 2 BP S85 EP S90 DI 10.1086/375885 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 715YJ UT WOS:000185001800008 PM 12942379 ER PT J AU Hadigan, C AF Hadigan, C TI Dietary habits and their association with metabolic abnormalities in human immunodeficiency virus-related lipodystrophy SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HIV-PROTEASE INHIBITOR; INSULIN-RESISTANCE; ANTIRETROVIRAL THERAPY; BODY-COMPOSITION; INFECTION; WOMEN; DYSLIPIDEMIA; GEMFIBROZIL; SENSITIVITY; MANAGEMENT AB Relatively little is known about the influence of dietary habits on the metabolic complications associated with human immunodeficiency virus (HIV) infection and lipodystrophy. Although recommendations to modify diet and exercise remain a first-line approach to the management of HIV-infected patients with dyslipidemia and glucose intolerance, it is important to determine to what extent, if any, these metabolic abnormalities may be attributed to or modified by dietary behaviors. I review previous work evaluating dietary behaviors and their relationship to lipid levels and insulin resistance in HIV-infected patients with and without lipodystrophy and discuss the implications of possible dietary interventions and results of preliminary studies of the effects of diet on dyslipidemia. Sound dietary guidelines based on investigational research among HIV-infected patients are clearly needed to help face the challenges of the emerging problems of hyperlipidemia, insulin resistance, the possible increased risk of cardiovascular disease among patients with HIV infection and lipodystrophy. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Hadigan, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,BUL457-B, Boston, MA 02114 USA. NR 21 TC 11 Z9 11 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2003 VL 37 SU 2 BP S101 EP S104 DI 10.1086/375887 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 715YJ UT WOS:000185001800011 PM 12942382 ER PT J AU Luthi-Carter, R Cha, JHJ AF Luthi-Carter, R Cha, JHJ TI Mechanisms of transcriptional dysregulation in Huntington's disease SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Article DE Huntington's disease; transcription; messenger RNA; expression profiling; huntingtin; polyglutamine disease ID GENE-EXPRESSION CHANGES; CREB-BINDING PROTEIN; MESSENGER-RNA LEVELS; NEURONAL INTRANUCLEAR INCLUSIONS; POLYGLUTAMINE TRACT-BINDING; TRANSGENIC MOUSE MODEL; MUTANT HUNTINGTIN; CELL-DEATH; EXPANDED POLYGLUTAMINE; BASAL GANGLIA AB Recent studies have provided strong evidence for transcription-related deficits in Huntington's disease (HD). These discoveries include consistent changes in steady-state mRNA levels, direct interactions between huntingtin and known transcription factor proteins, sequestration of transcription-related factors into polyglutamine aggregates, and inhibition of enzymes involved in chromatin remodeling. Also, there is increasing evidence that huntingtin itself may be a transcriptional regulator. This review discusses the cumulative body of evidence for transcriptional dysregulation as a mechanism of HD pathogenesis and possible implications for disease progression and treatment. (C) 2003 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat, Dept Neurol, Charlestown, MA 02129 USA. RP Cha, JHJ (reprint author), Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat, Dept Neurol, B114-2000,114 16th St, Charlestown, MA 02129 USA. NR 96 TC 27 Z9 28 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD SEP PY 2003 VL 3 IS 3 BP 165 EP 177 DI 10.1016/S1566-2772(03)00059-8 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 738ZQ UT WOS:000186318100007 ER PT J AU Gratz, KL Orsillo, SM AF Gratz, KL Orsillo, SM TI Scientific expert testimony in CSA cases: Legal, ethical, and scientific considerations SO CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE LA English DT Article DE child sexual abuse; expert testimony ID CHILDHOOD SEXUAL-ABUSE; SELF-DESTRUCTIVE BEHAVIOR; DISSOCIATIVE SYMPTOMATOLOGY; FAMILY EXPERIENCES; NONCLINICAL SAMPLE; COPING STRATEGIES; ADULT SURVIVORS; WOMEN; ADJUSTMENT; IMPACT AB We strongly agree with Sbraga and O'Donohue (2003, this issue) that the science and ethics of clinical psychology, as well as the legal standards of Daubert v. Merrell Dow Pharmaceuticals, Inc. (1993), prohibit testifying that a child has been sexually abused based on the child's postabuse psychological functioning. Moreover, based on a review of the literature, we argue that it is highly unlikely that a symptom marker of childhood sexual abuse (CSA) will ever emerge that could be used in court to prove a history of childhood abuse. In light of the current status of literature on CSA, we offer some practical suggestions and guidelines for practitioners who accept the role of expert witness in this area. C1 Boston VA Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. Univ Massachusetts, Boston, MA 02125 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Orsillo, SM (reprint author), Boston VA Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, 150 S Huntington Ave, Boston, MA 02130 USA. NR 42 TC 1 Z9 2 U1 2 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0969-5893 J9 CLIN PSYCHOL-SCI PR JI Clin. Psychol.-Sci. Pract. PD FAL PY 2003 VL 10 IS 3 BP 358 EP 363 DI 10.1093/clipsy/bpg035 PG 6 WC Psychology, Clinical SC Psychology GA 716QQ UT WOS:000185040200013 ER PT J AU Linder, JA Singer, DE Stafford, RS AF Linder, JA Singer, DE Stafford, RS TI Association between antibiotic prescribing and visit duration in adults with upper respiratory tract infections SO CLINICAL THERAPEUTICS LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 02-04, 2002 CL ATLANTA, GEORGIA SP Soc Gen Internal Med DE antibiotics; respiratory tract infections; efficiency; physician-patient relations ID EXPECTATIONS; RESISTANCE; PHYSICIANS; PATIENT; THROAT; CARE AB Background: Upper respiratory tract infections (URTIs) are the most common reason for individuals to seek health care in the United States. Inappropriate antibiotic use exposes patients unnecessarily to potential adverse events and increases the prevalence of antibiotic-resistant bacteria. One of the reasons physicians may prescribe an antibiotic inappropriately is to save time. Objective: The aim of this study was to determine whether there is an association between antibiotic use and a shorter visit duration in adults with URTIs. Methods: Visits to office-based primary care physicians made by adults aged 18 to 60 years from 1995 through 2000 were extracted from the National Ambulatory Medical Care Survey Visits that resulted in a primary diagnosis of acute URTI; acute nasopharyngitis; acute bronchitis; sinusitis; streptococcal sore throat, acute pharyngitis, or acute tonsillitis; or otitis media were included in the study Visits associated with > 1 diagnosis were included in a separate category. Visit duration was defined as the face-to-face time between the patient and physician. Results: There were 3764 visits that met the criteria for inclusion in this study, representing an estimated 27 million annual visits to office-based primary care physicians by adults with URTIs. Antibiotics were prescribed in 67% of visits. The mean visit duration associated with prescription of an antibiotic was 14.2 minutes, compared with 15.2 minutes without prescription of an antibiotic (P = 0.007). In multivariable modeling, independent predictors of visit duration were calendar year (additional 0.3 minute per year; 95 % CI, 0.1 to 0.6), internal medicine specialty (additional 2.2 minutes vs family practice; 95 % CI, 1.3 to 3.1), co-visit with a nurse-practitioner or physician assistant (6.6 minutes shorter; 95% CI, -2.7 to -10.6), and Midwestern location of practice (1.1 minutes shorter vs Northeast; 95% CI, -0.1 to -2.2). Antibiotic use was marginally associated with a shorter visit duration (0.7 minute shorter; 95% CI, 0.0 to -1.3; P = NS). Conclusions: In the present study, antibiotic use was marginally associated with a shorter visit duration for adults with URTIs. Any potential efficiencies gained by physicians through prescribing antibiotics for adults with URTIs are likely to be outweighed by increases in antimicrobial resistance and exposure of patients to unneeded medication. Copyright (C) 2003 Excerpta Medica, Inc. C1 Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Stanford Ctr Res Dis Prevent, Palo Alto, CA USA. RP Linder, JA (reprint author), Brigham & Womens Hosp, Div Gen Med, 75 Francis St,BC-3-2X, Boston, MA 02115 USA. FU BHP HRSA HHS [5T32PE11001-12] NR 21 TC 33 Z9 34 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD SEP PY 2003 VL 25 IS 9 BP 2419 EP 2430 DI 10.1016/S0149-2918(03)80284-9 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 731DR UT WOS:000185869700005 PM 14604741 ER PT J AU Wright, CD AF Wright, CD TI Minitracheostomy SO CLINICS IN CHEST MEDICINE LA English DT Article ID SPUTUM RETENTION AB Minitracheostomy is a safe bedside procedure that is a useful adjunct to facilitate secretion clearance in patients with sputum retention. It also can be used in a prophylactic fashion after operations in high-risk patients. Insertion requires a trained physician and an assistant. Complications are rare and are usually avoidable. C1 Massachusetts Gen Hosp, Gen Thorac Surg Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Wright, CD (reprint author), Massachusetts Gen Hosp, Gen Thorac Surg Unit, Blake 1570,32 Fruit St, Boston, MA 02114 USA. NR 8 TC 8 Z9 8 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 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD SEP PY 2003 VL 24 IS 3 BP 431 EP + DI 10.1016/S0272-5321(03)00046-7 PG 6 WC Respiratory System SC Respiratory System GA 722YD UT WOS:000185404900008 PM 14535217 ER PT J AU Gonzalez, S Swindells, K Rajadhyaksha, M Torres, A AF Gonzalez, S Swindells, K Rajadhyaksha, M Torres, A TI Changing paradigms in dermatology: Confocal microscopy in clinical and surgical dermatology SO CLINICS IN DERMATOLOGY LA English DT Article ID SCANNING LASER MICROSCOPY; MOHS MICROGRAPHIC SURGERY; IN-VIVO; REAL-TIME; HUMAN SKIN; REFLECTANCE MICROSCOPY; MALIGNANT-MELANOMA; CONTACT-DERMATITIS; ROUTINE HISTOLOGY; INVIVO AB The current practice of pathology and dermatopathology depends upon the evaluation of tissue in some manner extirpated from the patient and then processed and stained. While high resolution of detail can be accomplished by this method, there are certain risks and disadvantages. Recent imaging techniques now allow for a potential of achieving noninvasive high-resolution analysis of lesions in situ in the patient. Of these, Reflectance mode confocal microscopy offers the highest resolution imaging comparable to routine histology. Being entirely non invasive, skin can be observed in its native, dynamic state. This chapter will review the fundamentals of in vivo confocal imaging and the clinical applications in general and surgical dermatology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Dermatol, Wellman Labs Photomed, Boston, MA 02115 USA. Loma Linda Univ Hosp, Div Dermatol, Loma Linda, CA USA. RP Gonzalez, S (reprint author), Wellman Labs Photomed, Dept Dermatol, BAR 814,50 Blossom St, Boston, MA 02114 USA. FU NIOSH CDC HHS [R01 OH04029] NR 39 TC 57 Z9 64 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0738-081X J9 CLIN DERMATOL JI Clin. Dermatol. PD SEP-OCT PY 2003 VL 21 IS 5 BP 359 EP 369 DI 10.1016/j.clindermatol.2003.08.007 PG 11 WC Dermatology SC Dermatology GA 756XJ UT WOS:000187510800004 PM 14678715 ER PT J AU Wilbur, DC AF Wilbur, DC TI Gynecologic cytopathology - Preface SO CLINICS IN LABORATORY MEDICINE LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Wilbur, DC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St Warren 120, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD SEP PY 2003 VL 23 IS 3 BP XI EP XIV DI 10.1016/S0272-2712(03)00062-3 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 726TH UT WOS:000185615600001 ER PT J AU Tambouret, RH Wilbur, DC AF Tambouret, RH Wilbur, DC TI The many faces of atrophy in gynecologic cytology SO CLINICS IN LABORATORY MEDICINE LA English DT Article ID ATYPICAL SQUAMOUS-CELLS; HUMAN PAPILLOMAVIRUS INFECTION; REDUCTASE POLYMORPHISM C677T; UNDETERMINED SIGNIFICANCE; POSTMENOPAUSAL WOMEN; CERVICAL SMEARS; MEDROXYPROGESTERONE ACETATE; CERVICOVAGINAL SMEARS; VAGINAL EPITHELIUM; DEPO-PROVERA AB As more attention is paid to cervical cancer screening in the postmenopausal population, increased numbers of atrophic specimens will be evaluated in the cytology laboratory. In addition, specimens from patients who have cell patterns that mimic the nonestrogen or partially estrogen-stimulated state occur in a variety of situations, including pregnancy, the postpartum period, and in individuals who are treated with progesterone. A firm understanding of the cellular changes that are within the range of normal in such circumstances is critical to ensure the specificity of interpretation. This article details the conditions under which nonestrogen-stimulated patterns occur and the corresponding cytologic changes. Hints to avoid pitfalls are offered. There is no substitute for a thorough evaluation of each case, and with continued experience and understanding of these principles, the correct interpretations, and ultimately, the management of patients can be optimized. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Tambouret, RH (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,55 Fruit St, Boston, MA 02114 USA. NR 85 TC 4 Z9 5 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 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD SEP PY 2003 VL 23 IS 3 BP 659 EP + DI 10.1016/S0272-2712(03)00059-3 PG 22 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 726TH UT WOS:000185615600006 PM 14560533 ER PT J AU Black-Schaffer, WS AF Black-Schaffer, WS TI Choosing between competing technologies in the cytology laboratory SO CLINICS IN LABORATORY MEDICINE LA English DT Article AB Technological change often is internal to anatomic pathology services. When new technology requires collaborative development with clinical staff, it is important to systematically approach the rationale for the new technology, and be prepared to deal with its medical, financial, and, sometimes, even personal implications. Such a systematic approach involves sequentially evaluating the acceptability and the potential benefits of technologic alternatives among the laboratory leadership, with each potential vendor, the laboratory staff, and the clinical and institutional leadership, and must ultimately include effective communication with the entire clinical community. Among the benefits of such a systematic approach are resiliency of the process when challenged, and credibility of its leadership, within and outside of the laboratory. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Black-Schaffer, WS (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 214, Boston, MA 02114 USA. NR 7 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD SEP PY 2003 VL 23 IS 3 BP 681 EP + DI 10.1016/S0272-2712(03)00052-0 PG 16 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 726TH UT WOS:000185615600007 PM 14560534 ER PT J AU Wilbur, DC AF Wilbur, DC TI Cervical cytology automation: an update for 2003 - The end of the quest nears? SO CLINICS IN LABORATORY MEDICINE LA English DT Article ID MULTICENTER CLINICAL-TRIALS; PRIMARY SCREENING SYSTEM; FALSE-NEGATIVE SMEARS; THINPREP PAP TEST; QUALITY-CONTROL; AUTOCYTE PREP; AUTOPAP SYSTEM; INTRAEPITHELIAL LESIONS; GYNECOLOGIC CYTOLOGY; INTENDED-USE AB The field of cytology automation has arrived at the first levels of the "grail" of improvements in accuracy and productivity in cervical cytology screening. Despite many uncertainties about the future, the present (or nearly available) technology as presented in this article has the potential to improve the practice of cervical cytology. Improvements in accuracy that are necessary to provide the highest possible level of patient care and to protect practitioners from unreasonable levels of medico-legal risk are a reality. Improvements in productivity that are necessary to help in the impending labor shortage in the field of cytotechnology are also a reality. Automation is clearly the short-term solution to the most difficult of the challenges that we face. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wilbur, DC (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 120, Boston, MA 02114 USA. NR 69 TC 0 Z9 1 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 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD SEP PY 2003 VL 23 IS 3 BP 755 EP + DI 10.1016/S0272-2712(03)00060-X PG 21 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 726TH UT WOS:000185615600011 PM 14560538 ER PT J AU Giovanello, KS Verfaellie, M Keane, MM AF Giovanello, Kelly Sullivan Verfaellie, Mieke Keane, Margaret M. TI Disproportionate deficit in associative recognition relative to item recognition in global amnesia SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE LA English DT Article AB In two experiments, we tested the hypothesis that medial temporal lobe (MTL) amnesic patients and, likewise, diencephalic (DNC) amnesic patients evidence a disproportionate deficit in memory for associations in comparison with memory for single items. In Experiment 1, we equated item recognition in amnesic and control participants and found that, under these conditions, associative recognition remained impaired both for MTL patients and for DNC patients. To rule out an alternative interpretation of the results of Experiment 1, in Experiment 2 we compared the performance of amnesic and control participants on a one-item recognition task and a two-item recognition task that required no memory for the association between members of word pairs. In the MTL group, when single-item recognition was equated to that of the controls, two-item nonassociative pair memory was equivalent as well. In the DNC group, nonassociative pair memory was impaired, but this impairment did not fully account for the impairment in associative memory. These findings indicate that memory for novel associations between items is disproportionately impaired in comparison with memory for single items in amnesia. C1 [Giovanello, Kelly Sullivan; Verfaellie, Mieke; Keane, Margaret M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Verfaellie, Mieke] Boston VA Healthcare Syst, Boston, MA USA. [Keane, Margaret M.] Wellesley Coll, Wellesley, MA 02181 USA. RP Giovanello, KS (reprint author), Boston VA Healthcare Syst 151 A, Memory Disorders Res Ctr, 150 South Huntington Ave, Boston, MA 02130 USA. EM ksull@bu.edu FU National Institute of Mental Health [MH57681, MH65113]; National Institute of Neurological Disorders and Stroke [NS26985]; Medical Research Service of the United States Department of Veterans Affairs FX This research was supported by National Institute of Mental Health Grants MH57681 and MH65113, National Institute of Neurological Disorders and Stroke Grant NS26985, and the Medical Research Service of the United States Department of Veterans Affairs. Correspondence concerning this article should be addressed to K. Sullivan Giovanello, Memory Disorders Research Center, Boston VA Healthcare System (151-A), 150 South Huntington Ave., Boston, MA 02130 (e-mail: ksull@bu.edu). NR 35 TC 70 Z9 72 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-7026 EI 1531-135X J9 COGN AFFECT BEHAV NE JI Cogn. Affect. Behav. Neurosci. PD SEP PY 2003 VL 3 IS 3 BP 186 EP 194 DI 10.3758/CABN.3.3.186 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA V32MK UT WOS:000208955100003 PM 14672155 ER PT J AU Highfield, ES Kaptchuk, TJ Ott, MJ Barnes, L Kemper, KJ AF Highfield, ES Kaptchuk, TJ Ott, MJ Barnes, L Kemper, KJ TI Availability of acupuncture in the hospitals of a major academic medical center: a pilot study SO COMPLEMENTARY THERAPIES IN MEDICINE LA English DT Article ID UNITED-STATES; ALTERNATIVE MEDICINE; EXPERIENCE; BRAIN AB Background: Acupuncture is widely used by the American public, but little is known about its availability and use in academic medical settings. We performed a pilot study to compare acupuncture services provided by hospitals affiliated with a major academic teaching institution, and a parallel survey of services provided through an acupuncture school in one city in New England. Methods: Between December 2000 and July 2001, a telephone survey was conducted of the 13 hospitals affiliated with Harvard Medical School, and the clinics affiliated with the New England School of Acupuncture. Results: Acupuncture was available in 8 of the 13 hospitals. Acupuncture was provided in ambulatory clinics in all eight hospitals, but was available to inpatients in only one hospital. Six hospitals delivered acupuncture through an outpatient pain treatment service, one through a women's health center, one through an HIV clinic, and one hospital delivered acupuncture through two services; a program in the anesthesia department and a multi-disciplinary holistic program in a primary care department. In contrast, the acupuncture school clinics provided services through an on-site clinic at the school, through acupuncture departments at two community-based hospitals, and through a network of 12 satellite acupuncture-dedicated clinics operating throughout the state. Conclusion: Acupuncture is available on a limited basis in a majority of the teaching hospitals in this city. At the acupuncture school clinics, there are few barriers to care. Future health care studies will need to examine the role of acupuncture in diverse geographic settings and to examine its impact on quality of care, teaching and its role in research in academic centers. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Childrens Hosp, Acupuncture Program, Ctr Holist Pediat Educ & Res, Boston, MA 02115 USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA. Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. Dana Farber Canc Inst, Zakim Ctr Integrated Therapies, Pain & Palliat Care Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Osher Inst, Boston, MA USA. RP Highfield, ES (reprint author), Childrens Hosp, Acupuncture Program, Ctr Holist Pediat Educ & Res, 330 Longwood Ave, Boston, MA 02115 USA. FU NCCIH NIH HHS [AT00538] NR 17 TC 17 Z9 17 U1 3 U2 5 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0965-2299 J9 COMPLEMENT THER MED JI Complement. Ther. Med. PD SEP PY 2003 VL 11 IS 3 BP 177 EP 183 DI 10.1016/S0965-2299(03)00069-4 PG 7 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 747PZ UT WOS:000186814600009 PM 14659382 ER PT J AU Brugge, WR AF Brugge, WR TI Developments in endoscopy 2002-2003 SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, GI Endoscopy Unit, Boston, MA USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, GI Endoscopy Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD SEP PY 2003 VL 19 IS 5 BP 473 EP 473 DI 10.1097/00001574-200309000-00006 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 717EY UT WOS:000185074500006 ER PT J AU Thompson, CC Kelsey, PB AF Thompson, CC Kelsey, PB TI Duodenoscope assisted cholangiopancreatoscopy: a review of clinical applications SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Review DE duodenoscope assisted cholangiopancreatoscopy; pancreatic duct; bile duct ID ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY; MUCIN-PRODUCING TUMORS; BILE-DUCT STONES; PERORAL PANCREATOSCOPY; ELECTROHYDRAULIC LITHOTRIPSY; CHRONIC-PANCREATITIS; ELECTRONIC PANCREATOSCOPE; DIAGNOSIS; CHOLANGIOSCOPY; CHOLEDOCHOSCOPY AB Duodenoscope assisted cholangiopancreatoscopy allows direct visualization of the pancreatic duct and bile duct. There are several circumstances where direct ductal visualization might be helpful in clarifying a diagnosis or providing targeted treatment. Duodenoscope assisted cholangiopancreatoscopy is currently employed for a variety of indications including: indeterminate ductal strictures and filling defects, marginal chronic pancreatitis, treatment of large intraductal stones, localization of intraductal papillary mucinous tumors, and localization and treatment of hemobilia. There have however been no randomized controlled trials evaluating the diagnostic or therapeutic functions of duodenoscope assisted cholangicipancreatoscopy. This article reviews recent descriptive studies that attempt to clarify the clinical role of this technology. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Thompson, CC (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 36 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD SEP PY 2003 VL 19 IS 5 BP 487 EP 491 DI 10.1097/00001574-200309000-00010 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 717EY UT WOS:000185074500010 PM 15703595 ER PT J AU Turpie, AGG Eriksson, BI Lassen, MR Bauer, KA AF Turpie, AGG Eriksson, BI Lassen, MR Bauer, KA TI Fondaparinux, the first selective factor Xa inhibitor SO CURRENT OPINION IN HEMATOLOGY LA English DT Article DE fondaparinux; factor Xa inhibition; venous thromboembolism; arterial thrombosis ID RANDOMIZED DOUBLE-BLIND; HIP-REPLACEMENT SURGERY; DEEP-VEIN THROMBOSIS; VENOUS THROMBOEMBOLISM; PENTASACCHARIDE FONDAPARINUX; SYNTHETIC PENTASACCHARIDE; HEALTHY-VOLUNTEERS; POSTOPERATIVE FONDAPARINUX; ANTITHROMBOTIC AGENT; IN-VITRO AB Fondaparinux (Arixtra, Sanofi-Synthelabo, Paris, France) is a pentasaccharide that selectively inhibits factor Xa; it is the first of a new class of synthetic antithrombotic agents. Fondaparinux has a linear pharmacokinetic profile allowing once-daily subcutaneous administration. Absence of metabolism, complete bioavailability, and lack of nonspecific binding in plasma contribute to the predictability of its effect. Fondaparinux has been approved for use in the prophylaxis of venous thromboembolism following orthopedic surgery. In this setting, it was found to reduce VTE risk by more than 50% in comparison with the low molecular weight heparin enoxaparin, with an incidence of clinically important bleeding not significantly different from that of standard low molecular weight heparin regimens. Furthermore, 4 weeks of prophylaxis with fondaparinux after hip fracture surgery was shown to reduce the risk of venous thromboembolism by 96% compared with 1-week prophylaxis. Finally, the efficacy and safety of fondaparinux in the treatment of venous thromboembolism and acute coronary syndromes appears promising. C1 Hamilton Hlth Sci Gen Hosp, E Hamilton, ON L8L 2X2, Canada. Sahlgrens Univ Hosp, Dept Orthoped, S-41345 Gothenburg, Sweden. Hoersholm Hosp, Dept Spinal Surg, Horsholm, Denmark. Hoersholm Hosp, Dept Clin Sci, Horsholm, Denmark. VA Boston Healthcare Syst, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Turpie, AGG (reprint author), Hamilton Hlth Sci Gen Hosp, 237 Barton St, E Hamilton, ON L8L 2X2, Canada. NR 26 TC 35 Z9 36 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD SEP PY 2003 VL 10 IS 5 BP 327 EP 332 DI 10.1097/00062752-200309000-00001 PG 6 WC Hematology SC Hematology GA 709KB UT WOS:000184623400001 PM 12913785 ER PT J AU Mayer, AN Fishman, MC AF Mayer, AN Fishman, MC TI nil per os encodes a conserved RNA recognition motif protein required for morphogenesis and cytodifferentiation of digestive organs in zebrafish SO DEVELOPMENT LA English DT Article DE zebratish; genetics; intestine; digestive system; embryology; RNA-binding proteins ID TRANSCRIPTION FACTOR; EMBRYONIC-DEVELOPMENT; ENDODERM FORMATION; GENE-EXPRESSION; MULTIPLE ROLES; DANIO-RERIO; ORGANOGENESIS; PANCREAS; DIFFERENTIATION; EPIMORPHIN AB Digestive organ development occurs through a sequence of morphologically distinct stages, from overtly featureless endoderm, through organ primordia to, ultimately, adult form. The developmental controls that govern progression from one stage to the next are not well understood. To identify genes required for the formation of vertebrate digestive organs we performed a genetic screen in zebrafish. We isolated the nil per os (npo) mutation, which arrests morphogenesis and cytodifferentiation of the gut and exocrine pancreas in a primodial state. We identified the npo gene by positional cloning. It encodes a conserved protein, with multiple RNA recognition motifs, that is related to the yeast protein Mrd1p. During development npo is expressed in a dynamic fashion, functioning cell autonomously to promote organ cytodifferentiation. Antisense-mediated knockdown of npo results in organ hypoplasia, and overexpression of npo causes an overgrowth of gastrointestinal organs. Thus, npo is a gene essential for a key step in the gut morphogenetic sequence. C1 Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Pediat, Pediat Gastroenterol Unit, Charlestown, MA 02129 USA. RP Mayer, AN (reprint author), Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [2R01 HL 49579-08, 5R01 HL 63206-02]; NIDDK NIH HHS [DK 57521, 5R01 DK 55383-03, DK 43351, K08 DK 02968] NR 47 TC 54 Z9 55 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 SEP PY 2003 VL 130 IS 17 BP 3917 EP 3928 DI 10.1242/dev.00600 PG 12 WC Developmental Biology SC Developmental Biology GA 755HY UT WOS:000187398500002 PM 12874115 ER PT J AU Kenyon, KL Ranade, SS Curtiss, J Mlodzik, M Pignoni, F AF Kenyon, KL Ranade, SS Curtiss, J Mlodzik, M Pignoni, F TI Coordinating proliferation and tissue specification to promote regional identity in the Drosophila head SO DEVELOPMENTAL CELL LA English DT Article ID ECTOPIC EYE DEVELOPMENT; ANTENNA IMAGINAL DISK; PROXIMAL-DISTAL AXIS; MORPHOGENETIC FURROW; COMPOUND EYE; ABSENT GENE; SINE OCULIS; ADULT HEAD; NOTCH; MELANOGASTER AB The Decapentaplegic and Notch signaling pathways are thought to direct regional specification in the Drosophila eye-antennal epithelium by controlling the expression of selector genes for the eye (Eyeless/Pax6, Eyes absent) and/or antenna (Distal-less). Here, we investigate the function of these signaling pathways in this process. We find that organ primordia formation is indeed controlled at the level of Decapentaplegic expression but critical steps in regional specification occur earlier than previously proposed. Contrary to previous findings, Notch does not specify eye field identity by promoting Eyeless expression but it influences eye primordium formation through its control of proliferation. Our analysis of Notch function reveals an important connection between proliferation, field size, and regional specification. We propose that field size modulates the interaction between the Decapentaplegic and Wingless pathways, thereby linking proliferation and patterning in eye primordium development. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Mt Sinai Sch Med, Dept Mol Cell & Dev Biol, New York, NY 10029 USA. RP Pignoni, F (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [R01 EY 13167, R01 EY013167, R01 EY14597] NR 55 TC 92 Z9 95 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD SEP PY 2003 VL 5 IS 3 BP 403 EP 414 DI 10.1016/S1534-5807(03)00243-0 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 721GX UT WOS:000185309600009 PM 12967560 ER PT J AU Agaisse, H Petersen, UM Boutros, M Mathey-Prevot, B Perrimon, N AF Agaisse, H Petersen, UM Boutros, M Mathey-Prevot, B Perrimon, N TI Signaling role of hemocytes in Drosophila JAK/STAT-dependent response to septic injury SO DEVELOPMENTAL CELL LA English DT Article ID NF-KAPPA-B; PEPTIDOGLYCAN RECOGNITION PROTEIN; INNATE IMMUNE-RESPONSES; ACUTE-PHASE RESPONSE; C-REACTIVE PROTEIN; HOST-DEFENSE; INTERLEUKIN-6 GENE; DEFICIENCY IMD; ACTIVATION; EXPRESSION AB To characterize the features of JAK/STAT signaling in Drosophila immune response, we have identified totA as a gene that is regulated by the JAK/STAT pathway in response to septic injury. We show that septic injury triggers the hemocyte-specific expression of upd3, a gene encoding a novel Upd-like cytokine that is necessary for the JAK/STAT-dependent activation of totA in the Drosophila counterpart of the mammalian liver, the fat body. In addition, we demonstrate that totA activation also requires the NF-KB-like Relish pathway, indicating that fat body cells integrate the activity of NF-KB and JAK/STAT signaling pathways upon immune response. This study reveals that, in addition to the pattern recognition receptor-mediated NF-KB-dependent immune response, Drosophila undergoes a complex systemic response that is mediated by the production of cytokines in blood cells, a process that is similar to the acute phase response in mammals. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Pediat Oncol & Hematol, Boston, MA 02115 USA. RP Agaisse, H (reprint author), Harvard Univ, Sch Med, Dept Genet, 200 Longwood Ave, Boston, MA 02115 USA. RI Boutros, Michael/C-3566-2008; Marion-Poll, Frederic/D-8882-2011 OI Boutros, Michael/0000-0002-9458-817X; Marion-Poll, Frederic/0000-0001-6824-0180 FU NHLBI NIH HHS [R01 HL62434] NR 41 TC 242 Z9 250 U1 0 U2 26 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD SEP PY 2003 VL 5 IS 3 BP 441 EP 450 DI 10.1016/S1534-5807(03)00244-2 PG 10 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 721GX UT WOS:000185309600012 PM 12967563 ER PT J AU Herbert, MR Ziegler, DA Makris, N Bakardjiev, A Hodgson, J Adrien, KT Kennedy, DN Filipek, PA Caviness, VS AF Herbert, MR Ziegler, DA Makris, N Bakardjiev, A Hodgson, J Adrien, KT Kennedy, DN Filipek, PA Caviness, VS TI Larger brain and white matter volumes in children with developmental language disorder SO DEVELOPMENTAL SCIENCE LA English DT Article ID HIGH-LEVEL AUTISM; EARLY ADULT LIFE; IMPAIRED CHILDREN; TOPOGRAPHIC PARCELLATION; PROCESSING ABILITIES; IDENTIFYING CHILDREN; INHERITED SPEECH; SOCIAL COGNITION; CEREBRAL-CORTEX; FOLLOW-UP AB Developmental language disorder (DLD) is predominantly a language disorder, but children with DLD also manifest non-language impairments, and neuroanatomical abnormalities have been found in multiple areas of the brain, not all language-associated We therefore performed a whole brain general segmentation analysis of all major brain regions on MRI scans of 24 DID subjects (16M 8F) and 30 controls (15M, 15F), ages 5.7 to 11.3 years. Children with DID showed increased total brain volume, driven predominantly by a substantial increase in the volume of cerebral white matter Cerebral cortex and caudate were relatively but not absolutely smaller in DID. These findings are discussed in relation to issues of specificity vs. generality as they arise in debates about (1) modular vs. general processing deficits and connectionist modeling in DID, (2) language-specific vs. pervasive, non-specific deficits in DLD and (3) specificity of the disorder vs. overlap with other disorders, notably autism. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Morphometr Anal Pediat Neurol,Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Childrens Hosp Oakland, Dept Infect Dis, Oakland, CA 94609 USA. Augsburg Coll, Ctr Learning, Minneapolis, MN USA. Augsburg Coll, Adapt Student Serv, Minneapolis, MN USA. New England Coll Optometry, Boston, MA USA. Univ Calif Irvine, Dept Pediat, Irvine, CA 92717 USA. RP Herbert, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Morphometr Anal Pediat Neurol,Dept Neurol, Room CNY169-6012, Boston, MA 02114 USA. NR 81 TC 26 Z9 26 U1 5 U2 8 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 1363-755X J9 DEVELOPMENTAL SCI JI Dev. Sci. PD SEP PY 2003 VL 6 IS 4 BP F11 EP F22 DI 10.1111/1467-7687.00291 PG 12 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA 714JA UT WOS:000184909000002 ER PT J AU Valverde, AM Burks, DJ Fabregat, I Fisher, TL Carretero, J White, MF Benito, M AF Valverde, AM Burks, DJ Fabregat, I Fisher, TL Carretero, J White, MF Benito, M TI Molecular mechanisms of insulin resistance in IRS-2-deficient hepatocytes SO DIABETES LA English DT Article ID FORKHEAD TRANSCRIPTION FACTOR; PROTEIN-KINASE-B; STIMULATED GLUCOSE-METABOLISM; FETAL BROWN ADIPOCYTES; PHOSPHOENOLPYRUVATE CARBOXYKINASE; GENE-EXPRESSION; PHOSPHATIDYLINOSITOL 3-KINASE; TRANSGENIC MICE; FACTOR FKHR; C-ZETA AB To assess the role of insulin receptor (IR) substrate (IRS)-2 in insulin action and resistance in the liver, immortalized neonatal hepatocyte cell lines have been generated from IRS-2(-/-), IRS-2(+/-), and wild-type mice. These cells maintained the expression of the differentiated liver markers albumin and carbamoyl phosphate synthetase, as well as bear a high number of IRs. The lack of IRS-2 did not result in enhanced IRS-1 tyrosine phosphorylation or IRS-1-associated phosphatidylinositol (PI) 3-kinase activity on insulin stimulation. Total insulin-induced PI 3-kinase activity was decreased by 50% in IRS-2(-/-) hepatocytes, but the translocation of PI-3,4,5-trisphosphate to the plasma membrane in these cells was almost completely abolished. Downstream PI 3-kinase, activation of Akt, glycogen synthase kinase (GSK)-3 (alpha and beta isoforms), Foxo1, and atypical protein kinase C were blunted in insulin-stimulated IRS2(-/-) cells. Reconstitution of IRS-2(-/-) hepatocytes with adenoviral IRS-2 restored activation of these pathways, demonstrating that IRS-2 is essential for functional insulin signaling in hepatocytes. Insulin induced a marked glycogen synthase activity in wild-type and heterozygous primary hepatocytes; interestingly, this response was absent in IRS-2(-/-) cells but was rescued by infection with adenoviral IRS-2. Regarding gluconeogenesis, the induction of phosphoenolpyruvate carboxykinase and glucose 6-phosphatase by dibutyryl cAMP and dexamethasone was observed in primary hepatocytes of all genotypes. However, insulin was not able to suppress gluconeogenic gene expression in primary hepatocytes lacking IRS-2, but when IRS-2 signaling was reconstituted, these cells recovered this response to insulin. Suppression of gluconeogenic gene expression in IRS-2- deficient primary hepatocytes was also restored by infection with dominant negative Delta256Foxo1. C1 Univ Complutense, Fac Farm, Inst Bioquim,Ctr Mixto CSIC UCM, Dept Bioquim & Biol Mol 2, Madrid 28040, Spain. Fac Med, Dept Anat, Salamanca, Spain. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Valverde, AM (reprint author), Univ Complutense, Fac Farm, Inst Bioquim,Ctr Mixto CSIC UCM, Dept Bioquim & Biol Mol 2, Ciudad Univ, Madrid 28040, Spain. RI Carretero, Jose/L-6930-2014 OI Carretero, Jose/0000-0003-3143-6512 NR 57 TC 92 Z9 97 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2003 VL 52 IS 9 BP 2239 EP 2248 DI 10.2337/diabetes.52.9.2239 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 716KP UT WOS:000185027600007 PM 12941762 ER PT J AU Faulconbridge, LF Cummings, DE Kaplan, JM Grill, HJ AF Faulconbridge, LF Cummings, DE Kaplan, JM Grill, HJ TI Hyperphagic effects of brainstem ghrelin administration SO DIABETES LA English DT Article ID GROWTH-HORMONE SECRETAGOGUE; FOOD-INTAKE; MESSENGER-RNA; SOLITARY TRACT; ACYLATED PEPTIDE; NEUROPEPTIDE-Y; BLOOD-GLUCOSE; NUCLEUS; RAT; RECEPTOR AB The role of ghrelin in feeding control has been addressed from a largely hypothalamic perspective, with little attention directed at ingestive consequences of stimulation of the peptide's receptor, the growth hormone secretagogue receptor (GHS-R), in the caudal brainstem. Here, we demonstrate a hyperphagic response to stimulation of GHS-R in the caudal brainstem. Ghrelin (150 pmol) delivered to the third and fourth ventricles significantly and comparably increased cumulative food intake, with maximal response similar to3 It after injection. The meal patterning effects underlying this hyperphagia were also similar for the two placements (i.e., significant reduction in the time between injection and first-meal onset, an increase in the number of meals taken shortly after the injection, and a trend toward an increase in the average size of the first meals that approached but did not achieve statistical significance). In a separate experiment, ghrelin microinjected unilaterally into the dorsal vagal complex (DVC) significantly increased food intake measured 1.5 and 3 h after treatment. The response was obtained with a 10-pmol dose, establishing the DVC as a site of action with at least comparable sensitivity to that reported for the arcuate nucleus. Taken together, the results affirm a caudal brainstem site of action and recommend further investigation into multisite interactions underlying the modulation of ingestive behavior by ghrelin. C1 Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. Univ Washington, Dept Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Faulconbridge, LF (reprint author), Univ Penn, Dept Psychol, 3815 Walnut St, Philadelphia, PA 19104 USA. FU NIDDK NIH HHS [DK21397, DK42284] NR 25 TC 172 Z9 174 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2003 VL 52 IS 9 BP 2260 EP 2265 DI 10.2337/diabetes.52.9.2260 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 716KP UT WOS:000185027600009 PM 12941764 ER PT J AU Mulcahy, K Maryniuk, M Peeples, M Peyrot, M Tomky, D Weaver, T Yarborough, P AF Mulcahy, K Maryniuk, M Peeples, M Peyrot, M Tomky, D Weaver, T Yarborough, P TI Diabetes self-management education core outcomes measures SO DIABETES EDUCATOR LA English DT Review ID QUALITY-OF-LIFE; MEDICAL NUTRITION THERAPY; BLOOD-GLUCOSE; METABOLIC CONTROL; GLYCEMIC CONTROL; CONCEPTUAL-FRAMEWORK; REGIMEN ADHERENCE; ASPIRIN THERAPY; CARE; STRESS C1 Inova Diabet Ctr, Fairfax, VA USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Johns Hopkins Sch Med, Boston, MA USA. Loyola Coll, Ctr Social & Community Res, Albuquerque, NM USA. Lovelace Hlth Syst, Albuquerque, NM USA. Amer Diabet Educators, Chicago, IL USA. RP Mulcahy, K (reprint author), Inova Diabet Ctr, 2832 Juniper St, Fairfax, VA USA. NR 98 TC 107 Z9 110 U1 3 U2 10 PU AMER ASSOC DIABETES EDUCATORS PI CHICAGO PA STE 1240, 444 NORTH MICHIGAN AVE, CHICAGO, IL 60611-3901 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD SEP-OCT PY 2003 VL 29 IS 5 BP 768 EP + DI 10.1177/014572170302900509 PG 27 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 730MZ UT WOS:000185835700008 PM 14603868 ER PT J AU Junior, GM Colleoni, GWB Cangi, MG Murphy, M Sherburne, B Bordin, JO Loda, M AF Junior, GM Colleoni, GWB Cangi, MG Murphy, M Sherburne, B Bordin, JO Loda, M TI Reciprocal Cdc25A and p27 expression in B-cell non-Hodgkin lymphomas SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE Cdc25A; p27; non-Hodgkin lymphoma ID KINASE INHIBITOR P27(KIP1); HUMAN BREAST-CANCER; G(1)/S TRANSITION; CYCLE; PHOSPHORYLATION; PHOSPHATASE; CARCINOMAS; ACTIVATION; DEGRADATION; CHECKPOINT AB Cell cycle regulation is often altered in cancer and deregulation of the cell cycle checkpoints is common in human neoplasia. The dual-specificity phosphatase Cdc25A and the cell cycle inhibitor p27 both play an important role in the regulation of the G1-S transition. We evaluated Cdc25A mRNA expression by in situ hybridization and p27 protein expression by immunohistochemistry in 42 histologically indolent B-cell non-Hodgkin lymphoma (NHLand 51 histologically aggressive B-cell NHL. Overexpression of Cdc25A (>50% tumor cells positive) was detected in 5 of 42 cases (12%) of histologically indolent B-cell NHL and in 29 of 51 (57%) of histologically aggressive B-cell NHL (P < 0.001). In contrast, high p27 protein expression (>50% tumor cells positive) was observed in 29 (69%) cases of indolent but in only one case (2%) of aggressive B-cell NHL (P < 0.0001). Thus, overexpression of Cdc25A and concomitant loss of p27 expression are associated with high grade B-cell NHL and may contribute to their aggressive biologic behavior. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. UNIFESP EPM, Hematol & Transfus Med Serv, Sao Paulo, SP, Brazil. RP Loda, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Dana 740B, Boston, MA 02215 USA. RI Colleoni, Gisele/F-9185-2014 NR 27 TC 1 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD SEP PY 2003 VL 12 IS 3 BP 128 EP 132 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA 716GB UT WOS:000185019500003 ER PT J AU Tsai, B Gilbert, JM Stehle, T Lencer, W Benjamin, TL Rapoport, TA AF Tsai, B Gilbert, JM Stehle, T Lencer, W Benjamin, TL Rapoport, TA TI Gangliosides are receptors for murine polyoma virus and SV40 SO EMBO JOURNAL LA English DT Article DE endoplasmic reticulum; gangliosides; glycolipids; polyoma virus; SV40 ID MAJOR HISTOCOMPATIBILITY PROTEINS; CLASS-I MOLECULES; ENDOPLASMIC-RETICULUM; SIMIAN VIRUS-40; CHOLERA-TOXIN; SIALYLOLIGOSACCHARIDE RECEPTORS; CAVEOLAR ENDOCYTOSIS; DISULFIDE-ISOMERASE; TUMOR-INDUCTION; SIALIC-ACID AB Polyoma virus (Py) and simian virus 40 (SV40) travel from the plasma membrane to the endoplasmic reticulum (ER) from where they enter the cytosol and then the nucleus to initiate infection. Here we demonstrate that specific gangliosides can serve as plasma membrane receptors for these viruses, GD1a and GT1b for Py and GM1 for SV40. Binding and flotation assays were used to show that addition of these gangliosides to phospholipid vesicles allowed specific binding of the respective viruses. The crystal structure of polyoma VP1 with a sialic acid-containing oligosaccharide was used to derive a model of how the two terminal sugars (sialic acid-alpha2,3-galactose) in one branch of GD1a and GT1b are recognized by the virus. A rat cell line deficient in ganglioside synthesis is poorly infectible by polyoma and SV40, but addition of the appropriate gangliosides greatly facilitates virus uptake, transport to the ER and infection. Lipid binding sites for polyoma are shown to be present in rough ER membranes, suggesting that the virus travel with the ganglioside(s) from the plasma membranes to the ER. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. RP Rapoport, TA (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, 240 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA-082395, R01 CA082395]; NIAID NIH HHS [R01 AI045716, R01 AI45716]; NIDDK NIH HHS [P30 DK034854, DK34854, DK48106, R01 DK048106, R37 DK048106] NR 40 TC 235 Z9 240 U1 0 U2 22 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD SEP 1 PY 2003 VL 22 IS 17 BP 4346 EP 4355 DI 10.1093/emboj/cdg439 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 718LP UT WOS:000185147900002 PM 12941687 ER PT J AU Katznelson, L AF Katznelson, L TI The diagnosis and treatment of acromegaly SO ENDOCRINOLOGIST LA English DT Article DE acromegaly; pegvisomant; pituitary tumor; IGF-I; GH ID HORMONE-RECEPTOR ANTAGONIST; LONG-TERM TREATMENT; RELEASE LANREOTIDE TREATMENT; GROWTH-FACTOR-I; TRANSSPHENOIDAL SURGERY; SOMATOSTATIN ANALOGS; PITUITARY-ADENOMAS; SANDOSTATIN-LAR; THERAPY; PEGVISOMANT AB Acromegaly is an endocrine disorder that affects multiple organ systems and increases mortality by 2 to 4 times that of the general population. Elevated growth hormone (GH) levels are the hallmark of acromegaly, but GH secretion is pulsatile and not an accurate marker of disease. IGF-I provides a reliable indication of overall GH secretion and is the single most reliable screening test for acromegaly. In addition, many of the somatotrophic effects of GH are mediated by IGF-I. The goals of treatment of acromegaly are to achieve biochemical control, stabilize or reduce tumor size, and maintain or recover pituitary function. Treatment options for acromegaly include surgery, radiation therapy, and drug therapy. Available medical therapies include somatostatin analogs and dopamine agonists. The advantages and limitations of these therapies are reviewed. A novel medical therapy is pegvisomant, a GH receptor antagonist that binds to GH receptors on the cell surface of target cells and blocks GH signal transduction and GH action. Unlike other medical therapies, effectiveness of pegvisomant is independent of receptor expression on pituitary tumors. Pegvisomant has been demonstrated to be highly effective in reducing IGF-I concentrations to normal levels and significantly improving signs and symptoms of acromegaly in up to 97% of treated patients. Therefore, pegvisomant is a promising new agent that offers significant advances in the treatment of acromegaly. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Katznelson, L (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457,55 Fruit St, Boston, MA 02114 USA. NR 48 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD SEP-OCT PY 2003 VL 13 IS 5 BP 428 EP 434 DI 10.1097/01.ten.0000090922.12899.31 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 727RX UT WOS:000185673700009 ER PT J AU Badger, TM Ronis, MJJ Frank, SJ Chen, Y He, L AF Badger, TM Ronis, MJJ Frank, SJ Chen, Y He, L TI Effects of chronic ethanol on hepatic and renal CYP2C11 in the male rat: Interactions with the Janus-Kinase 2-signal transducer and activators of transcription proteins 5b pathway SO ENDOCRINOLOGY LA English DT Article ID GROWTH-HORMONE-RECEPTOR; CHRONIC ALCOHOL-CONSUMPTION; GENE-EXPRESSION; BINDING-PROTEIN; LIVER; CELLS; CYTOCHROME-P450; PROLACTIN; STAT5B; DEHYDROGENASE AB Chronic alcohol intake in male rats results in: 1) demasculinization of the GH pulse pattern; 2) reduced serum testosterone concentrations; and 3) decreased expression hepatic CYP2C11. Hepatic CYP2C11 expression is regulated by the male pattern of GH through the Janus-kinase/signal transducer and activators of transcription proteins (JAK/STAT) signal transduction pathway in the male rat. Renal CYP2C11 is regulated by testosterone, not GH. The involvement of the JAK/STAT5b signal transduction pathway in renal CYP2C11 signaling has not been studied. We tested the hypothesis that ethanol reduces CYP2C11 levels by interfering with the JAK/STAT5b pathway. Using a total enteral nutrition (TEN) model to feed rats a well-balanced diet, we have studied the effects of chronic ethanol intake (21 d) on hepatic and renal JAK/STAT pathway of adult male rats (8-10/group). We found decreased hepatic and renal expression of CYP2C11 in ethanol-fed rats with concomitant decreases in STAT5b and phospho-STAT5b, decreased in vitro hepatic STAT5b binding to a CYP2C11 promoter element and no effects on hepatic GHR levels. Ethanol caused tissue specific effects in phospho-JAK2 and JAK2, with increased levels in the liver, but decreased JAK2 expression in the kidney. We conclude that ethanol suppression of CYP2C11 expression is clearly associated with reductions in STAT5b levels, but not necessarily in reductions of JAK2 levels. The mechanisms underlying ethanol-induced suppression of STAT5b is yet to be determined, as is the question of whether this is secondary to hormonal effects or a direct ethanol effect. C1 Univ Arkansas Med Sci Hosp, Arkansas Childrens Nutr Ctr, Little Rock, AR 72202 USA. Univ Arkansas Med Sci Hosp, Dept Physiol Biophys, Little Rock, AR 72202 USA. Univ Arkansas Med Sci Hosp, Dept Pharmacol Toxicol, Little Rock, AR 72202 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Med Serv, Birmingham, AL 35294 USA. RP Badger, TM (reprint author), Univ Arkansas Med Sci Hosp, Arkansas Childrens Nutr Ctr, 1120 Marshall St, Little Rock, AR 72202 USA. FU NIAAA NIH HHS [AA008645]; NIDDK NIH HHS [DK46395] NR 31 TC 10 Z9 10 U1 1 U2 1 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 SEP 1 PY 2003 VL 144 IS 9 BP 3969 EP 3976 DI 10.1210/en.2002-0163 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 713XN UT WOS:000184883400033 PM 12933671 ER PT J AU Chiusaroli, R Maier, A Knight, MC Byrne, M Calvi, LM Baron, R Krane, SM Schipani, E AF Chiusaroli, R Maier, A Knight, MC Byrne, M Calvi, LM Baron, R Krane, SM Schipani, E TI Collagenase cleavage of type I collagen is essential for both basal and parathyroid hormone (PTH)/PTH-related peptide receptor-induced osteoclast activation and has differential effects on discrete bone compartments SO ENDOCRINOLOGY LA English DT Article ID NECROSIS-FACTOR RECEPTOR; PRIMARY HYPERPARATHYROIDISM; OSTEOBLASTIC CELLS; OSTEOPROTEGERIN LIGAND; POSTMENOPAUSAL WOMEN; OVARIECTOMIZED RATS; TRABECULAR BONE; STROMAL CELLS; EXPRESSION; MICE AB Expression of a constitutively active PTH/PTHrP receptor in cells of osteoblast lineage in vivo (CL2+) causes increases in trabecular bone volume and trabecular bone formation and, conversely, a decrease in the periosteal mineral apposition rate. Collagenase-3 (matrix metalloprotease-13) is a downstream target of PTH action. To investigate the relevance of collagenase cleavage of type I collagen for the CL2+ bone phenotype, we bred CL2+ animals with mice carrying a mutated col1alpha1 gene that encodes a protein resistant to digestion by collagenase-3 and other collagenases (rr). Adult tibias and parietal bones from 4-wk-old double-mutant animals (CL2+/rr) and from control littermates were analyzed. Trabecular bone volume was higher in CL2+/rr than in CL2+ mice. This increase occurred despite a modest reduction in bone formation rate, which was, however, still significantly higher that in wild-type littermates, and therefore must reflect decreased bone resorption in rr mice. Osteoclast number was increased in CL2+/rr animals compared with either wild-type or CL2+ mice, suggesting that collagenase-dependent collagen cleavage affected osteoclast function rather than osteoclast number and/or differentiation. Interestingly, the periosteal mineral apposition rate was similar in CL2+/rr and CL2+ animals and was significantly lower than that in wild-type animals. Our study provides evidence that collagenase activity is important for both basal and PTH/PTHrP receptor-dependent osteoclast activation. Furthermore, it indicates that a mild impairment of osteoclast activity is still compatible with increased osteoblast function. Lastly, it supports the hypothesis that collagenases can be a downstream effector of PTH/PTHrP receptor action in trabecular bone, but not in periosteum. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Arthritis Unit, Boston, MA 02114 USA. Yale Univ, New Haven, CT 06520 USA. RP Schipani, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. OI Calvi, Laura Maria/0000-0001-6969-239X FU NIAMS NIH HHS [AR-45354, AR-44855, AR-44815]; NIDDK NIH HHS [K08 DK064381, K08 DK064381-01] NR 53 TC 27 Z9 28 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 SEP 1 PY 2003 VL 144 IS 9 BP 4106 EP 4116 DI 10.1210/en.2003-0254 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 713XN UT WOS:000184883400047 PM 12933685 ER PT J AU Hauser, R Chen, ZY Pothier, L Ryan, L Altshul, L AF Hauser, R Chen, ZY Pothier, L Ryan, L Altshul, L TI The relationship between human semen parameters and environmental exposure to polychlorinated biphenyls and p,p '-DDE SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE DDT; environmental health; polychlorinated biphenyls; reproductive health; semen; sperm ID TOXIC EQUIVALENCY FACTORS; REPRODUCTIVE FUNCTION; SPERM CONCENTRATION; PREDICTIVE VALUE; PCB CONGENERS; FERTILE MEN; HUMAN-SERUM; CORD BLOOD; QUALITY; POPULATION AB Scientific and public concern exists about potential reproductive health effects of persistent chlorinated organic chemicals, such as polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), and dichlorodiphenyidichloroethylene (DDE, the most stable daughter compound of DDT). To explore the hypothesis that environmental exposures to PCBs and DDE are associated with altered semen parameters, we conducted a cross-sectional study of 212 male partners of subfertile couples who presented to the Massachusetts General Hospital Andrology Laboratory. Semen parameters were analyzed as both a continuous measure and dichotomized based on World Health Organization reference values for sperm concentration (< 20 million/mL), motility (< 50% motile), and Kruger strict criteria for morphology (< 4% normal). The comparison group for the dichotomized analysis was men with all three semen parameters above the reference values. In serum, 57 PCB congeners and p,p'-DDE were measured by congener-specific analysis using gas chromatography with electron capture detection. There were dose-response relationships among PCB-138 and sperm motility (odds ratio per tertile, adjusted for age, abstinence, and smoking, and p-value for trend were, respectively, 1.00, 1.68, 2.35, and p-value = 0.03) and morphology (1.00, 1.36, 2.53, p-value = 0.04). There was limited evidence of an inverse relationship between sum of PCBs, as well as those PCBs classified as cytochrome P450 enzyme inducers, with sperm motility and sperm morphology, as well as limited evidence of an inverse association between p,p'-DDE and sperm motility. The lack of a consistent relationship among semen parameters and other individual PCB congeners and groupings of congeners may indicate a difference in spermatotoxicity between congeners. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Androl Lab, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, In Vitro Fertilizat Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Environm Sci & Engn Program, Boston, MA 02115 USA. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Bldg 1,Rm 1405,665 Huntington Ave, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NIEHS NIH HHS [ES 09718, ES 00002] NR 54 TC 113 Z9 116 U1 2 U2 10 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 2003 VL 111 IS 12 BP 1505 EP 1511 DI 10.1289/ehp.6175 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 733HZ UT WOS:000185995500032 PM 12948891 ER PT J AU Keshaviah, AP Weller, E Spiegelman, D AF Keshaviah, AP Weller, E Spiegelman, D TI Occupational exposure to methyl tertiary butyl ether in relation to key health symptom prevalence: the effect of measurement error correction SO ENVIRONMETRICS LA English DT Article DE measurement error; validation study; main study; MTBE; oxygenate ID CONFIDENCE-INTERVALS; HUMAN BLOOD AB In 1995, White et al. reported that methyl tertiary butyl ether (MTBE), an oxygenate added to gasoline, was significantly associated with key health symptoms, including headaches, eye irritation, and burning of the nose and throat, among 44 people occupationally exposed to the compound and for whom serum MTBE measurements were available (odds ratio (OR)=8.9, 95% CI=[1.2, 75.6]). However, these serum MTBE measurements were available for only 29 per cent of the 150 subjects enrolled. Around the same time, Mannino et al. conducted a similar study among individuals occupationally exposed to low levels of MTBE and did not find a significant association between exposure to MTBE and the presence of one or more key health symptoms among the 264 study participants (OR=0.60, 95% CI=[0.3, 1.21]). In this article, we evaluate the effect of MTBE on the prevalence of key health symptoms by applying a regression calibration method to White et al.'s and Mannino et al.'s data. Unlike White et al., who classified exposure using actual MTBE levels among a subset of the participants, and Mannino et al., who classified exposure based on job category among all participants, we use all of the available data to obtain an estimate of the effect of MTBE in units of serum concentration, adjusted for measurement error due to using job category instead of measured exposure. After adjusting for age, gender and smoking status, MTBE exposure was found to be significantly associated with a 50 per cent increase in the prevalence of one or more key health symptoms per order of magnitude increase in blood concentration on the logo scale, using data from the 409 study participants with complete information on the covariates (95% CI = [ 1.00, 2.25]). Simulation results indicated that under conditions similar to those observed in these data, the estimator is unbiased and has a coverage probability close to the nominal value. The methodology illustrated in this article is advantageous because all of the available data were used in the analysis, obtaining a more precise estimate of exposure effect on health outcome, and the estimate is adjusted for measurement error due to using job category instead of measured exposure. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Spiegelman, D (reprint author), Dana Farber Canc Inst, Binney St,Mayer 2nd Floor, Boston, MA 02115 USA. NR 16 TC 3 Z9 3 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1180-4009 J9 ENVIRONMETRICS JI Environmetrics PD SEP PY 2003 VL 14 IS 6 BP 573 EP 582 DI 10.1002/env.604 PG 10 WC Environmental Sciences; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Environmental Sciences & Ecology; Mathematics GA 718AP UT WOS:000185123200002 ER PT J AU Miller, DP Neuberg, D De Vivo, I Wain, JC Lynch, TJ Su, L Christiani, DC AF Miller, DP Neuberg, D De Vivo, I Wain, JC Lynch, TJ Su, L Christiani, DC TI Smoking and the risk of lung cancer - Susceptibility with GSTP1 polymorphisms SO EPIDEMIOLOGY LA English DT Article DE GSTP1; lung cancer; case-control; susceptibility ID GLUTATHIONE-S-TRANSFERASE; AFRICAN-AMERICANS; CIGARETTE-SMOKING; TOBACCO-SMOKE; GSTM1; POPULATION; GENOTYPE; M1; P1; EXPRESSION AB Background: GSTP1 is a gene that helps detoxify foreign substances in the body. Functional polymorphisms of GSTP1 have been studied as risk factors for lung cancer. Past studies have compared the effect of the "at risk" polymorphism in two strata of smoking pack-years (usually defined by the median among controls). We examined the interaction between GSTP1 polymorphisms and cumulative exposure to smoking and their association with lung cancer risk. Methods: Data are from a large hospital-based case-control study of persons treated for primary lung cancer at the Massachusetts General Hospital since 1992. Controls were drawn from friends and nonrelated family members. We genotyped 1,042 cases and 1,161 controls for GSTP1 using polymerase chain reaction-restriction fragment length polymorphism techniques. Findings: The GSTP1 GG genotype approximately doubled the lung cancer risk associated with pack-years. This interaction was stronger among current smokers. At 26 pack-years (median among controls with a smoking history), the adjusted odds ratio for the association between pack-years and lung cancer risk was 13 (95% confidence interval = 6.5-25) among current smokers with the GSTP1 GG genotype compared with 6.1 (95% confidence interval 4.9-7.5) among those with the GSTP1 AA genotype. Conclusions: GSTP1 GG increases the lung cancer risk associated with pack-years of smoking. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Labs, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Dept Surg,Thorac Surg Unit, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Hematol Oncol Unit, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, 665 Huntington Ave,Bldg 1,Room 1402, Boston, MA 02115 USA. FU NCI NIH HHS [CA 74386]; NIEHS NIH HHS [ES/CA 06409, ES00002] NR 26 TC 35 Z9 37 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2003 VL 14 IS 5 BP 545 EP 551 DI 10.1097/01.ede.0000073120.46981.24 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 718EV UT WOS:000185132900008 PM 14501269 ER PT J AU O'Neill, M Veves, A Zanobetti, A Gold, D Economides, PF Horton, E Schwartz, J AF O'Neill, M Veves, A Zanobetti, A Gold, D Economides, PF Horton, E Schwartz, J TI Air pollution and cardiovascular health among subjects with diabetes in greater Boston: A preliminary analysis SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 15th Conference of the International-Society-for-Environment-Epidemiology CY SEP 23-26, 2003 CL PERTH, AUSTRALIA SP Int Soc Environm Epidemiol, CommonWealth Dept Hlth & Aged Care, US EPA C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Beth Israel Deacones Hosp, Boston, MA USA. Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2003 VL 14 IS 5 SU 1 BP S116 EP S117 DI 10.1097/00001648-200309001-00283 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 724LG UT WOS:000185488600284 ER PT J AU Krahl, SE Senanayake, SS Handforth, A AF Krahl, SE Senanayake, SS Handforth, A TI Right-sided vagus nerve stimulation reduces generalized seizure severity in rats as effectively as left-sided SO EPILEPSY RESEARCH LA English DT Article DE VNS; pentylenetetrazole; anticonvulsant; epilepsy; vagus nerve ID C-FIBERS; SUPPRESSION; REFLEX; HEART AB As currently utilized, vagus nerve stimulation (VNS) is applied to the cervical trunk of the left vagus nerve to suppress seizures clinically. Demonstration that VNS can also reduce seizure severity when electrodes are placed on the right cervical vagus nerve in rats would provide empirical evidence that the antiepileptic effects of VNS are not an exclusive property of the left vagus nerve. Rats were implanted with a custom cuff electrode on either the left or right cervical vagus nerve. Two days later, continuous VNS was begun in half the rats with left-sided and half with right-sided electrodes. The remaining rats were connected to the stimulator, but did not receive VNS. After 30 s, pentylenetetrazole (PTZ) was administered systemically and seizures were rated by a blinded observer. The PTZ test was repeated two days later, with VNS administered to the previously unstimulated rats, while the others received no stimulation. VNS significantly reduced the severity of PTZ-induced seizures in rats regardless of the side of stimulation as compared to their no-VNS (control condition) seizure severity. No significant differences in efficacy existed based on the side of stimulation. These results indicate that right-sided VNS in rats is just as effective as left-sided VNS, suggesting that fibers necessary for seizure suppression are not unique to the left vagus nerve. Published by Elsevier B.V. C1 VA Greater Los Angeles Healthcare Syst, Neurol Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Div Neurosurg, Los Angeles, CA 90095 USA. RP Krahl, SE (reprint author), VA Greater Los Angeles Healthcare Syst, Neurol Serv, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 10 TC 22 Z9 24 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD SEP PY 2003 VL 56 IS 1 BP 1 EP 4 DI 10.1016/S0920-1211(03)00122-0 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 732MZ UT WOS:000185951300001 PM 14529948 ER PT J AU Singh, BN AF Singh, BN TI Increased heart rate as a risk factor for cardiovascular disease SO EUROPEAN HEART JOURNAL SUPPLEMENTS LA English DT Article DE agents that exclusively reduce heart rate; beta-blockade; cardiovascular mortality; hypertension; increased heart rate; myocardial infarction; sudden death ID ACUTE MYOCARDIAL-INFARCTION; CORONARY ATHEROSCLEROSIS; VAGAL-STIMULATION; FOLLOW-UP; MORTALITY; AGE; MEN; HYPERTENSION; ISCHEMIA; SEVERITY AB Heart rate is a major determinant of oxygen consumption in patients with ischaemic heart disease. Its pharmacological modulation is increasingly the focus of therapeutic approaches to alleviate symptoms and prolong survival. It is the simplest cardiovascular variable to measure accurately and reproducibly. Many long-term follow-up studies suggest that elevated heart rate increases all-cause mortality, cardiovascular disease and sudden death in patients with known or suspected coronary heart disease, survivors of myocardial infarction and patients with hypertension. These links hold for men and women, and are unrelated to ethnic origin. The effect on sudden death or total mortality increases as a function of heart rate such that an increase in heart rate by more than 40 beats/min doubles total mortality. Conversely, tow heart rate reduces risk for coronary artery disease and sudden death. Primary and secondary prevention studies in myocardial infarction indicated that elevated heart rate in susceptible patients predicts risk for developing myocardial infarction and death. Prophylactic beta-blockers attenuate risks for reinfarction, sudden death and total mortality; these effects correlate with reduced heart rate, thus providing a compelling basis for developing agents that reduce heart rate exclusively as antianginal agents for the therapy of myocardial ischaemia with broader therapeutic implications. (C) 2003 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved. C1 W Los Angeles Vet Affairs Med Ctr, Dept Cardiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Ctr Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Singh, BN (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Cardiol, 1301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 29 TC 12 Z9 17 U1 1 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1520-765X J9 EUR HEART J SUPPL JI Eur. Heart J. Suppl. PD SEP PY 2003 VL 5 IS G BP G3 EP G9 DI 10.1016/S1520-765X(03)90001-0 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 733ZQ UT WOS:000186031100002 ER PT J AU Demetri, GD AF Demetri, GD TI OncoloGIST, BioloGIST, RadioloGIST: the big impact on the field of oncology of a molecularly-targeted therapy designed to treat a rare disease SO EUROPEAN JOURNAL OF CANCER LA English DT Editorial Material ID GASTROINTESTINAL STROMAL TUMORS; TYROSINE KINASE INHIBITOR; C-KIT; IMATINIB MESYLATE; EFFICACY; PATIENT; STI571; CANCER; SAFETY C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Demetri, GD (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 12 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2003 VL 39 IS 14 BP 1976 EP 1977 DI 10.1016/S0959-8049(03)00555-0 PG 2 WC Oncology SC Oncology GA 724WV UT WOS:000185510400011 PM 12957451 ER PT J AU Biederman, J Faraone, S Spencer, T Michelson, D Jones, D Adler, L AF Biederman, J Faraone, S Spencer, T Michelson, D Jones, D Adler, L TI Effects of atomoxetine treatment on executive functioning in adults with attention-deficit/hyperactivity disorder (ADHD) SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 16th Congress of the European-College-of-Neuropsychopharmacology CY SEP 20-24, 2003 CL PRAGUE, CZECH REPUBLIC SP European Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Eli Lilly & Co, Lilly Res Lab, Indianapolis, IN 46285 USA. New York Univ, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2003 VL 13 SU 4 BP S458 EP S458 DI 10.1016/S0924-977X(03)92373-X PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 723BJ UT WOS:000185412300779 ER PT J AU Biederman, J AF Biederman, J TI Treatment of attention-deficit/hyperactivity disorder with the once-daily OROS formulation of methylphenidate: Effect on growth in children SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 16th Congress of the European-College-of-Neuropsychopharmacology CY SEP 20-24, 2003 CL PRAGUE, CZECH REPUBLIC SP European Coll Neuropsychopharmacol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Res Unit, Boston, MA 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 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2003 VL 13 SU 4 BP S448 EP S449 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 723BJ UT WOS:000185412300758 ER PT J AU Biederman, J AF Biederman, J TI Evaluation of once-daily OROS methylphenidate in children with attention-deficit/hyperactivity disorder: Effects on sleep, appetite, and tics SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 16th Congress of the European-College-of-Neuropsychopharmacology CY SEP 20-24, 2003 CL PRAGUE, CZECH REPUBLIC SP European Coll Neuropsychopharmacol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Res Unit, Boston, MA 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 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2003 VL 13 SU 4 BP S447 EP S448 DI 10.1016/S0924-977X(03)92350-9 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 723BJ UT WOS:000185412300756 ER PT J AU Biederman, J AF Biederman, J TI Open-label study of risperidone in children with bipolar disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 16th Congress of the European-College-of-Neuropsychopharmacology CY SEP 20-24, 2003 CL PRAGUE, CZECH REPUBLIC SP European Coll Neuropsychopharmacol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2003 VL 13 SU 4 BP S314 EP S314 DI 10.1016/S0924-977X(03)92032-3 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 723BJ UT WOS:000185412300438 ER PT J AU Fava, M Burt, T Batzar, E Sackeim, H AF Fava, M Burt, T Batzar, E Sackeim, H TI Conditional probability of remission at 8 weeks given early global improvement in major depressive disorder (MDD) SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 16th Congress of the European-College-of-Neuropsychopharmacology CY SEP 20-24, 2003 CL PRAGUE, CZECH REPUBLIC SP European Coll Neuropsychopharmacol ID FLUOXETINE C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Pfizer Inc, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RI Burt, Tal/O-1951-2013 OI Burt, Tal/0000-0002-5853-6110 NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2003 VL 13 SU 4 BP S214 EP S214 DI 10.1016/S0924-977X(03)91805-0 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 723BJ UT WOS:000185412300211 ER PT J AU Fava, M Alpert, J Kremer, C AF Fava, M Alpert, J Kremer, C TI Gepirone extended release (ER) in patients with anxious depression SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 16th Congress of the European-College-of-Neuropsychopharmacology CY SEP 20-24, 2003 CL PRAGUE, CZECH REPUBLIC SP European Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Depression Clin & Res Prog, Boston, MA 02114 USA. Organon USA Inc, Roseland, NJ USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2003 VL 13 SU 4 BP S187 EP S188 DI 10.1016/S0924-977X(03)91742-1 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 723BJ UT WOS:000185412300148 ER PT J AU Hackett, D Stein, MB Mangano, R Pollack, M AF Hackett, D Stein, MB Mangano, R Pollack, M TI Long-term treatment of generalized social anxiety disorder with venlafaxine XR SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 16th Congress of the European-College-of-Neuropsychopharmacology CY SEP 20-24, 2003 CL PRAGUE, CZECH REPUBLIC SP European Coll Neuropsychopharmacol C1 Wyeth Res, Clin Res & Dev, Paris, France. Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. Wyeth Res, Collegeville, PA USA. Massachusetts Gen Hosp, Anxiety Disorders Program, 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 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2003 VL 13 SU 4 BP S380 EP S381 DI 10.1016/S0924-977X(03)92183-3 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 723BJ UT WOS:000185412300589 ER PT J AU Lepola, U Pollack, M Emilien, G Tzanis, E Whitaker, T AF Lepola, U Pollack, M Emilien, G Tzanis, E Whitaker, T TI Venlafaxine XR and paroxetine in the short-term treatment of panic disorder. SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 16th Congress of the European-College-of-Neuropsychopharmacology CY SEP 20-24, 2003 CL PRAGUE, CZECH REPUBLIC SP European Coll Neuropsychopharmacol C1 Kuopion Psykiatripalvelu Oy, Kuopio, Finland. Massachusetts Gen Hosp, Anxiety Disorders Program, Boston, MA 02114 USA. Wyeth Res, Clin Res & Dev, Paris, France. Wyeth Res, Collegeville, PA USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2003 VL 13 SU 4 BP S378 EP S378 DI 10.1016/S0924-977X(03)92178-X PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 723BJ UT WOS:000185412300584 ER PT J AU Michelson, D Spencer, T Ruff, D Feldman, PD AF Michelson, D Spencer, T Ruff, D Feldman, PD TI Long-term effects of atomoxetine on growth in children with ADHD SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 16th Congress of the European-College-of-Neuropsychopharmacology CY SEP 20-24, 2003 CL PRAGUE, CZECH REPUBLIC SP European Coll Neuropsychopharmacol C1 Eli Lilly & Co, Lilly Res Lab, Indianapolis, IN 46285 USA. Massachusetts Gen Hosp, 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 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2003 VL 13 SU 4 BP S458 EP S459 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 723BJ UT WOS:000185412300781 ER PT J AU Michelson, D Adler, L Spencer, T Milton, D Jones, D AF Michelson, D Adler, L Spencer, T Milton, D Jones, D TI Long-term treatment effects of atomoxetine in adults with attention-deficit/hyperactivity disorder (ADHD) SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 16th Congress of the European-College-of-Neuropsychopharmacology CY SEP 20-24, 2003 CL PRAGUE, CZECH REPUBLIC SP European Coll Neuropsychopharmacol C1 Eli Lilly & Co, Lilly Res Lab, Indianapolis, IN 46285 USA. NYU, Sch Med, Dept Psychiat & Neurol, New York, NY USA. Massachusetts Gen Hosp, 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 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2003 VL 13 SU 4 BP S458 EP S458 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 723BJ UT WOS:000185412300780 ER PT J AU Michelson, D Buitelaar, J Danckaerts, M Gillberg, C Spencer, TJ Zuddas, A Zhang, S Biederman, J AF Michelson, D Buitelaar, J 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 NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 16th Congress of the European-College-of-Neuropsychopharmacology CY SEP 20-24, 2003 CL PRAGUE, CZECH REPUBLIC SP European Coll Neuropsychopharmacol C1 Eli Lilly & Co, Lilly Res Lab, Indianapolis, IN 46285 USA. Univ Med Ctr St Radboud, Nijmegen, Netherlands. KU, Dept Child & Adolescent Psychiat, Louvain, Belgium. Univ Gothenburg, Gothenburg, Sweden. Massachusetts Gen Hosp, Boston, MA 02114 USA. Clin Neuropsichiatria Infantile, Dept Neurosci, Cagliari, Italy. RI Buitelaar, Jan/E-4584-2012 OI Buitelaar, Jan/0000-0001-8288-7757 NR 1 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2003 VL 13 SU 4 BP S455 EP S456 DI 10.1016/S0924-977X(03)92368-6 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 723BJ UT WOS:000185412300774 ER PT J AU Parikh, RM Sonawalla, SB Chakraborthy, N Mehra, G Dracass, S Fava, M AF Parikh, RM Sonawalla, SB Chakraborthy, N Mehra, G Dracass, S Fava, M TI Gender differences in depressive symptoms among college students in Bombay SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 16th Congress of the European-College-of-Neuropsychopharmacology CY SEP 20-24, 2003 CL PRAGUE, CZECH REPUBLIC SP European Coll Neuropsychopharmacol C1 Jaslok Hosp & Res Ctr, Bombay, Maharashtra, India. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Deppress Clin & Res Prog, Boston, MA USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2003 VL 13 SU 4 BP S277 EP S278 DI 10.1016/S0924-977X(03)91952-3 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 723BJ UT WOS:000185412300358 ER PT J AU Sonawalla, SB Mahal, Y Masson, E Yeung, A Petersen, T Mischoulon, D Fava, M AF Sonawalla, SB Mahal, Y Masson, E Yeung, A Petersen, T Mischoulon, D Fava, M TI Symptom questionnaire assessment of depressive symptoms among college students SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 16th Congress of the European-College-of-Neuropsychopharmacology CY SEP 20-24, 2003 CL PRAGUE, CZECH REPUBLIC SP European Coll Neuropsychopharmacol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2003 VL 13 SU 4 BP S277 EP S277 DI 10.1016/S0924-977X(03)91951-1 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 723BJ UT WOS:000185412300357 ER PT J AU Wunderbaldinger, P Turetschek, K Bremer, C AF Wunderbaldinger, P Turetschek, K Bremer, C TI Near-infrared fluorescence imaging of lymph nodes using a new enzyme sensing activatable macromolecular optical probe SO EUROPEAN RADIOLOGY LA English DT Article DE lymphatic system; contrast media; experimental studies; optical imaging; near-infrared fluorescence imaging ID SUPERPARAMAGNETIC IRON-OXIDE; IN-VIVO CHARACTERIZATION; CONTRAST AGENTS; BREAST-CANCER; MR LYMPHOGRAPHY; CATHEPSIN-B; TUMORS; NANOPARTICLES; SPECTROSCOPY; TOMOGRAPHY AB The aim of this study was to validate the use of near infrared fluorescence imaging (NIRF) using enzyme-sensitive optical probes for lymph node detection. An optical contrast probe that is activated by cystein proteases, such as cathepsin B, was used to visualize lymph nodes by NIRF reflectance imaging. In order to quantitate the uptake of the optical probe in lymphatic tissue, the biodistribution was assessed using the Indium-111 labeled optical probe. Sixteen Balb-c mice were injected either intravenously (i.v.) or subcutaneously (s.c.) with the NIRF-probe (2 mumol cyanine (Cy)/animal; i.v., n=10; s.c., n=6) and imaged 24 h after injection. Signal intensities and target-to-background ratios of various lymph nodes were measured by manual regions of interest (ROIs). Additional signal intensity measurements were performed of excised lymph nodes (n=21) from i.v. injected mice (24 h after injection) and compared with excised lymph nodes (n=8) of noninjected mice. The probe employed in this study was lymphotropic with approximately 3-4% accumulation in lymph nodes (3.4 +/- 0.8% ID/g). Measurements of the excised lymph nodes (after i.v. injection) confirmed a significant increase in lymph node fluorescence signal from baseline 26 +/- 7.6 arbitary units (AU) to 146 +/- 10.9 AU (p<0.0001). A significant increase in lymph node fluorescence signal was also seen in vivo throughout the body after i.v. injection (96 +/- 7.8 AU) and/or regionally after s.c. injection (141 +/- 11.5 AU) in comparison with baseline autofluorescence (26 7.6 AU). Target-to-background ratio was significantly higher after s.c. injection (6.6% +/- 0.81) compared with i.v. injection (4.8 +/- 0.67%). Detection and visualization of lymph nodes is feasible by NIRF imaging using a cystein-protease sensitive optical probe. C1 Univ Vienna, Dept Radiol, A-1090 Vienna, Austria. Univ Munster, Dept Clin Radiol, Munster, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. RP Wunderbaldinger, P (reprint author), Univ Vienna, Dept Radiol, Waehringer Guertel 18-20, A-1090 Vienna, Austria. NR 39 TC 28 Z9 29 U1 0 U2 5 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD SEP PY 2003 VL 13 IS 9 BP 2206 EP 2211 DI 10.1007/s00330-003-1932-6 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 725HG UT WOS:000185537700021 PM 12802615 ER PT J AU Le Guern, AC Giovino, MA Abe, M Theodore, PR Qi, J Down, JD Sachs, DH Sykes, M Yang, YG AF Le Guern, AC Giovino, MA Abe, M Theodore, PR Qi, J Down, JD Sachs, DH Sykes, M Yang, YG TI Stem cell activity of porcine c-kit(+) hematopoietic cells SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID BONE-MARROW CELLS; LEUKOCYTE DIFFERENTIATION ANTIGENS; C-KIT; MONOCLONAL-ANTIBODIES; XENOGENEIC BARRIER; XENOGRAFT REJECTION; TOLERANCE INDUCTION; MIXED CHIMERISM; IN-VIVO; T-CELLS AB Objective. A marker for hematopoietic stem cells (HSCs) of pigs, which are considered to be the most suitable donors for clinical xenotransplantation, has not yet been identified. In this study, we examined the HSC activity of porcine c-kit(+) bone marrow cells (BMCs). Methods. The HSC activity of porcine c-kit(+) BMCs was evaluated both in vitro using colony-forming unit (CFU) and cobblestone area-forming cell (CAFC) assays and in vivo in nonobese diabetic/severe- combined immunodeficiency transgenic (NOD/SCID-Tg) mice carrying porcine cytokine transgenes. Results. Purified c-kit(+) BMCs were substantially enriched for both CFUs and CAFCs in vitro and their transplantation led to long-term porcine hematopoiesis in vivo in mice. Although porcine chimerism was detectable in the peripheral blood of NOD/SCID-Tg mice receiving porcine c-kit(-) BMCs at early time points after transplantation, the levels were markedly lower than those in mice receiving purified c-kit(+) BMCs (0.2% +/- 0.14% vs 7.7% +/- 1.6% and 0.17% +/- 0.17% vs 5.6% +/- 2.1% at weeks 3 and 6, respectively). Importantly, all mouse recipients of porcine c-kit(+) BMCs showed durable multilineage chimerism (>19 weeks), whereas no recipients of porcine c-kit- BMCs sustained long-term engraftment. Moreover, porcine HSCs that had engrafted for 19 weeks in the recipients of porcine c-kit+ BMCs gave rise to clonogenic progenitors in vitro and reconstituted porcine hematopoiesis in secondary recipients. Conclusion. The present study demonstrates that c-kit is an essential marker of both long-term-repopulating HSCs and progenitor cells with early engraftment capacity. (C) 2003 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr,Surg Serv, Boston, MA 02129 USA. BioTransplant Inc, Charlestown, MA USA. Immerge Bio Therapeut Inc, Charlestown, MA USA. RP Yang, YG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr,Surg Serv, MGH E Bldg 149-5102,13th St, Boston, MA 02129 USA. EM yongguang.yang@tbrc.mgh.harvard.edu FU NHLBI NIH HHS [P01 HL18646, R01 HL54038] NR 48 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2003 VL 31 IS 9 BP 833 EP 840 DI 10.1016/S0301-472X(03)00197-8 PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 814HA UT WOS:000220964600012 PM 12962730 ER PT J AU Kim, MH Roh, JK Yoon, BW Kang, L Kim, YJ Aronin, N DiFiglia, M AF Kim, MH Roh, JK Yoon, BW Kang, L Kim, YJ Aronin, N DiFiglia, M TI Huntingtin is degraded to small fragments by calpain after ischemic injury SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Huntington's disease; N-terminal huntingtin; huntingtin proteolysis; calpain; ischemia; neurodegeneration ID FOCAL CEREBRAL-ISCHEMIA; NEURONAL INTRANUCLEAR INCLUSIONS; PRIMARY CORTICAL-NEURONS; MUTANT HUNTINGTIN; CELL-DEATH; EXCITOTOXIC INJURY; CASPASE CLEAVAGE; NMDA RECEPTOR; GERBIL BRAIN; RAT-BRAIN AB The gene defect in Huntington's disease (HD) causes a polyglutamine expansion in the N-terminal region of huntingtin (N-htt). In vitro studies suggest that mutant N-htt fragments can aggregate and cause cell death in HD. The physiological and pathological conditions that affect htt proteolysis in the brain are unclear. We examined htt expression by Western blot in the rat brain after transient ischemic injury, which causes striatal neurodegeneration similar to that seen in HD and activates proteases including calcium-dependent calpains. Focal brain ischemia reduced levels of full-length htt in the infarcted cortex and striatum and increased expression of a 55-kDa N-htt fragment that was also produced by treating control brain extracts with calpain. N-htt fragments between 65 and 80 kDa also rose after injury, but these fragments were not as long-lived as the 55-kDa N-htt fragment. The results suggest that after ischemic injury full-length htt is degraded in degenerating neurons and an N-htt fragment accumulates. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Cellular Neurobiol, Charlestown, MA 02129 USA. Seoul Natl Univ, Clin Res Inst, Dept Neurol, Seoul, South Korea. Univ Massachusetts, Med Ctr, Dept Med & Cell Biol, Worcester, MA 01655 USA. RP DiFiglia, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Cellular Neurobiol, 114 16th St, Charlestown, MA 02129 USA. RI Kim, Manho/J-2738-2012; Roh, Jae Kyu/J-5459-2012; Yoon, Byung Woo/J-5557-2012; Kim, Yun Joong/E-7117-2015 OI Kim, Yun Joong/0000-0002-2956-1552 FU NINDS NIH HHS [NS 38194, NS16367, NS35711] NR 49 TC 27 Z9 27 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD SEP PY 2003 VL 183 IS 1 BP 109 EP 115 DI 10.1016/S0014-4886(03)00132-8 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 718VG UT WOS:000185166700014 PM 12957494 ER PT J AU Gardner, B Zhu, LX Sharma, S Tashkin, DP Dubinett, SM AF Gardner, B Zhu, LX Sharma, S Tashkin, DP Dubinett, SM TI Methanandamide increases COX-2 expression and tumor growth in murine lung cancer SO FASEB JOURNAL LA English DT Article DE cannabinoid; PGE(2); MAPK ID MESSENGER-RNA EXPRESSION; CYCLOOXYGENASE-2 EXPRESSION; CANNABINOID RECEPTOR; ENDOGENOUS CANNABINOIDS; IN-VIVO; PROGNOSTIC-SIGNIFICANCE; SIGNALING PATHWAYS; ANTITUMOR IMMUNITY; EPITHELIAL-CELLS; GASTRIC-CANCER AB Increased COX-2 expression and elevated PGE(2) have been associated with a poor prognosis in lung cancer. Cannabinoids have been known to exert some of their biological effects via modulation of prostaglandin production. We evaluated the impact of methanandamide on COX-2 expression, PGE(2) production, and tumor growth in murine lung cancer. Methanandamide administration (5 mg/kg, four times/wk i.p.) resulted in an increased rate of tumor growth (P<0.01 compared with diluent treated controls). The CB1 and CB2 receptor antagonists, SR141716 and SR144528, did not block the methanandamide-mediated increase in tumor growth. In vivo, methanandamide treatment increased the production of PGE(2) at the tumor site as well as in splenocytes. Consistent with these results, methanandamide increased PGE(2) and COX-2 levels in murine lung cancer cells in vitro via a cannabinoid receptor-independent mechanism. The COX-2-specific inhibitor, SC58236, abrogated methanandamide induction of PGE2 production in vitro and blocked methanandamide-enhanced tumor growth in vivo. Furthermore, the p38/MAPK inhibitor, SB203528, and the p42/44 inhibitor, PD98059, blocked methanandamide-mediated induction of PGE(2) and COX-2. These results suggest that methanandamide augments tumor growth by a cannabinoid receptor-independent pathway that is associated with the up-regulation of COX-2. C1 Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Lung Canc Res Program,Ctr Hlth Sci 37 131, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Lung Canc Res Program,Ctr Hlth Sci 37 131, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM sdubinett@mednet.ucla.edu NR 56 TC 28 Z9 30 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD SEP PY 2003 VL 17 IS 12 BP 2157 EP + DI 10.1096/fj.03-0254fje PG 18 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 732DG UT WOS:000185925100017 PM 12958151 ER PT J AU Eroglu, A Elliott, G Bhowmick, P Wright, D Toner, M Toth, TL AF Eroglu, A Elliott, G Bhowmick, P Wright, D Toner, M Toth, TL TI Developing mouse embryos progressively eliminate microinjected trehalose. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 11-15, 2003 CL SAN ANTONIO, TEXAS SP Amer Soc Reprod Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2003 VL 80 SU 3 MA O169 BP S64 EP S64 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 727RM UT WOS:000185672400170 ER PT J AU Gonzalez, RR Rueda, BR Ramos, MP Littell, RD Glasser, SR Leavis, PC AF Gonzalez, RR Rueda, BR Ramos, MP Littell, RD Glasser, SR Leavis, PC TI Leptin regulates the expression of leukemia inhibitory factor by human endometrial cells. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 11-15, 2003 CL SAN ANTONIO, TEXAS SP Amer Soc Reprod Med C1 Boston Biomed Res Inst, Watertown, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Tufts Univ, Sch Med, Dept Physiol, Watertown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2003 VL 80 SU 3 MA O25 BP S10 EP S10 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 727RM UT WOS:000185672400026 ER PT J AU Iwasaki, W Kawachiya, S Nakagawa, K Takahashi, Y Kaneko, T Saito, H AF Iwasaki, W Kawachiya, S Nakagawa, K Takahashi, Y Kaneko, T Saito, H TI Different expressions of mitogen-activated protein kinase (MAPK) family between cumulus and mural granulosa cells. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 11-15, 2003 CL SAN ANTONIO, TEXAS SP Amer Soc Reprod Med C1 Natl Ctr Child Hlth & Dept, Tokyo, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2003 VL 80 SU 3 MA P493 BP S284 EP S284 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 727RM UT WOS:000185672400794 ER PT J AU Kuohung, W Laufer, MR Marcus, KJ Cheng, DM Diller, LR AF Kuohung, W Laufer, MR Marcus, KJ Cheng, DM Diller, LR TI Ovarian function in pediatric brain cancer survivors after laparoscopic oophoropexy. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 11-15, 2003 CL SAN ANTONIO, TEXAS SP Amer Soc Reprod Med C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2003 VL 80 SU 3 MA O235 BP S90 EP S90 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 727RM UT WOS:000185672400236 ER PT J AU Fauza, DO Kohane, DS Beeuwkes, EB Clayton, N Maher, TJ AF Fauza, DO Kohane, DS Beeuwkes, EB Clayton, N Maher, TJ TI Local anesthetics inhibit uterine activity in vitro - Possible application on preterm labor prevention and treatment SO FETAL DIAGNOSIS AND THERAPY LA English DT Article DE labor; premature labor; fetal surgery; uterus; myometrium; local anesthetic ID EPIDURAL ANALGESIA; FETAL SURGERY; NULLIPAROUS LABOR; CESAREAN-SECTION; NERVE BLOCKADE; MICROSPHERES; BUPIVACAINE; DYSTOCIA AB Objective: Analysis of the effects of local anesthetics upon the gravid uterus. Methods: Isolated strips of pregnant-rat myometrium were placed within tissue baths. Muscular activity was then recorded by a force transducer, at cumulative concentrations of either procaine, lidocaine, or ropivacaine. Results: The effects of myometrial activity were non-monotonic. At lower concentrations, an increase in contraction frequency was noted, concomitant with a depression in amplitude. As the concentrations increased, both amplitude and frequency were depressed until, eventually, activity was abolished. Conclusions: Local anesthetics administered in situ consistently inhibit or completely arrest overall myometrial activity. These agents may prove clinically useful in pre-term labor management, if administered locally to the myometrium via suitable slow release drug delivery systems, warranting further trials in vivo. Copyright (C) 2003 S. Karger AG, Basel. C1 Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Ctr Minimally Invas Surg, Boston, MA USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, Boston, MA USA. RP Fauza, DO (reprint author), Childrens Hosp, Dept Surg, 300 Longwood Ave,Fegan 3, Boston, MA 02115 USA. NR 25 TC 7 Z9 7 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-3837 J9 FETAL DIAGN THER JI Fetal Diagn. Ther. PD SEP-OCT PY 2003 VL 18 IS 5 BP 292 EP 296 DI 10.1159/000071968 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 714FV UT WOS:000184902400002 PM 12913336 ER PT J AU Smith, DG Assal, M Reiber, GE Vath, C LeMaster, J Wallace, C AF Smith, DG Assal, M Reiber, GE Vath, C LeMaster, J Wallace, C TI Minor environmental trauma and lower extremity amputation in high-risk patients with diabetes: Incidence, pivotal events, etiology, and amputation level in a prospectively followed cohort SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE diabetes mellitus; amputation; foot injuries; shoes ID PREVENTION; MEDICARE AB This study determined the incidence, pivotal events, etiology, and levels of amputation in a prospectively followed cohort of 400 people with diabetes and a prior healed foot ulcer who participated in a randomized footwear trial. Participants were seen every 17 weeks for 2 years. Subjects with foot lesions were referred to their healthcare provider for treatment. In this cohort, 11 participants required lower limb amputation (rate 13.8 per 1000 person-years). Pivotal event analysis revealed that only one amputation was related to footwear, six amputations were due to non-footwear-related minor environmental trauma, two were due to progression of vascular disease (dry gangrene from critical ischemia), one was due to a self-care injury while cutting the toenails, and one was due to a decubitus ulcer. Previously proposed strategies to reduce the amputation rates in individuals with diabetes have focused heavily on footwear and education. However, even with this emphasis, amputation rates in the United States are still high. This study suggests that the prevention of minor environmental trauma, including household accidents, merits additional attention. We believe that further efforts to reduce amputation rates for individuals with diabetes will need to emphasize the prevention of minor trauma, especially in those already compromised with neuropathy and vascular disease. C1 Univ Washington, Harborview Med Ctr, Dept Orthopaed, Seattle, WA 98104 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98104 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98104 USA. Univ Washington, Dept Family Med, Seattle, WA 98104 USA. Dept Vet Affairs, VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Smith, DG (reprint author), Univ Washington, Harborview Med Ctr, Dept Orthopaed, 325 9Th Ave, Seattle, WA 98104 USA. NR 12 TC 7 Z9 7 U1 0 U2 0 PU AMER ORTHOPAEDIC FOOT & ANKLE SOC, INC PI SEATTLE PA 2517 EASTLAKE AVE EAST, STE 200, SEATTLE, WA 98102 USA SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD SEP PY 2003 VL 24 IS 9 BP 690 EP 695 PG 6 WC Orthopedics SC Orthopedics GA 721GB UT WOS:000185307700006 PM 14524519 ER PT J AU Lopes-Virella, MF Virella, G AF Lopes-Virella, MF Virella, G TI The role of immune and inflammatory processes in the development of macrovascular disease in diabetes SO FRONTIERS IN BIOSCIENCE LA English DT Review DE diabetes; macrovascular disease; inflammation; autoimmunity; atherosclerosis; modified LDL antibodies; LDL autoantibodies; LDL immune complexes; autoimmunity; atherosclerosis; review ID LOW-DENSITY-LIPOPROTEIN; C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; HUMAN ATHEROSCLEROTIC PLAQUES; HUMAN-ENDOTHELIAL-CELLS; SMOOTH-MUSCLE-CELLS; ACUTE MYOCARDIAL-INFARCTION; MONOCYTE-DERIVED MACROPHAGES; HUMAN VASCULAR ENDOTHELIUM; COLONY-STIMULATING FACTOR AB Diabetes is associated with a high incidence of cardiovascular disease, which is the major cause of morbidity and mortality in this disease. There is considerable interest in defining factors responsible for the accelerated development of atherosclerosis in diabetes. There is no evidence to suggest that the inflammatory process in diabetic patients is different from those in nondiabetic individuals. The main difference may lie on factors able to trigger the inflammatory process. Diabetes is a major predisposing factor for the generation of modified proteins though advanced glycation and oxidation, two intimately interrelated processes. Advanced glycation end-products modified low density lipoprotein (AGE-LDL) and other AGE-modified proteins as well as oxidized LDL (oxLDL) are able to interact with a variety of cells and induce cell dysfunction and the release of pro-inflammatory mediators. But AGE-LDL and oxLDL are also immunogenic. Activated T lymphocytes reacting with peptides derived from oxidized LDL have been detected in atheromatous lesions. Their pro-inflammatory potential is directly linked to the release of interferon-gamma and other cytokines able to activate macrophages, smooth muscle cells, and endothelial cells. On the other hand, antibodies to oxidized and AGE-modified LDL have been isolated from diabetic patients and shown to belong predominantly to the IgG isotype, subclasses 1 and 3, which have well-defined proinflammatory properties. These autoantibodies to modified lipoproteins have sufficient affinity to form stable antigen-antibody complexes, which have been also shown to have pro-atheromatous and pro-inflammatory properties. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Dept Vet Affairs, Charleston, SC 29403 USA. RP Lopes-Virella, MF (reprint author), Ralph H Johnson VA Med Ctr, Strom Thurmond Res Bldg,114 Doughty St,Room 529, Charleston, SC 29425 USA. NR 245 TC 32 Z9 34 U1 0 U2 2 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP PY 2003 VL 8 BP S750 EP S768 DI 10.2741/1141 PG 19 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 719VX UT WOS:000185226700022 PM 12957881 ER PT J AU McGinty, D Szymusiak, R AF McGinty, D Szymusiak, R TI Hypothalamic regulation of sleep and arousal SO FRONTIERS IN BIOSCIENCE LA English DT Review DE sleep; arousal; hypothalamus; preoptic area; median preoptic nucleus; thermoregulation; monoamines; gaba; galanin; hypocretin; orexin; review ID MEDIAN PREOPTIC NUCLEUS; EYE-MOVEMENT SLEEP; WAKING DISCHARGE PATTERNS; POSTERIOR LATERAL HYPOTHALAMUS; DORSAL RAPHE NUCLEUS; C-FOS PROTEIN; BASAL FOREBRAIN; LOCUS-COERULEUS; AMBIENT-TEMPERATURES; RETICULAR-FORMATION AB The hypnogenic function of the rostral hypothalamic region, particularly the preoptic area (POA) was established previously on the basis of lesion, neuronal unit recording, and neurochemical and thermal stimulation studies. Recent studies have mapped the locations of putative sleep-promoting neurons in the POA using c-Fos immunostaining techniques and confirmed these findings with electrophysiological methods. Segregated groups of sleep-active neurons have been localized in the ventrolateral POA (vlPOA) and median preoptic nucleus (MnPN). MnPN and vlPOA sleep-active neurons express the inhibitory transmitter, GABA. In vlPOA neurons, GABA is co-localized with a second inhibitory transmitter, galanin. Descending projections from these sites terminate in putative arousal-promoting cell groups, including histaminergic, serotonergic, orexinergic, noradrenergic, and cholinergic neurons. These findings suggest the hypothesis that non-REM sleep occurs as a consequence of GABAergic and galaninergic inhibition of arousal-promoting neurons resulting from activation of vlPOA and MnPN sleep-promoting neurons. In support of this hypothesis, it was shown that putative sleep-promoting and arousal-promoting neurons exhibit reciprocal changes in discharge across the sleep-wake cycle and that GABA release in wake-promoting sites increases during nonREM sleep. In addition, some POA sleep-active neurons are warm-sensitive. Local POA warming inhibits discharge of multiple arousal-promoting neuronal groups. POA warming, unit recording, and lesion studies also show that POA regulates the amount of delta EEG activity within nonREM sleep, and index of the depth of sleep. Finally, there is evidence that arousal systems inhibit vlPOA and MnPN neurons and the POA hypnogenic mechanism. Mutually-inhibitory interactions between sleep-promoting and arousal-promoting systems are hypothesized to form a functional sleep-wake switch. C1 VA Greater Los Angeles Healthcare Syst, Neurophysiol Res 151A3, Res Serv, North Hills, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. RP McGinty, D (reprint author), VA Greater Los Angeles Healthcare Syst, Neurophysiol Res 151A3, Res Serv, 16111 Plummer St, North Hills, CA 91343 USA. FU NHLBI NIH HHS [HL60296]; NIMH NIH HHS [MH47480, MH63323] NR 105 TC 29 Z9 30 U1 1 U2 9 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP PY 2003 VL 8 BP S1074 EP S1083 DI 10.2741/1159 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 719VX UT WOS:000185226700048 PM 12957869 ER PT J AU Johnson, CD Toledano, AY Herman, BA Dachman, AH McFarland, EG Barish, MA Brink, JA Ernst, RD Fletcher, JG Halvorsen, RA Hara, AK Hopper, KD Koehler, RE Lu, DSK Macari, M MacCarty, RL Miller, FH Morrin, M Paulson, EK Yee, J Zalis, M AF Johnson, CD Toledano, AY Herman, BA Dachman, AH McFarland, EG Barish, MA Brink, JA Ernst, RD Fletcher, JG Halvorsen, RA Hara, AK Hopper, KD Koehler, RE Lu, DSK Macari, M MacCarty, RL Miller, FH Morrin, M Paulson, EK Yee, J Zalis, M CA Amer Coll Radiology Imaging Networ TI Computerized tomographic colonography: Performance evaluation in a retrospective multicenter setting SO GASTROENTEROLOGY LA English DT Article ID CONTRAST BARIUM ENEMA; COLORECTAL-CANCER; CT COLONOGRAPHY; FLEXIBLE SIGMOIDOSCOPY; VIRTUAL COLONOSCOPY; CONVENTIONAL COLONOSCOPY; SCREENING SIGMOIDOSCOPY; HIGH-RISK; POLYPS; NEOPLASIA AB Background & Aims: No multicenter study has been reported evaluating the performance and interobserver variability of computerized tomographic colonography. The aim of this study was to assess the accuracy of computerized tomographic colonography for detecting clinically important colorectal neoplasia (polyps greater than or equal to10 mm in diameter) in a multi-institutional study. Methods: A retrospective study was developed from 341 patients who had computerized tomographic colonography and colonoscopy among 8 medical centers. Colonoscopy and pathology reports provided the standard. A random sample of 117 patients, stratified by criterion standard, was requested. Ninety-three patients were included (47% with polyps greater than or equal to10 mm; mean age, 62 years; 56% men; 84% white; 40% reported colorectal symptoms; 74% at increased risk for colorectal cancer). Eighteen radiologists blinded to the criterion standard interpreted computerized tomography colonography examinations, each using 2 of 3 different software display platforms. Results: The average area under the receiver operating characteristic curve for identifying patients with at least 1 lesion greater than or equal to10 mm was 0.80 (95% lower confidence bound, 0.74). The average sensitivity and specificity were 75% (95% lower confidence bound, 68%) and 73% (95% lower confidence bound, 66%), respectively. Per-polyp sensitivity was 75%. A trend was observed for better performance with more observer experience. There was no difference in performance across software display platforms. Conclusions: Computerized tomographic colonography performance compared favorably with reported performance of fecal occult blood testing, flexible sigmoidoscopy, and barium enema. A prospective study evaluating the performance of computerized tomography polonography in a screening population is indicated. C1 Mayo Clin, Dept Radiol, Rochester, MN 55905 USA. Brown Univ, Providence, RI 02912 USA. Univ Chicago, Chicago, IL 60637 USA. Edward Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. Boston Med Ctr, Boston, MA USA. Yale New Haven Med Ctr, New Haven, CT 06504 USA. Emory Univ, Atlanta, GA 30322 USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. Milton S Hershey Med Ctr, Hershey, PA USA. Univ Alabama, Birmingham, AL USA. Univ Calif Los Angeles, Los Angeles, CA USA. NYU, New York, NY USA. Northwestern Univ, Evanston, IL USA. Beth Israel Hosp, Boston, MA USA. Duke Univ, Durham, NC USA. Vet Adm Med Ctr, San Francisco, CA 94121 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Johnson, CD (reprint author), Mayo Clin, Dept Radiol, 200 1st St SW, Rochester, MN 55905 USA. RI Morrin, Maureen/F-2010-2011 FU NCI NIH HHS [CA80098, CA79778] NR 50 TC 83 Z9 83 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2003 VL 125 IS 3 BP 688 EP 695 DI 10.1016/S0016-5085(03)01058-8 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 718XT UT WOS:000185172300010 PM 12949715 ER PT J AU Bakowska, JC Di Maria, MV Camp, SM Wang, Y Allen, PD Breakefield, XO AF Bakowska, JC Di Maria, MV Camp, SM Wang, Y Allen, PD Breakefield, XO TI Targeted transgene integration into transgenic mouse fibroblasts carrying the full-length human AAVS1 locus mediated by HSV/AAV rep(+) hybrid amplicon vector SO GENE THERAPY LA English DT Article DE AAV; AAVS1; transgenic mice; amplicon ID SITE-SPECIFIC INTEGRATION; ADENOASSOCIATED VIRUS AAV; TERMINAL REPEAT; HELPER VIRUS; IN-VIVO; MAMMALIAN-CELLS; GENE-EXPRESSION; DNA-SEQUENCES; RECOMBINATION; GENOME AB Herpes simplex virus type 1/adeno-associated virus (HSV/AAV) rep(+) hybrid amplicon vectors containing AAV inverted terminal repeats (ITRs) and rep gene sequences can mediate site-specific integration into the human genome. In this study, we have generated and characterized the first transgenic mice that bear the full-length (8.2 kb) human AAVS1 locus. Immortalized mouse embryonic fibroblasts from this mouse line were transduced with the rep(+), rep (containing only ITRs flanking the transgene) hybrid amplicon vectors, and the standard amplicon vector to determine stable integration frequency and the site of integration. Transduction of transgenic fibroblasts resulted in a 10-fold higher stable integration frequency with rep(+) hybrid amplicon vector than with rep or standard amplicon vectors. Southern blot analysis of genomic DNA from transgenic cells stably transduced with the rep(+) hybrid amplicon vector revealed site-specific integration of transgenes at the AAVS1 locus in 50% of clones. Some site-specific and random integration events were limited to the ITR-flanked transgene cassette. In contrast, transduction of transgenic mouse cells with the rep or standard amplicon vectors resulted in random integrations of the entire rep hybrid amplicon or amplicon DNA that were incorporated into the host genome as a concatenate of various sizes. These results demonstrate for the first time that the genome of transgenic mice bearing the human AAVS1 locus serves as a platform for site-specific integration of AAV ITR-flanked transgene cassettes within the hybrid amplicon vector in the presence of Rep. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Dept Neurol, Charlestown, MA 02129 USA. NINDS, Cellular Neurol Unit, NIH, Bethesda, MD 20892 USA. Albany Med Sch, Albany, NY USA. Johns Hopkins Sch Med, Div Pulm & Crit Care, Ctr Asthma & Allergy, Baltimore, MD USA. Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Harvard Med Sch, Program Neurosci, Boston, MA USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Dept Neurol, CNY 6205,Bldg 149,13th St, Charlestown, MA 02129 USA. OI Di Maria, Michael/0000-0003-0346-8517 FU NCI NIH HHS [CA69346]; NINDS NIH HHS [NS24279] NR 48 TC 33 Z9 34 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD SEP PY 2003 VL 10 IS 19 BP 1691 EP 1702 DI 10.1038/sj.gt.3302061 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 712KF UT WOS:000184796300008 PM 12923568 ER PT J AU Huffman, JC Stern, TA AF Huffman, JC Stern, TA TI The diagnosis and treatment of Munchausen's syndrome SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Munchausen's syndrome; Munchausen's disease; factitious disorder ID FACTITIOUS DISORDERS; FEATURES; FEVER AB Patients with Munchausen's syndrome-a syndrome characterized by the intentional production of physical symptoms to gain the sick role-present a variety of challenges to health care providers. Their treaters quickly become frustrated by their demanding interpersonal styles, by deception and manipulation, and by multiple unrevealing diagnostic procedures. These difficulties can lead to poor outcomes for patients and staff alike. We present the case of a young woman whose presentation and subsequent evaluation led to significant distress among the hospital staff responsible for her care, and discuss the epidemiaology, diagnosis, and management of pateints with Munchausen's syndrome. The most important role of the psychiatrist in the treatment of Munchausen's syndrome is to help the primary treatment team manage the patient in the safest and most appropriate way. Such management includes avoiding unnecessary procedures, preventing further self-harm, and avoiding angry or threatening interactions with the patient. The prognosis for patients with Munchausen's syndrome appears to be poor; flexible and creative approaches that emphasize consistency of care and regular outpatient psychiatric treatment have had the greatest success. (C) 2003 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RP Huffman, JC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. NR 21 TC 28 Z9 30 U1 2 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD SEP-OCT PY 2003 VL 25 IS 5 BP 358 EP 363 DI 10.1016/S0163-8343(03)00061-6 PG 6 WC Psychiatry SC Psychiatry GA 723QB UT WOS:000185442100009 PM 12972228 ER PT J AU Reynolds, PA Smolen, GA Palmer, RE Sgroi, D Yajnik, V Gerald, WL Haber, DA AF Reynolds, PA Smolen, GA Palmer, RE Sgroi, D Yajnik, V Gerald, WL Haber, DA TI Identification of a DNA-binding site and transcriptional target for the EWS-WT1(+KTS) oncoprotein SO GENES & DEVELOPMENT LA English DT Article DE DSRCT; EWS-WT1; alternative splicing; promoter; zinc finger; invasion ID ROUND-CELL TUMOR; ADJACENT ZINC FINGERS; LEUCINE-RICH REPEAT; WILMS-TUMOR; TRANSLOCATION PRODUCT; FRASIER-SYNDROME; PROSTATE-CANCER; REACTIVE STROMA; FUSION PROTEIN; HUMAN GENOME AB Desmoplastic small round cell tumor (DSRCT) is defined by a chimeric transcription factor, resulting from fusion of the N-terminal domain of the Ewing's sarcoma gene EWS to the three C-terminal zinc fingers of the Wilms' tumor suppressor WT1. Although DNA-binding sites have been defined for the uninterrupted WT1 zinc finger domains, the most prevalent isoforms of both WT1 and EWS-WT1 have an insertion of three amino acids [lysine, threonine, and serine (KTS)], which abrogates binding to known consensus sequences and transactivation of known target genes. Here, we used cDNA subtractive hybridization to identify an endogenous gene, LRRC15, which is specifically up-regulated after inducible expression of EWS-WT1(+KTS) in cancer cell lines, and is expressed within primary DSRCT cells. The chimeric protein binds in vitro and in vivo to a specific element upstream of LRRC15, leading to dramatic transcriptional activation. Mutagenesis studies define the optimal binding site of the (+KTS) isoform of EWS-WT1 as 5'-GGAGG(A/G)-3'. LRRC15 encodes a leucine-rich transmembrane protein, present at the leading edge of migrating cells, the expression of which in normal tissues is restricted to the invasive cytotrophoblast layer of the placenta; small interfering (siRNA)-mediated suppression of LRRC15 expression in breast cancer cells leads to abrogation of invasiveness in vitro. Together, these observations define the consequence of (KTS) insertion within WT1-derived zinc fingers, and identify a novel EWS-WT1 transcriptional target implicated in tumor invasiveness. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM Haber@helix.mgh.harvard.edu OI Reynolds, Paul/0000-0001-8738-1245 FU NCI NIH HHS [CA 90627, R01 CA090627] NR 54 TC 31 Z9 33 U1 2 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD SEP 1 PY 2003 VL 17 IS 17 BP 2094 EP 2107 DI 10.1101/gad.1110703 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 717UN UT WOS:000185109300004 PM 12923058 ER PT J AU Zhang, M Brancaccio, A Weiner, L Missero, C Brissette, JL AF Zhang, M Brancaccio, A Weiner, L Missero, C Brissette, JL TI Ectodysplasin regulates pattern formation in the mammalian hair coat SO GENESIS LA English DT Article DE eda; tabby; ectodermal dysplasia; ED1; Edar ID HYPOHIDROTIC ECTODERMAL DYSPLASIA; FOLLICLE DEVELOPMENT; TRANSGENIC MICE; TABBY MICE; EDA GENE; MORPHOGENESIS; MUTATIONS; PROTEIN; HOMOLOG; MOUSE AB In mammalian skin, hair follicles develop at regular intervals and with site-specific morphologies. This process generates distinct patterns of hair, but the mechanisms that establish these patterns remain largely unknown. Here we present evidence of follicular patterning by ectodysplasin-A1 (Eda-A1), a signaling protein necessary for the proper development of hair and other appendages. In transgenic mice, Eda-A1 was targeted to the epithelial compartment of the developing skin. At periodic locations, multiple hair follicles were induced side by side, without any interfollicular space. These follicles grew into the dermis as a fusion and subsequently branched to create discrete stalks and hair bulbs. Thus, at sites where interfollicular skin normally forms, hair follicles developed instead. This result shows that Eda-A1 can regulate basic developmental decisions, as cells were switched from interfollicular to follicular fates. Given these effects, it is likely that Eda-A1 is among the key regulators of pattern formation in the skin. (C) 2003 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. TIGEM, Naples, Italy. RP Brissette, JL (reprint author), Massachusetts Gen Hosp E, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. OI Missero, Caterina/0000-0003-0905-5123 FU Telethon [TGM06S01, TGM03P14] NR 49 TC 23 Z9 24 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 1526-954X J9 GENESIS JI Genesis PD SEP PY 2003 VL 37 IS 1 BP 30 EP 37 DI 10.1002/gene.10230 PG 8 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 729VH UT WOS:000185795400006 PM 14502575 ER PT J AU Natowicz, MR Isman, F Prence, EM Cedrone, P Allen, JJ AF Natowicz, MR Isman, F Prence, EM Cedrone, P Allen, JJ TI Rapid prenatal testing for human beta-glucuronidase deficiency (MPS VII) SO GENETIC TESTING LA English DT Article ID NONIMMUNE HYDROPS-FETALIS; AMNIOTIC-FLUID; MUCOPOLYSACCHARIDOSIS; DIAGNOSIS; DISEASES AB Prenatal diagnosis for the lysosomal storage disorders is typically achieved by enzymatic analysis of the relevant lysosomal enzyme in cultured amniocytes or chorionic villi. While prenatal diagnosis of some genetic diseases can be done by analysis of pertinent metabolites in amniotic fluid, there are few data regarding prenatal diagnosis of lysosomal disorders by enzyme analysis of amniotic fluid. Prenatal diagnosis by enzyme analysis of amniotic fluid has the potential advantage of providing a more rapid prenatal test result. In this study we describe an assay for the prenatal diagnosis of the mucopolysaccharidosis beta-glucuronidase deficiency (MPS VII; MIM #253220) using amniotic fluid and we confirm its reliability in detecting an affected fetus in an at-risk pregnancy by enzyme analysis of cultured amniocytes and fetal fibroblasts. Because MPS VII is rare and few instances of prenatal diagnosis for this and nearly all other lysosomal disorders have been accomplished by enzyme analysis of amniotic fluid, confirmation of results obtained from enzyme analysis of amniotic fluid should be carried out by enzyme or mutation analysis using cultured amniocytes or chorionic villus specimens. C1 Eunice Kennedy Shriver Ctr Mental Retardat Inc, Div Med Genet, Waltham, MA 02254 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. RP Natowicz, MR (reprint author), Cleveland Clin Fdn, Dept Neurol, S-71,9500 Euclid Ave, Cleveland, OH 44195 USA. NR 12 TC 3 Z9 5 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PD FAL PY 2003 VL 7 IS 3 BP 241 EP 243 DI 10.1089/109065703322537269 PG 3 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 741BT UT WOS:000186439200008 PM 14642000 ER PT J AU Cotta-De-Almeida, V Schonhoff, S Shibata, T Leiter, A Snapper, SB AF Cotta-De-Almeida, V Schonhoff, S Shibata, T Leiter, A Snapper, SB TI A new method for rapidly generating gene-targeting vectors by engineering BACs through homologous recombination in bacteria SO GENOME RESEARCH LA English DT Article ID ESCHERICHIA-COLI; CROHNS-DISEASE; SUSCEPTIBILITY; SYSTEM; STEP; DNA AB Generating knockout mice is still an expensive and highly time-consuming process. Target construct generation, the first labor-intensive step in this process, requires the manipulation of large fragments of DNA and numerous, and often cumbersome, cloning steps. Here we show the development of a rapid approach for generating targeting constructs that capitalizes on efficient homologous recombination between linear DNA fragments and circular plasmids in Escherichia coli ("recombineering"), the availability of bacterial artificial chromosomes (BACs), and the accessibility of the sequence of the mouse genome. Employing recombineering, we demonstrate with only 1-2 template plasmids, short homologies (40-50bp) between donor and target DNA, and one subcloning step that we can efficiently manipulate BACs in Situ to generate a complicated targeting vector. This procedure avoids the need to construct or screen genomic libraries and permits the generation of most standard, conditional, or knock-in targeting vectors, often within two weeks. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Oswaldo Cruz Fdn, Inst Oswaldo Cruz, Dept Ultrastruct & Cell Biol, BR-21045900 Rio De Janeiro, Brazil. Tufts Univ, Sch Med, New England Med Ctr, GRASP Digest Dis Ctr,Div Gastroenterol, Boston, MA 02111 USA. RP Snapper, SB (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RI Cotta-de-Almeida, Vinicius/G-3939-2012 FU NHLBI NIH HHS [P01 HL059561, HL59561]; NIAID NIH HHS [AI50950, R56 AI050950, R01 AI050950] NR 15 TC 33 Z9 37 U1 1 U2 6 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD SEP PY 2003 VL 13 IS 9 BP 2190 EP 2194 DI 10.1101/gr.1356503 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 717JL UT WOS:000185085300022 PM 12915491 ER PT J AU Shuster, DL Farley, KA Sisterson, J Burnett, DS AF Shuster, DL Farley, KA Sisterson, J Burnett, DS TI He-4/He-3 thermochronometry SO GEOCHIMICA ET COSMOCHIMICA ACTA LA English DT Meeting Abstract CT 13th Annual VM Goldschmidt Conference CY SEP 07-12, 2003 CL KURASHIKI, JAPAN C1 CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA. Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. EM dshuster@caltech.edu RI Shuster, David/A-4838-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0016-7037 J9 GEOCHIM COSMOCHIM AC JI Geochim. Cosmochim. Acta PD SEP PY 2003 VL 67 IS 18 SU 1 BP A436 EP A436 PG 1 WC Geochemistry & Geophysics SC Geochemistry & Geophysics GA 724ZF UT WOS:000185517600860 ER PT J AU Arai, K Lee, SR Lo, EH AF Arai, K Lee, SR Lo, EH TI Essential role for ERK mitogen-activated protein kinase in matrix metalloproteinase-9 regulation in rat cortical astrocytes SO GLIA LA English DT Article DE astrocytes; matrix metalloprotease-9; mitogen-activated protein kinase; edema; hemorrhage; neuroprotection ID BLOOD-BRAIN-BARRIER; FOCAL CEREBRAL-ISCHEMIA; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; GENE KNOCK-OUT; MATRIX METALLOPROTEINASES; IN-VITRO; SIGNALING PATHWAY; NERVOUS-SYSTEM; MAP KINASE; INJURY AB Matrix metalloproteinases (MMPs) contribute to the pathophysiology of brain injury and inflammation but little is known about their regulatory signaling pathways in brain cells. Here we examine the role of mitogen-activated protein (MAP) kinase pathways in MMP-9 regulation in cortical rat astrocytes. The protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) induced MMP-9 but not MMP-2 secretion as measured by gelatin zymography. Northern blot and RT-PCR analysis showed that MMP-9 responses occurred at the mRNA level. Although PMA increased phosphorylation in all three major MAP kinase pathways (ERK, p38 MAP kinase, and JNK), only inhibition of the ERK pathway by the MEK/ERK inhibitor U0126 (0.1-10 muM) significantly reduced MMP-9 upregulation, even when treatment was delayed for 4 h after PMA exposure. Inhibitors of p38 MAP kinase (SB203580) and JNK (SP600125) had no effect. This PKC pathway was compared to a cytokine response by exposing astrocytes to TNFalpha, which also activated MAP kinase and induced MMP-9 upregulation. But in this case, all three MAP kinase inhibitors (U0126, S13203580, and SP600125) reduced TNFalpha-induced MMP-9 upregulation. Taken together, these results suggest that the ERK MAP kinase is essential for MMP-9 upregulation via PKC and cytokine pathways in astrocytes. (C) 2003 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. Harvard Univ, Sch Med, Neurosci Program, Charlestown, MA USA. Univ Tokyo, Lab Cell Signaling, Grad Sch Pharmaceut Sci, Tokyo, Japan. RP Lo, EH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Neurol, E 149-2401, Charlestown, MA 02129 USA. FU NINDS NIH HHS [P50-NS10828, R01-NS37074, R01-NS38731, R01-NS40529] NR 41 TC 93 Z9 94 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0894-1491 J9 GLIA JI Glia PD SEP PY 2003 VL 43 IS 3 BP 254 EP 264 DI 10.1002/glia.10255 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 713KX UT WOS:000184858000006 PM 12898704 ER PT J AU Sun, T Ligon, K Hafler, B Lu, R Alberta, J Stiles, C Rowitch, D AF Sun, T Ligon, K Hafler, B Lu, R Alberta, J Stiles, C Rowitch, D TI Olig2 regulation and function during CNS development and tumorgenesis SO GLIA LA English DT Meeting Abstract CT 6th European Meeting on Glial Cell Function in Health and Disease CY SEP 03-06, 2003 CL BERLIN, GERMANY C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0894-1491 J9 GLIA JI Glia PD SEP PY 2003 SU 2 BP 1 EP 1 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 714XB UT WOS:000184938300004 ER PT J AU Wilt, SG Masuda, M Yiannoulos, G Dugger, NV Hoffman, PM AF Wilt, SG Masuda, M Yiannoulos, G Dugger, NV Hoffman, PM TI Role of oxidative injury in a retroviral induced neurodegenerative disease SO GLIA LA English DT Meeting Abstract CT 6th European Meeting on Glial Cell Function in Health and Disease CY SEP 03-06, 2003 CL BERLIN, GERMANY C1 Bronx Vet Adm Med Ctr, Res & Dev Program, Bronx, NY USA. Dokkyo Univ, Sch Med, Dept Microbiol, Mibu, Tochigi, Japan. Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. VA Maryland Healthcare Syst, Res Serv, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0894-1491 J9 GLIA JI Glia PD SEP PY 2003 SU 2 BP 34 EP 34 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 714XB UT WOS:000184938300144 ER PT J AU Campos, SM Matulonis, UA Penson, RT Lee, H Berkowitz, RS Duska, LR Fuller, AF Wilson, KS Puchalski, TA Supko, JG Seiden, MV AF Campos, SM Matulonis, UA Penson, RT Lee, H Berkowitz, RS Duska, LR Fuller, AF Wilson, KS Puchalski, TA Supko, JG Seiden, MV TI Phase II study of liposomal doxorubicin and weekly paclitaxel for recurrent Mullerian tumors SO GYNECOLOGIC ONCOLOGY LA English DT Article ID CONTINUOUS INTRAVENOUS-INFUSION; LIQUID-CHROMATOGRAPHIC ASSAY; EPITHELIAL OVARIAN-CANCER; METASTATIC BREAST-CANCER; REFRACTORY OVARIAN; HUMAN-PLASMA; CARCINOMA; CHEMOTHERAPY; CARDIOTOXICITY; COMBINATION AB Objective. Pegylated liposomally encapsulated doxorubicin (Doxil. Ortho-Biotech) and paclitaxel (Taxol, Bristol Myers Squibb) are both active against Mullerian malignancies. A phase II trial was performed to determine the toxicity and efficacy of these agents when administered in combination. Methods. Patients were initially treated with 30 mg/m(2) of liposomal doxorubicin every 21 days and 70 mg/m(2) of paclitaxel every week for I g weeks. The plasma pharmacokinetics of paclitaxel was determined when administered alone and concurrently with liposomal doxorubicin. Results. Forty women with recurrent gynecologic malignancies of Mullerian origin including 34 with ovary and primary peritoneal cancer (85%) were enrolled. Toxicity was evaluated for all 508 cycles of therapy. Paclitaxel and liposomal doxorubicin were delivered at 95% (66.4 mg/m(2)/week) and 77% (7.65 mg/m(2)/week) of their intended weekly dose intensities, respectively. Reductions in the dose of liposomal doxorubicin were frequently required for palmar plantar erythrodysesthesia during the latter cycles of therapy. There were 4 patients with a complete response and 7 with partial responses, for an overall objective response rate of 29%, among the 38 evaluable patients. Response rates for the subset of 13 women with tumor recurrence occurring at least 6 months after prior platinum-based therapy was 54%. The concurrent administration of liposomal doxorubicin did not alter the pharmacokinetic disposition of paclitaxel. Conclusion. Liposomal doxorubicin with weekly paclitaxel is active in Mullerian malignancies. The concurrent delivery of the weekly paclitaxel with liposomal doxorubicin may increase liposomal doxorubicin skin toxicity. Liposomal doxorubicin does not alter the pharmacokinetics of paclitaxel. (C) 2003 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Biostat, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Gynecol Oncol, Gynecol Oncol Res Program, Boston, MA 02115 USA. Dana Farber Harvard Canc Ctr, Boston, MA USA. Dana Farber Partners Canc Care, Boston, MA USA. RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Div Med Oncol, 100 Blossom St,Cox 640, Boston, MA 02114 USA. NR 24 TC 17 Z9 17 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD SEP PY 2003 VL 90 IS 3 BP 610 EP 618 DI 10.1016/S0090-8258(03)00373-1 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 725AT UT WOS:000185521000019 PM 13678734 ER PT J AU Perlis, RH AF Perlis, RH TI Special issue - Mood stabilization: From basic science to clinical practice - Introduction SO HARVARD REVIEW OF PSYCHIATRY LA English DT Editorial Material C1 Harvard Univ, Dept Psychiat, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Perlis, RH (reprint author), Harvard Univ, Dept Psychiat, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD SEP-OCT PY 2003 VL 11 IS 5 BP 229 EP 229 DI 10.1080/10673220390250613 PG 1 WC Psychiatry SC Psychiatry GA 739GR UT WOS:000186337200001 ER PT J AU McQuillen, AD Licht, MH Licht, BG AF McQuillen, AD Licht, MH Licht, BG TI Contributions of disease severity and perceptions of primary and secondary control to the prediction of psychosocial adjustment to Parkinson's disease SO HEALTH PSYCHOLOGY LA English DT Article; Proceedings Paper CT 52nd Annual Meeting of the Gerontological-Society-of-America CY NOV 19-23, 1999 CL SAN FRANCISCO, CALIFORNIA SP Gerontol Soc Amer DE Parkinson's disease; perceived control; primary control; secondary control; psychosocial adjustment; control beliefs; locus of control ID MINI-MENTAL-STATE; QUALITY-OF-LIFE; PERCEIVED CONTROL; DEPRESSION; ILLNESS; AGE AB Seventy-four people with Parkinson's disease (PD) completed questionnaires and were interviewed to determine the degree to which the severity of PD and perceptions of primary and secondary control over PD predicted psychosocial adjustment. Significant unique contributions to PD-related participation restrictions were made by disease severity (positive relationship) and perceived internal secondary control (negative relationship). Also, participation restrictions had a significant direct effect, and disease severity and perceived internal secondary control significant indirect effects, on both depressive symptomatology and life satisfaction. Results are consistent with theories that suggest the importance of enhancing internal secondary control processes in situations in which actual control over objective circumstances is limited, such as with chronic and progressive diseases like PD. C1 Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. Audie L Murphy Mem Vet Adm Med Ctr, Dept Psychol, San Antonio, TX 78284 USA. RP Licht, MH (reprint author), Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. NR 39 TC 21 Z9 21 U1 0 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD SEP PY 2003 VL 22 IS 5 BP 504 EP 512 DI 10.1037/0278-6133.22.5.504 PG 9 WC Psychology, Clinical; Psychology SC Psychology GA 730KJ UT WOS:000185829700008 PM 14570534 ER PT J AU Goodman, SS Withnell, RH Shera, CA AF Goodman, SS Withnell, RH Shera, CA TI The origin of SFOAE microstructure in the guinea pig SO HEARING RESEARCH LA English DT Article DE microstructure; otoacoustic emission; SFOAE ID FREQUENCY OTOACOUSTIC EMISSIONS; FINE-STRUCTURE; MODEL; DPOAE; SUPPRESSION; GENERATION; TONE AB Human stimulus-frequency otoacoustic emissions (SFOAEs) evoked by low-level stimuli have previously been shown to have properties consistent with such emissions arising from a linear place-fixed reflection mechanism with SFOAE microstructure thought to be due to a variation in the effective reflectance with position along the cochlea [Zweig and Shera, J. Acoust. Soc. Am. 98 (1995) 2018-2047]. Here we report SFOAEs in the guinea pig obtained using a nonlinear extraction paradigm from the ear-canal recording that show amplitude and phase microstructure akin to that seen in human SFOAEs. Inverse Fourier analysis of the SFOAE spectrum indicates that SFOAEs in the guinea pig are a stimulus level-dependent mix of OAEs arising from linear-reflection and nonlinear-distortion mechanisms. Although the SFOAEs are dominated by OAE generated by a linear-reflection mechanism at low and moderate stimulus levels, nonlinear distortion can dominate some part of, or all of, the emission spectrum at high levels. Amplitude and phase microstructure in the guinea pig SFOAE is evidently a construct of (i) the complex addition of nonlinear-distortion and linear-reflection components; (ii) variation in the effective reflectance with position along the cochlea; and perhaps (iii) the complex addition of multiple intra-cochlear reflections. (C) 2003 Elsevier B.V. All rights reserved. C1 Indiana Univ, Dept Speech & Hearing Sci, Bloomington, IN 47405 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Withnell, RH (reprint author), Indiana Univ, Dept Speech & Hearing Sci, 200 S Jordan Ave, Bloomington, IN 47405 USA. OI Withnell, Robert/0000-0002-5827-9433 FU NIDCD NIH HHS [T32 DC00012, DC03687, DC04921, R01 DC003687] NR 21 TC 30 Z9 32 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD SEP PY 2003 VL 183 IS 1-2 BP 7 EP 17 DI 10.1016/S0378-5955(03)00193-X PG 11 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 726DH UT WOS:000185582800002 PM 13679133 ER PT J AU Hecker, E AF Hecker, E TI Cyclothymia, a circular mood disorder SO HISTORY OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 6th Hannah Conference on the History of Medicine CY APR, 2001 CL TORONTO, CANADA DE cyclothymia; Hecker; history of psychiatry; Kahlbaum; psychopathology ID BIPOLAR DISORDER; TRANSLATION; KAHLBAUM,KARL,LUDWIG; HECKER,EWALD; SPECTRUM; INSANITY; ILLNESS; BIRTH; MANIA AB Ewald Hecker (1843-1909) was a collaborator of Karl Ludwig Kahlbaum (1828-1899). Both worked outside the university and public mental institutions of Germany. By meticulously observing clinical signs and illness-course, they laid the groundwork for modern descriptive psychiatry. Their clinical approach influenced Kraepelin and continues to dominate psychiatric classification. Hecker popularized several of Kahlbaum's syndromal concepts, including hebephrenia. Another was cyclothymia, a relatively benign form of manic-depressive illness, introduced by Kahlbaum in 1882. It included depressive (dysthymia), hypomanic (hyperthymia), and mixed hypomanic-depressive phases. The Kahlbaum-Hecker syndrome of cyclothymia survives in DSM-IV bipolar II disorder and cyclothymia. An annotated English translation of Hecker's 1898 paper is provided, with historical notes on Hecker and the significance of his work. C1 Free Univ Berlin, Dept Psychiat & Psychotherapy, Berlin, Germany. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, McLean dvi, Bipolar & Psychot Disorders Program & Int Comsort, Belmont, MA USA. Univ Parma, Inst Clin Psychiat, I-43100 Parma, Italy. RP Hecker, E (reprint author), Free Univ Berlin, Dept Psychiat & Psychotherapy, Berlin, Germany. NR 66 TC 3 Z9 4 U1 0 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0957-154X EI 1740-2360 J9 HIST PSYCHIATR JI Hist. Psychiatr. PD SEP PY 2003 VL 14 IS 55 BP 377 EP 399 DI 10.1177/0957154X030143007 PN 3 PG 23 WC History Of Social Sciences; Psychiatry SC Social Sciences - Other Topics; Psychiatry GA 737HY UT WOS:000186225400007 ER PT J AU Tang, Y Shah, K Messerli, SM Snyder, E Breakefield, X Weissleder, R AF Tang, Y Shah, K Messerli, SM Snyder, E Breakefield, X Weissleder, R TI In vivo tracking of neural progenitor cell migration to glioblastomas SO HUMAN GENE THERAPY LA English DT Article ID STEM-CELLS; GENE-THERAPY; NERVOUS-SYSTEM; BRAIN; EXPRESSION; DELIVERY; LINES; ACTIVATION; RETROVIRUS; VECTORS AB The ability to noninvasively track the migration, engraftment, and proliferation of neural progenitor cells (NPCs) has significant clinical and research implications. The purpose of our study was to explore the macroscopic migratory capabilities of NPCs toward brain tumors after implantation into nude mice. We stably transfected C17.2 NPCs with the firefly luciferase gene (F-luc) and implanted cells into (1) the contralateral brain parenchyma (2x10(6) cells), (2) the ventricles (2x10(6) cells), ( 3) the vasculature (1x10(5) cells), or (4) the intraperitoneal cavity (5x10(6) cells) of mice bearing intracranial gliomas (Gli36). Using serial bioluminescence imaging, migration of parenchymally injected cells was observed across the corpus callosum, first detected at 1 week, with maximal density at the tumor site 2-3 weeks after implantation. Similar patterns were also observed with intraventricular injections; however, tumors were populated earlier, presumably because of the shorter distance to travel. Intravenous injections resulted in more modest tumoral NPC populations, whereas virtually no cells could be identified in tumors after intraperitoneal injection. These results confirm the migratory capability of NPCs over considerable distances and their preferential accumulation in brain tumors on CNS rather than peripheral injection. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Mol Neurogenet Unit, Charlestown, MA 02129 USA. Childrens Hosp, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Ctr Mol Imaging Res, 13th St,Bldg 149,Room 5403, Charlestown, MA 02129 USA. EM Weissleder@helix.mgh.harvard.edu NR 24 TC 147 Z9 160 U1 2 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD SEP PY 2003 VL 14 IS 13 BP 1247 EP 1254 DI 10.1089/104303403767740786 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 712JL UT WOS:000184794500004 PM 12952596 ER PT J AU El-Zimaity, HMT Ramchatesingh, J Clarridge, JE Abudayyeh, S Osato, MS Graham, DY AF El-Zimaity, HMT Ramchatesingh, J Clarridge, JE Abudayyeh, S Osato, MS Graham, DY TI Enterococcus gastritis SO HUMAN PATHOLOGY LA English DT Article DE Helicobacter pylori; gastritis; Enterococcus ID VANCOMYCIN-RESISTANT; FLORA AB Helicobacter pylori infection is the most common cause of gastritis with its associated sequelae. Gastritis secondary to other bacteria is rare. This report describes Enterococcus-associated gastritis in a 59-year-old diabetic man. Nine months after receiving treatment for H. pylori-associated gastritis, he underwent endoscopy to confirm H. pylori eradication and to evaluate the status of previously seen ulcers. Mucosal biopsy specimens revealed severe active but focal gastritis adjacent to gram-positive coccobacilli in short to long chains with no H. pylori. Culture grew an Enterococcus similar to E. hirae and E. durans. No treatment was given, and endoscopy done 2 months later showed complete resolution of the gastritis and absence of H. pylori or enterococci. Our patient's gastritis represents a previously undescribed manifestation of Enterococcus infection. It is possible that the presence of NSAID gastric mucosal injury and diabetes predisposed this individual to the development of transient Enterococcus gastritis. (C) 2003 Elsevier Inc. All rights reserved. C1 VA Med Ctr, Dept Med, Houston, TX 77030 USA. VA Med Ctr, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP El-Zimaity, HMT (reprint author), VA Med Ctr, Dept Med, 111-D,2002 Holcombe Blvd, Houston, TX 77030 USA. NR 14 TC 4 Z9 4 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD SEP PY 2003 VL 34 IS 9 BP 944 EP 945 DI 10.1016/S0046-8177(03)00287-9 PG 2 WC Pathology SC Pathology GA 726UB UT WOS:000185617500017 PM 14562292 ER PT J AU Goodfriend, TL Ball, DL Egan, BM Campbell, WB Nithipatikom, K AF Goodfriend, TL Ball, DL Egan, BM Campbell, WB Nithipatikom, K TI Epoxy-keto-linoleic acid (EKODE) stimulates aldosterone secretion by rat adrenal cells, and its levels in human blood correlate with those of aldosterone SO HYPERTENSION LA English DT Meeting Abstract CT 57th Annual Fall Conference of the Council-for-High-Blood-Pressure-Research CY SEP 23-26, 2003 CL WASHINGTON, D.C. SP Council High Blood Pressure Res, Amer Heart Assoc, Council Nutrit, Phys Activ & Metabolism C1 William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. Med Univ S Carolina, Charleston, SC 29425 USA. Med Coll Wisconsin, Milwaukee, WI 53226 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 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 2003 VL 42 IS 3 MA 82 BP 403 EP 403 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 718FY UT WOS:000185135500114 ER PT J AU Tofovic, SP Maddy, H Jackson, EK AF Tofovic, SP Maddy, H Jackson, EK TI Estradiol metabolites attenuate renal and cardiovascular injury induced by chronic angiotensin II administration SO HYPERTENSION LA English DT Meeting Abstract CT 57th Annual Fall Conference of the Council-for-High-Blood-Pressure-Research CY SEP 23-26, 2003 CL WASHINGTON, D.C. SP Council High Blood Pressure Res, Amer Heart Assoc, Council Nutrit, Phys Activ & Metabolism C1 Univ Pittsburgh, Sch Med, Dept Med, Ctr Clin Pharmacol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Ctr Clin Pharmacol, Pittsburgh, PA 15261 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 2003 VL 42 IS 3 MA P52 BP 414 EP 414 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 718FY UT WOS:000185135500170 ER PT J AU Tofovic, SP Mady, H Salah, E Jackson, EK Melhem, M AF Tofovic, SP Mady, H Salah, E Jackson, EK Melhem, M TI Estradiol metabolites retard the progression of pulmonary hypertension preclinical evidence for clinical development SO HYPERTENSION LA English DT Meeting Abstract CT 57th Annual Fall Conference of the Council-for-High-Blood-Pressure-Research CY SEP 23-26, 2003 CL WASHINGTON, D.C. SP Council High Blood Pressure Res, Amer Heart Assoc, Council Nutrit, Phys Activ & Metabolism C1 Univ Pittsburgh, Sch Med, Dept Med, Ctr Clin Pharmacol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Ctr Clin Pharmacol, Pittsburgh, PA 15261 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 2003 VL 42 IS 3 MA P62 BP 416 EP 416 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 718FY UT WOS:000185135500180 ER PT J AU Iwaki, S Yamamoto, C Takehara, S Tonoike, M Yamamoto, T AF Iwaki, S Yamamoto, C Takehara, S Tonoike, M Yamamoto, T TI Rejection of stimulus-related artifacts from electro-gustatory magnetoencephalographic signals using independent component analysis SO IEEE TRANSACTIONS ON MAGNETICS LA English DT Article; Proceedings Paper CT International Magnetics Conference CY MAR 30-APR 03, 2003 CL BOSTON, MASSACHUSETTS DE artifact rejection; electro-gustatory stimulus; independent component analysis; magnetoencephalography ID BRAIN AB Electro-gustatory stimuli have been used to investigate the gustatory information processing in the human brain with precise temporal and spatial accuracy. But this technique was not widely applicable to magnetoencephalographic (MEG) measurements due to the difficulty in eliminating huge stimulus-related artifact. In this study, we used independent component decomposition of the measured signal to reject the stimulus-related artifact from other brain activities. The results indicate that the proposed technique is able to differentiate the electro-gustatory stimulus-related artifact successfully. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Charlestown, MA 02129 USA. Natl Inst Adv Ind Sci & Technol, Osaka 5638577, Japan. Osaka Univ, Grad Sch Human Sci, Osaka 5650871, Japan. Osaka Univ, Sch Human Sci, Osaka 5650871, Japan. RP Iwaki, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Charlestown, MA 02129 USA. RI Iwaki, Sunao/B-1079-2011 OI Iwaki, Sunao/0000-0002-7123-7203 NR 6 TC 0 Z9 0 U1 0 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9464 J9 IEEE T MAGN JI IEEE Trans. Magn. PD SEP PY 2003 VL 39 IS 5 BP 3381 EP 3383 DI 10.1109/TMAG.2003.816157 PN 2 PG 3 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA 728MZ UT WOS:000185722100373 ER PT J AU DiGiovine, CP Cooper, RA Fitzgerald, SG Boninger, ML Wolf, EJ Guo, SF AF DiGiovine, CP Cooper, RA Fitzgerald, SG Boninger, ML Wolf, EJ Guo, SF TI Whole-body vibration during manual wheelchair propulsion with selected seat cushions and back supports SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE back supports; individual with a disability; manual wheelchair propulsion; seat cushions; seating systems; shock; vibration; wheelchairs; whole-body vibration (WBV) ID VERTICAL VIBRATION; SUSPENSION DESIGN; APPARENT MASS; PAIN; TRANSMISSION; POSTURE; HEAD; DISCOMFORT; EXPOSURE; SUBJECT AB Although the exposure to whole-body vibrations (WBV) has been shown to be detrimental to seated humans, the effects of wheelchairs and seating systems on the transmission of vibration to an individual have not been thoroughly examined. The purpose of this study was to determine if the selected wheelchair seat cushions and back supports minimize the transmission of vibrations. Thirty-two wheelchair users traversed an activities of daily living course three times using 16 randomly selected seating systems as well as their own. Vibrations were measured using triaxial accelerometers at the seat and participant's head. The weighted fore-to-aft (T-x), vertical (T-z), and resultant (T-r) transmissibility based on the vibrational-dose-value (VDV) were used to determine if differences existed among the four seat cushions and back supports. The obstacles that seem to have the largest effect on the transmission of WBV are the single event shocks and the repeated event shocks. Comparisons between the individuals own seating system and the tested seating systems suggest that the individuals are not using the most appropriate seating system in terms of the reduction of vibration transmission. C1 Assist Technol Unit, Chicago, IL 60608 USA. Univ Illinois, Dept Disabil & Human Dev, Chicago, IL 60608 USA. Univ Illinois, Dept Bioengn, Chicago, IL 60608 USA. VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151R 1, Ctr Excellence Wheelchairs & Related Technol, Dept Vet Affairs,VA Rehabil Res & Dev Ctr, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. RP DiGiovine, CP (reprint author), Assist Technol Unit, Chicago, IL 60608 USA. RI DiGiovine, Carmen/E-2982-2011; OI Wolf, Erik/0000-0002-6353-7978; Boninger, Michael/0000-0001-6966-919X NR 51 TC 8 Z9 8 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1534-4320 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD SEP PY 2003 VL 11 IS 3 BP 311 EP 322 DI 10.1109/TNSRE.2003.816872 PG 12 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA 723ED UT WOS:000185418700014 PM 14518796 ER PT J AU Schmidt-Supprian, M Courtois, G Tian, J Coyle, AJ Israel, A Rajewsky, K Pasparakis, M AF Schmidt-Supprian, M Courtois, G Tian, J Coyle, AJ Israel, A Rajewsky, K Pasparakis, M TI Mature T cells depend on signaling through the IKK complex SO IMMUNITY LA English DT Article ID NF-KAPPA-B; TRANSCRIPTION FACTORS; TRANSGENIC MICE; DEFICIENT MICE; KINASE-ALPHA; CYTOKINE PRODUCTION; LIVER DEGENERATION; GENE-EXPRESSION; NEMO/IKK-GAMMA; ACTIVATION AB The transcription factor NF-kappaB is implicated in various aspects of T cell development and function. The IkappaB kinase (IKK) complex, consisting of two kinases, IKK1/alpha and IKK2/beta, and the NEMO/IKKgamma regulatory subunit, mediates NF-kappaB activation by most known stimuli. Adoptive transfer experiments had demonstrated that IKK1 and IKK2 are dispensable for T cell development. We show here that T lineage-specific deletion of IKK2 allows survival of naive peripheral T cells but interferes with the generation of regulatory and memory T cells. T cell-specific ablation of NEMO or replacement of IKK2 with a kinase-dead mutant prevent development of peripheral T cells altogether. Thus, IKK-induced NF-kappaB activation, mediated by either IKK1 or IKK2, is essential for the generation and survival of mature T cells, and IKK2 has an additional role in regulatory and memory T cell development. C1 Univ Cologne, Inst Genet, D-50931 Cologne, Germany. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Inst Pasteur, CNRS, URA 2582, Unite Biol Mol Express Gen, F-75724 Paris, France. Millenium Pharmaceut Inc, Cambridge, MA 02139 USA. European Mol Biol Lab, Mouse Biol Programme, I-00016 Monterotondo, Italy. RP Rajewsky, K (reprint author), Univ Cologne, Inst Genet, Weyertal 121, D-50931 Cologne, Germany. RI Schmidt-Supprian, Marc/F-5893-2011 OI Schmidt-Supprian, Marc/0000-0002-8543-6166 NR 49 TC 148 Z9 151 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD SEP PY 2003 VL 19 IS 3 BP 377 EP 389 DI 10.1016/S1074-7613(03)00237-1 PG 13 WC Immunology SC Immunology GA 724RD UT WOS:000185499800009 PM 14499113 ER PT J AU Shimaoka, M Salas, A Yang, W Weitz-Schmidt, G Springer, TA AF Shimaoka, M Salas, A Yang, W Weitz-Schmidt, G Springer, TA TI Small molecule integrin antagonists that bind to the beta(2) subunit I-like domain and activate signals in one direction and block them in the other SO IMMUNITY LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-1; EXTRACELLULAR SEGMENT; ADHESION RECEPTORS; CRYSTAL-STRUCTURE; DISULFIDE BOND; HIGH-AFFINITY; LFA-1; CONFORMATION; INHIBITION; ICAM-1 AB Leukocyte integrins contain an inserted (I) domain in their alpha subunits and an I-like domain in their beta(2) subunit, which directly bind ligand and regulate ligand binding, respectively. We describe a novel mechanistic class of integrin inhibitors that bind to the metal ion-dependent adhesion site of the beta(2) I-like domain and prevent its interaction with and activation of the alpha(L) I domain. The inhibitors do not bind to the alpha(L) I domain but stabilize alpha/beta subunit association and can show selectivity for alpha(L)beta(2) compared to alpha(M)beta(2). The inhibitors reveal a crucial intersection for relaying conformational signals within integrin extracellular domains. While blocking signals in one direction to the I domain, the antagonists induce the active conformation of the I-like domain and stalk domains, and thus transmit conformational signals in the other direction toward the transmembrane domains. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia & Pathol, Boston, MA 02115 USA. Novartis Pharma AG, Preclin Res, CH-4002 Basel, Switzerland. RP Shimaoka, M (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. OI Salas, Azucena/0000-0003-4572-2907 FU NCI NIH HHS [CA31798] NR 57 TC 100 Z9 101 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD SEP PY 2003 VL 19 IS 3 BP 391 EP 402 DI 10.1016/S1074-7613(03)00238-3 PG 12 WC Immunology SC Immunology GA 724RD UT WOS:000185499800010 PM 14499114 ER PT J AU Iwasaki, H Mizuno, S Wells, RA Cantor, AB Watanabe, S Akashi, K AF Iwasaki, H Mizuno, S Wells, RA Cantor, AB Watanabe, S Akashi, K TI GATA-1 converts lymphoid and myelomonocytic progenitors into the megakaryocyte/erythrocyte lineages SO IMMUNITY LA English DT Article ID T-CELL DEVELOPMENT; TRANSCRIPTION FACTOR GATA-1; HEMATOPOIETIC STEM-CELLS; ZINC-FINGER PROTEIN; GENE-EXPRESSION; DNA-BINDING; MEGAKARYOCYTIC DIFFERENTIATION; B-LYMPHOPOIESIS; TRANSGENIC MICE; IN-VIVO AB GATA-1 is an essential transcription factor for megakaryocyte and erythrocyte (MegE) development. Here we show that hematopoietic progenitors can be reprogrammed by the instructive action of GATA-1. Enforced expression of GATA-1 in hematopoietic stem cells led to loss of self-renewal activity and the exclusive generation of MegE lineages. Strikingly, ectopic GATA-1 reprogrammed common lymphoid progenitors as well as granulocyte/monocyte (GM) progenitors to differentiate into MegE lineages, while inhibiting normal lymphoid or GM differentiation. GATA-1 upregulated critical MegE-related transcription factors such as FOG-1 and GATA-2 in lymphoid and GM progenitors, and their MegE development did not require "permissive" erythropoietin signals. Furthermore, GATA-1 induced apoptosis of proB and myelomonocytic cells, which could not be prevented by enforced permissive Bcl-2 or myeloid cytokine signals. Thus, GATA-1 specifically instructs MegE commitment while excluding other fate outcomes in stem and progenitor cells, suggesting that regulation of GATA-1 is critical in maintaining multilineage homeostasis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Ontario Canc Inst, Dept Cell & Mol Biol, Toronto, ON M4X 1K9, Canada. Harvard Univ, Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. Univ Tokyo, Inst Med Sci, Dept Mol & Dev Biol, Tokyo, Japan. RP Akashi, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA072009]; NIDDK NIH HHS [DK050654, DK061320] NR 60 TC 126 Z9 129 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD SEP PY 2003 VL 19 IS 3 BP 451 EP 462 DI 10.1016/S1074-7613(03)00242-5 PG 12 WC Immunology SC Immunology GA 724RD UT WOS:000185499800015 PM 14499119 ER PT J AU Wan, J Martinvalet, D Ji, X Lois, C Kaech, SM Von Andrian, UH Lieberman, J Ahmed, R Manjunath, N AF Wan, J Martinvalet, D Ji, X Lois, C Kaech, SM Von Andrian, UH Lieberman, J Ahmed, R Manjunath, N TI The Bcl-2 family pro-apoptotic molecule, BNIP3 regulates activation-induced cell death of effector cytotoxic T lymphocytes SO IMMUNOLOGY LA English DT Article ID RECEPTOR TRANSGENIC MICE; TUMOR-NECROSIS-FACTOR; IN-VIVO; LIGAND INTERACTIONS; DOWN-REGULATION; PROTEIN NIP3; MEMBER BIM; BH3 DOMAIN; CD95 FAS; DELETION AB BNIP3 is a recently described pro-apoptotic member of the Bcl-2 family and in BNIP3 cDNA-transfected cell lines, cell death occurs via a caspase-independent pathway with opening of the mitochondrial permeability transition (PT) pore and rapid loss of mitochondrial transmembrane potential (Deltapsi(m)). However, its expression or function in physiologic cell types is not known. Our results using the T-cell receptor transgenic mice P14, specific for lymphocyte choreomeningitis virus (LCMV) glycoprotein, show that in contrast to the other Bcl-2 family pro-apoptotic molecules, BNIP3 is transcriptionally highly up-regulated in effector cytotoxic T lymphocytes (CTL). Because CTL have a propensity to undergo activation-induced cell death (AICD) upon restimulation, we tested for other features associated with BNIP3-induced cell death. AICD of CTL was caspase-independent as determined by measuring caspase activation during target cell killing as well as by lack of inhibition with caspase inhibitors. Moreover, similar to BNIP3-induced cell death, CTL apoptosis was associated with increased production of reactive oxygen species and decreased Deltapsi(m). Finally, retroviral transduction of BNIP3 antisense RNA diminished AICD in effector CTL. These results suggest that BNIP3 may play an important role in T-cell homeostasis by regulating effector CTL numbers. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA USA. RP Manjunath, N (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI von Andrian, Ulrich/A-5775-2008; Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [R21 AI046566, R01 AI046566, AI46566] NR 36 TC 24 Z9 24 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD SEP PY 2003 VL 110 IS 1 BP 10 EP 17 DI 10.1046/j.1365-2567.2003.01710.x PG 8 WC Immunology SC Immunology GA 717WV UT WOS:000185114500002 PM 12941136 ER PT J AU Hou, RH Goloubeva, O Neuberg, DS Strominger, JL Wilson, SB AF Hou, RH Goloubeva, O Neuberg, DS Strominger, JL Wilson, SB TI Interleukin-12 and interleukin-2-induced invariant natural killer T-cell cytokine secretion and perforin expression independent of T-cell receptor activation SO IMMUNOLOGY LA English DT Article ID V(ALPHA)14 NKT CELLS; DENDRITIC CELLS; ALPHA-GALACTOSYLCERAMIDE; STIMULATORY FACTOR; HUMAN-LYMPHOCYTES; ANTIGEN RECEPTOR; IMMUNE-RESPONSES; IL-12 PRODUCTION; GENE-EXPRESSION; IFN-GAMMA AB Human invariant natural killer (iNK) T cells expressing an invariant Valpha24-Jalpha15 T-cell receptor (TCR) are thought to be important regulators of autoimmunity and tumour surveillance. Two major subsets of iNK T cells, CD4(+) or CD4(-) CD8(-) are known to exist, but the in vivo importance of CD4 expression is unclear. Since interleukin-12 (IL-12) is a key iNK T-cell-activating cytokine, the effect of IL-12 plus or minus the T-cell growth factor IL-2 on a large panel of CD4(+) versus CD4- CD8- iNK T-cell clones was examined. Strikingly, IL-12 and IL-2 significantly activated iNK T cells to secrete IL-4, interferon-gamma and granulocyte-macrophage colony-stimulating factor, and up-regulated perforin expression in the absence of TCR stimulation. Furthermore, IL-2 and IL-12 treatment resulted in a preferential increase in apoptosis of CD4(-) CD8(-) clones. Thus, independent of TCR activation, IL-2 and IL-12 can directly activate iNK T cells and provide a selective advantage to the CD4(+) iNK T-cell population. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Wilson, SB (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [R01 AI045051, R01 AI45051] NR 59 TC 13 Z9 13 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD SEP PY 2003 VL 110 IS 1 BP 30 EP 37 DI 10.1046/j.1365-2567.2003.01701.x PG 8 WC Immunology SC Immunology GA 717WV UT WOS:000185114500004 PM 12941138 ER PT J AU Li, Q Cherayil, BJ AF Li, Q Cherayil, BJ TI Role of toll-like receptor 4 in macrophage activation and tolerance during Salmonella enterica serovar typhimurium infection SO INFECTION AND IMMUNITY LA English DT Article ID TOLL-LIKE RECEPTORS; NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; MOUSE PERITONEAL-MACROPHAGES; INNATE IMMUNE-RESPONSE; NITRIC-OXIDE SYNTHASE; GENE-EXPRESSION; C3H-HEJ MICE; INTRACELLULAR REPLICATION; AVIRULENT SALMONELLA AB Toll-like receptors (TLRs) play an important role in the innate immune response, particularly in the initial interaction between the infecting microorganism and phagocytic cells, such as macrophages. We investigated the role of TLR4 during infection of primary murine peritoneal macrophages with Salmonella enterica serovar Typhimurium. We found that macrophages from the C3H/HeJ mouse strain, which carries a functionally inactive Tlr4 gene, exhibit marked impairment of tumor necrosis factor alpha (TNF-alpha) secretion in response to S. enterica serovar Typhimurium infection. However, activation of extracellular growth factor-regulated kinase and NF-kappaB signaling pathways was relatively unaffected, as was increased expression of TNF-alpha mRNA. Furthermore, macrophage tolerance, which is associated with increased expression of the NF-kappaB p50 and p52 subunits, was induced by S. enterica serovar Typhimurium even in the absence of functional TLR4. These results indicate that during infection of macrophages by S. enterica serovar Typhimurium, TLR4 signals are required at a posttranscriptional step to maximize secretion of TNF-alpha. Signals delivered by pattern recognition receptors other than TLR4 are sufficient for the increased expression of the TNF-alpha transcript and at least some genes associated with macrophage tolerance. C1 Massachusetts Gen Hosp, Mucosal Immunol Lab, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Cherayil, BJ (reprint author), Pediat Gastroenterol Unit, Room 3400,MGH E,Bldg 114,16th St, Charlestown, MA 02129 USA. FU NIAID NIH HHS [R01 AI048815, R01 AI48815] NR 56 TC 25 Z9 26 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 SEP PY 2003 VL 71 IS 9 BP 4873 EP 4882 DI 10.1128/IAI.71.9.4873-4882.2003 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 715WR UT WOS:000184996600007 PM 12933828 ER PT J AU Gyurko, R Boustany, G Huang, PL Kantarci, A Van Dyke, TE Genco, CA Gibson, FC AF Gyurko, R Boustany, G Huang, PL Kantarci, A Van Dyke, TE Genco, CA Gibson, FC TI Mice lacking inducible nitric oxide synthase demonstrate impaired killing of Porphyromonas gingivalis SO INFECTION AND IMMUNITY LA English DT Article ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; BACTEROIDES-GINGIVALIS; PERIODONTITIS SUBJECTS; SUPEROXIDE-PRODUCTION; ENDOTHELIAL-CELLS; NADPH OXIDASE; NEUTROPHILS; PEROXYNITRITE; APOPTOSIS; LIPOPOLYSACCHARIDE AB Porphyromonas gingivalis is a primary etiological agent of generalized severe periodontitis, and emerging data suggest the importance of reactive oxygen and nitrogen species in periodontal tissue damage, as well as in microbial killing. Since nitric oxide (NO) released from inducible NO synthase (iNOS) has been shown to possess immunomodulatory, cytotoxic, and antibacterial effects in experimental models, we challenged iNOS-deficient (iNOS(-/-)) mice with P. gingivalis by using a subcutaneous chamber model to study the specific contribution of NO to host defense during P. gingivalis infection. iNOS(-/-) mice inoculated with P. gingivalis developed skin lesions and chamber rejection with higher frequency and to a greater degree than similarly challenged C57BL/6 wild-type (WT) mice. Chamber fluid from iNOS(-/-) mice possessed significantly more P. gingivalis than that of WT mice. The immunoglobulin G responses to P. gingivalis in serum was similar in WT and iNOS(-/-) mice, and the inductions of tumor necrosis factor alpha, interleukin-1beta and interleukin-6, and prostaglandin E-2 were comparable between the two mouse strains. Although no differences in total leukocyte counts in chamber fluids were observed between iNOS(-/-) and WT mice, the percentage of dead polymorphonuclear leukocytes (PMNs) was significantly greater in iNOS(-/-) mouse chamber fluids than that of WT samples. Interestingly, casein-elicited PMNs from iNOS(-/-) mice released more superoxide than did WT PMNs when stimulated with P. gingivalis. These results indicate that modulation of superoxide levels is a mechanism by which NO influences PMN function and that NO is an important element of the host defense against P. gingivalis. C1 Boston Univ, Goldman Sch Dent Med, Dept Periodontol & Oral Biol, Boston, MA 02118 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02118 USA. Harvard Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Med Ctr, Infect Dis Sect, Dept Med, Boston, MA 02118 USA. Boston Univ, Med Ctr, Dept Microbiol, Boston, MA 02118 USA. RP Gyurko, R (reprint author), Boston Univ, Goldman Sch Dent Med, Dept Periodontol & Oral Biol, 100 E Newton St, Boston, MA 02118 USA. OI Gyurko, Robert/0000-0003-1457-6812; Gibson, Frank/0000-0003-1988-1170 FU NHLBI NIH HHS [HLS7818]; NIDCR NIH HHS [F32-DE05739, K22 DE014568, P01 DE013191, 1 K22 DE 14568-01A1, DE 13191, F32 DE005739, P01-DE13191, R01-DE12517] NR 55 TC 33 Z9 34 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2003 VL 71 IS 9 BP 4917 EP 4924 DI 10.1128/IAI.71.9.4917-4924.2003 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 715WR UT WOS:000184996600012 PM 12933833 ER PT J AU Campos-Neto, A Suffia, I Cavassani, KA Jen, S Greeson, K Ovendale, P Silva, JS Reed, SG Skeiky, YAW AF Campos-Neto, A Suffia, I Cavassani, KA Jen, S Greeson, K Ovendale, P Silva, JS Reed, SG Skeiky, YAW TI Cloning and characterization of a gene encoding an immunoglobulin-binding receptor on the cell surface of some members of the family Trypanosomatidae SO INFECTION AND IMMUNITY LA English DT Article ID BLOOD-STREAM FORMS; AFRICAN PATHOGENIC TRYPANOSOMES; HUMAN MONONUCLEAR PHAGOCYTES; STREPTOCOCCAL PROTEIN-G; ASP-CONTAINING REGION; SCHISTOSOMA-MANSONI; LEISHMANIA-DONOVANI; CRUZI; MACROPHAGES; HOST AB Several members of the Trypanosomatidae family, when freshly isolated from their mammalian hosts, have immunoglobulins adsorbed to their cell surfaces. However, a significant portion of these antibody molecules is not parasite specific, i.e., the immunoglobulins are bound to the parasite's cell surface molecules via noncognitive interactions. It has been proposed that this noncognitive adsorption of immunoglobulins to the parasite is mediated by an Fc-like receptor present in several members of the Trypanosomatidae family. However, the molecular identification of this receptor has never been defined. Here, we describe the cloning of a gene encoding a protein that might represent this molecule. The gene, named Lmsp1, was cloned by screening a Leishmania major cDNA expression library using a rabbit antiserum. Lmsp1 is present in both Leishmania and Trypanosoma and is expressed in all developmental stages of these parasites. The predicted protein has a molecular mass of 16.6 kDa and contains an RGD sequence starting at residue 104 and three cysteine residues at positions 55, 74, and 116. The purified recombinant protein strongly binds to normal immunoglobulins of various animal species (humans, rabbits, sheep, goats, guinea pigs, donkeys, rats, and mice) and the binding to human immunoglobulins appears to be immunoglobulin G (IgG) and IgM isotype specific. Moreover, Lmsp1 binds to both purified Fc and Fab fragments of IgG from both humans and rabbits. The mapping of the Lmsp1 epitopes that bind human IgG revealed that different sequences of the molecule bind to Fc or Fab. In addition, fluorescence-activated cell sorter analyses with a specific rabbit anti-Lmsp1 antiserum showed that Lmsp1 is associated with the parasite's cell surface. Finally, inhibition experiments point to an active role of this molecule in the immunoglobulin-mediated attachment and penetration of Trypanosoma cruzi in its macrophage host cells, thus suggesting that Lmsp1 is a putative Trypanosomatidae immunoglobulin receptor. C1 Infect Dis Res Inst, Seattle, WA USA. Corixa Corp, Seattle, WA USA. Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Immunol, BR-05508 Sao Paulo, Brazil. RP Campos-Neto, A (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. RI Silva, Joao/A-4484-2008 FU NIAID NIH HHS [AI25038, R01 AI025038] NR 39 TC 7 Z9 7 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2003 VL 71 IS 9 BP 5065 EP 5076 DI 10.1128/IAI.71.9.5065-5076.2003 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 715WR UT WOS:000184996600028 PM 12933849 ER PT J AU Craig, WA AF Craig, WA TI Basic pharmacodynamics of antibacterials with clinical applications to the use of beta-lactams, glycopeptides, and linezolid SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID ACUTE OTITIS-MEDIA; RESPIRATORY-TRACT INFECTIONS; GRAM-POSITIVE INFECTIONS; MOUSE PERITONITIS MODEL; CRITICALLY ILL PATIENTS; STAPHYLOCOCCUS-AUREUS; STREPTOCOCCUS-PNEUMONIAE; CONTINUOUS-INFUSION; IN-VIVO; PHARMACOKINETIC PARAMETERS AB Pharmacodynamics (PDs) deals with the relationship between measures of drug exposure and the antimicrobial effect. Although different antimicrobials have been shown to vary in both their killing pattern and the presence and duration of persistent effects, drugs can still be divided into three major groups. The first group includes antibacterials that induce concentration-dependent killing and produce moderate to prolonged persistent effects. The second group is virtually the opposite of first group in that these drugs exhibit primarily time-dependent killing and produce minimal or no persistent effects with most organisms. The third and last group includes drugs that also have time-dependent killing but differ from the second group in that they produce moderate to prolonged persistent effects. This article focuses on the pharmacodynamics for beta-lactams, glycopeptides, and linezolid. C1 Univ Wisconsin, Madison, WI 53705 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Craig, WA (reprint author), Univ Wisconsin, 2500 Overlook Terrace,Room D-2221, Madison, WI 53705 USA. NR 101 TC 271 Z9 282 U1 1 U2 30 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD SEP PY 2003 VL 17 IS 3 BP 479 EP + DI 10.1016/S0891-5520(03)00065-5 PG 24 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 755YM UT WOS:000187439100001 PM 14711073 ER PT J AU Papakostas, GI Petersen, T Worthington, JJ Roffi, PA Alpert, JE Fava, M Nierenberg, AA AF Papakostas, GI Petersen, T Worthington, JJ Roffi, PA Alpert, JE Fava, M Nierenberg, AA TI A pilot, open study of sertraline in outpatients with treatment-resistant depression (TRD) or with a history of TRD who responded but later relapsed SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE antidepressant non-response; depression; medication switch; refractory depression; sertraline; SSRI; treatment-resistant ID MAJOR DEPRESSION; DOUBLE-BLIND; PAROXETINE; NORTRIPTYLINE; DISORDER AB While most depressed patients are prescribed a selective serotonin reuptake inhibitor (SSRI) as an initial treatment, the use of SSRIs as a second or third-line treatment for depression is not as prevalent. This trial assessed the efficacy of sertraline for patients with treatment-resistant depression (TRD) or patients with a history of TRD who responded but later relapsed. Twelve patients with TRD who had not responded to a number of antidepressant trials (n=7), or had responded but subsequently suffered a relapse (n=5), were enrolled in an 8-week, open trial of sertraline. Both a completer analysis (n=6) and an intent-to-treat (ITT) analysis (n=12) were performed to evaluate sertraline response rates. Using a completer analysis, four patients (66.6%) were classified as responders; one (16.7%) as a partial responder and one (16.7%) as a non-responder. An ITT analysis resulted in five (41.7%) patients being classified as responders; one (8.3%) as a partial responder and six (50%) as non-responders. Of the four responders in the completer analysis, three (50%) achieved remission. Of the five responders in the ITT analysis, four (33.3%) achieved remission. Overall, two of seven (28.6%) non-responders and three of five (60.0%) relapsers responded to sertraline. The present results suggest the potential utility of sertraline for patients with TRD, or those with a history of TRD who responded but later relapsed, and warrant larger, placebo-controlled studies to further explore the potential role of sertraline for such patients. (C) 2003 Lippincott Williams Wilkins. 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 [R29 MH 46952] NR 20 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-1315 EI 1473-5857 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD SEP PY 2003 VL 18 IS 5 BP 293 EP 296 DI 10.1097/01.yic.0000080800.87368.da PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 715WA UT WOS:000184994700006 PM 12920390 ER PT J AU Niederman, R Theodosopoulou, JN AF Niederman, R Theodosopoulou, JN TI A systematic review of in vivo retrograde obturation materials SO INTERNATIONAL ENDODONTIC JOURNAL LA English DT Review DE obturation; retrograde; systematic review ID GLASS-IONOMER CEMENT; GUTTA-PERCHA; AMALGAM; FAILURE; APICECTOMY; COMPOSITE; SUCCESS; EBA AB Purpose The aim of this study was to answer the question: For patients requiring apicoectomy (apicectomy/ root-end resection) and retrograde (root-end) obturation (filling), which retrograde obturation (root-end filling) material(s) is/are the most effective, as determined by reduction in periapical radiolucency and elimination of signs and symptoms? Materials and methods A MEDLINE and a Cochrane search (two specified searches) were conducted to identify randomised (RCT) and nonrandomised controlled clinical trials (CCT), cohort studies (CS) and case-control studies (CCS), published between 1966 and 2002, October week 4, conducted on humans, and published in English, German and French language, relating to retrograde obturation materials following apicoectomy. Results The MEDLINE and the Cochrane search identified 324 and 21 published articles, respectively. The Cochrane search identified three additional articles to the MEDLINE-search articles. Fourteen studies met the inclusion criteria: two were RCTs, six were CCTs, none was a CS and six were retrospective CCSs. Nine of the 14 studies compared a new retrograde (root-end)-filling material to amalgam, 4 of the 14 studies compared orthograde root canal fillings to retrograde (root-end) amalgam and the fourteenth study compared variations of a resin composite (Retroplast) when used in combination with the bonding agent Gluma (BayerAG, Gluma 1 and 2). The two RCTs indicated that glass ionomer cement appeared to be equivalent to amalgam. The six CCTs indicated that orthograde filling with gutta-percha and sealer was more effective than amalgam retrograde (root-end)-filling (one trial). Similarly, retrograde (root-end)filling with (i) composite and Gluma (Bayer AG, Leverkusen, Germany) as bonding agent (one trial), (ii) reinforced zinc oxide eugenol cement (EBA cement) (Stailine, Staident, Middlesex, England; one trial) and (iii) gold leaf (one trial) appeared to be better than amalgam retrograde (root-end)-filling. Finally, gutta-percha retrograde (root-end)-filling appears to be less effective than amalgam (one trial) and Retroplast with ytterbium trifluoride is better than Retroplast with silver, when they are both used with Gluma as bonding agent (one trial). Conclusions For the highest level of evidence (RCT) retrograde (root-end)-filling with glass ionomer cement is almost as effective as amalgam. However, there was a significant caveat as there were only two RCTs. At the next highest level of evidence (CCT), and given the additional caveat that there was only one controlled trial for each material, retrograde (root-end) EBA cement, composite with Gluma and gold leaf, as well as orthograde gutta-percha, may be more effective than retrograde (root-end) amalgam filling. In conclusion, these results suggest that additional validating CCTs and RCTs are needed. C1 Forsyth Inst, Boston, MA 02115 USA. RP Niederman, R (reprint author), Ctr Evidence Based Dent, 140 Fenway, Boston, MA 02115 USA. OI niederman, richard/0000-0001-6674-1774 NR 30 TC 23 Z9 24 U1 1 U2 8 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0143-2885 J9 INT ENDOD J JI Int. Endod. J. PD SEP PY 2003 VL 36 IS 9 BP 577 EP 585 DI 10.1046/j.1365-2591.2003.00696.x PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 722QY UT WOS:000185388800001 PM 12950570 ER PT J AU Fromigue, O Louis, K Wu, EX Belhacene, N Loubat, A Shipp, M Auberger, P Mari, B AF Fromigue, O Louis, K Wu, EX Belhacene, N Loubat, A Shipp, M Auberger, P Mari, B TI Active stromelysin-3 (MMP-11) increases MCF-7 survival in three-dimensional matrigel culture via activation of p42/p44 MAP-kinase SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE stromelysin-3; MMP; apoptosis; matrigel; MAP-kinase ID BREAST-CANCER CELLS; GENE-EXPRESSION; IN-VIVO; METALLOPROTEINASE INHIBITORS; FROG METAMORPHOSIS; MESSENGER-RNA; APOPTOSIS; TUMOR; GROWTH; CARCINOMA AB Stromelysin-3 (ST3) has the characteristic structure of matrix metalloproteinases (MMP), but its substrate specificity and pattern of expression differ markedly from that of other MMP family members. ST3 was originally isolated on the basis of its expression in primary breast cancers and has been shown to be overexpressed in virtually all primary carcinomas, suggesting that ST3 participates in the initial development of epithelial malignancies. Recent data using murine models reported that ST3 expression was able to increase tumor take by suppressing cell apoptosis. Our present goal was to set up an in vitro model in which we could study this new function. For this purpose, we analyzed survival of MCF-7 transfectants expressing either wild-type or catalytically inactive ST3 (ST3wt or ST3cat-) in three-dimensional (3-D) culture conditions by inclusion in Matrigel. In such conditions, that mimic the in vivo microenvironment, we found a marked decrease in the percentage of cell death when active ST3 was expressed (ST3wt transfectants vs. ST3cat- or vector only transfectants) as assessed by FACS and TUNEL analysis. The addition of batimastat, a broad spectrum MMP inhibitor, reversed the increased cell survival in ST3wt transfectants, confirming that ST3 enzymatic activity was required for this effect. Finally, we analyzed the expression of anti- and pro-apoptotic proteins as well as activation of cell survival pathways and we found that ST3-mediated cell survival was accompanied by activation of both p42/p44 MAPK and AKT. Our data confirm and extend the anti-apoptotic function of ST3 and provide a useful model to dissect this new role and identify new physiological substrates. (C) 2003 Wiley-Liss, Inc. C1 INSERM, U526, Fac Med Pasteur, Equipe Labellisee LNC, F-06107 Nice 2, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. INSERM, U364, IFR50, Fac Med, Nice, France. RP Mari, B (reprint author), INSERM, U526, Fac Med Pasteur, Equipe Labellisee LNC, Ave Valombrose, F-06107 Nice 2, France. RI Mari, Bernard/F-8960-2013; Mari, Bernard/D-7445-2015; AUBERGER, Patrick/G-1491-2013 OI Mari, Bernard/0000-0002-0422-9182; AUBERGER, Patrick/0000-0002-2481-8275 NR 53 TC 14 Z9 17 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 1 PY 2003 VL 106 IS 3 BP 355 EP 363 DI 10.1002/ijc.11232 PG 9 WC Oncology SC Oncology GA 703KA UT WOS:000184277500009 PM 12845673 ER PT J AU Skates, S Troiano, R Knapp, RC AF Skates, S Troiano, R Knapp, RC TI Longitudinal CA125 detection of sporadic papillary serous carcinoma of the peritoneum SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE longitudinal CA125; papillary serous carcinoma of the peritoneum ID OVARIAN-CANCER; MARKERS AB In this case, rising longitudinal levels of CA125 were significant in the detection of peritoneal papillary serous carcinoma, and led to the indication for surgery. Rising longitudinal CA125 has been shown to be important in the detection of ovarian cancer, but little data exist as to its relevance for the detection of peritoneal papillary serous carcinoma. This rare primary tumor is usually associated with women at high risk for epithelial ovarian carcinoma, although this patient was not at high risk as she had no familial breast or ovarian cancer history. C1 Massachusetts Gen Hosp, MGH Biostat Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Cornell Univ, Weill Med Coll, Dept Obstet & Gynecol, New York, NY USA. Cornell Univ, Weill Med Coll, Dept Radiol, New York, NY USA. RP Skates, S (reprint author), 50 Staniford St,Suite 560, Boston, MA 02114 USA. FU NCI NIH HHS [CA 83639] NR 7 TC 14 Z9 14 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD SEP-OCT PY 2003 VL 13 IS 5 BP 693 EP 696 DI 10.1046/j.1525-1438.2003.t01-1-13050.x PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 731GD UT WOS:000185843600021 PM 14675358 ER PT J AU Murff, HJ Gandhi, TK Karson, AK Mort, EA Poon, EG Wang, SJ Fairchild, DG Bates, DW AF Murff, HJ Gandhi, TK Karson, AK Mort, EA Poon, EG Wang, SJ Fairchild, DG Bates, DW TI Primary care physician attitudes concerning follow-up of abnormal test results and ambulatory decision support systems SO INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS LA English DT Article DE electronic medical records; clinical decision support systems; patient safety; results follow-up; primary care; physician satisfaction ID ACADEMIC MEDICAL-CENTER; ORDER-ENTRY; MALPRACTICE CLAIMS; PRACTICE GUIDELINES; PATIENT; SATISFACTION; INFORMATION; PERFORMANCE; FEATURES; QUALITY AB Objectives: Failures to follow-up abnormal test results are common in ambulatory care. Information systems could assist providers with abnormal test result tracking, yet little is known about primary care providers attitudes toward outpatient decision support systems. Methods: A cross-sectional survey of 216 primary care physicians (PCPs) that utilize a single electronic medical record (EMR) without computer-based clinical decision support. Results: The overall response rate was 65% (140/216). Less than one-third of the respondents were satisfied with their current system to manage abnormal laboratory, radiographs, Pap smear, or mammograms results. Only 15% of providers were satisfied with their system to notify patients of abnormal results. over 90% of respondents felt automated systems to track abnormal test results would be useful. Seventy-nine percent of our respondents believed that they could comply better with guidelines through electronic clinical reminders. Conclusions: Most PCPs were not satisfied with their methods for tracking abnormal results. Respondents believed that clinical decision support systems (CDSS) would be useful and could improve their ability to track abnormal results. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Vanderbilt Univ, Med Ctr, Div Gen Internal Med, Nashville, TN 37212 USA. Dept Vet Affairs, TVH, GRECC Unit, Nashville, TN 37212 USA. Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. Partners HealthCare Syst, Boston, MA USA. RP Murff, HJ (reprint author), Vanderbilt Univ, Med Ctr, Div Gen Internal Med, 1310 24th Ave S, Nashville, TN 37212 USA. FU AHRQ HHS [R01 #1 U18 HS11046] NR 38 TC 51 Z9 52 U1 3 U2 6 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1386-5056 J9 INT J MED INFORM JI Int. J. Med. Inform. PD SEP PY 2003 VL 71 IS 2-3 BP 137 EP 149 DI 10.1016/S1386-5056(03)00133-3 PG 13 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 733WN UT WOS:000186023800005 PM 14519406 ER PT J AU Biederman, J Mick, E Faraone, SV Spencer, T Wilens, TE Wozniak, J AF Biederman, J Mick, E Faraone, SV Spencer, T Wilens, TE Wozniak, J TI Current concepts in the validity, diagnosis and treatment of paediatric bipolar disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE adolescents; ADHD; bipolar disorder; children; conduct disorder ID DEFICIT HYPERACTIVITY DISORDER; HOSPITALIZED AGGRESSIVE-CHILDREN; POSTTRAUMATIC-STRESS-DISORDER; MANIC-DEPRESSIVE ILLNESS; PROSPECTIVE FOLLOW-UP; CONDUCT DISORDER; PREPUBERTAL CHILDREN; DOUBLE-BLIND; PSYCHIATRIC-ILLNESS; COMORBID DISORDERS AB Despite ongoing controversy, the view that paediatric bipolar disorder is rare or non-existent has been increasingly challenged not only by case reports but also by systematic research. This research strongly suggests that paediatric bipolar disorder may not be rare but that it may be difficult to diagnose. Since children with bipolar disorder are likely to become adults with bipolar disorder, the recognition and characterization of childhood-onset bipolar disorder may help identify a meaningful developmental subtype of bipolar disorder worthy of further investigation. As recommended by Robins and Guze [American Journal of Psychiatry (1970), 126, 983-987], a psychiatric disorder may be considered a valid diagnostic entity if it can be shown to have differentiating features, evidence of familiality, specific treatment responsivity and a unique course. The goal of this article is to review our work and the extant literature within this framework to describe the evidence supporting bipolar disorder in children as a valid clinical diagnosis. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC 725, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC 725, 15 Parkman St, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 NR 61 TC 33 Z9 34 U1 7 U2 9 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD SEP PY 2003 VL 6 IS 3 BP 293 EP 300 DI 10.1017/S1461145703003547 PG 8 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 739GJ UT WOS:000186336500012 PM 12974996 ER PT J AU Ryan, AS Nicklas, BJ Berman, DM Elahi, D AF Ryan, AS Nicklas, BJ Berman, DM Elahi, D TI Adiponectin levels do not change with moderate dietary induced weight loss and exercise in obese postmenopausal women SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE adiponectin; adipose tissue; physical activity; weight reduction; leptin ID ADIPOSE-SPECIFIC PROTEIN; PLASMA ADIPONECTIN; INSULIN-RESISTANCE; OLDER WOMEN; BODY-FAT; HYPERINSULINEMIA; EXPRESSION; REDUCTION; RISK; AGE AB Objective: The purpose of this study was to determine changes in adiponectin levels with moderate weight loss, weight loss plus aerobic exercise, or weight loss plus resistive exercise in overweight and obese, sedentary postmenopausal women. Design: Longitudinal, clinical intervention study of 6-month (3 x/week) program of either weight loss (WL, n=15), weight loss + aerobic exercise (WL+AEX, n=16), or weight loss + resistive exercise (WL+RT, n=9) Subjects: We studied 40 sedentary, overweight and obese (body mass index, BMI=32+/-1 kg/m(2), X+/-s.e.m.) postmenopausal (57+/-1y) women. Measurements: Fat mass and fat-free mass (FFM) by dual-energy X-ray absorptiometry, plasma insulin, leptin, and adiponectin by radioimmunoassay. Results: Age, body weight, BMI, waist and hip circumferences, waist-to-hip ratio, VO(2)max, percent fat, total body fat mass, FFM, and fasting plasma glucose, insulin, leptin, and adiponectin concentrations were similar among WL, WL+AEX, and WL+RT groups before the interventions. In all women combined, body weight, BMI, and waist and hip circumferences decreased (P<0.001). There was a significant absolute decrease in percent body fat from 47 to 44%, representing a 13% decrease in total fat mass and a -1.6% change in FFM. Fasting concentrations of plasma adiponectin did not change (40&PLUSMN;16%, P=NS), whereas fasting plasma glucose, insulin, and leptin all decreased (P<0.001). Conclusions: Plasma adiponectin levels do not change with a 6-month moderate weight reduction program even when accompanied by aerobic or resistive exercise training in overweight and obese postmenopausal women. C1 Univ Maryland, Sch Med, Baltimore Vet Affairs Med Ctr, Dept Med,Div Gerontol, Baltimore, MD 21201 USA. VA Maryland Hlth Care Syst, GRECC, Baltimore, MD USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. RP Ryan, AS (reprint author), Univ Maryland, Sch Med, Baltimore Vet Affairs Med Ctr, Dept Med,Div Gerontol, BT-18-GR,10 N Greene St, Baltimore, MD 21201 USA. FU NIA NIH HHS [K01-AG00747, K01-AG00685]; PHS HHS [R29-A614066] NR 26 TC 115 Z9 121 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD SEP PY 2003 VL 27 IS 9 BP 1066 EP 1071 DI 10.1038/sj.ijo.0802387 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 712KH UT WOS:000184796500010 PM 12917712 ER PT J AU Yildiz, A Turgay, A Alpay, M Sachs, GS AF Yildiz, A Turgay, A Alpay, M Sachs, GS TI Observational data on the antiagitation effect of risperidone tablets in emergency settings: A preliminary report SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN CLINICAL PRACTICE LA English DT Article DE acute agitation; atypical antipsychotics; oral formulations ID INTRAMUSCULAR HALOPERIDOL; RAPID TRANQUILIZATION; DOUBLE-BLIND; ACUTE AGITATION; ACUTE-PSYCHOSIS; EFFICACY; OLANZAPINE; LORAZEPAM; PATIENT; CONCENTRATE AB OBJECTIVE: To provide preliminary data on the effectiveness of risperidone in tablet form in the emergency treatment of agitation. METHOD: Eighteen acutely agitated psychiatric patients who were given either haloperidol (2-5 mg intramuscular (i.m.)) or risperidone (1-2-mg tablet) were evaluated hourly using the four different agitation rating scales for 2 h. Concomitant use of lorazepam was allowed at the clinical discretion of the acute psychiatry service (APS) physician for both study groups. RESULTS: Baseline agitation scores of both groups were comparable. Both haloperidol and risperidone were found to be effective in decreasing agitation/aggression. CONCLUSIONS: This pilot study provides preliminary data suggesting that atypical antipsychotics in oral formulations may be effective in decreasing agitation in emergency settings. Further investigations of the use of oral formulations - including the tablet forms - of atypical antipsychotics in the emergency treatment of agitation are warranted. C1 Dokuz Eylul Med Sch, Dept Psychiat, Izmir, Turkey. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Bipolar Program, Boston, MA 02114 USA. Univ Toronto, Toronto, ON, Canada. Scarborough Gen Hosp, Toronto, ON, Canada. RP Yildiz, A (reprint author), 170 Sok Guller Apt 8-8,PK 35360,Basin Sitesi, Izmir, Turkey. NR 15 TC 5 Z9 5 U1 1 U2 1 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1365-1501 J9 INT J PSYCHIAT CLIN JI Int. J. Psychiat. Clin. PD SEP PY 2003 VL 7 IS 3 BP 217 EP 221 DI 10.1080/13651500310000889 PG 5 WC Psychiatry SC Psychiatry GA 718FK UT WOS:000185134300011 ER PT J AU Hoffelt, SC Marshall, LM Garzotto, M Hung, A Holland, J Beer, TM AF Hoffelt, SC Marshall, LM Garzotto, M Hung, A Holland, J Beer, TM TI A comparison of CT scan to transrectal ultrasound-measured prostate volume in untreated prostate cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; prostate volume; CT; ultrasonography ID 3-DIMENSIONAL CONFORMAL RADIOTHERAPY; INTEROBSERVER VARIABILITY; RADIATION-THERAPY; LOCALIZATION; APEX; MRI; IMPLANTATION; DOSIMETRY; ACCURACY; IMPACT AB (P) under bar(u) under bar(r) under bar(p) under bar(o) under bar(s) under bar(e) under bar To compare CT and transrectal ultrasound (TRUS)-measured prostate volumes in patients with untreated prostate cancer. (M) under bar(e) under bar(t) under bar(h) under bar(o) under bar(d) under bar(s) under bar (a) under bar(n) under bar(d) under bar (M) under bar(a) under bar(t) under bar(e) under bar(r) under bar(i) under bar(a) under bar(l) under bar(s) under bar: Between 1995 and 1999, 48 consecutive patients at the Portland Veterans Affairs Medical Center were treated with external beam radiotherapy. In 36 of these patients, TRUS and CT measurements of the prostate volume were obtained before treatment and <6 months apart. The TRUS volume was calculated using the prolate ellipsoid formula. The CT volume was calculated from the contours of the prostate drawn by one physician, who was unaware of the TRUS volume calculation, on axial CT images. (R) under bar(e) under bar(s) under bar(u) under bar(l) under bar(t) under bar(s) under bar: The TRUS and CT prostate volume measurements correlated strongly (Pearson's correlation coefficient = 0.925, 95% confidence interval 0.856-0.961, p < 0.0001). The CT volume was consistently larger than the TRUS volume by a factor of approximately 1.5. In men with a TRUS prostate volume less than the median (<28 cm(3)), the CT/TRUS volume ratio was 1.7, and it was 1.4 for men whose volume was greater than the median. The CT volumes were correlated similarly with the TRUS volumes regardless of the CT slice interval. (C) under bar(o) under bar(n) under bar(c) under bar(l) under bar(u) under bar(s) under bar(i) under bar(o) under bar(n) under bar: A strong correlation was found between CT scan and TRUS measurement of the prostate volume; however, CT consistently overestimated the prostate volume by approximately 50% compared with TRUS. (C) 2003 Elsevier Inc. C1 Oregon Hlth Sci Univ, Dept Radiat Oncol & Div, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Endocrinol Diabet & Clin Nutr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Urol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Hematol & Med Oncol, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Div Urol, Portland, OR USA. RP Beer, TM (reprint author), Oregon Hlth Sci Univ, Dept Med, 3181 SW Sam Jackson Pk Rd,Mial Code L586, Portland, OR 97239 USA. FU NCRR NIH HHS [3 M01RR00334-33S2] NR 22 TC 51 Z9 51 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2003 VL 57 IS 1 BP 29 EP 32 DI 10.1016/S0360-3016(03)00509-1 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 710JB UT WOS:000184676100009 PM 12909212 ER PT J AU Dahiya, MC Redding, SW Dahiya, RS Eng, TY Kirkpatrick, WR Coco, BJ Sadkowski, LC Fothergill, AW Waite, A Rinaldi, MG Patterson, TF Thomas, CR AF Dahiya, MC Redding, SW Dahiya, RS Eng, TY Kirkpatrick, WR Coco, BJ Sadkowski, LC Fothergill, AW Waite, A Rinaldi, MG Patterson, TF Thomas, CR TI Oropharyngeal candidiasis caused by non-albicans yeast in patients receiving external beam radiotherapy for head-and-neck cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE non-albicans Candida; oropharyngeal candidiasis; head-and-neck cancer; radiotherapy; chromogenic medium ID VIRUS-INFECTED PATIENTS; ORAL CANDIDIASIS; FLUCONAZOLE SUSCEPTIBILITY; RADIATION; DUBLINIENSIS; COLONIZATION; RESISTANCE; AIDS AB Purpose: To characterize non-albicans Candida oral infections in patients with head-and-neck cancer receiving external beam radiotherapy (EBRT) with or without concurrent chemotherapy. Methods and Materials: Thirty-seven patients with head-and-neck cancer received EBRT in 2.0-Gy daily fractions to a median dose of 60.4 Gy (range 38-82.8, mean 64.6). They were followed for oropharyngeal candidiasis (OPC) confirmed by positive examination, positive KOH smear, and/or positive swab or swish culture. Samples were identified and plated on chromogenic media to identify non-albicans yeasts. Colonies were plated on Sabouraud dextrose slants for microdilution antifungal susceptibility testing to fluconazole. DNA typing, including karyotyping, restriction fragment length polymorphism analysis, and Southern blot hybridization with the moderately repetitive Ca3 probe, was performed on selected isolates to confirm individual species. Results: Of the 37 patients, 10 (27%) developed OPC, and 26 (70.3%) displayed Candida carriage state. The median EBRT dose at time of positive culture was 22.5 Gy and at time of OPC was 28.6 Gy. Of the 6 patients receiving chemotherapy and EBRT, 4 (66%) developed OPC at median dose of 27.6 Gy. Three (8%) of 37 patients were infected with non-albicans Candida, and 3 (30%) of all 10 infections were caused by these organisms. Conclusion: Non-albicans Candida is emerging as a relatively common cause of OPC in head-and-neck cancer patients. Chromogenic media are helpful to screen these infections. Our data also suggest a greater likelihood of developing OPC in patients receiving concomitant chemotherapy and EBRT. (C) 2003 Elsevier Inc. C1 Univ Texas, Hlth Sci Ctr, Dept Radiat Oncol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Gen Dent, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Dept Pathol, San Antonio, TX USA. RP Dahiya, MC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Radiat Oncol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 19 TC 25 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2003 VL 57 IS 1 BP 79 EP 83 DI 10.1016/S0360-3016(03)00415-2 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 710JB UT WOS:000184676100015 PM 12909218 ER PT J AU DeLaney, TF Chen, GT Mauceri, TC Munro, JJ Hornicek, FJ Pedlow, FX Suit, HD AF DeLaney, TF Chen, GT Mauceri, TC Munro, JJ Hornicek, FJ Pedlow, FX Suit, HD TI Intraoperative dural irradiation by customized (192)iridium and (90)yttrium brachytherapy plaques SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE sarcoma; spine; brachytherapy; surgery; radiotherapy ID PROGNOSTIC-FACTORS; PARASPINAL TUMORS; RADIATION-THERAPY; RADIOTHERAPY; SARCOMAS; SPINE; BONE; EXTREMITY; CHORDOMA AB Purpose: After vertebral or paravertebral tumor resection, tumor cells may remain on the dura. Because a tumoricidal dose is difficult to achieve using external beam radiotherapy without exceeding the spinal cord tolerance, we developed intraoperative applicators to deliver additional dose to the dura. Methods and Materials: Eight patients with vertebral or paravertebral tumor underwent conformal external beam radiotherapy, tumor resection, and intraoperative radiotherapy to the dura involved by tumor. At surgery, vertebra, soft tissue, and epidural tumor were resected. A radioactive applicator plaque was placed on the dura to deliver 7.5-15 Gy, and then removed. Vertebral reconstruction and stabilization was completed. Chemotherapy was administered for large, high-grade sarcomas. Results: We progressed through three plaque designs, initially Ir-192, subsequently liquid Y-90, and finally Y-90 foil in a semicylindrical polycarbonate plaque, in the treatment of 8 patients. The low-energy Y-90 beta-emissions provided a more attractive depth dose profile than that achievable with iridium and gave negligible staff radiation exposure. The 90Y depth dose measured 29% at 2 mm and 9% at 4 mm from the surface of the foil plaque, with acceptable surface dose homogeneity. The average surface dose rate ranged from 18.7 to 47.6 cGy/min for the iridium plaques and 45.2 to 187.5 cGy/min for the 90Y plaques. The treatments have been without acute or late neurologic complications. The disease of 6 of 8 patients was locally controlled at median potential follow-up of 24 months. Conclusions: The 90Y foil applicator is technically elegant, easy to use, and superior to the earlier models. It has been incorporated into a protocol for spinal tumor treatment. (C) 2003 Elsevier Inc. C1 Massachusetts Gen Hosp, NE Proton Therapy Ctr, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Implant Sci, Wakefield, MA USA. RP DeLaney, TF (reprint author), Massachusetts Gen Hosp, NE Proton Therapy Ctr, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. RI Grams, Michael/G-5197-2011 NR 21 TC 21 Z9 22 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2003 VL 57 IS 1 BP 239 EP 245 DI 10.1016/S0360-3016(03)00505-4 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 710JB UT WOS:000184676100036 PM 12909239 ER PT J AU Ferencik, M Ferullo, A Achenbach, S Abbara, S Chan, RC Booth, SL Brady, TJ Hoffmann, U AF Ferencik, M Ferullo, A Achenbach, S Abbara, S Chan, RC Booth, SL Brady, TJ Hoffmann, U TI Coronary calcium quantification using various calibration phantoms and scoring thresholds SO INVESTIGATIVE RADIOLOGY LA English DT Article DE coronary calcium; quantification; calibration phantoms; multidetector computed tomography ID ELECTRON-BEAM CT; ARTERY CALCIUM; COMPUTED-TOMOGRAPHY; IMPROVED REPRODUCIBILITY; CALCIFICATION; QUANTITATION; VARIABILITY; AGREEMENT; ALGORITHM; DISEASE AB Rationale and Objectives: To compare scoring threshold and calibration method-dependent accuracy and variability of coronary calcium measurements by multidetector computed tomography (MDCT). Methods: Ninety-five subjects were scanned with MDCT. We calculated Agatston score and volume score. Mineral mass (MM) was calculated using patient-based and scanner-based calibration methods. Accuracy of calibration was validated using artificial calcium cylinders. Results: Patient-based and scanner-based calibration permitted accurate quantification of artificial calcium cylinders (bias: 0 mg and -2 mg). In the subjects, the mean relative difference of MM measurements performed at 90 and 130 Hounsfield units threshold (59%) was lower than for Agatston score (94%) and volume score (109%; P<0.05). Patient-based and scanner-based calibration yielded systematically different MM measurements (bias: 22%). Conclusions: MM lowers threshold-dependent variability of coronary calcium measurements. Patient-based and scanner-based calibration allows accurate calcium quantification ex vivo but reveal systematic differences in subjects. Patient-based calibration may better account for subject size and composition. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. USDA, Jean Mayer Human Nutr Res Ctr Aging, Boston, MA USA. RP Ferencik, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, 100 Charles River Plaza,Suite 400, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL 69272]; NIA NIH HHS [AG 19147] NR 33 TC 19 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD SEP PY 2003 VL 38 IS 9 BP 559 EP 566 DI 10.1097/01.RLI.0000073449.90302.75 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 716DA UT WOS:000185012500003 PM 12960525 ER PT J AU Hirose, K Liberman, MC AF Hirose, K Liberman, MC TI Lateral wall histopathology and endocochlear potential in the noise-damaged mouse cochlea SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE acoustic trauma; stria vascularis; spiral ligament; cochlea ID INDUCED HEARING-LOSS; GUINEA-PIG COCHLEA; ION-TRANSPORT MECHANISMS; QUIET-AGED GERBILS; STRIA VASCULARIS; INNER-EAR; MARGINAL CELLS; ACOUSTIC TRAUMA; FINE-STRUCTURE; TUNING CURVES AB Noise exposure damages the stria and spiral ligament and may contribute to noise-induced threshold shift by altering the endocochlear potential (EP). The aim of this study was to correlate lateral wall histopathology with changes in EP and ABR thresholds. CBA/CaJ mice were exposed to octave band (8-16 kHz) noise for 2 h at intensities ranging from 94 to 116 dB SPL and evaluated 0 h to 8 weeks postexposure. EP in control mice averaged 86 and 101 mV in apical and basal turns, respectively. The 94 dB exposures caused a 40 dB temporary threshold shift (TTS), and there was with no corresponding change in EP. The 112 and 116 dB exposures caused >60 dB threshold shifts at 24 h, and EP was transiently decreased, e.g., to 21 and 27 mV in apical and basal turns after 116 dB. By 1 week postexposure, EP returned to control values in all exposure groups, although those exposed to 112 or 116 dB showed large permanent threshold shifts (PTS). Cochleas were plastic-embedded and serial-sectioned for light microscopic and ultrastructural analysis. Acute changes included degeneration of type II fibrocytes of the spiral ligament and strial edema. The strial swelling peaked at 24 h when significant EP recovery had taken place, suggesting that these changes reflect compensatory volume changes. In the chronic state, massive loss of type H fibrocytes and degeneration of strial intermediate and marginal cells was observed with drastic reduction in membrane surface area. The results suggest that EP shifts do not occur with TTS and also do not add significantly to PTS in the steady state. However, EP loss could contribute to acute threshold shifts that resolve to a PTS. EP recovery despite significant strial degeneration may be partly due to decreased transduction current caused by hair cell damage. C1 Cleveland Clin Fdn, Dept Neurosci, Cleveland Clin Fdn NC 30, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Otolaryngol & Communicat Disorders, Cleveland, OH 44195 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Hirose, K (reprint author), Cleveland Clin Fdn, Dept Neurosci, Cleveland Clin Fdn NC 30, 9500 Euclid Ave, Cleveland, OH 44195 USA. FU NIDCD NIH HHS [P30 DC005209, R01 DC 00188, R01 DC000188] NR 52 TC 130 Z9 138 U1 1 U2 6 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1525-3961 J9 JARO JI JARO PD SEP PY 2003 VL 4 IS 3 BP 339 EP 352 DI 10.1007/s10162-002-3036-4 PG 14 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 726XD UT WOS:000185626100004 PM 14690052 ER PT J AU Rosowski, JJ Brinsko, KM Tempel, BI Kujawa, SG AF Rosowski, JJ Brinsko, KM Tempel, BI Kujawa, SG TI The aging of the middle ear in 129S6/SvEvTac and CBA/CaJ mice: Measurements of umbo velocity, hearing function, and the incidence of pathology SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE middle ear; aging; presbycusis; middle-ear infection ID AGE-RELATED LOSS; TYMPANIC MEMBRANE; OTITIS-MEDIA; MOUSE; GENOTYPES; STRAINS AB Measurements of umbo velocity and auditory brainstem response (ABR) were made on two different strains of mice, 129S6/SvEvTac (129S6) and CBA/CaJ (CB), within three different age ranges. The velocity measurements were made with a laser Doppler vibrometer using a semiclosed sound delivery system; the frequency range of accurate velocity measurements is from 1 to 21 kHz. The visual detection threshold of the ABR was determined at selected frequencies between 2 and 32 kHz. The velocity results suggest a small but significant change in umbo velocity with age in both strains, between the youngest (1.5-3 months) and mid-aged (12-14 months) groups. There is also a clear difference in the umbo velocity in the youngest animals of the two strains, with tire 129S6 having more sensitive middle-ear function than the CB. These results support the existence of a small age-related loss in middle-ear sensitivity in the mouse that was first described in the BALB/6J strain. The age-related changes in middle-ear function observed in both CB and 129S6 are much smaller than the age-related decreases in ABR. Our results also describe a statistically significant increase in the incidence of middle-ear pathology with age in the 129S6. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Univ Washington, Virginia Merrill Bloedel Hearoing Res Ctr, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. RP Rosowski, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. NR 29 TC 23 Z9 25 U1 0 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1525-3961 J9 JARO JI JARO PD SEP PY 2003 VL 4 IS 3 BP 371 EP 383 DI 10.1007/s10162-002-3047-1 PG 13 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 726XD UT WOS:000185626100007 PM 14690055 ER PT J AU Coull, BA Mezzetti, M Ryan, LM AF Coull, BA Mezzetti, M Ryan, LM TI A Bayesian hierarchical model for risk assessment of methylmercury SO JOURNAL OF AGRICULTURAL BIOLOGICAL AND ENVIRONMENTAL STATISTICS LA English DT Editorial Material DE benchmark dose; dose-response; Gibbs sampling; linear mixed model; meta-analysis; multiple outcomes; WinBUGS ID SEYCHELLES CHILD-DEVELOPMENT; LINEAR MIXED MODELS; MULTIPLE OUTCOMES; METAANALYSIS; EXPOSURE; REGRESSION; RESPONSES AB This article uses a Bayesian hierarchical model to quantify the adverse health effects associated with in-utero exposure to methylmercury. By allowing for study-to-study as well as outcome-to-outcome variability, the approach provides a useful meta-analytic tool for multi-outcome, multi-study environmental risk assessments. The analysis presented here expands on the findings of a National Academy of Sciences (NAS) committee, charged with advising the United States Environmental Protection Agency (EPA) on an appropriate approach to conducting a risk assessment for methylmercury. The NAS committee, for which the senior author (Ryan) was a committee member, reviewed the findings from several conflicting studies and reported the results from a Bayesian hierarchical model that synthesized information across several studies and for several outcomes. Although the NAS committee did not suggest that the hierarchical model be used as the actual basis for a methylmercury risk assessment, the results from the model were used to justify and support the final recommendation that the risk analysis be based on data from a study conducted in the Faroe Islands, which had found an association between in-utero exposure to methylmercury and impaired neurological development. We consider a variety of statistical issues, but particularly sensitivity to model specification. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Bocconi, Ist Metodi Quantitativi, Milan, Italy. Harvard Univ, Sch Publ Hlth, Dept Biostat Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Coull, BA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 31 TC 11 Z9 11 U1 1 U2 4 PU AMER STATISTICAL ASSOC & INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1444 I ST NW, STE 700, WASHINGTON, DC 20005 USA SN 1085-7117 J9 J AGRIC BIOL ENVIR S JI J. Agric. Biol. Environ. Stat. PD SEP PY 2003 VL 8 IS 3 BP 253 EP 270 DI 10.1198/1085711032291 PG 18 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 726NK UT WOS:000185605500001 ER PT J AU Torriani, M Hadigan, C Jensen, ME Grinspoon, S AF Torriani, M Hadigan, C Jensen, ME Grinspoon, S TI Psoas muscle attenuation measurement with computed tomography indicates intramuscular fat accumulation in patients with the HIV-lipodystrophy syndrome SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE insulin resistance; protease inhibitor; acquired immunodeficiency syndrome; human immunodeficiency virus ID ACTIVE ANTIRETROVIRAL THERAPY; TYPE-2 DIABETES-MELLITUS; VIRUS-INFECTED PATIENTS; INSULIN-RESISTANCE; ABDOMINAL FAT; TOTAL-BODY; MEN; ABNORMALITIES; SENSITIVITY; GLUCOSE AB The human immunodeficiency virus (HIV)-lipodystrophy syndrome is characterized by abnormalities of lipid metabolism, glucose homeostasis, and fat distribution. Overaccumulation of intramuscular lipid may contribute to insulin resistance in this population. We examined 63 men: HIV positive with lipodystrophy (n = 22), HIV positive without lipodystrophy (n = 20), and age- and body mass index-matched HIV-negative controls (n = 21). Single-slice computed tomography was used to determine psoas muscle attenuation and visceral fat area. Plasma free fatty acids (FFA), lipid profile, and markers of glucose homeostasis were measured. Muscle attenuation was significantly decreased in subjects with lipodystrophy [median (interquartile range), 55.0 (51.0-58.3)] compared with subjects without lipodystrophy [57.0 ( 55.0-59.0); P = 0.05] and HIV-negative controls [59.5 (57.3-64.8); P < 0.01]. Among HIV-infected subjects, muscle attenuation correlated significantly with FFA (r = -0.38; P = 0.02), visceral fat (r = -0.49; P = 0.002), glucose (r = -0.38; P = 0.02) and insulin (r = -0.60; P = 0.0001) response to a 75-g oral glucose tolerance test. In forward stepwise regression analysis with psoas attenuation as the dependent variable, visceral fat (P = 0.02) and FFA (P < 0.05), but neither body mass index, subcutaneous fat, nor antiretroviral use, were strong independent predictors of muscle attenuation (r(2) = 0.39 for model). Muscle attenuation (P = 0.02) and visceral fat (P = 0.02), but not BMI, subcutaneous fat, FFA, or antiretroviral use, were strong independent predictors of insulin response ( area under the curve) to glucose challenge (r(2) = 0.47 for model). These data demonstrate that decreased psoas muscle attenuation due to intramuscular fat accumulation may contribute significantly to hyperinsulinemia and insulin resistance in HIV-lipodystrophy patients. Further studies are needed to assess the mechanisms and consequences of intramuscular lipid accumulation in HIV-infected patients. C1 Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Torriani, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, 15 Parkman St,WACC 515, Boston, MA 02114 USA. FU NCRR NIH HHS [RR-01066, RR-300088]; NIDDK NIH HHS [DK-59535] NR 36 TC 37 Z9 37 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD SEP PY 2003 VL 95 IS 3 BP 1005 EP 1010 DI 10.1152/japplphysiol.00336.2003 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 711HP UT WOS:000184733800014 PM 12766180 ER PT J AU McKay, LC Evans, KC Frackowiak, RSJ Corfield, DR AF McKay, LC Evans, KC Frackowiak, RSJ Corfield, DR TI Neural correlates of voluntary breathing in humans SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE respiratory control; brain stem; cortex; functional magnetic resonance imaging ID CEREBRAL BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; VOLITIONAL INSPIRATION; CORTICAL INVOLVEMENT; VENTILATORY RESPONSE; SENSORY STIMULATION; BRAIN; CORTEX; ACTIVATION; MOVEMENTS AB To investigate the functional neuroanatomy of voluntary respiratory control, blood O(2) level-dependent functional magnetic resonance imaging was performed in six healthy right-handed individuals during voluntary hyperpnea. Functional images of the whole brain were acquired during 30-s periods of spontaneous breathing alternated with 30-s periods of isocapnic hyperpnea [ spontaneous vs. voluntary: tidal volume = 0.5 +/- 0.01 vs. 1.3 +/- 0.1 (SE) liters and breath duration = 4.0 +/- 0.4 vs. 3.2 +/- 0.4 (SE) s]. For the group, voluntary hyperpnea was associated with significant ( P < 0.05, corrected for multiple comparisons) neural activity bilaterally in the primary sensory and motor cortices, supplementary motor area, cerebellum, thalamus, caudate nucleus, and globus pallidum. Significant increases in activity were also identified in the medulla ( corrected for multiple comparisons on the basis of a small volume correction for a priori region of interest) in a superior dorsal position ( P = 0.012). Activity within the medulla suggests that the brain stem respiratory centers may have a role in mediating the voluntary control of breathing in humans. C1 Univ Keele, Mackay Inst Commun & Neurosci, Sch Life Sci, Keele ST5 5BG, Staffs, England. UCL, Wellcome Dept Imaging Neurosci, Neurol Inst, London WC1N 3BG, England. Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London W6 8RP, England. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, McLean Hosp, Boston, MA 02115 USA. RP Corfield, DR (reprint author), Univ Keele, Mackay Inst Commun & Neurosci, Sch Life Sci, Keele ST5 5BG, Staffs, England. EM d.corfield@keele.ac.uk RI Frackowiak, Richard/I-1809-2013; Frackowiak, Richard/H-4383-2011 OI Frackowiak, Richard/0000-0002-3151-822X NR 47 TC 112 Z9 116 U1 4 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD SEP PY 2003 VL 95 IS 3 BP 1170 EP 1178 DI 10.1152/japplphysiol.00641.2002 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 711HP UT WOS:000184733800035 PM 12754178 ER PT J AU Wagner, B Galey, WR AF Wagner, B Galey, WR TI Kinetic analysis of hexose transport to determine the mechanism of amygdalin and prunasin absorption in the intestine SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE amygdalin; prunasin/D-mandelonitrile beta-D-glucoside; phloridzin; rat; monosaccharide transport; everted sac; glycoside transport; small intestine; absorption; D-[C-14]-glucose ID ACTIVE-TRANSPORT; RAT INTESTINE; DOSAGE FORMS; LAETRILE; INVITRO; METABOLISM; TOXICITY; SYSTEM; MEXICO; CANCER AB Evidence is accumulating that glucose-conjugated compounds may be carried across the gut mucosa via the epithelial sodium-dependent monosaccharide transporter SGLT1. A modification of the everted intestinal sac technique was utilized to study the transport of the cyanogenic glycoside amygdalin (D-mandelonitrile beta-D-gentiobioside) and its metabolite D-mandelontrile P-D-glucoside (prunasin). Everted sacs of rat jejunum and ileum were bathed in isotonic oxygenated sodium chloride-potassium phosphate buffer containing 2.8 muCi D-[H-3]-mannose and 0.187 muCi D-[C-14]-glucose. For treatment groups, buffers contained phloridzin, galactose, amygdalin or prunasin. The rate constant (k) for the transport process was calculated. Compared with the control (n = 33), phloridzin (n = 25) significantly reduced the rate constants of both D-[C-14]-glucose and D-[H-3]-mannose. Substitution of sodium with choline and incremental galactose treatments similarly reduced D-[C-14]-glucose influx, indicating that a fraction of the transport is carrier-mediated. Treatment with amygdalin did not significantly affect the rate constants Of D- [C-14]-glucose or D- [H-3]-mannose transport. However, treatment with 1 mM prunasin (a = 16) did reduce the influx of D-[C-14]-glucose without affecting D-[H-3]-mannose values. This is consistent with the reports finding that glycoside absorption may be mediated by SGLT1. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol,S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Howard Hughes Med Inst, HHMI NIH Med Scholars Program, Chevy Chase, MD 20815 USA. RP Wagner, B (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol,S Texas Vet Hlth Care Syst, 7703 Floyd Curl Dr,MC 7882, San Antonio, TX 78229 USA. OI Wagner, Brent/0000-0002-7063-0142 NR 38 TC 4 Z9 4 U1 1 U2 9 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD SEP-OCT PY 2003 VL 23 IS 5 BP 371 EP 375 DI 10.1002/jat.934 PG 5 WC Toxicology SC Toxicology GA 724LX UT WOS:000185490000010 PM 12975776 ER PT J AU Weaver, F Hynes, D Hopkinson, W Wixson, R Khuri, S Daley, J Henderson, WG AF Weaver, F Hynes, D Hopkinson, W Wixson, R Khuri, S Daley, J Henderson, WG TI Preoperative risks and outcomes of hip and knee arthroplasty in the veterans health administration SO JOURNAL OF ARTHROPLASTY LA English DT Article DE joint replacement; outcomes; veterans; Surgery ID AFFAIRS SURGICAL RISK; CARDIAC-SURGERY; POSTOPERATIVE MORTALITY; ORTHOPEDIC-SURGERY; QUALITY; CARE; REPLACEMENT; MEDICARE; COMPLICATIONS; IMPROVEMENT AB The relationship between patient characteristics and outcomes of total joint arthroplasty (TJA) was examined in a population of veterans treated in VA hospitals. Outcomes included 30-day mortality and morbidity, postoperative length of stay, and readmission caused by surgical complications. A larger proportion of women then men were functionally impaired before Surgery in both the hip (22% vs. 14%) and knee samples (14% vs. 7%; all P<.01). Rates of adverse outcomes in this Population were very low. Preoperative comorbid conditions, abnormal laboratory values, and being nonwhite were related to poor outcomes of TJA. Gender was a significant independent predictor of morbidity and length of stay for total knee arthroplasty. (C) 2003 Elsevier Inc. All rights reserved. C1 Hines VAMC, Midw Ctr Hlth Serv & Policy Res, Hines, IL USA. Northwestern Univ, Inst Hlth Serv Res & Policy Studies, Chicago, IL 60611 USA. Hines VAMC, Cooperat Studies Program Coordinating Ctr, Hines, IL USA. Hines VAMC, VA Informat Resource Ctr, Hines, IL USA. Loyola Univ Chicago, Maywood, IL USA. Northwestern Univ, Sch Med, Chicago, IL USA. Boston VA Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Tenet Healthcare Syst, Dallas, TX USA. Dartmouth Coll Sch Med, Hanover, NH USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. RP Weaver, F (reprint author), Edward Hines Jr Vet Adm Hosp, Midw Ctr Hlth Serv & Policy Res, POB 5000 151H, Hines, IL 60141 USA. NR 31 TC 79 Z9 81 U1 2 U2 3 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD SEP PY 2003 VL 18 IS 6 BP 693 EP 708 DI 10.1054/S0883-5403(03)00259-6 PG 16 WC Orthopedics SC Orthopedics GA 725ZL UT WOS:000185572500003 PM 14513441 ER PT J AU Nelson, KE Fleischmann, RD DeBoy, RT Paulsen, IT Fouts, DE Eisen, JA Daugherty, SC Dodson, RJ Durkin, AS Gwinn, M Haft, DH Kolonay, JF Nelson, WC Mason, T Tallon, L Gray, J Granger, D Tettelin, H Dong, H Galvin, JL Duncan, MJ Dewhirst, FE Fraser, CM AF Nelson, KE Fleischmann, RD DeBoy, RT Paulsen, IT Fouts, DE Eisen, JA Daugherty, SC Dodson, RJ Durkin, AS Gwinn, M Haft, DH Kolonay, JF Nelson, WC Mason, T Tallon, L Gray, J Granger, D Tettelin, H Dong, H Galvin, JL Duncan, MJ Dewhirst, FE Fraser, CM TI Complete genome sequence of the oral pathogenic bacterium Porphyromonas gingivalis strain W83 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID MICROBIAL GENE IDENTIFICATION; BACTEROIDES-GINGIVALIS; CYSTEINE PROTEINASE; ESCHERICHIA-COLI; STREPTOCOCCUS-GORDONII; TREPONEMA-DENTICOLA; HELICOBACTER-PYLORI; EXPRESSION; PROTEASE; CLONING AB The complete 2,343,479-bp genome sequence of the gram-negative, pathogenic oral bacterium Porphyromonas gingivalis strain W83, a major contributor to periodontal disease, was determined. Whole-genome comparative analysis with other available complete genome sequences confirms the close relationship between the Cytophaga-Flavobacteria-Bacteroides (CFB) phylum and the green-sulfur bacteria. Within the CFB phyla, the genomes most similar to that of P. gingivalis are those of Bacteroides thetaiotaomicron and B. fragilis. Outside of the CFB phyla the most similar genome to P. gingivalis is that of Chlorobium tepidum, supporting the previous phylogenetic studies that indicated that the Chlorobia and CFB phyla are related, albeit distantly. Genome analysis of strain W83 reveals a range of pathways and virulence determinants that relate to the novel biology of this oral pathogen. Among these determinants are at least six putative hemagglutinin-like genes and 36 previously unidentified peptidases. Genome analysis also reveals that P. gingivalis can metabolize a range of amino acids and generate a number of metabolic end products that are toxic to the human host or human gingival tissue and contribute to the development of periodontal disease. C1 Inst Genom Res, Rockville, MD 20850 USA. Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. RP Nelson, KE (reprint author), Inst Genom Res, 9712 Med Ctr Dr, Rockville, MD 20850 USA. RI Paulsen, Ian/K-3832-2012; Nelson, William/E-9263-2016; OI Paulsen, Ian/0000-0001-9015-9418; Nelson, William/0000-0002-1873-3929; Fraser, Claire/0000-0003-1462-2428; Eisen, Jonathan A./0000-0002-0159-2197 FU NIDCR NIH HHS [R01DE-13914] NR 74 TC 243 Z9 533 U1 0 U2 14 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 2003 VL 185 IS 18 BP 5591 EP 5601 DI 10.1128/JB.185.18.5591-5601.2003 PG 11 WC Microbiology SC Microbiology GA 719AR UT WOS:000185181500029 PM 12949112 ER PT J AU Bae, DS Waters, PM Zurakowski, D AF Bae, DS Waters, PM Zurakowski, D TI Reliability of three classification systems measuring active motion in brachial plexus birth palsy SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID NATURAL-HISTORY; INJURIES; REPAIR; RECONSTRUCTION; PARALYSIS; PROGNOSIS AB Background: Several classification systems for the categorization of function in patients with brachial plexus birth palsy have been proposed. The purpose of this investigation was to determine the intraobserver and interobserver reliability of the modified Mallet Classification, Toronto Test Score, and Hospital for Sick Children Active Movement Scale in the evaluation of these patients. Methods: Eighty children with brachial plexus birth palsy were evaluated by two trained examiners on two different occasions. Intraobserver and interobserver reliability was determined with use of the kappa statistic. Results: On the basis of the kappa statistic, intraobserver reliability was good to excellent for individual elements of the modified Mallet Classification, Toronto Test Score, and Active Movement Scale in all age-groups. Interobserver reliability for individual elements of these three systems ranged from fair to excellent. When aggregate Toronto Test and modified Mallet scores were assessed, positive intraobserver and interobserver correlations were noted (Pearson r = 0.70 to 0.98, p < 0.001). Internal consistency (test-retest reliability) as determined by the Cronbach alpha for the aggregate Toronto Test and modified Mallet scores was excellent for each age-group (alpha > 0.90, p < 0.001). Conclusions: The modified Mallet Classification, Toronto Test Score, and Active Movement Scale are reliable instruments for assessing upper-extremity function in patients with brachial plexus birth palsy. The natural history and surgical outcomes of these patients can now be conducted with use of these reliable outcomes instruments. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Bae, DS (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRB 622, Boston, MA 02114 USA. NR 32 TC 67 Z9 73 U1 0 U2 5 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD SEP PY 2003 VL 85A IS 9 BP 1733 EP 1738 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 722XN UT WOS:000185403500012 PM 12954832 ER PT J AU Yun, AG Rubash, HE Scott, RD Laskin, RS AF Yun, AG Rubash, HE Scott, RD Laskin, RS TI Quadriceps rupture associated with a proximal quadriceps release in total knee arthroplasty - A report of three cases SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID EXTENSOR MECHANISM COMPLICATIONS; V-Y QUADRICEPSPLASTY; EXPOSURE; TENDON C1 Centinela Hosp, Arthritis Inst, Inglewood, CA 90301 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. Hosp Special Surg, Dept Orthopaed Surg, New York, NY 10021 USA. RP Yun, AG (reprint author), Centinela Hosp, Arthritis Inst, 501 E Hardy St,Suite 300, Inglewood, CA 90301 USA. NR 12 TC 4 Z9 5 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD SEP PY 2003 VL 85A IS 9 BP 1809 EP 1811 PG 3 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 722XN UT WOS:000185403500024 PM 12954843 ER PT J AU Abe, Y Chen, W Isoda, R Yang, S Nishino, M Li, YP AF Abe, Y Chen, W Isoda, R Yang, S Nishino, M Li, YP TI The bHLH transcription factor P8 enhances bone formation by promoting osteoblast cell proliferation and inhibiting osteocalcin expression. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 Harvard Univ, Sch Dent Med, Forsyth Inst, Boston, MA 02115 USA. Univ Tokushima, Sch Dent, Dept Pediat Dent, Tokushima 770, Japan. RI Yang, Shuying/G-4599-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S78 EP S78 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500303 ER PT J AU Bastepe, M Frohlich, L Juppner, H AF Bastepe, M Frohlich, L Juppner, H TI The paternally imprinted autosomal dominant form of pseudohypoparathyroidism type-Ib is associated with a 2998-bp deletion centromeric SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S34 EP S34 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500128 ER PT J AU Bischoff, DS Jia, S Yamaguchi, DT AF Bischoff, DS Jia, S Yamaguchi, DT TI Analysis of protein secretion profiles in undifferentiated and ATRA-differentiated C3H10T1/2 cells upon TGFB stimulation using the Ciphergen ProteinChip System. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Ciphergen Biosyst Inc, Fremont, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S331 EP S331 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080501333 ER PT J AU Calvi, LM Weber, J Adams, GB Harvey, J Schipani, E Puzas, JE Kronenberg, HM Scadden, DT Milner, LA AF Calvi, LM Weber, J Adams, GB Harvey, J Schipani, E Puzas, JE Kronenberg, HM Scadden, DT Milner, LA TI Osteoblastic and stromal cell activation of the PTH/PTHrP receptor alters the bone marrow microenvironment and increases osteoblastic expression of the notch ligand Jagged1 SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 Univ Rochester, Sch Med, Rochester, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S6 EP S6 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500018 ER PT J AU Erben, RG Mayer, D Weber, K Johnson, T Jonsson, K Juppner, H Lanske, B AF Erben, RG Mayer, D Weber, K Johnson, T Jonsson, K Juppner, H Lanske, B TI Ubiquitous overexpression of Phex does not fully rescue the Hyp mouse phenotype SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 Univ Munich, Inst Anim Physiol, Munich, Germany. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Dent Med, Forsyth Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S22 EP S22 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500081 ER PT J AU Frohlich, L Gensure, RC Juppner, H Bastepe, A AF Frohlich, L Gensure, RC Juppner, H Bastepe, A TI Linkage disequilibrium analysis of the PTH/PTHrP receptor gene across different human populations. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S209 EP S209 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500825 ER PT J AU Gamer, LW Nove, J Rosen, V AF Gamer, LW Nove, J Rosen, V TI BMP-3 is a negative regulator of cell maturation during skeletogenesis. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 HSDM, Boston, MA USA. Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S58 EP S58 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500227 ER PT J AU Gensure, RC Ponugoti, B Gunes, Y Papasani, M Bastepe, M Rubin, DA Juppner, H AF Gensure, RC Ponugoti, B Gunes, Y Papasani, M Bastepe, M Rubin, DA Juppner, H TI Identification and characterization of two PTH-like molecules in zebrafish. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 Harvard Univ, Endocrine Unit, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Illinois State Univ, Dept Biol Sci, Normal, IL 61761 USA. RI PONUGOTI, BHASKAR/H-2230-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S399 EP S399 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080501619 ER PT J AU Gori, F Demay, MB AF Gori, F Demay, MB TI The effects of BIG-3 on osteoblast differentiation are not dependent upon endogenously produced BMPs. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S74 EP S75 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500289 ER PT J AU Gori, F Demay, MB AF Gori, F Demay, MB TI BIG-3, a novel WD-40 protein, accelerates chondrocyte differentiation in vitro. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S60 EP S60 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500233 ER PT J AU Guo, J Short, G Szczepanik, A Elmessadi, N Bringhurst, FR Kronenberg, HM AF Guo, J Short, G Szczepanik, A Elmessadi, N Bringhurst, FR Kronenberg, HM TI Transcriptional profiling of embryonic tibia after PTH treatment in vivo reveals numerous genes that are affected by PTHR activation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Microaaray Facil, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S176 EP S176 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500687 ER PT J AU Guo, J Chung, U Szczepanik, A Yang, D Bringhurst, FR Kronenberg, HM AF Guo, J Chung, U Szczepanik, A Yang, D Bringhurst, FR Kronenberg, HM TI PTH/PTHrP receptor delays chondrocyte hypertrophy via both Runx2-dependent and independent pathways. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S38 EP S38 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500145 ER PT J AU Hansen, KE Vallarta-Ast, N Krueger, D Drezner, M Binkley, N AF Hansen, KE Vallarta-Ast, N Krueger, D Drezner, M Binkley, N TI A comparison of lumbar vertebral T-scores by three methods: Average L1-L4 BMD, lumbar BMD by ISCD criteria, and lowest vertebral body T-score. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 Univ Wisconsin, Osteoprososis Clin Ctr, Madison, WI 53706 USA. Univ Wisconsin, Res Program, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S117 EP S117 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500457 ER PT J AU Hattersley, G Garnet, D Fajardo, R von Stechow, D Adams, J Rosenblatt, M Alexander, JM AF Hattersley, G Garnet, D Fajardo, R von Stechow, D Adams, J Rosenblatt, M Alexander, JM TI IkB kinase beta (IKKb) inhibition prevents ovariectomy-induced bone loss in mice. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 Millennium Pharmaceut Inc, Cambridge, MA USA. Harvard Univ, Sch Med, BIDMC, Div Bone & Mineral Metab Res, Boston, MA USA. Harvard Univ, Sch Med, BIDMC, Orthoped Biomech Lab, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S95 EP S95 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500372 ER PT J AU Hershey, CL Fisher, DE AF Hershey, CL Fisher, DE TI Genomic structure and regulation of expression of the microphthalmia transcription factor (Mitf) in osteoclasts. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S148 EP S148 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500580 ER PT J AU Huang, W Rudkin, GH Sukkarieh, M Ishida, K Yamaguchi, DT Miller, TA AF Huang, W Rudkin, GH Sukkarieh, M Ishida, K Yamaguchi, DT Miller, TA TI Differentiation of MC3T3-E1 pre-osteoblastic cells on two-dimensional poly(lactide-co-glycolide) (PLGA) films and three-dimensional PLGA scaffolds - A real-time RT-PCR study. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 VA Greater LA Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S342 EP S343 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080501383 ER PT J AU Inada, M Wang, Y Byrne, MH Miyaura, C Krane, SM AF Inada, M Wang, Y Byrne, MH Miyaura, C Krane, SM TI The collagenase, matrix metalloproteinase-13 (MMP-13), is required for osteoclast formation and function. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 Tokyo Univ Pharm & Life Sci, Dept Biochem, Tokyo, Japan. Massachusetts Gen Hosp, Rheumatol CIID, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S195 EP S195 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500769 ER PT J AU Kobayashi, T Hinoi, E Kronenberg, HM AF Kobayashi, T Hinoi, E Kronenberg, HM TI Osteoblast kinetics in vivo. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S102 EP S102 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500399 ER PT J AU Leder, BZ Rohrer, JL Rubin, SD Gallo, J Finkelstein, JS AF Leder, BZ Rohrer, JL Rubin, SD Gallo, J Finkelstein, JS TI Aromatase inhibition does not alter bone turnover, serum OPG or bone density in elderly men with mild hypogonadism. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 Eximias Pharmaceut, Berwyn, PA USA. AstraZeneca Pharmaceut, Wilmington, DE USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S42 EP S42 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500160 ER PT J AU Mahon, MJ Segre, GV AF Mahon, MJ Segre, GV TI NHERF-1 is required for phospholipase C-dependent calcium influx induced by parathyroid hormone in opossum kidney cells. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S291 EP S291 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080501163 ER PT J AU Papasani, MR Gensure, RC Postlethwait, JH Gunes, Y Ponugoti, B Juppner, H Rubin, DA AF Papasani, MR Gensure, RC Postlethwait, JH Gunes, Y Ponugoti, B Juppner, H Rubin, DA TI Identification and characterization of the zebrafish gene encoding tuberoinfundibular peptide of 39 residues. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 Illinois State Univ, Normal, IL 61761 USA. Harvard Univ, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02115 USA. Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA. RI PONUGOTI, BHASKAR/H-2230-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S400 EP S400 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080501624 ER PT J AU Patterson, EK Watson, PH Canaff, LE Hendy, GN Bringhurst, R Hodsman, AB Fraher, LJ AF Patterson, EK Watson, PH Canaff, LE Hendy, GN Bringhurst, R Hodsman, AB Fraher, LJ TI Expression of GFP-PTH/PTHrP receptor constructs in LLC-PK1 (Clone 46) cells restores responsiveness to hPTH (1-34). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 Univ Western Ontario, London, ON, Canada. McGill Univ, Calcium Res Lab, Montreal, PQ, Canada. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S291 EP S291 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080501166 ER PT J AU Shimizu, N Tsang, JC Khatri, A Gardella, TJ AF Shimizu, N Tsang, JC Khatri, A Gardella, TJ TI Development of PTH(1-14)-based antagonist analogs that bind to the juxtamembrane portion of the PTH-1 receptor. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S176 EP S176 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500689 ER PT J AU Vallarta-Ast, NL Krueger, D Binkley, N AF Vallarta-Ast, NL Krueger, D Binkley, N TI Does radius bone density measurement over-diagnosis osteoporosis in men? SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. Univ Wisconsin, Osteoporosis Clin Ctr, Madison, WI 53706 USA. Univ Wisconsin, Res Program, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S116 EP S117 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500456 ER PT J AU Ward, LM Bastepe, M French, I Lawrence, SE Glorieux, FH Jueppner, H Lawson, ML AF Ward, LM Bastepe, M French, I Lawrence, SE Glorieux, FH Jueppner, H Lawson, ML TI Pseudohypoparathyroidisim without Albright's Hereditary Osteodystrophy features: A novel, autosomal recessive form in a Kuwaiti kindred. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 Childrens Hosp Eastern Ontario, Div Endocrinol & Metab, Ottawa, ON K1H 8L1, Canada. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Shriners Hosp Children, Genet Unit, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S98 EP S98 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500382 ER PT J AU Wiren, K Zhang, XW Toombs, A Harada, S Jepsen, K AF Wiren, K Zhang, XW Toombs, A Harada, S Jepsen, K TI Targeted overexpression of androgen receptor in osteoblasts results in complex skeletal phenotype in growing animals. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 OHSU, Portland VA Med Ctr, Portland, OR USA. Merck Res Labs, W Point, PA USA. Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S293 EP S293 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080501173 ER PT J AU Wiren, K Toombs, A Zhang, XW AF Wiren, K Toombs, A Zhang, XW TI Inhibition of MEK-ERK-Elk signaling by androgens may influence osteoblast apoptosis. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 OHSU, Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S138 EP S138 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500537 ER PT J AU Wittelsberger, A Corich, M Lee, B Barazza, A Yacobi, R Czodrowski, P Mierke, DF Alexander, JM Rosenblatt, M Chorev, M AF Wittelsberger, A Corich, M Lee, B Barazza, A Yacobi, R Czodrowski, P Mierke, DF Alexander, JM Rosenblatt, M Chorev, M TI Interactions between the mid-region of PTH-(1-34) and the receptor orient the hormone for receptor activation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res ID PHOTOAFFINITY CROSS-LINKING C1 Harvard Univ, Sch Med, BIDMC, Boston, MA 02115 USA. Brown Univ, Providence, RI 02912 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S101 EP S101 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500394 ER PT J AU Yamamoto, T Imanishi, Y Koshiyama, H Miyoshi, Y Shimizu, N Kinoshita, E Nakagomi, Y Miyauchi, A Satomura, K Inaba, M Sugimoto, T Nishizawa, Y Juppner, H Ozono, K AF Yamamoto, T Imanishi, Y Koshiyama, H Miyoshi, Y Shimizu, N Kinoshita, E Nakagomi, Y Miyauchi, A Satomura, K Inaba, M Sugimoto, T Nishizawa, Y Juppner, H Ozono, K TI Increased circulating level of FGF-23 in patients with McCune-Albright syndrome. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, PediatEndocrine Unit, Boston, MA 02114 USA. Kobe Univ, Grad Sch Med, Dept Clin Mol Med, Div Endocrinol Metab, Kobe, Hyogo, Japan. Natl Hyogo Chuo Hosp, Sanda, Japan. Yamanashi Univ, Sch Med, Kofu, Yamanashi 400, Japan. Nagasaki Univ, Sch Med, Nagasaki 852, Japan. Res Inst Maternal & Child Hlth, Izumi, Japan. Osaka Med Ctr, Div Pediat 2, Izumi, Japan. Osaka Univ, Grad Sch Med, Suita, Osaka, Japan. Kitano Hosp, Med Res Inst, Osaka, Japan. Osaka City Univ, Grad Sch Med, Osaka 558, Japan. Minoh City Hosp, Mino, Japan. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S44 EP S44 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500169 ER PT J AU Yang, S Chen, W Abe, Y Li, YP AF Yang, S Chen, W Abe, Y Li, YP TI RGS12 is essential for signaling by RANKL for terminal differentiation of osteoclasts via Ca2+ oscillation pathway. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 Harvard Univ, Sch Dent Med, Forsyth Inst, Boston, MA 02115 USA. RI Yang, Shuying/G-4599-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S48 EP S48 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500188 ER PT J AU Mataix-Cols, D Alonso, P Hernandez, R Deckersbach, T Savage, CR Menchon, JM Vallejo, J AF Mataix-Cols, D Alonso, P Hernandez, R Deckersbach, T Savage, CR Menchon, JM Vallejo, J TI Relation of neurological soft signs to nonverbal memory performance in obsessive-compulsive disorder SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID NEUROPSYCHOLOGICAL PERFORMANCE; SCHIZOPHRENIA; RELIABILITY; IMPAIRMENT; SYSTEM; SCALE AB Few studies have examined the relation between neurological soft signs (NSS) and neuropsychological performance in Obsessive-Compulsive Disorder (OCD). Thirty outpatients with primary OCD and 30 matched normal controls were administered the Cambridge Neurological Inventory and the Rey-Osterrieth Complex Figure Test (RCFT). A series of multiple regression models tested the relationship between NSS and performance on the RCFT. Patients presented significantly more neurological soft signs than controls on both sides of the body, and were impaired on the free recall and organization scores of the RCFT. Nonverbal memory deficits in OCD were predicted independently by organizational strategies during the copy condition of the RCFT, and neurological soft signs. There might be at least two variables independently mediating nonverbal memory deficits in OCD: (1) a cognitive organization and planning component, and (2) a complex motor regulatory component. C1 GKT Sch Med, Dept Psychol Med, London, England. Inst Psychiat, London, England. Bellvitge Univ Hosp, Dept Psychiat, Barcelona, Catalunya, Spain. Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. RP Mataix-Cols, D (reprint author), Guys Hosp, GKT Sch Med, Dept Psychol Med, 5th Floor,Thomas Guy House, London SE1 9RT, England. RI Menchon, Jose/A-5242-2009; Mataix-Cols, David/G-3843-2010 OI Menchon, Jose/0000-0002-6231-6524; Mataix-Cols, David/0000-0002-4545-0924 NR 28 TC 26 Z9 26 U1 5 U2 6 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD SEP PY 2003 VL 25 IS 6 BP 842 EP 851 DI 10.1076/jcen.25.6.842.16470 PG 10 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 739WL UT WOS:000186369700010 PM 13680461 ER PT J AU Binkley, N Krueger, D Vallarta-Ast, N AF Binkley, N Krueger, D Vallarta-Ast, N TI An overlying femur bone fat panniculus affects mass measurement SO JOURNAL OF CLINICAL DENSITOMETRY LA English DT Article DE bone density; obesity; DXA; femur ID X-RAY ABSORPTIOMETRY; MINERAL DENSITY; LUMBAR SPINE; SOFT-TISSUE; OSTEOPOROSIS; IMPACT; WEIGHT; ERRORS; HIP AB Dual-energy X-ray absorptiometry (DXA) is currently the gold standard technique for osteoporosis diagnosis. However, DXA has limitations, including artifacts, such as degenerative disease or metallic foreign bodies, that may confound bone mineral density (BMD) results. Because fat folds overlying the proximal femur may alter soft-tissue density in a nonuniform manner, this may be a currently unappreciated confounder of proximal femur BMD measurement. This possibility was evaluated in 127 patients (52 women/75 men) referred for routine BMD measurement who were identified as having a fat panniculus overlying their proximal femur scan area. Presence of a fat panniculus within the scan field was confirmed by visual assessment of images obtained utilizing a GE Lunar Expert-XL. Subsequently, these individuals were rescanned while retracting their fat panniculus away from the femur scan area without other repositioning between scans. In 49% of the men, and 56% of the women, either the femoral neck, trochanter, or total femur BNID differed by more than the least significant change at our facility. No pattern was observed to predict whether BMD would increase or decrease upon fat retraction. Subsequently, 30 patients were scanned using the standard and retracted technique twice, with repositioning between scans to establish precision. Retracted and standard precision was similar. In conclusion, an overlying fat panniculus may alter proximal femur BMD measurement, which would be expected to impair the ability to accurately diagnose low bone mass and monitor osteoporosis therapy. When a fat panniculus overlays the proximal femur scan area, its retraction should be part of routine densitometric practice. C1 Univ Wisconsin, Inst Aging, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Med Ctr, Dept Radiol, Madison, WI 53705 USA. RP Binkley, N (reprint author), Univ Wisconsin, Inst Aging, 1300 Univ Ave,2245 MSC, Madison, WI 53706 USA. NR 17 TC 37 Z9 37 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1094-6950 J9 J CLIN DENSITOM JI J. Clin. Densitom. PD FAL PY 2003 VL 6 IS 3 BP 199 EP 204 DI 10.1385/JCD:6:3:199 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 726QX UT WOS:000185611500001 PM 14514987 ER PT J AU Bastepe, M Juppner, H AF Bastepe, M Juppner, H TI Pseudohypoparathyroidism and mechanisms of resistance toward multiple hormones: Molecular evidence to clinical presentation SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID PROTEIN ALPHA-SUBUNIT; MOUSE GNAS LOCUS; HEREDITARY OSTEODYSTROPHY; PARENTAL ORIGIN; GENE; METHYLATION; TRANSCRIPTS; ANTISENSE; MUTATIONS; TYPE-1A C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp Children, Boston, MA 02114 USA. RP Juppner, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Endocrine Unit, Wellman 5, Boston, MA 02114 USA. EM jueppner@helix.mgh.harvard.edu NR 45 TC 18 Z9 19 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2003 VL 88 IS 9 BP 4055 EP 4058 DI 10.1210/jc.2003-031271 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720JY UT WOS:000185258700003 PM 12970261 ER PT J AU Nelson, AE Bligh, RC Mirams, M Gill, A Au, A Clarkson, A Juppner, H Ruff, S Stalley, P Scolyer, RA Robinson, BG Mason, RS Bligh, PC AF Nelson, AE Bligh, RC Mirams, M Gill, A Au, A Clarkson, A Juppner, H Ruff, S Stalley, P Scolyer, RA Robinson, BG Mason, RS Bligh, PC TI Clinical case seminar - Fibroblast growth factor 23: A new clinical marker for oncogenic osteomalacia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DOMINANT HYPOPHOSPHATEMIC RICKETS; TUMOR-INDUCED OSTEOMALACIA; PHOSPHATE-TRANSPORT; MINERAL HOMEOSTASIS; MESENCHYMAL TUMOR; UNIQUE PROPERTIES; NUDE-MICE; FGF-23; PATIENT; PHEX AB The phosphate-wasting condition, oncogenic osteomalacia, is problematic to diagnose and manage clinically due to difficulty in locating the causative tumor. Fibroblast growth factor 23 (FGF23) has recently been implicated in the pathogenesis of oncogenic osteomalacia. In this case the patient presented with clinical features typical of oncogenic osteomalacia. Removal of an angiolipoma from the thigh did not correct the clinical or biochemical abnormalities. Subsequent identification and removal of a benign giant cell tumor in the pubic ramus, however, did result in normalization of his symptoms and signs. Positive staining for FGF23 protein by immunohistochemistry was demonstrated in the giant cell tumor, but not in the angiolipoma. The serum concentration of FGF23 was elevated in preoperative serum, then normalized after removal of the giant cell tumor. Expression of both FGF23 mRNA and protein was demonstrated in the giant cell tumor tissue, and FGF23 mRNA expression and renal phosphate uptake inhibitory activity were also detected in cultured giant cell tumor cells. This case provides further evidence for the involvement of FGF23 in the pathogenesis of oncogenic osteomalacia and for the utility of serum FGF23 measurement and immunohistochemical detection of FGF23 in the diagnosis and clinical management of this condition. C1 Royal N Shore Hosp, Kolling Inst Med Res, Canc Genet Dept, Sydney, NSW 2065, Australia. Univ Sydney, Kolling Inst Med Res, Canc Genet Dept, Sydney, NSW 2065, Australia. Royal N Shore Hosp, Dept Endocrinol, Sydney, NSW 2065, Australia. Royal N Shore Hosp, Dept Surg, Sydney, NSW 2065, Australia. Royal N Shore Hosp, Dept Anat Pathol, Sydney, NSW 2065, Australia. Univ Sydney, Inst Biomed Res, Dept Physiol, Sydney, NSW 2006, Australia. Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Royal Prince Alfred Hosp, Dept Surg, Sydney, NSW 2050, Australia. Royal Prince Alfred Hosp, Dept Anat Pathol, Sydney, NSW 2050, Australia. RP Nelson, AE (reprint author), Royal N Shore Hosp, Kolling Inst Med Res, Canc Genet Dept, Sydney, NSW 2065, Australia. EM annen@med.usyd.edu.au RI Gill, Anthony/D-4215-2015; OI Gill, Anthony/0000-0002-9447-1967; Scolyer, Richard/0000-0002-8991-0013 NR 34 TC 47 Z9 52 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2003 VL 88 IS 9 BP 4088 EP 4094 DI 10.1210/jc.2002-021919 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720JY UT WOS:000185258700010 PM 12970268 ER PT J AU Horr, R Kattany, L Robinson, EM AF Horr, R Kattany, L Robinson, EM TI Mrs. T's story: An interview SO JOURNAL OF CLINICAL ETHICS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Cardiac Surg Stepdown Unit, Boston, MA 02114 USA. RP Horr, R (reprint author), Massachusetts Gen Hosp, Cardiac Surg Stepdown Unit, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 138 W WASHINGTON ST, STE 403-405, HAGERSTOWN, MD 21740 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD FAL PY 2003 VL 14 IS 3 BP 190 EP 193 PG 4 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 757KE UT WOS:000187560900007 ER PT J AU Kattany, L Horr, R AF Kattany, L Horr, R TI The nurses' story about Mr. T SO JOURNAL OF CLINICAL ETHICS LA English DT Article C1 Massachusetts Gen Hosp, Cardiac Surg Step Down Unit, Boston, MA 02114 USA. RP Kattany, L (reprint author), Massachusetts Gen Hosp, Cardiac Surg Step Down Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 138 W WASHINGTON ST, STE 403-405, HAGERSTOWN, MD 21740 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD FAL PY 2003 VL 14 IS 3 BP 194 EP 198 PG 5 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 757KE UT WOS:000187560900008 PM 14740356 ER PT J AU Cassem, N AF Cassem, N TI Comments from the optimum care committee consultant SO JOURNAL OF CLINICAL ETHICS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Cassem, N (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 138 W WASHINGTON ST, STE 403-405, HAGERSTOWN, MD 21740 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD FAL PY 2003 VL 14 IS 3 BP 199 EP 200 PG 2 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 757KE UT WOS:000187560900009 ER PT J AU Robinson, EM Jurchak, M AF Robinson, EM Jurchak, M TI Ethical issues raised by LVADs and Mr. T's story SO JOURNAL OF CLINICAL ETHICS LA English DT Article ID VENTRICULAR ASSIST DEVICE; QUALITY-OF-LIFE; CARE; END; IMPLANTATION C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Eth Serv, Boston, MA 02115 USA. RP Robinson, EM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 18 TC 2 Z9 2 U1 0 U2 0 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 138 W WASHINGTON ST, STE 403-405, HAGERSTOWN, MD 21740 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD FAL PY 2003 VL 14 IS 3 BP 201 EP 207 PG 7 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 757KE UT WOS:000187560900010 PM 14740357 ER PT J AU Colgan, SP Pitman, RS Nagaishi, T Mizoguchi, A Mizoguchi, E Mayer, LF Shao, L Sartor, RB Subjeck, JR Blumberg, RS AF Colgan, SP Pitman, RS Nagaishi, T Mizoguchi, A Mizoguchi, E Mayer, LF Shao, L Sartor, RB Subjeck, JR Blumberg, RS TI Intestinal heat shock protein 110 regulates expression of CD1d on intestinal epithelial cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HEAT-SHOCK PROTEINS; I-LIKE MOLECULE; T-CELLS; RECEPTOR; ACTIVATION; COLITIS; HSP70; IDENTIFICATION; PATHWAY; COMPLEX AB CD1d is expressed on the surface of professional and nonprofessional APCs, including intestinal epithelial cells (IECs), for a role in the presentation of glycolipid-based antigens to subsets of T cells. The mechanisms that regulate CD1d expression in any cell type are unknown. To investigate the possibility that expression of CD1d is influenced by exogenous factors present within the intestinal lumen, CD1d expression was analyzed in several IEC lines after culturing in the presence of lumenal contents (LC) of the normal human intestine. Exposure of the colon-derived cell lines T84, HT-29, and Caco-2 to soluble LC resulted in a marked induction of CD1d expression as determined by RT-PCR, confocal microscopy, cell surface ELISA, and Western blot analysis. Similarly, exposure of human IECs to LC isolated from mice bred in both specific pathogen-free and germfree conditions also resulted in the induction of CD1d expression, with the maximum CD1d-inducing activity observed in the small intestine. Biochemical and biophysical characterization of the human CD1d-inducing activity identified heat shock protein 110 (Hsp110) as a major functional component of the LC that contributes to CD1d surface regulation, and immunolocalization studies revealed Hsp110 expression in subsets of human IECs in vivo. These data support the presence of a novel autocrine pathway of CD1d regulation by Hsp110. C1 Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Brigham & Womens Hosp, Ctr Expt Therapeut, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Immunopathol Unit, Boston, MA 02114 USA. Mt Sinai Sch Med, Immunobiol Ctr, New York, NY USA. Univ N Carolina, Chapel Hill, NC USA. Roswell Pk Canc Inst, Dept Mol & Cellular Biophys, Buffalo, NY 14263 USA. RP Blumberg, RS (reprint author), Brigham & Womens Hosp, Div Gastroenterol, Thorn Bldg,Room 1410,75 Francis St, Boston, MA 02115 USA. RI Colgan, Sean/B-4573-2009 FU NIDDK NIH HHS [R37 DK050189, R37 DK044319, DK-53056, DK-44319, DK-50189, DK-51362, R01 DK044319, R01 DK050189, R01 DK051362, R01 DK053056, R29 DK050189] NR 36 TC 26 Z9 29 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2003 VL 112 IS 5 BP 745 EP 754 DI 10.1172/JC1200317241 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 719NN UT WOS:000185209900018 PM 12952923 ER PT J AU Day, CL Seth, NP Lucas, M Appel, H Gauthier, L Lauer, GM Robbins, GK Szczepiorkowski, ZM Casson, DR Chung, RT Bell, S Harcourt, G Walker, BD Klenerman, P Wucherpfennig, KW AF Day, CL Seth, NP Lucas, M Appel, H Gauthier, L Lauer, GM Robbins, GK Szczepiorkowski, ZM Casson, DR Chung, RT Bell, S Harcourt, G Walker, BD Klenerman, P Wucherpfennig, KW TI Ex vivo analysis of human memory CD4 T cells specific for hepatitis C virus using MHC class II tetramers SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MEDIATED IMMUNE-RESPONSE; ALPHA-BETA-HETERODIMERS; CHAIN-DERIVED PEPTIDES; MYELIN BASIC-PROTEIN; HLA-DR MOLECULES; PERIPHERAL-BLOOD; IN-VITRO; INFECTION; ANTIGEN; BINDING AB Containment of hepatitis C virus (HCV) and other chronic human viral infections is associated with persistence of virus-specific CD4 T cells, but ex vivo characterization of circulating CD4 T cells has not been achieved. To further define the phenotype and function of these cells, we developed a novel approach for the generation of tetrameric forms of MHC class II/peptide complexes that is based on the cellular peptide-exchange mechanism. HLA-DR molecules were expressed as precursors with a covalently linked CLIP peptide, which could be efficiently exchanged with viral peptides following linker cleavage. In subjects who spontaneously resolved HCV viremia, bur not in those with chronic progressive infection, HCV tetramer-labeled cells could be isolated by magnetic bead capture despite very low frequencies (1: 1,200 to 1: 111,000) among circulating CD4 T cells. These T cells expressed a set of surface receptors (CCR7(+)CD45RA(-)CD27(+)) indicative of a surveillance function for secondary lymphoid structures and had undergone significant in vivo selection since they utilized a restricted Vbeta repertoire. These studies demonstrate a relationship between clinical outcome and the presence of circulating CD4 T cells directed against this virus. Moreover, they show that rare populations of memory CD4 T cells can be studied ex vivo in human diseases. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Howard Hughes Med Inst, Partners AIDS Res Ctr, Boston, MA USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Oxford, Nuffield Dept Med, Peter Medawar Bldg Pathogen Res, Oxford, England. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,Dana 1410, Boston, MA 02115 USA. RI Robbins, Gregory/F-7988-2011; Yang, Chen/G-1379-2010; Szczepiorkowski, Zbigniew/A-1359-2007; Day, Cheryl/J-9844-2012 OI Szczepiorkowski, Zbigniew/0000-0003-2357-9564; FU NIAID NIH HHS [AI31563, AI45757, P01 AI045757, R01 AI031563, T32 AI007387, T332 AI07387-12]; NIDDK NIH HHS [R01 DK057857, DK57857] NR 41 TC 197 Z9 206 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2003 VL 112 IS 6 BP 831 EP 842 DI 10.1172/JCI200318509 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 722LN UT WOS:000185376400007 PM 12975468 ER PT J AU Day, YJ Huang, LP McDuffie, MJ Rosin, DL Ye, H Chen, JF Schwarzchild, MA Fink, JS Linden, J Okusa, MD AF Day, YJ Huang, LP McDuffie, MJ Rosin, DL Ye, H Chen, JF Schwarzchild, MA Fink, JS Linden, J Okusa, MD TI Renal protection from ischemia mediated by A(2A) adenosine receptors on bone marrow-derived cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ENDOTHELIAL PROGENITOR CELLS; REPERFUSION INJURY; T-LYMPHOCYTES; STEM-CELLS; RAT-KIDNEY; INHIBITION; MICE; NEOVASCULARIZATION; NEUTROPHILS; RESPONSES AB Activation of A(2A) adenosine receptors (A(2A)Rs) protects kidneys from ischemia-reperfusion injury (IRI). A2ARs are expressed on bone marrow-derived (BM-derived) cells and renal smooth muscle, epithelial, and endothelial cells. To measure the contribution of A(2A)Rs on BM-derived cells in suppressing renal IRI, we examined the effects of a selective agonist of A(2A)Rs, ATL146e, in chimeric mice in which BM was ablated by lethal radiation and reconstituted with donor BM cells derived from GFP, A(2A)R-KO, or WT mice to produce GFP-->WT, A(2A)-KO-->WT, or WT-->WT mouse chimera. We found little or no repopulation of renal vascular endothelial cells by donor BM with or without renal IRI. ATL146e had no effect on IRI in A(2A)-KO mice or A(2A)-KO-->WT chimera, but reduced the rise in plasma creatinine from IRI by 75% in WT mice and by 60% in WT-->WT chimera. ATL146e reduced the induction of IL-6, IL-1beta, IL-1ra, and TGF-alpha mRNA in WT-->WT mice but not in A(2A)-KO-->WT mice. Plasma creatinine was significantly greater in A2A-KO than in WT mice after IRI, suggesting some renal protection by endogenous adenosine. We conclude that protection from renal IRI by A(2A)R agonists or endogenous adenosine requires activation of receptors expressed on BM-derived cells. C1 Univ Virginia, Hlth Syst, Div Nephrol, Dept Med, Charlottesville, VA 22908 USA. Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA USA. Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA. Univ Virginia, Dept Pharmacol, Charlottesville, VA 22908 USA. Massachusetts Gen Hosp, Dept Neurol, Mol Neurobiol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Okusa, MD (reprint author), Univ Virginia, Hlth Syst, Div Nephrol, Dept Med, Box 800133, Charlottesville, VA 22908 USA. FU NHLBI NIH HHS [HL37942, R01 HL037942]; NIDDK NIH HHS [DK58413, DK56223, R01 DK056223, R41 DK058413, R44 DK058413]; NIEHS NIH HHS [ES10804, R01 ES010804] NR 33 TC 156 Z9 164 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 SEP PY 2003 VL 112 IS 6 BP 883 EP 891 DI 10.1172/JCI200315483 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 722LN UT WOS:000185376400012 PM 12975473 ER PT J AU Stratmann, T Martin-Orozco, N Mallet-Designe, V Poirot, L McGavern, D Losyev, G Dobbs, CM Oldstone, MBA Yoshida, K Kikutani, H Mathis, D Benoist, C Haskins, K Teyton, L AF Stratmann, T Martin-Orozco, N Mallet-Designe, V Poirot, L McGavern, D Losyev, G Dobbs, CM Oldstone, MBA Yoshida, K Kikutani, H Mathis, D Benoist, C Haskins, K Teyton, L TI Susceptible MHC alleles, not background genes, select an autoimmune T cell reactivity SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NONOBESE DIABETIC MICE; MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-II MOLECULES; RECEPTOR TRANSGENIC MICE; NOD MICE; TOLERANCE INDUCTION; PEPTIDE BINDING; SELF-ANTIGEN; MOUSE; RECOGNITION AB To detect and characterize autoreactive T cells in diabetes-prone NOD mice, we have developed a multimeric MHC reagent with high affinity for the BDC-2.5 T cell receptor, which is reactive against a pancreatic autoantigen. A distinct population of T cells is detected in NOD mice that recognizes the same MHC/peptide target. These T cells are positively selected in the thymus at a surprisingly high frequency and exported to the periphery. They are activated specifically in the pancreatic LNs, demonstrating an autoimmune specificity that recapitulates that of the BDC-2.5 cell. These phenomena are also observed in mouse lines that share with NOD the H-2(g7) MHC haplotype but carry diabetes-resistance background genes. Thus, a susceptible haplotype at the MHC seems to be the only element required for the selection and emergence of autoreactive T cells, without requiring other diabetogenic loci from the NOD genome. C1 Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Sect Immunol & Immunogenet,Joslin Diabet Ctr,Dept, Boston, MA USA. Scripps Res Inst, Dept Neuropharmacol, Div Virol, La Jolla, CA 92037 USA. Univ Colorado, Hlth Sci Ctr, Dept Immunol, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr Childhood Diabet, Denver, CO 80262 USA. Osaka Univ, Microbial Dis Res Inst, Dept Mol Immunol, Suita, Osaka 565, Japan. RP Stratmann, T (reprint author), Scripps Res Inst, Dept Immunol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM ltreyton@scripps.edu RI Martin Orozco, Natalia/E-4794-2010; Kikutani, Hitoshi/C-9525-2009 FU NIA NIH HHS [AG04342, P01 AG004342, AG00080, T32 AG000080]; NIAID NIH HHS [AI41439]; NIDDK NIH HHS [DK55037, R01 DK059658, R56 DK050561, R01 DK050561, R01 DK055037, DK50561, 1 R01 DK 59658-01] NR 73 TC 66 Z9 68 U1 1 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2003 VL 112 IS 6 BP 902 EP 914 DI 10.1172/JCI200318337 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 722LN UT WOS:000185376400014 PM 12975475 ER PT J AU Wu, XB Li, YN Schneider, A Yu, WQ Rajendren, G Iqbal, J Yamamoto, M Alam, M Brunet, LJ Blair, HC Zaidi, M Abe, E AF Wu, XB Li, YN Schneider, A Yu, WQ Rajendren, G Iqbal, J Yamamoto, M Alam, M Brunet, LJ Blair, HC Zaidi, M Abe, E TI Impaired osteoblastic differentiation, reduced bone formation, and severe osteoporosis in noggin-overexpressing mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FACTOR-KAPPA-B; MORPHOGENETIC PROTEIN-4; SPEMANN ORGANIZER; GENE-EXPRESSION; SMAD-BINDING; MARROW; MOUSE; OSTEOCLAST; PROMOTER; ELEMENT AB We describe the effects of the overexpression of noggin, a bone morphogenetic protein (BMP) inhibitor, on osteoblast differentiation and bone formation. Cells of the osteoblast and chondrocyte lineages, as well as bone marrow macrophages, showed intense beta-gal histo- or cytostaining in adult noggin(+/-) mice that had a LacZ transgene inserted at the site of noggin deletion. Despite identical BMP levels, however, osteoblasts of 20-month-old C57BL/6J and 4-month-old senescence-accelerated mice (SAM-P6 mice) had noggin expression levels that were approximately fourfold higher than those of 4-month-old C57BL/6J and SAM-R1 (control) mice, respectively. U-33 preosteoblastic cells overexpressing the noggin gene showed defective maturation and, in parallel, a decreased expression of Runx-2, bone sialoprotein, osteocalcin, and RANK-L. Noggin did not inhibit the ligandless signaling and prodifferentiation action of the constitutively activated BMP receptor type 1A, ca-ALK-3. Transgenic mice overexpressing noggin in mature osteocalcin-positive osteoblasts showed dramatic decreases in bone mineral density and bone formation rates with histological evidence of decreased trabecular bone and CFU-osteoblast colonies at 4 and 8 months. Together, the results provide compelling evidence that noggin, expressed in mature osteoblasts, inhibits osteoblast differentiation and bone formation. Thus, the overproduction of noggin during biological aging may result in impaired osteoblast formation and function and hence, net bone loss. C1 Mt Sinai Sch Med, Div Endocrinol Diabet & Bone Dis, Mt Sinai Bone Program, New York, NY 10029 USA. Bronx Vet Adm Med Ctr, New York, NY USA. Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA USA. Vet Adm Med Ctr, Pittsburgh, PA USA. Univ Arkansas Med Sci, Div Endocrinol & Metab, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Ctr Osteoporosis & Metab Bone Dis, Little Rock, AR 72205 USA. Univ Calif Berkeley, Div Biochem & Mol Biol, Berkeley, CA 94720 USA. RP Abe, E (reprint author), Mt Sinai Sch Med, Div Endocrinol Diabet & Bone Dis, Mt Sinai Bone Program, 1 Gustave L Levy Pl,Box 1055, New York, NY 10029 USA. FU NIA NIH HHS [AG-14197-08] NR 42 TC 123 Z9 139 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2003 VL 112 IS 6 BP 924 EP 934 DI 10.1172/JCI200315543 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 722LN UT WOS:000185376400016 PM 12975477 ER PT J AU Sequist, LV Lynch, TJ AF Sequist, LV Lynch, TJ TI Aggressive treatment for the fit elderly with non-small-cell lung cancer? Yes! SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID THERAPY ONCOLOGY GROUP; LEUKEMIA GROUP-B; PHASE-III TRIAL; SURVIVAL; AGE; CHEMOTHERAPY; OLDER; DETERMINANTS; RADIOTHERAPY; BURDEN C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr,Dana Farber Partners Canc Care, Boston, MA 02114 USA. RP Sequist, LV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr,Dana Farber Partners Canc Care, Boston, MA 02114 USA. NR 17 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2003 VL 21 IS 17 BP 3186 EP 3188 DI 10.1200/JCO.2003.04.002 PG 3 WC Oncology SC Oncology GA 717LT UT WOS:000185091300002 PM 12874267 ER PT J AU Chakravarti, A Heydon, K Wu, CL Hammond, E Pollack, A Roach, M Wolkov, H Okunieff, P Cox, J Fontanesi, J Abrams, R Pilepich, M Shipley, W AF Chakravarti, A Heydon, K Wu, CL Hammond, E Pollack, A Roach, M Wolkov, H Okunieff, P Cox, J Fontanesi, J Abrams, R Pilepich, M Shipley, W TI Loss of p16 expression is of prognostic significance in locally advanced prostate cancer: An analysis from the Radiation Therapy Oncology Group protocol 86-10 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID DEPENDENT KINASE INHIBITOR; CELL LUNG-CARCINOMA; LOCALIZED CARCINOMA; RB/E2F PATHWAY; COMPETING RISK; P16(INK4A); PROTEINS; P53; RETINOBLASTOMA; ADENOCARCINOMA AB Purpose: The retinoblastoma (RB) cell cycle regulatory pathway is known to be deregulated in virtually all known human tumors. The protein product of the RB gene, pRB, and its upstream regulator, p16 'are among the most commonly affected members of this pathway. We investigated the prognostic significance of both pRB and p 16 expression in locally advanced prostate cancers, from patients treated on the Radiation Therapy Oncology Group (RTOG) protocol 86-10. Materials and Methods: Sixty-seven cases from RTOG 86-10 had immunohistochemically stained slides, judged interpretable for both p 16 and pRB, available for analysis. Median follow-up was 8.9 years (range, 6.0 to 11.8 years) for surviving patients. Staining for each marker was then correlated with overall survival, local progression, distant metastasis, and disease-specific survival. Results: Loss of p 16 expression, as defined by expression was significantly associated with reduced overall survival (P = .039), disease-specific survival (P = .006), and higher risk of local progression (P = .0007) and distant metastasis (P = .026) in the univariate analysis. In the multivariate analysis, loss of p16 was significantly associated with reduced disease-specific survival (P = .0078) and increased risk of local failure (P = .0035) and distant metastasis (P = .026). A borderline association with reduced overall survival (P = .07) was also evident. Loss of pRB was associated with improved disease-specific survival on univariate (P = .028) and multivariate, analysis (P = .043), but carried no other significant outcome associations. Conclusion: Loss of p16 is significantly associated with adverse clinical outcome in cases of locally advanced prostate cancer. (C) 2003 by American Society of Clinical Oncology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Latter Day St Hosp, Dept Pathol, Salt Lake City, UT 84143 USA. Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Sutter Canc Ctr, Sacramento, CA USA. Univ Rochester, Rochester, NY USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Wayne State Univ, Harper Hosp, Detroit, MI USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. St Joseph Mercy Hosp, Ann Arbor, MI 48104 USA. RP Chakravarti, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St,Founders House,Room 536, Boston, MA 02114 USA. FU NCI NIH HHS [U10 CA37422, U10 CA32115, U01 CA21661] NR 30 TC 46 Z9 48 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2003 VL 21 IS 17 BP 3328 EP 3334 DI 10.1200/JCO.2003.12.151 PG 7 WC Oncology SC Oncology GA 717LT UT WOS:000185091300023 PM 12947069 ER PT J AU Soiffer, R Hodi, FS Haluska, F Jung, K Gillessen, S Singer, S Tanabe, K Duda, R Mentzer, S Jaklitsch, M Bueno, R Clift, S Hardy, S Neuberg, D Mulligan, R Webb, I Mihm, M Dranoff, G AF Soiffer, R Hodi, FS Haluska, F Jung, K Gillessen, S Singer, S Tanabe, K Duda, R Mentzer, S Jaklitsch, M Bueno, R Clift, S Hardy, S Neuberg, D Mulligan, R Webb, I Mihm, M Dranoff, G TI Vaccination with irradiated, autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor by adenoviral-mediated gene transfer augments antitumor immunity in patients with metastatic melanoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; ACTIVE-SPECIFIC IMMUNOTHERAPY; HIGH-RISK MELANOMA; CYTOTOXIC T-CELLS; PHASE-I TRIAL; DENDRITIC CELLS; MALIGNANT-MELANOMA; PEPTIDE VACCINE; RESPONSES; ANTIGENS AB Purpose : Vaccination with irradiated, autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) by retroviral-mediated gene transfer generates potent antitumor immunity in patients with metastatic melanoma. Further clinical development of this immunization scheme requires simplification of vaccine manufacture. We conducted a phase I clinical trial testing the biologic activity of vaccination with irradiated, autologous melanoma cells engineered to secrete GM-CSF by adenoviral-mediated gene transfer. Patients and Methods: Excised metastases were processed to single cells, transduced with a replication-defective adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines were composed of I x 10(6), 4 x 10(6), or 1 x 10(7) tumor cells, depending on overall yield, and were injected intradermally and subcutaneously at weekly and biweekly intervals. Results: Vaccines were successfully manufactured for 34 (97%) of 35 patients. The average GM-CSF secretion was 745 ng/10(6) cells/24 hours. Toxicities were restricted to grade 1 to 2 local skin reactions. Eight patients were withdrawn early because of rapid disease progression. Vaccination elicited dense dendritic cell, macrophage, granulocyte, and lymphocyte infiltrates at injection sites in 19 of 26 assessable patients. Immunization stimulated the development of delayed-type hypersensitivity reactions to irradiated, dissociated, autologous, nontransduced tumor cells in 17 of 25 patients. Metastatic lesions that were resected after vaccination showed brisk or focal T-lymphocyte and plasma cell infiltrates with tumor necrosis in 10 of 16 patients. One complete, one partial, and one mixed response were noted. Ten patients (29%) are alive, with a minimum follow-up of 36 months; four of these patients have no evidence of disease. Conclusion: Vaccination with irradiated, autologous melanoma cells engineered to secrete GM-CSF by adenoviral-mediated gene transfer augments antitumor immunity in patients with metastatic melanoma. (C) 2003 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Biostat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. Childrens Hosp, Boston, MA 02115 USA. Cell Genesys, Foster City, CA USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 510E,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA74886] NR 46 TC 188 Z9 201 U1 2 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2003 VL 21 IS 17 BP 3343 EP 3350 DI 10.1200/JCO.2003.07.005 PG 8 WC Oncology SC Oncology GA 717LT UT WOS:000185091300025 PM 12947071 ER PT J AU Goldhirsch, A Wood, WC Gelber, RD Coates, AS Thurlimann, B Senn, HJ AF Goldhirsch, A Wood, WC Gelber, RD Coates, AS Thurlimann, B Senn, HJ TI Meeting highlights: Updated international expert consensus on the primary therapy of early breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SURGICAL-ADJUVANT-BREAST; RANDOMIZED CLINICAL-TRIALS; QUALITY-OF-LIFE; FOLLOW-UP; HIGH-RISK; PREMENOPAUSAL PATIENTS; PLASMINOGEN-ACTIVATOR; EXPRESSING ESTROGEN; RADICAL-MASTECTOMY; ENDOCRINE THERAPY AB This account of the highlights of the eighth St Gallen (Switzerland) meeting in 2003 emphasizes new information that has emerged during the 2 years since the seventh meeting in 2001. This article should be read in conjunction with the report of that earlier meeting. Recommendations for patient care are so critically dependent an assessment of endocrine responsiveness that the importance of high-quality steroid hormone receptor determination and standardized quantitative reporting cannot be overemphasized. The International Consensus Panel modified the risk categories so that only endocrine receptor-absent status was sufficient to reclassify an otherwise low-risk, node-negative disease into the category of average risk. Absence of steroid hormone receptors also was recognized as indicating endocrine nonresponsiveness. Some important areas highlighted at the recent meeting include: (1) recognition of the separate nature of endocrine-nonresponsive breast cancer-both invasive cancers and ductal carcinoma-in-situ; (2) improved understanding of the mechanisms of acquired endocrine resistance, which offer exciting prospects for extending the impact of successful sequential endocrine therapies; (3) presentation of high-quality evidence indicating that chemotherapy and tamoxifen should be used sequentially rather than concurrently, (4) availability of a potential alternative to tamoxifen for treatment of postmenopausal women with endocrine-responsive disease; and (5) the promise of newly defined prognostic and predictive markers. (C) 2003 by American Society of Clinical Oncology. C1 European Inst Oncol, Int Breast Canc Study Grp, I-20141 Milan, Italy. Oncol Inst So Switzerland, Int Breast Canc Study Grp, Lugano, Switzerland. Kantonsspital, Div Gynecol Oncol, St Gallen, Switzerland. Zentrum Tumordiagnost & Pravent, St Gallen, Switzerland. Emory Univ, Dept Surg, Atlanta, GA 30322 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Canc Council Australia, Sydney, NSW, Australia. RP Goldhirsch, A (reprint author), European Inst Oncol, Int Breast Canc Study Grp, Via Ripamonti 435, I-20141 Milan, Italy. NR 99 TC 455 Z9 472 U1 1 U2 8 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2003 VL 21 IS 17 BP 3357 EP 3365 DI 10.1200/JCO.2003.04.576 PG 9 WC Oncology SC Oncology GA 717LT UT WOS:000185091300027 PM 12847142 ER PT J AU Page, RC Martin, J Krall, EA Mancl, L Garcia, R AF Page, RC Martin, J Krall, EA Mancl, L Garcia, R TI Longitudinal validation of a risk calculator for periodontal disease SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE risk factors; periodontal diagnosis; periodontal treatment; quantification of risk ID ATTACHMENT LOSS; TOOTH LOSS; LONG-TERM; PATHOGENESIS; ADULTS; PROGRESSION; RADIOGRAPHS; AGREEMENT; CARIES; TRIAL AB Background: Risk assessment and utilization of the results are important components of prevention, diagnosis and treatment of periodontal diseases. Risk assessment is relatively new to dentistry. Currently risk is assessed by subjective evaluation and results vary widely among clinicians. We have developed a computer-based risk assessment tool, the Periodontal Risk Calculator (PRC), for objective, quantitative assessment of risk. The purpose of the study reported here was to evaluate the accuracy and validity of this tool. Methods: Clinical records and radiographs of 523 subjects enrolled in the VA Dental Longitudinal Study of Oral Health and Disease, covering a period of 15 years, were used. Information from baseline examinations was entered into the risk calculator and a risk score on a scale of 1-5 for periodontal deterioration was calculated for each subject. Actual periodontal status in terms of alveolar bone loss determined using digitized radiographs, and tooth loss determined from the clinical records, was assessed at years 3, 9 and 15. The strength of the association between risk prediction and actual outcome was determined statistically. Results: The risk scores were strong predictors of future periodontal status measured as worsening severity and extent of alveolar bone loss and tooth loss, especially loss of periodontally affected teeth. Over the entire 15-year period, risk scores consistently ranked groups from least to most bone loss and tooth loss. Risk groups differed greatly from one another. By year 3, the incidence rate of bone loss of group 5 was 3.7-fold greater than for group 2, and by year 15, the loss of periodontally affected teeth was 22.7-fold greater than for group 2 (p < 0.001). By year 15, 83.7% of subjects in risk group 5 had lost one or more periodontally affected teeth compared to 20.2% of subjects in group 2. Conclusions: Risk scores calculated using the PRC and information gathered during a standard periodontal examination predict future periodontal status with a high level of accuracy and validity. Use of the risk assessment tool over time may be expected to result in more uniform and accurate periodontal clinical decision-making, improved oral health, reduction in the need for complex therapy and reduction in health-care cost. C1 Univ Washington, Sch Dent, Reg Clin Dent Res Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Periodont, Seattle, WA 98195 USA. VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Boston Univ, Goldman Sch Dent Med, Dept Hlth Policy & Hlth Serv Res, Boston, MA 02118 USA. Univ Washington, Sch Dent, Dept Dent Publ Hlth Sci, Seattle, WA 98195 USA. RP Page, RC (reprint author), Univ Washington, Sch Dent, Reg Clin Dent Res Ctr, Box 357480-B-530 Hlth Sci Bldg,1959 NE Pacific St, Seattle, WA 98195 USA. FU NIDCR NIH HHS [K24 DE00419] NR 29 TC 39 Z9 41 U1 1 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD SEP PY 2003 VL 30 IS 9 BP 819 EP 827 DI 10.1034/j.1600-051X.2003.00370.x PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 717WZ UT WOS:000185114900008 PM 12956658 ER PT J AU Calabrese, JR Bowden, CL Sachs, G Yatham, LN Behnke, K Mehtonen, OP Montgomery, P Ascher, J Paska, W Earl, N DeVeaugh-Geiss, J AF Calabrese, JR Bowden, CL Sachs, G Yatham, LN Behnke, K Mehtonen, OP Montgomery, P Ascher, J Paska, W Earl, N DeVeaugh-Geiss, J CA Lamictal 605 Study Grp TI A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 15th Congress of the European-College-of-Neuropsychopharmacology CY OCT 05-09, 2002 CL BARCELONA, SPAIN SP European Coll Neuropsychopharmcol ID RECURRENT AFFECTIVE DISORDERS; DOUBLE-BLIND; PROPHYLACTIC LITHIUM; AFFECTIVE-ILLNESS; UNITED-STATES; OUTPATIENTS; MONOTHERAPY; CARBONATE; SCALE AB Background: The anticonvulsant lamotrigine was previously shown to be effective for bipolar depression. This study assessed the efficacy and tolerability of lamotrigine and lithium compared with placebo for the prevention of mood episodes in bipolar disorder. Method: During an 8- to 16-week open-label phase, lamotrigine (titrated to 200 mg/day) was added to current therapy for currently or recently depressed DSM-IV-defined bipolar I outpatients (N = 966) and concomitant drugs were gradually withdrawn. Patients stabilized on open-label treatment (N = 463) were then randomly assigned to lamotrigine (50, 200, or 400 mg/day; N = 22 1), lithium (0.8-1.1 mEq/L; N = 121), or placebo (N = 12 1) monotherapy for up to 18 months. The primary outcome measure was time from randomization to intervention (addition of pharmacotherapy) for any mood episode (depressive, manic, hypomanic, or mixed). Data were gathered from September 1997 to August 2001. Results: Time to intervention for any mood episode was statistically superior (p = .029) for both lamotrigine and lithium compared with placebo-median survival times were 200, 170, and 93 days, respectively. Intervention for depression was more frequent than for mania by a factor of nearly 3:1. Lamotrigine was statistically superior to placebo at prolonging the time to intervention for a depressive episode (p = .047). The proportions of patients who were intervention-free for depression at I year were lamotrigine 57%, lithium 46%, and placebo 45%. Lithium was statistically superior to placebo at prolonging the time to intervention for a manic or hypomanic episode (p = .026). The proportions of patients who were intervention-free for mania at I year were lamotrigine 77%, lithium 86%, and placebo 72%. Headache was the most frequent adverse event for all 3 treatment groups. Conclusion: Lamotrigine and lithium were superior to placebo for the prevention of mood episodes in bipolar I patients, with lamotrigine predominantly effective against depression and lithium predominantly effective against mania. C1 Case Western Reserve Univ, Univ Hosp Cleveland, Sch Med, Cleveland, OH 44106 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Tampere Univ Hosp, Psychiat Clin, Pitkaiemi, Finland. GlaxoSmithKline Res & Dev, Res Triangle Pk, NC USA. GlaxoSmithKline Res & Dev, Greenford, Middx, England. RP Calabrese, JR (reprint author), Case Western Reserve Univ, Univ Hosp Cleveland, Sch Med, 11400 Euclid Ave,Ste 200, Cleveland, OH 44106 USA. NR 28 TC 370 Z9 380 U1 2 U2 21 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 2003 VL 64 IS 9 BP 1013 EP 1024 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 723XV UT WOS:000185457600006 PM 14628976 ER PT J AU Mori, DL Lambert, JF Niles, BL Orlander, JD Grace, M LoCastro, JS AF Mori, DL Lambert, JF Niles, BL Orlander, JD Grace, M LoCastro, JS TI The BAI-PC as a screen for anxiety, depression, and PTSD in primary care SO JOURNAL OF CLINICAL PSYCHOLOGY IN MEDICAL SETTINGS LA English DT Article DE primary care; screening; anxiety; depression; PTSD ID POSTTRAUMATIC-STRESS-DISORDER; PSYCHOMETRIC PROPERTIES; MEDICAL OUTPATIENTS; MENTAL-DISORDERS; INVENTORY; PREVALENCE; VETERANS AB Despite the prevalence of psychiatric disorders in medical settings, mental health problems often go undetected and patients do not receive appropriate treatment. The main goal of this study is to provide additional information about the Beck Anxiety Inventory - Primary Care (BAI-PC), a brief instrument that screens for patients with anxiety. This study provides information on the performance of the BAI-PC as a screening instrument for depression and PTSD in addition to its original purpose as a screening instrument for anxiety. This efficient tool can identify patients who can benefit from effective psychological treatments and facilitate referrals to psychologists working in medical settings. C1 Vet Adm Boston Healthcare Syst, Psychiat Serv 116B, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. RP Mori, DL (reprint author), Vet Adm Boston Healthcare Syst, Psychiat Serv 116B, 150 S Huntington Ave, Boston, MA 02130 USA. NR 30 TC 16 Z9 16 U1 3 U2 5 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9583 J9 J CLIN PSYCHOL MED S JI J. Clin. Psychol. Med. Settings PD SEP PY 2003 VL 10 IS 3 BP 187 EP 192 DI 10.1023/A:1025410812221 PG 6 WC Psychology, Clinical SC Psychology GA 715ET UT WOS:000184958100007 ER PT J AU Li, Y Ryan, L Bellamy, S Satten, GA AF Li, Y Ryan, L Bellamy, S Satten, GA TI Inference on clustered survival data using imputed frailties SO JOURNAL OF COMPUTATIONAL AND GRAPHICAL STATISTICS LA English DT Article DE asymptotic normality; bootstrap; consistency; cox models; frailty models; imputed frailty partial likelihood score (IFPLS); Monte Carlo estimating equation; S-U algorithm ID PROPORTIONAL HAZARDS MODEL; MAXIMUM-LIKELIHOOD-ESTIMATION; INTERVAL-CENSORED-DATA; DATA AUGMENTATION; ASYMPTOTIC THEORY; EM ALGORITHM; REGRESSION; CONSISTENCY; JACKKNIFE; BOOTSTRAP AB This article proposes a new method for fitting frailty models to clustered survival data that is intermediate between the fully parametric and nonparametric maximum likelihood estimation approaches. A parametric form is assumed for the baseline hazard, but only for the purpose of imputing the unobserved frailties. The regression coefficients are then estimated by solving an estimating equation that is the average of the partial likelihood score with respect to the conditional distribution of frailties given the observed data. We prove consistency and asymptotic normality of the resulting estimators and give associated closed-form estimators of their variance. The algorithm is easy to implement and reduces to the ordinary Cox partial likelihood approach when the frailties have a degenerate distribution. Simulations indicate high efficiency and robustness of the resulting estimates. We apply our new approach to a study with clustered survival data on asthma in children in east Boston. C1 Harvard Univ, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Penn, Dept Biostat, Philadelphia, PA 19104 USA. Ctr Dis Control, Atlanta, GA 30333 USA. RP Li, Y (reprint author), Harvard Univ, Dept Biostat, 44 Binney St,M232, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 34 TC 2 Z9 2 U1 0 U2 1 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 1061-8600 J9 J COMPUT GRAPH STAT JI J. Comput. Graph. Stat. PD SEP PY 2003 VL 12 IS 3 BP 640 EP 662 DI 10.1198/1061860032247 PG 23 WC Statistics & Probability SC Mathematics GA 722VA UT WOS:000185397600008 ER PT J AU Pinto, DJ Jones, SR Kaper, TJ Kopell, N AF Pinto, DJ Jones, SR Kaper, TJ Kopell, N TI Analysis of state-dependent transitions in frequency and long-distance coordination in a model oscillatory cortical circuit SO JOURNAL OF COMPUTATIONAL NEUROSCIENCE LA English DT Article DE rhythms; synchrony; neocortex; neuromodulation; alpha; beta; gamma; arousal ID SHORT-TERM PLASTICITY; SLEEP-WAKE STATE; CEREBRAL-CORTEX; PYRAMIDAL NEURONS; IN-VIVO; GAMMA-RHYTHMS; SYNCHRONIZED OSCILLATIONS; THALAMOCORTICAL PATHWAY; AUGMENTING RESPONSES; IONIC MECHANISMS AB Changes in behavioral state are typically accompanied by changes in the frequency and spatial coordination of rhythmic activity in the neocortex. In this article, we analyze the effects of neuromodulation on ionic conductances in an oscillating cortical circuit model. The model consists of synaptically-coupled excitatory and inhibitory neurons and supports rhythmic activity in the alpha, beta, and gamma ranges. We find that the effects of neuromodulation on ionic conductances are, by themselves, sufficient to induce transitions between synchronous gamma and beta rhythms and asynchronous alpha rhythms. Moreover, these changes are consistent with changes in behavioral state, with the rhythm transitioning from the slower alpha to the faster gamma and beta as arousal increases. We also observe that it is the same set of underlying intrinsic and network mechanisms that appear to be simultaneously responsible for both the observed transitions between the rhythm types and between their synchronization properties. Spike time response curves (STRCs) are used to study the relationship between the transitions in rhythm and the underlying biophysics. C1 Brown Univ, Dept Neurosci, Providence, RI 02912 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Boston Univ, Ctr Biodynam, Boston, MA 02215 USA. RP Pinto, DJ (reprint author), Brown Univ, Dept Neurosci, Box 1953, Providence, RI 02912 USA. FU NIDA NIH HHS [DA 12500]; NINDS NIH HHS [NS 25983, R01 NS 46058] NR 59 TC 18 Z9 18 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5313 J9 J COMPUT NEUROSCI JI J. Comput. Neurosci. PD SEP-OCT PY 2003 VL 15 IS 2 BP 283 EP 298 DI 10.1023/A:1025825102620 PG 16 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA 724YB UT WOS:000185514900009 PM 14512752 ER PT J AU Lin, AL Johnson, DA Stephan, KT Yeh, CK AF Lin, AL Johnson, DA Stephan, KT Yeh, CK TI Alteration in salivary function in early HIV infection SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE HIV; xerostomia; saliva; salivary glands ID CANDIDA-ALBICANS; PAROTID-SALIVA; FLOW-RATES; AIDS; XEROSTOMIA; PROTEINS; DISEASE AB The etiology of salivary gland hypofunction in HIV(+) patients is unclear. This study was designed to determine the effect of early-stage HIV(+) infection (CD4(+) > 200 cells/muL; n = 139) on salivary gland function and the relationship of this dysfunction to the taking of xerostomic medications. Salivary flow rates and the content of electrolytes and antimicrobial proteins in stimulated parotid and submandibular/sublingual saliva were determined. Compared with healthy controls (n = 50), the HIV(+) group showed significant reductions in flow rates of unstimulated whole (35%),. stimulated parotid (47%), unstimulated submandibular/sublingual (23%), and stimulated submandibular/sublingual (39%) saliva. The flow rates for the HIV(+) patients taking xerostomic medications did not differ from those of patients who did not. Concentrations of some salivary gland components were altered in the HIV(+) group. Analysis of these data suggests that salivary gland function is adversely affected early in HIV infection and that these changes do not appear to be compounded by the taking of xerostomic medications. C1 Univ Texas, Ctr Hlth Sci, Dept Dent Diagnost Sci, San Antonio, TX USA. Univ Texas, Ctr Hlth Sci, Dept Community Dent, San Antonio, TX USA. Wilford Hall USAF Med Ctr, HIV Unit, Dept Infect Dis, Lackland AFB, TX 78236 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Res Serv, San Antonio, TX 78229 USA. RP Yeh, CK (reprint author), Univ Texas, Ctr Hlth Sci, Dept Dent Diagnost Sci, San Antonio, TX USA. FU NIDCR NIH HHS [DE12188] NR 21 TC 22 Z9 25 U1 1 U2 2 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD SEP PY 2003 VL 82 IS 9 BP 719 EP 724 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 716JF UT WOS:000185024500012 PM 12939357 ER PT J AU Sullivan, AM Lakoma, MD Block, SD AF Sullivan, AM Lakoma, MD Block, SD TI The status of medical education in end-of-life care - A national report SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT Annual Conference of the American-Academy-of-Hospice-and-Palliative-Medicine CY FEB 02, 2002 CL PALM SPRINGS, CALIFORNIA SP Amer Acad Hospice & Palliat Med DE medical education; end-of-life care; palliative care ID INCORPORATING PALLIATIVE CARE; HIDDEN CURRICULUM; STUDENTS; OPPORTUNITIES; PERSPECTIVES; PHYSICIANS; PRINCIPLES; CHALLENGES; RESIDENTS; SCHOOL AB OBJECTIVE: To assess the status of medical education in end-of-life care and identify opportunities for improvement. DESIGN: Telephone survey. SETTING: U.S. academic medical centers. PARTICIPANTS: National probability sample of 1,455 students, 296 residents, and 287 faculty (response rates 62%, 56%, and 41%, respectively) affiliated with a random sample of 62 accredited U.S. medical schools. MEASUREMENTS AND MAIN RESULTS: Measurements assessed attitudes, quantity and quality of education, preparation to provide or teach care, and perceived value of care for dying patients. Ninety percent or more of respondents held positive views about physicians' responsibility and ability to help dying patients. However, fewer than 18% of students and residents received formal end-of-life care education, 39% of students reported being unprepared to address patients' fears, and nearly half felt unprepared to manage their feelings about patients' deaths or help bereaved families. More than 40% of residents felt unprepared to teach end-of-life care. More than 40% of respondents reported that dying patients were not considered good teaching cases, and that meeting psycho-social needs of dying patients was not considered a core competency. Forty-nine percent of students had told patients about the existence of a life-threatening illness, but only half received feedback from residents or attendings; nearly all residents had talked with patients about wishes for end-of-life care, and 33% received no feedback. CONCLUSIONS: Students and residents in the United States feel unprepared to provide, and faculty and residents unprepared to teach, many key components of good care for the dying. Current educational practices and institutional culture in U.S. medical schools do not support adequate end-of-life care, and attention to both curricular and cultural change are needed to improve end-of-life care education. C1 Dana Farber Canc Inst, Div Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Sullivan, AM (reprint author), Dana Farber Canc Inst, Div Psychosocial Oncol & Palliat Care, 44 Binney St,Room G420D, Boston, MA 02115 USA. NR 45 TC 179 Z9 183 U1 2 U2 11 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2003 VL 18 IS 9 BP 685 EP 695 DI 10.1046/j.1525-1497.2003.21215.x PG 11 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 719EA UT WOS:000185189600002 PM 12950476 ER PT J AU Landefeld, CS AF Landefeld, CS TI Training in the care of older adults - Opportunity knocks for general internal medicine SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID DELIRIUM C1 Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Aging, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Landefeld, CS (reprint author), Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. NR 18 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 SEP PY 2003 VL 18 IS 9 BP 770 EP 771 DI 10.1046/j.1525-1497.2003.30703.x PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 719EA UT WOS:000185189600014 PM 12950488 ER PT J AU Peskind, ER Bonner, LT Hoff, DJ Raskind, MA AF Peskind, ER Bonner, LT Hoff, DJ Raskind, MA TI Prazosin reduces trauma-related nightmares in older men with chronic posttraumatic stress disorder SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE PTSD; prazosin; nightmares; veterans; Holocaust ID CORTICOTROPIN-RELEASING-FACTOR; COMBAT VETERANS; ALZHEIMERS-DISEASE; MILITARY VETERANS; HORMONE-LEVELS; PTSD; NOREPINEPHRINE; SYMPTOMS; SLEEP; SERTRALINE AB Trauma-related nightmares in posttraumatic stress disorder (PTSD) rarely respond. to pharmacologic treatment. Neurobiologic data suggest that enhanced brain responsiveness to adrenergic stimulation may contribute to the pathophysiology of trauma-related nightmares in PTSD. Nine older men with chronic PTSD secondary to military or Holocaust trauma were prescribed the lipophilic alpha-1 adrenergic antagonist prazosin for treatment-resistant trauma-related nightmares. Prazosin 2 mg to 4 mg 1 hour before bedtime substantially reduced nightmares and moderately or markedly reduced overall PTSD severity in 8 of 9 subjects. Prazosin was well tolerated. These open-label results are consistent with demonstrated therapeutic efficacy of prazosin for PTSD nightmares and sleep disturbance in a recent placebo-controlled trial in Vietnam veterans. C1 NW Network Mental Illness Res Educ & Clin Ctr, Dept Vet Affairs, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Peskind, ER (reprint author), VA Puget Sound Hlth Care Syst, S-116,1660 S Columbian Way, Seattle, WA 98108 USA. EM murray.raskind@med.va.gov FU NIA NIH HHS [R01 AG18644] NR 44 TC 64 Z9 66 U1 3 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD SEP PY 2003 VL 16 IS 3 BP 165 EP 171 DI 10.1177/0891988703256050 PG 7 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 847GJ UT WOS:000223380400007 PM 12967060 ER PT J AU Weintraub, D Moberg, PJ Duda, JE Katz, IR Stern, MB AF Weintraub, D Moberg, PJ Duda, JE Katz, IR Stern, MB TI Recognition and treatment of depression in Parkinson's disease SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE Parkinson's disease; depression; diagnosis; treatment; response; antidepressant ID CONTROLLED-TRIAL; INCREASED RISK; PRIMARY-CARE; SYMPTOMS; SCALE; CITALOPRAM; PREVALENCE; PAROXETINE; DISORDER; VALIDITY AB Depression in Parkinson's disease (PD) is common, but little is known about its recognition and treatment. The authors report the antidepressant experience (N = 100) and outcome of depression assessment (n = 77) of a convenience sample of patients at a PD center. Subjects were assessed with a psychiatric and neurological battery, and information was gathered on depression treatment. One third (34%) of subjects met criteria for a depressive disorder, and two thirds (65%) of them were not currently receiving antidepressant treatment. Approximately one quarter (23%) of subjects were taking an antidepressant, but almost half (47%) of them still met criteria for a depressive disorder. Few antidepressant users with persistent depression had received either antidepressant treatment at dosages within the highest recommended range (11%) or more than 1 antidepressant trial (33%). Most depressed patients are untreated, and half of antidepressant users remain depressed, suggesting that even when delivered, treatment is often inadequate or ineffective. C1 Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. RP Weintraub, D (reprint author), Univ Penn, Sch Med, Dept Psychiat, 3535 Market St,Room 3003, Philadelphia, PA 19104 USA. EM weintrau@mail.med.upenn.edu NR 44 TC 94 Z9 95 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD SEP PY 2003 VL 16 IS 3 BP 178 EP 183 DI 10.1177/0891988703256053 PG 6 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 847GJ UT WOS:000223380400009 PM 12967062 ER PT J AU Thomas, SY Hou, RH Boyson, JE Means, TK Hess, C Olson, DP Strominger, JL Brenner, MB Gumperz, JE Wilson, SB Luster, AD AF Thomas, SY Hou, RH Boyson, JE Means, TK Hess, C Olson, DP Strominger, JL Brenner, MB Gumperz, JE Wilson, SB Luster, AD TI CD1d-restricted NKT cells express a chemokine receptor profile indicative of Th1-type inflammatory homing cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID KILLER T-CELLS; HUMAN DENDRITIC CELLS; CUTTING EDGE; CXC CHEMOKINE; LYMPHOCYTES; SUBSETS; RECOGNITION; CD1D; TRAFFICKING; MATURATION AB CD1d-restricted T cells (NKT cells) are innate memory cells activated by lipid Ags and play important roles in the initiation and regulation of the immune response. However, little is known about the trafficking patterns of these cells or the tissue compartment in which they exert their regulatory activity. In this study, we determined the chemokine receptor profile expressed by CD1d-restricted T cells found in the peripheral blood of healthy volunteers as well as CD1d-restricted T cell clones. CD1d-restricted T cells were identified by Abs recognizing the invariant Valpha24 TCR rearrangement or by binding to CD1d-Fc fusion tetramers loaded with alpha-GalCer. CD1d-restricted T cells in the peripheral blood and CD1d-restricted T cell clones expressed high levels of CXCR3, CCR5, and CCR6; intermediate levels of CXCR4 and CXCR6; and low levels of CXCR1, CCR1, CCR2, and CX3CR1, a receptor pattern often associated with tissue-infiltrating effector Th1 cells and CD8(+) T cells. Very few of these cells expressed the lymphoid-homing receptors CCR7 or CXCR5. CCR4 was expressed predominantly on CD4(+), but not on double-negative CD1d-restricted T cells, which may indicate differential trafficking patterns for these two functionally distinct subsets. CD1d-restricted T cell clones responded to chemokine ligands for CXCR1/2, CXCR3, CXCR4, CXCR6, CCR4, and CCR5 in calcium flux and/or chemotaxis assays. These data indicate that CD1d-restricted T cells express a chemokine receptor profile most similar to Th1 inflammatory homing cells and suggest that these cells perform their function in peripheral tissue sites rather than in secondary lymphoid organs. C1 Harvard Univ, Sch Med,Ctr Immunol & Inflammatory Dis, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Diabet Res Labs, Charlestown, MA 02129 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Luster, AD (reprint author), Harvard Univ, Sch Med,Ctr Immunol & Inflammatory Dis, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Bldg 149,13th St, Charlestown, MA 02129 USA. OI Thomas, Seddon/0000-0003-0075-0744 FU NCI NIH HHS [CA 69212]; NHLBI NIH HHS [T32 HL 07874]; NIAID NIH HHS [AI 45051, AI 46999] NR 34 TC 158 Z9 163 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2003 VL 171 IS 5 BP 2571 EP 2580 PG 10 WC Immunology SC Immunology GA 715KM UT WOS:000184970900049 PM 12928408 ER PT J AU Lehmann, JCU Jablonski-Westrich, D Haubold, U Gutierrez-Ramos, JC Springer, T Hamann, A AF Lehmann, JCU Jablonski-Westrich, D Haubold, U Gutierrez-Ramos, JC Springer, T Hamann, A TI Overlapping and selective roles of endothelial intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 in lymphocyte trafficking SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL INTERACTION; FACTOR-KAPPA-B; TRANSENDOTHELIAL MIGRATION; PULMONARY INFLAMMATION; MONOCLONAL-ANTIBODIES; COUNTER-RECEPTOR; IN-VITRO; LFA-1; MICE; EXPRESSION AB The integrin LFA-1 interacts with a variety of ligands termed ICAMs. ICAM-1 and ICAM-2 are both expressed on endothelium and serve as counterreceptors during lymphocyte trafficking. In this study, we analyzed their relative contribution to lymphocyte recirculation through lymph nodes and to recruitment into lung and inflamed skin by blocking mAbs against ICAM-1 and ICAM-2 and mice deficient for ICAM-1. The entry of lymphocytes into peripheral and mesenteric lymph nodes was found to be unaffected by the functional deletion of either ICAM-1 or ICAM-2. However, when both pathways were blocked, recirculation through lymph nodes was strongly reduced. Trapping of lymphocytes in the lung after i.v. injection is partly mediated by LFA-1/ICAM interactions; the data presented in this study show an exclusive role of ICAM-1 in LFA-1-dependent lung trapping. Similarly, ICAM-1, but not ICAM-2, was required for the migration of T effector cells into the inflamed skin. These results indicate that ICAM-1 and ICAM-2 have redundant functions in lymphocyte recirculation through lymph nodes, but ICAM-1 is unique in supporting migration into inflamed sites and trapping within the lung. C1 Humboldt Univ, Univ Klin Charite, Berlin, Germany. Deutsch Rheumaforschungszentrum, Berlin, Germany. Millenium Pharmaceut, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Hamann, A (reprint author), Dt Rheumaforschungszentrum, Charite, Schumannstr 21-22, D-10117 Berlin, Germany. NR 55 TC 64 Z9 66 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2003 VL 171 IS 5 BP 2588 EP 2593 PG 6 WC Immunology SC Immunology GA 715KM UT WOS:000184970900051 PM 12928410 ER PT J AU Liu, DX Cai, SH Gu, XG Scafidi, J Wu, X Davis, AE AF Liu, DX Cai, SH Gu, XG Scafidi, J Wu, X Davis, AE TI C1 inhibitor prevents endotoxin shock via a direct interaction with lipopolysaccharide SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SALMONELLA-TYPHIMURIUM LIPOPOLYSACCHARIDES; C1-ESTERASE INHIBITOR; PROTEASE INHIBITORS; SEPTIC SHOCK; BINDING; INACTIVATION; LPS; PATHOGENESIS; COMPLEMENT; SEPSIS AB C1 inhibitor (C1INH) is beneficial in animal models of endotoxemia and sepsis. However, the mechanism(s) of C1INH protection remain(s) ill-defined. In this study, we demonstrated that both active C1INH and reactive center-cleaved, inactive C1INH protected mice from lethal Gram-negative endotoxemia. Both forms of C1INH blocked the LPS-binding protein-dependent binding of Salmonella typhimurium LPS to the murine macrophage cell line, RAW 264.7, and suppressed LPS-induced TNF-alpha mRNA expression. Inhibition of LPS binding to RAW 264.7 cells was reversed with anti-C1INH Ab and was more efficient when C1INH was incubated first with LPS rather than with the cells. C1INH also suppressed LPS-induced up-regulation of TNF-alpha mRNA in whole human blood. The interaction of C1INH with LPS was directly demonstrated both by ELISA and by nondenaturing PAGE, but deletion of the amino-terminal 97-aa residues abrogated this binding. Therefore, C1INH, in addition to its function as a serine protease inhibitor, has a novel anti-inflammatory function mediated via its heavily glycosylated amino-terminal non-serpin domain. C1 Harvard Univ, Childrens Hosp, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Surg Res Labs, Boston, MA 02115 USA. RP Davis, AE (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NICHD NIH HHS [HD 22082, HD 33727] NR 42 TC 46 Z9 53 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2003 VL 171 IS 5 BP 2594 EP 2601 PG 8 WC Immunology SC Immunology GA 715KM UT WOS:000184970900052 PM 12928411 ER PT J AU Middelkamp-Hup, MA Sanchez-Carpintero, I Kossodo, S Waterman, P Gonzalez, S Mihm, MC Anderson, RR AF Middelkamp-Hup, MA Sanchez-Carpintero, I Kossodo, S Waterman, P Gonzalez, S Mihm, MC Anderson, RR TI Photodynamic therapy for cutaneous proliferative vascular tumors in a mouse model SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE angiosarcoma; benzoporphyrin derivative monoacid ring A hemangioma; laser ID SKIN PHOTOSENSITIVITY; CHOROIDAL HEMANGIOMA; VERTEPORFIN; VESSELS AB Photodynamic therapy with benzoporphyrin derivative monoacid ring A and red light (PDT-BPD) has been used to treat human choroidal hemangiomas, and may be useful for cutaneous vascular lesions. The potential for PDT-BPD to inhibit selectively vascular tumor growth was tested in a mouse angiosarcoma model, of which the tumor growth mimics the proliferative phase of hemangiomas. Vascular tumors arising after intradermal injection of immortalized murine endothelial cells were exposed to 50 to 150 J per cm(2) of 690 nm laser light 15 min after intravenous injection of 1 mg per kg BPD. Tumor volume and gross response were followed after PDT-BPD and compared with control tumors receiving no treatment, light alone, or BPD alone. At 2 wk, hematoxylin-eosin and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling stained tumor sections was performed. There was a selective, fluence-dependent inhibition of tumor growth after PDT-BPD (pless than or equal to0.05), typically with eradication of tumors exposed to higher fluences. A common effect was the replacement of tumor by small scar. Surrounding PDT-BPD exposed normal skin showed no changes. Based on these results, we conclude that PDT-BPD can lead to selective eradication of these tumors. Further studies investigating the efficacy of PDT-BPD for human hemangiomas are warranted. C1 Univ Clin Navarre, Dept Dermatol, Pamplona 31080, Spain. Harvard Univ, Sch Med, Dept Dermatol, Wellman Labs Photomed, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol Dermatopathol, Boston, MA 02115 USA. RP Sanchez-Carpintero, I (reprint author), Univ Clin Navarre, Dept Dermatol, Pamplona 31080, Spain. NR 19 TC 13 Z9 14 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2003 VL 121 IS 3 BP 634 EP 639 DI 10.1046/j.1523-1747.2003.12412.x PG 6 WC Dermatology SC Dermatology GA 717EV UT WOS:000185073800035 PM 12925226 ER PT J AU Chan, EM Bulman, DE Paterson, AD Turnbull, J Andermann, E Andermann, F Rouleau, GA Delgado-Escueta, AV Scherer, SW Minassian, BA AF Chan, EM Bulman, DE Paterson, AD Turnbull, J Andermann, E Andermann, F Rouleau, GA Delgado-Escueta, AV Scherer, SW Minassian, BA TI Genetic mapping of a new Lafora progressive myoclonus epilepsy locus (EPM2B) on 6p22 SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; LINKAGE ANALYSIS; CORPORA-AMYLACEA; BODIES; IDENTIFICATION; DISEASE AB Background: Lafora disease is a progressive myoclonus epilepsy with polyglucosan accumulations and a peculiar neurodegeneration with generalised organellar disintegration. It causes severe seizures, leading to dementia and eventually death in early adulthood. Methods: One Lafora disease gene, EPM2A, has been identified on chromosome 6q24. Locus heterogeneity led us to search for a second gene using a genome wide linkage scan in French-Canadian families. Results: We mapped a second Lafora disease locus, EPM2B, to a 2.2 Mb region at 6p22, a region known to code for several proteins, including kinesins. Kinesins are microtubule dependent motor proteins that are involved in transporting cellular components. In neurones, they play a major role in axonal and dendritic transport. Conclusion: Analysis of the present locus in other non-EPM2A families will reveal whether there is further locus heterogeneity. Identification of the disease gene will be of major importance towards our understanding of the pathogenesis of Lafora disease. C1 Hosp Sick Children, Dept Pediat, Div Neurol, Program Genet & Genom Biol, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Mol & Med Genet, Toronto, ON M5G 1X8, Canada. Ottawa Gen Hosp, Ottawa Hlth Res Inst, Div Neurol, Ottawa, ON K1H 8L6, Canada. McGill Univ, Montreal Neurol Hosp & Inst, Dept Neurol & Neurosurg, Neurogenet Unit, Montreal, PQ H3A 2B4, Canada. McGill Univ, Montreal Neurol Hosp & Inst, Dept Human Genet, Neurogenet Unit, Montreal, PQ H3A 2B4, Canada. McGill Univ, Montreal Neurol Hosp & Inst, Epilepsy Serv, Montreal, PQ H3A 2B4, Canada. McGill Univ, Dept Paediat, Montreal, PQ H3A 2B4, Canada. McGill Univ, Montreal Gen Hosp, Ctr Hlth, Res Inst,Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada. Univ Calif Los Angeles, Sch Med, W Los Angeles DVA Med Ctr, Dept Neurol,Comprehens Epilepsy Program, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, W Los Angeles DVA Med Ctr, Brain Res Inst, Los Angeles, CA 90073 USA. RP Minassian, BA (reprint author), Hosp Sick Children, Dept Pediat, Div Neurol, Program Genet & Genom Biol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. RI Howe, Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013; Paterson, Andrew/A-4088-2011 OI Scherer, Stephen /0000-0002-8326-1999; Paterson, Andrew/0000-0002-9169-118X FU NINDS NIH HHS [R01 NS042376] NR 25 TC 32 Z9 33 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD SEP 1 PY 2003 VL 40 IS 9 BP 671 EP 675 DI 10.1136/jmg.40.9.671 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 718ZP UT WOS:000185177700005 PM 12960212 ER PT J AU Ozcan, C Bienengraeber, M Hodgson, DM Mann, DL Terzic, A AF Ozcan, C Bienengraeber, M Hodgson, DM Mann, DL Terzic, A TI Mitochondrial tolerance to stress impaired in failing heart SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE mitochondria; oxidative stress; calcium; heart failure; TNF alpha; energy metabolism ID TUMOR-NECROSIS-FACTOR; CARDIAC MITOCHONDRIA; HUMAN MYOCARDIUM; TRANSGENIC MICE; FAILURE; OVEREXPRESSION; ATP; CREATINE; DISEASE; DOGS AB Mitochondrial integrity is critical in the maintenance of bioenergetic homeostasis of the myocardium, with oxidative or metabolic challenge to mitochondria precipitating cell injury. In heart failure, where cardiac cell, are exposed to elevated stress, mitochondrial vulnerability could contribute to the disease state. However, the mitochondrial response to stress is yet to be established in heart failure. Here, mitochondrial function and structure was evaluated prior and following stress using a transgenic (TG) model of heart failure, generated by cardiac overexpression of the cytokine TNFalpha. Compared to the wild type, mitochondria from TG failing hearts demonstrated impaired oxidative phosphorylation, mitochondrial DNA damage, reduced mitochondrial creatine kinase activity, abnormal calcium handling, and altered ultrastructure. Under anoxia/reoxygenation or calcium stress, mitochondria from failing hearts suffered exacerbated energetic failure with pronounced cytochrome c release. Thus, mitochondria from TNFalpha-TG failing hearts demonstrate structural and functional abnormalities, with reduced tolerance to stress manifested by impaired bioenergetics and increased susceptibility to injury. This abnormal vulnerability to stress underscores the impact of mitochondrial dysfunction in the pathobiology of heart failure. (C) 2003 Elsevier Ltd. All rights reserved. C1 Mayo Clin & Mayo Fdn, Div Cardiovasc Dis, Dept Med, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Div Cardiovasc Dis, Dept Mol Pharmacol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Div Cardiovasc Dis, Dept Expt Therapeut, Rochester, MN 55905 USA. Baylor Coll Med, Winters Ctr Heart Failure Res, Houston, TX 77030 USA. Houston Vet Adm Med Ctr, Houston, TX 77030 USA. RP Terzic, A (reprint author), Mayo Clin & Mayo Fdn, Div Cardiovasc Dis, Dept Med, Guggenheim 7F, Rochester, MN 55905 USA. EM terzic.andre@mayo.edu OI Mann, Douglas /0000-0002-2516-0145 FU NHLBI NIH HHS [HL 64822, HL 07111] NR 22 TC 12 Z9 13 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD SEP PY 2003 VL 35 IS 9 BP 1161 EP 1166 DI 10.1016/S0022-2828(03)00204-9 PG 6 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 724NZ UT WOS:000185494800020 PM 12967639 ER PT J AU Haq, E Giri, S Singh, I Singh, AK AF Haq, E Giri, S Singh, I Singh, AK TI Molecular mechanism of psychosine-induced cell death in human oligodendrocyte cell line SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE apoplosis; beta-galactosidase; oligodendroglial cells; psychosine; redox ID NF-KAPPA-B; ACTIVATED PROTEIN-KINASE; MEDIATED APOPTOSIS; TWITCHER MOUSE; TNF-ALPHA; C-MYC; JNK ACTIVATION; CYTOCHROME-C; MURINE MODEL; MICE LACKING AB This study delineates the molecular mechanism underlying psychosine-induced oligodendroglial cell death. An immortalized human oligodendroglial cell line, MO3.13, was treated with exogenous psychosine (P-galactosylsphingosine), a toxic metabolite that accumulates in the tissues of patients with Krabbe's disease. The mode of cell death induced by psychosine was found to be apoptotic, as revealed by different apoptotic markers viz., TUNEL, DNA fragmentation and caspase cleavage/activation. The action of psychosine was redox sensitive, as measured by changes in mitochondrial membrane potential ( A), and this effect of psychosine could be reversed by pre-treatment with the antioxidant molecules N-acetyl-L-cysteine or pro-cysteine. Psychosine directly affects the mitochondria as revealed by the activation of caspase 9 but not caspase 8. Up-regulation of the c-jun/c-jun N-terminal kinase pathway by psychosine leads to the induction of AP-1 and, at the same time, psychosine also down-regulates the lipopolysaccharide-induced NF-kappaB transactivation. These observations indicate that the mechanism of action of psychosine is, through the up-regulation of AP-1, a pro-apoptotic pathway as well as, through the down-regulation of the NF-kappaB pathway, an antiapoptotic pathway. C1 Ralph Johnson Vet Affairs Med Ctr, Dept Pathol & Lab Med, Charleston, SC USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. RP Singh, AK (reprint author), Ralph Johnson Vet Affairs Med Ctr, Dept Pathol & Lab Med, Charleston, SC USA. EM singha@musc.edu OI Haq, Ehtishamul/0000-0002-4195-0606 FU NINDS NIH HHS [NS 37766, NS-22576, NS-34741, NS-40810] NR 57 TC 63 Z9 65 U1 1 U2 5 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2003 VL 86 IS 6 BP 1428 EP 1440 DI 10.1046/j.1471-4159.2003.01941.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 764ZQ UT WOS:000188241400011 PM 12950451 ER PT J AU Liu, HL Nowak, R Chao, W Bloch, KD AF Liu, HL Nowak, R Chao, W Bloch, KD TI Nerve growth factor induces anti-apoptotic heme oxygenase-1 in rat pheochromocytoma PC12 cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE apoptosis; gene transcription; MEK; ROS; serum deprivation ID CARBON-MONOXIDE PRODUCTION; VASCULAR SMOOTH-MUSCLE; OXIDATIVE STRESS; GENE-EXPRESSION; KINASE-ACTIVITY; CEREBRAL-ISCHEMIA; SODIUM ARSENITE; NEURONAL DEATH; LUNG INJURY; IN-VITRO AB Nerve growth factor (NGF) and heme oxygenases (HOs) both exert neuroprotective effects. To characterize the role of HOs in the prevention of apoptosis by NGF, we investigated the effect of NGF on the expression of HOs in serum-deprived PC12 cells. Serum deprivation (SD) led to a rapid decrease in HO-1 gene expression followed by induction of apoptosis. Incubation of serum-deprived PC12 cells with NGF prevented apoptosis and increased HO-1 mRNA and protein levels, as well as HO enzyme activity. HO-2 gene expression was unaffected by SD or NGF. Incubation of cells with mitogen-activated protein kinase kinase (MEK) inhibitors (PD98059 or U0126) attenuated the ability of NGF to increase HO-1 expression and to protect PC12 cells against SD-induced apoptosis. NGF augmented HO-1 gene transcription but did not alter HO-1 mRNA stability. HO inhibitors or antisense HO-1 RNA decreased the ability of NGF to prevent cell apoptosis. Inhibition of HO activity enhanced intracellular reactive oxygen species (ROS) production and attenuated NGF-induced reduction of ROS in serum-deprived PC12 cells. These results demonstrate that NGF enhances HO-1 gene transcription via MEK activation and that the induction of HO-1 plays an important role in the antioxidative and antiapoptotic effects of NGF in serum-deprived PC12 cells. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Dept Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. RP Liu, HL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Dept Med, CNY4,E,149 13th St, Charlestown, MA 02129 USA. EM Liu@CVRC.MGH.HARVARD.EDU FU NHLBI NIH HHS [HL57172] NR 49 TC 39 Z9 44 U1 0 U2 5 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2003 VL 86 IS 6 BP 1553 EP 1563 DI 10.1046/j.1471-4159.2003.01978.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 764ZQ UT WOS:000188241400024 PM 12950464 ER PT J AU Garabedian, CE Jones, SR Merzenich, MM Dale, A Moore, CI AF Garabedian, CE Jones, SR Merzenich, MM Dale, A Moore, CI TI Band-pass response properties of rat SI neurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID PRIMARY AUDITORY-CORTEX; RECEPTIVE-FIELD PROPERTIES; BARREL CORTEX; SOMATOSENSORY CORTEX; THALAMIC RELAY; IN-VIVO; THALAMOCORTICAL SYNAPSES; TACTILE DISCRIMINATION; TEMPORAL-MODULATION; SENSORY RESPONSES AB Rats typically employ 4- to 12-Hz "whisking" movements of their vibrissae during tactile exploration. The intentional sampling of signals in this frequency range suggests that neural processing of tactile information may be differentially engaged in this bandwidth. We examined action potential responses in rat primary somatosensory cortex ( SI) to a range of frequencies of vibrissa motion. Single vibrissae were mechanically deflected with 5-s pulse trains at rates less than or equal to 40 Hz. As previously reported, vibrissa deflection evoked robust neural responses that consistently adapted to stimulus rates greater than or equal to 3 Hz. In contrast with this low-pass feature of the response, several other characteristics of the response revealed bandpass response properties. While average evoked response amplitudes measured 0 - 35 ms after stimulus onset typically decreased with increasing frequency, the later components of the response ( > 15 ms post stimulus) were augmented at frequencies between 3 and 10 Hz. Further, during the steady state, both rate and temporal measures of neural activity, measured as total spike rate or vector strength ( a measure of temporal fidelity of spike timing across cycles), showed peak signal values at 5 - 10 Hz. A minimal biophysical network model of SI layer IV, consisting of an excitatory and inhibitory neuron and thalamocortical input, captured the spike rate and vector strength band-pass characteristics. Further analyses in which specific elements were selectively removed from the model suggest that slow inhibitory influences give rise to the band-pass peak in temporal precision, while thalamocortical adaptation can account for the band-pass peak in spike rate. The presence of these band-pass characteristics may be a general property of thalamocortical circuits that lead rodents to target this frequency range with their whisking behavior. C1 Univ Calif San Francisco, Keck Ctr Integrat Neurosci, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Imaging Ctr, Charlestown, MA 02141 USA. MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Garabedian, CE (reprint author), Univ Calif San Francisco, Keck Ctr Integrat Neurosci, 513 Parnassus Ave,HSE-808, San Francisco, CA 94142 USA. RI Moore, Christopher/C-5588-2009; Dale, Anders/A-5180-2010 NR 69 TC 62 Z9 63 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 2003 VL 90 IS 3 BP 1379 EP 1391 DI 10.1152/jn.01158.2002 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 719RG UT WOS:000185217700004 PM 12750410 ER PT J AU Matejuk, A Hopke, C Dwyer, J Subramanian, S Jones, RE Bourdette, DN Vandenbark, AA Offner, H AF Matejuk, A Hopke, C Dwyer, J Subramanian, S Jones, RE Bourdette, DN Vandenbark, AA Offner, H TI CNS gene expression pattern associated with spontaneous experimental autoimmune encephalomyelitis SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE spontaneous EAE; microarray; spinal cord ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS LESIONS; CEREBROSPINAL-FLUID; TRANSGENIC MICE; NERVOUS-SYSTEM; T-CELLS; PROTEIN; RECEPTOR; IDENTIFICATION; TRANSCRIPTION AB Transgenic mice with T-cell receptor (TCR) specific for myelin basic protein (MBP)-Ac1-11 peptide and homozygous for the RAG-1 mutation (T/R-mice) spontaneously develop acute progressive experimental autoimmune encephalomyelitis (Sp-EAE) mediated by CD4+ T cells. Microarray analysis of spinal cord tissue obtained from symptomatic versus non-symptomatic T/R- mice revealed strongly upregulated transcripts for genes involved in antigen presentation and processing, signal transduction, transcription regulation, metabolism, development, cell cycle, and many other processes involved in the induction of clinical and pathological signs of Sp-EAE. Several highly expressed genes were related directly to inflammation, including cytokines/receptors, chemokines/receptors, acute phase, complement molecules, and others. Many CNS-specific genes were also upregulated in sick mice. Abundance of message for the Tg TCR BV8S2 gene as well as several monocyte/ macrophage-associated genes would suggest that both components play a crucial role in the pathogenesis of Sp-EAE. The profile of transcriptional changes found during the development of Sp-EAE provides the first description of the encephalitogenic process in the absence of purposeful immunization with myelin peptides and immune-enhancing adjuvants. This unique approach is the first to implicate molecules and pathways that contribute naturally to onset of paralysis and demyelination, and thus may provide unique insights and novel treatment strategies for human diseases such as multiple sclerosis. (C) 2003 Wiley-Liss, Inc. C1 Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Polish Acad Sci, L Hirszfeld Inst Immunol & Expt Therapy, Wroclaw, Poland. RP Offner, H (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp, Portland, OR 97239 USA. FU NIAID NIH HHS [AI42376]; NINDS NIH HHS [NS23221, NS23444] NR 44 TC 18 Z9 20 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD SEP 1 PY 2003 VL 73 IS 5 BP 667 EP 678 DI 10.1002/jnr.10689 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 719RL UT WOS:000185218100009 PM 12929134 ER PT J AU Cohen, MC Siewers, AE Dickens, JD Hill, T Muller, JE AF Cohen, MC Siewers, AE Dickens, JD Hill, T Muller, JE TI Perioperative and long-term prognostic value of dipyridamole Tc-99m sestamibi myocardial tomography in patients evaluated for elective vascular surgery SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article; Proceedings Paper CT 5th Symposium and Scientific Sessions of the American-Society-of-Nuclear-Cardiology CY SEP 21-24, 2000 CL CHICAGO, ILLINOIS SP Amer Soc Nuclear Cardiol DE peripheral vascular disease; single photon emission computed tomography; technetium 99m sestamibi; left anterior descending territory ID CORONARY-ARTERY DISEASE; LATE CARDIAC EVENTS; EMISSION COMPUTED-TOMOGRAPHY; NONCARDIAC SURGERY; THALLIUM SCINTIGRAPHY; DIABETES-MELLITUS; RISK PATIENTS; TL-201; PREDICTION; PERFUSION AB Background. Patients with peripheral vascular disease are at increased risk for perioperative and long-term cardiac morbidity and mortality. Substantial data exist supporting the use of preoperative clinical risk stratification and planar thallium myocardial scintigraphy. Only limited data are available assessing the role of technetium-99m (Tc-99m) single photon emission computed tomography (SPECT) for preoperative evaluation in this population. Methods and Results. In our study 153 patients who underwent peripheral vascular surgery were followed up for up to 4 years after preoperative dipyridamole Tc-99m sestamibi SPECT to determine clinical and SPECT predictors of perioperative and long-term adverse cardiac events by multivariate analysis. There were no statistically significant clinical or SPECT predictors of perioperative risk, although no perioperative events occurred in patients with normal scans. Abnormality in the left anterior descending (LAD) territory (risk ratio = 3.1; 95% confidence interval, 1.4-7.1) was the only statistically significant univariate predictor of long-term death or myocardial infarction. Only abnormality in the LAD territory appeared to improve model fit beyond clinical risk (risk ratio = 2.9; 95% confidence interval, 1.2-7.3; P = .02). Conclusions. Patients with normal preoperative scans have a low risk of perioperative cardiac events and may safely undergo peripheral vascular surgery without further coronary intervention. However, scan abnormality in the LAD distribution confers poor long-term prognosis, suggesting that patients with this finding before peripheral vascular surgery should receive aggressive medical therapy and possibly invasive intervention to improve long-term survival. C1 Maine Med Ctr, Div Cardiol, Portland, ME 04102 USA. Maine Med Ctr, Ctr Outcomes Res, Dept Med, Portland, ME 04102 USA. Univ Vermont, Coll Med, Burlington, VT 05405 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiovasc, Boston, MA 02114 USA. RP Cohen, MC (reprint author), Maine Cardiol Associates, 66 Bramhall St, Portland, ME 04102 USA. FU NHLBI NIH HHS [F32 HL08912] NR 26 TC 8 Z9 8 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD SEP-OCT PY 2003 VL 10 IS 5 BP 464 EP 472 DI 10.1067/S1071-3581(03)00550-6 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 732CB UT WOS:000185922300004 PM 14569239 ER PT J AU Stern, LL Shane, B Bagley, PJ Nadeau, M Shih, V Selhub, J AF Stern, LL Shane, B Bagley, PJ Nadeau, M Shih, V Selhub, J TI Combined marginal folate and riboflavin status affect homocysteine methylation in cultured immortalized lymphocytes from persons homozygous for the MTHFR C677T mutation SO JOURNAL OF NUTRITION LA English DT Article DE folate; methylenetetrahydrofolate reductase homocysteine; immortalized cells ID METHYLENETETRAHYDROFOLATE REDUCTASE POLYMORPHISM; COMMON MUTATION; COLORECTAL-CANCER; RISK; PLASMA; GENE; HYPERHOMOCYSTEINEMIA; CHROMATOGRAPHY; DISEASE AB Methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the methyl donor for the synthesis of methionine from homocysteine. A common C677T mutation in the MTHFR gene renders the enzyme similar to50% less active than the wild-type enzyme as shown in in vitro studies using cell extracts. We developed an immortalized cell culture model to determine whether the lower in vitro activity imparted by the homozygous (T/T) genotype is demonstrated in situ when exposed to adequate and marginal physiologic concentrations of folate and riboflavin. T/T MTHFR activity was compared with that of C/C genotype cell extracts by an in vitro assay and in intact cells by measuring the distribution of folate forms, the accumulation of homocysteine in the medium and the synthesis of methionine from formate and homocysteine. Under adequate nutrient conditions, the in vitro activity of the T/T MTHFR enzyme was approximately half that of the C/C genotype. Similarly, the proportion of 5-methyltetrahydrofolate in cells with the T/T genotype was approximately half that of the cells with wild-type MTHFR. In contrast, homocysteine accumulation in the culture medium was low and not different between genotypes, nor was there a difference in methionine synthetic capacity. Significant differences were observed between genotypes only when the supply of both folate and riboflavin was limited in the medium, which resulted in increased homocysteine accumulation and decreased methionine production in the T/T genotype. These data are consistent with the current understanding of the molecular interaction of the MTHFR mutant with folate substrates and the FAD prosthetic group. C1 Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr, Vitamin Metab & Aging Lab, Boston, MA 02111 USA. Univ Calif Berkeley, Dept Nutr Sci, Berkeley, CA 94720 USA. Massachusetts Gen Hosp, Amino Acid Disorder Lab, Charlestown, MA 02129 USA. RP Selhub, J (reprint author), Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr, Vitamin Metab & Aging Lab, Boston, MA 02111 USA. RI Bagley, Pamela/N-1906-2015 OI Bagley, Pamela/0000-0002-1214-7814 NR 21 TC 16 Z9 17 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD SEP PY 2003 VL 133 IS 9 BP 2716 EP 2720 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 720KC UT WOS:000185259100005 ER PT J AU Perrott, DH Yuen, JP Andresen, RV Dodson, TB AF Perrott, DH Yuen, JP Andresen, RV Dodson, TB TI Office-based ambulatory anesthesia: Outcomes of clinical practice of oral and maxillofacial surgeons SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID SOUTHERN-CALIFORNIA-SOCIETY; OUTPATIENT ANESTHESIA; MORTALITY SURVEY; MORBIDITY AB Purpose: The delivery of office-based ambulatory anesthesia services is an integral component of the daily practice of oral and maxillofacial surgeons (OMSs). The purpose of this report was to provide an overview of current anesthetic practices of OMSs in the office-based ambulatory setting. Materials and Methods: To address the research purpose, we used a prospective cohort study design and a sample composed of patients undergoing procedures in the office-based ambulatory setting of OMSs practicing in the United States who received local anesthesia (LA), conscious sedation (CS), or deep sedation/general anesthesia (DS/GA). The predictor variables were categorized as demographic, anesthetic technique, staffing, adverse events, and patient-oriented outcomes. Appropriate descriptive and bivariate statistics were computed as indicated. Statistical significance was set at less than or equal to.05. Results: The sample was composed of 34,191 patients, of whom 71.9% received DS/GA, 15.5% received CS, and 12.6% received LA. The complication rate was 1.3 per 100 cases, and the complications were minor and self-limiting. Two patients had complications requiring hospitalization. Most patients (80.3%) reported some degree of anxiety before the procedure. After the procedure, 61.2% of patients reported having no anxiety about future operations. Overall, 94.3% of patients reported satisfaction with the anesthetic, and more than 94.7% of all patients would recommend the anesthetic technique to a loved one. Conclusion: The findings of this study show that the office-based administration of LA, CS, or DS/GA delivered via OMS anesthesia teams was safe and associated with a high level of patient satisfaction. (C) 2003 American Association of Oral and Maxillofacial Surgeons. C1 Salinas Valley Mem Healthcare Syst, Med Affairs, Salinas, CA 93901 USA. Amer Assoc Oral & Maxillofacial Surg, Outcomes Comm, Rosemont, IL USA. Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Perrott, DH (reprint author), Salinas Valley Mem Healthcare Syst, Med Affairs, 450 E Romie Ln, Salinas, CA 93901 USA. FU NIDCR NIH HHS [DE 000448] NR 21 TC 55 Z9 55 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD SEP PY 2003 VL 61 IS 9 BP 983 EP 995 DI 10.1016/S0278-2391(03)00668-2 PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 716UA UT WOS:000185046500002 PM 12966471 ER PT J AU Studer, RK Decker, K Melhem, S Georgescu, H AF Studer, RK Decker, K Melhem, S Georgescu, H TI Nitric oxide inhibition of IGF-1 stimulated proteoglycan synthesis: role of cGMP SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE nitric oxide; cartilage; chondrocytes; cGMP dependent kinase; arthritis ID DEPENDENT PROTEIN-KINASE; ARTICULAR CHONDROCYTES; CYCLIC-GMP; NOS2-DEFICIENT MICE; I ISOFORMS; EXPRESSION; METABOLISM; ARTHRITIS; SYNTHASE; CELLS AB Insulin-like growth factor (IGF-1) is critical for normal development and maintenance of cartilage, however arthritic cartilage responds poorly to IGF-1; part of this insensitivity is mediated by nitric oxide (NO). These studies test if cGMP is responsible for NO dependent insensitivity to IGF-1 in chondrocytes in situ in organ culture and in monolayer culture. Lapine cartilage and chondrocytes in monolayer culture and cartilage from osteoarthritic human knees were used. Tissues were exposed to NO from iNOS induced by IL-1, and proteoglycan synthesis in response to IGF-1 was evaluated in the presence and absence of cGMP dependent protein kinase (PKG) inhibitors. PKG activators inhibited IGF-1 responses in cartilage but not chondrocytes in monolayer. IL-1 stimulated cGMP synthesis in both monolayer and organ cultures. However, PKG inhibitors in cartilage slices but not in monolayer cultures restored response to IGF-1. PKG activity was detected in both fresh and monolayer chondrocytes, confirming this part of the cGMP signal cascade is intact in both of the preparations evaluated. Arthritic cartilage response to IGF-1 was restored by both N-G-monomethyl-(L)-arginine inhibition of NO synthesis and PKG inhibitors. The data suggests that cGMP mediated effects are critical to NO actions on chondrocytes in situ in the cartilage matrix and supports a role for cGMP in the pathophysiologic effects of NO in osteoarthritis. (C) 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. C1 Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Ferguson Lab,Dept Orthopaed Surg,MSRC, Pittsburgh, PA 15240 USA. RP Studer, RK (reprint author), Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Ferguson Lab,Dept Orthopaed Surg,MSRC, Univ Dr C,151U VA Med Ctr, Pittsburgh, PA 15240 USA. NR 29 TC 12 Z9 12 U1 2 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD SEP PY 2003 VL 21 IS 5 BP 914 EP 921 DI 10.1016/S0736-0266(03)00029-9 PG 8 WC Orthopedics SC Orthopedics GA 717HC UT WOS:000185080600022 PM 12919881 ER PT J AU McCluggage, WG Oliva, E Herrington, CS McBride, H Young, RH AF McCluggage, WG Oliva, E Herrington, CS McBride, H Young, RH TI CD10 and calretinin staining of endocervical glandular lesions, endocervical stroma and endometrioid adenocarcinomas of the uterine corpus SO JOURNAL OF PATHOLOGY LA English DT Meeting Abstract CT 2nd Joint Meeting of the British Division of the International-Academy-of-Pathology/185th Meeting of the Pathological-Society-of-Great-Britian-and-Ireland CY JUL 01-04, 2003 CL UNIV BRISTOL, BRISTOL, ENGLAND SP Int Acad Path, Britian Div, Pathol Soc Great Britan & Ireland HO UNIV BRISTOL C1 Royal Grp Hosp Trust, Dept Pathol, Belfast, Antrim, North Ireland. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD SEP PY 2003 VL 201 SU S BP 53A EP 53A PG 1 WC Oncology; Pathology SC Oncology; Pathology GA 721XX UT WOS:000185344700210 ER PT J AU Mericq, V Cassorla, F Bowers, CY Avila, A Gonen, B Merriam, GR AF Mericq, V Cassorla, F Bowers, CY Avila, A Gonen, B Merriam, GR TI Changes in appetite and body weight in response to long-term oral administration of the ghrelin agonist GHRP-2 in growth hormone deficient children SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article DE ghrelin; appetite; growth hormone deficiency; children ID ACYLATED PEPTIDE; SECRETAGOGUE; RECEPTOR; HUMANS; ACTIVATION; OBESITY AB GHRP-2 (GPA-748, Wyeth-Ayerst) is an orally active peptide growth hormone (GH) secretagogue which acts through a G-protein coupled receptor for which the natural ligand an acylated 28 amino acid peptide, ghrelin - was recently isolated. Ghrelin and its analogs have potent GH-releasing activities, but in animal studies ghrelin also causes weight gain. As part of a study examining the effect of GHRP-2 on GH secretory dynamics and growth, we evaluated its effects on appetite and body weight. Ten prepubertal children with GH deficiency (growth velocity less than or equal to4 cm/year in association with a GH response to two provocative stimuli <10 ng/ml) were included in the study. At the beginning of the study their age was 10.4 +/- 2 years (mean SD), with a height of -3.8 +/- 0.1 SDS. Body mass index (BMI) was 17.9 +/- 3.6 kg/m(2), and the BMI Z score 0.21 +/- 1.51 SDS. GHRP-2 was administered orally at a dose of 900 mug/kg b.i.d. for 12 months. Seven out of ten patients reported a significant increase in appetite during the first 6 months of the study. There was a tendency for the BMI SDS to increase during the study, but this increase did not reach statistical significance (0.21 +/- 1.5 vs 0.25 +/- 1.5 SDS). These results suggest that at a dose of 900 mug/kg b.i.d., GHRP-2 appears to have a transient stimulatory effect on appetite, but does not have a chronic clinically significant effect on BMI in children with GH deficiency. C1 Univ Chile, Inst Invest Materno Infantil, Santiago, Chile. Wyeth Ayerst Res, Philadelphia, PA USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. VA Puget Sound HCS, Seattle, WA 98195 USA. RP Mericq, V (reprint author), Univ Chile, Inst Invest Materno Infantil, Casilla 226-3, Santiago, Chile. EM vmericq@machi.med.uchile.cl RI Mericq, Veronica/F-3927-2010 NR 20 TC 16 Z9 16 U1 0 U2 0 PU FREUND PUBLISHING HOUSE LTD PI LONDON PA STE 500, CHESHAM HOUSE, 150 REGENT ST, LONDON W1R 5FA, ENGLAND SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD SEP PY 2003 VL 16 IS 7 BP 981 EP 985 PG 5 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 721XD UT WOS:000185343000005 PM 14513874 ER PT J AU Shah, MA Albright, MB Vogt, MT Moreland, MS AF Shah, MA Albright, MB Vogt, MT Moreland, MS TI Superior mesenteric artery syndrome in scoliosis surgery: Weight percentile for height as an indicator of risk SO JOURNAL OF PEDIATRIC ORTHOPAEDICS LA English DT Article DE superior inesenteric artery (SMA) syndrome; cast syndrome; scoliosis surgery ID CAST SYNDROME; VASCULAR COMPRESSION; DUODENUM AB A retrospective analysis of charts identified cases of superior mesenteric artery (SMA) syndrome occurring after scoliosis surgery over a 23-year period. Despite numerous reports on this potentially fatal complication of scoliosis surgery, no method exists to stratify patients for risk of developing disease after spine surgery. A study of charts was performed to identify all cases of SMA syndrome occurring after scoliosis surgery from 1972 to 1995. An upper gastrointestinal study with findings specific for the syndrome was requisite for inclusion. Patients' weight and height at the time of diagnosis of SMA syndrome were recorded. Based on standard national data tables, a percentile for weight, percentile for height, and a weight percentile for height were derived for each patient. The syndrome occurred after posterior spinal fusion in six patients (three boys, three girls). The average weight percentile for height, available in five of the six patients, was 3%, significantly different from both age-matched controls in the general population and from age-matched controls undergoing posterior spinal fusion for adolescent idiopathic scoliosis. This study, the largest reported from a single institution, suggests that a weight percentile for height of 5% is the degree of asthenia that allows compromise of the duodenum. The percentile identifies patients at risk for SMA syndrome for the purposes of increasing postoperative vigilance for gastrointestinal complaints, decreasing the threshold for diagnostic workup, and guiding perioperative dietary supplementation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Univ Texas, Med Branch, Dept Orthopaed & Rehabil, Galveston, TX 77550 USA. Univ Pittsburgh, Sch Med, Dept Orthopaed Surg, Pittsburgh, PA 15261 USA. RP Albright, MB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. NR 17 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-6798 J9 J PEDIATR ORTHOPED JI J. Pediatr. Orthop. PD SEP-OCT PY 2003 VL 23 IS 5 BP 665 EP 668 PG 4 WC Orthopedics; Pediatrics SC Orthopedics; Pediatrics GA 715KF UT WOS:000184970200018 PM 12960634 ER PT J AU Grikscheit, T Srinivasan, A Vacanti, JP AF Grikscheit, T Srinivasan, A Vacanti, JP TI Tissue-engineered stomach: A preliminary report of a versatile in vivo model with therapeutic potential SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE microgastria; tissue-engineered stomach ID POUCH RECONSTRUCTION; TOTAL GASTRECTOMY AB Background/Purpose: Microgastria and postgastrectomy morbidities are substantial. The authors hypothesized a functional living tissue-engineered stomach could function as a replacement alternative. Methods: Stomach organoid units, mesenchymal cores surrounded by epithelia, were isolated from neonatal and adult rats and transplanted paratopically on biodegradable polymer tubes, which were implanted in syngeneic hosts, varying the inclusion of stomach regions. Four weeks later, tissue-engineered stomach (TES) was either harvested or anastomosed. GFP labeling was performed before implantation. Histology and immunohistochemical detection of the antigensgastrin and actin smooth muscle were performed. Results: Ninety-eight percent of all animals generated TES, including TES formation from adult tissue. Immunohisto-chemistry for alpha-actin smooth muscle and gastrin confirms the presence of a smooth muscle layer and a well-developed gastric epithelium containing all the elements of the native rat stomach including gastric pits and squamous layers, varying by included regions at harvest. TES architecture was maintained in anastomosis: GFP-labeled TES maintained signal in anastomosis, proving the donor origin of the TES. Conclusions: TES resembles native stomach and maintains robust histology in anastomosis, a new versatile model for the study of gastric physiology and possible therapy. (C) 2003 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Pediat Surg, Warren 1157,55 Fruit St, Boston, MA 02114 USA. NR 11 TC 21 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD SEP PY 2003 VL 38 IS 9 BP 1305 EP 1309 DI 10.1016/S0022-3468(03)00386-5 PG 5 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 728XL UT WOS:000185741600006 PM 14523810 ER PT J AU Fuchs, JR Pomerantseva, I Ochoa, ER Vacanti, JP Fauza, DO AF Fuchs, JR Pomerantseva, I Ochoa, ER Vacanti, JP Fauza, DO TI Fetal tissue engineering: In vitro analysis of muscle constructs SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the American-Pediatric-Surgical-Association CY MAY 20-23, 2001 CL NAPLES, FLORIDA SP Amer Pediatr Surg Assoc DE tissue engineering; fetal; muscle; myoblast; fetal surgery; congenital anomalies; transplantation ID CONGENITAL DIAPHRAGMATIC-HERNIA; EXTRACORPOREAL MEMBRANE-OXYGENATION; HYBRID MUSCULAR TISSUES; SKELETAL-MUSCLE; GENE-THERAPY; MYOBLASTS; ORGANOIDS AB Background/Purpose: This study was aimed at examining the impact of different tissue engineering techniques on fetal muscle construct architecture. Methods: Myoblasts from ovine specimens of fetal skeletal muscle were expanded in culture and their growth rates determined. Cells were seeded at different densities onto 3 scaffold types, namely polyglycolic acid (PGA) treated with poly-L-lactic acid (PLLA), a composite of PGA with poly-4-hydroxylbutyrate (P4HB), and a collagen hydrogel. Constructs were maintained in a bioreactor and submitted to histologic, scanning electron microscopy, and DNA analyses at different time-points. Statistical analysis was by the likelihood ratio and paired Student's t tests (P < .05). Results: Fetal myoblasts proliferated at faster rates than expected from neonatal cells. Cell attachment was enhanced in the PGA/PLLA matrix and collagen hydrogel when compared with the PGA/P4HB composite. Necrosis was observed at the center of all constructs, directly proportional to cell seeding density and time in the bioreactor. Conclusions: Fetal myoblasts can be expanded rapidly in culture and attach well to PGA/PLLA, as well as collagen hydrogel but less optimally to PGA/P4HB. Excessive cell seeding density and bioreactor time may worsen final construct architecture. These findings should be considered during in vivo trials of muscle replacement by engineered fetal constructs. (C) 2003 Elsevier Inc. All rights reserved. C1 Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Ctr Minimally Invas Surg, Boston, MA USA. Massachusetts Gen Hosp, Ctr Integrat Med & Innovat Technol, Boston, MA 02114 USA. RP Fauza, DO (reprint author), Childrens Hosp, Fegan 3,300 Longwood Ave, Boston, MA 02115 USA. NR 22 TC 20 Z9 26 U1 1 U2 9 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD SEP PY 2003 VL 38 IS 9 BP 1348 EP 1353 DI 10.1016/S0022-3468(03)00394-4 PG 6 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 728XL UT WOS:000185741600014 PM 14523818 ER PT J AU LaFranchi, SH Snyder, DB Sesser, DE Skeels, MR Singh, N Brent, GA Nelson, JC AF LaFranchi, SH Snyder, DB Sesser, DE Skeels, MR Singh, N Brent, GA Nelson, JC TI Follow-up of newborns with elevated screening T4 concentrations SO JOURNAL OF PEDIATRICS LA English DT Article ID MCCUNE-ALBRIGHT SYNDROME; THYROTROPIN-RECEPTOR GENE; THYROID-HORMONE; CONGENITAL HYPERTHYROIDISM; DYSALBUMINEMIC HYPERTHYROXINEMIA; NEONATAL HYPERTHYROIDISM; GENERALIZED RESISTANCE; BETA GENE; MUTATION; ABNORMALITIES AB Objective To determine the type and incidence of hyperthyroxinemic disorders detected by follow-up of infants with elevated screening total T4 (TT4) values. Study design Infants born in Oregon with a screening TT4 measurement >3 SD above the mean were offered enrollment. Serum TT4, free T4, total T3, free T3, and thyroid-stimulating hormone concentrations were measured in. study infants and their mothers. Results Over a 20-month period, 101 infants (51 boys) and their mothers enrolled in the study (of 241 eligible infants), from a total screening population of 80,884; 17 infants were identified with persistent hyperthyroxinemia (TT4 >16 mug/dL). Ten had thyroxine-binding globulin excess (1:8088), 5 had evidence for increased T4 binding but not thyroxine-binding globulin excess (1:16,177), and 2 had findings compatible with thyroid hormone resistance (1:40,442); the other 84 infants had transient hyperthyroxinemia. Sequence analysis revealed a point mutation in the thyroid hormone receptor-beta gene in one infant with thyroid hormone resistance; no mutation was identified in the other infant. Conclusions Although neonatal Graves' disease occurs in approximately 1 in 25,000 newborn infants, we did not detect any case among 80, 84 infants, most likely because their mothers were receiving antithyroid drugs. Although the other hyperthyroxinemic disorders in the aggregate occur frequently (1:4758) and may benefit from detection, in general they do not require treatment. C1 Legacy Emanuel Childrens Hosp, Portland, OR USA. Oregon State Publ Hlth Lab, Portland, OR USA. Univ Calif Los Angeles, VA Greater Los Angeles Hlth Care Syst, Dept Med, Sch Med, Los Angeles, CA USA. Quest Diagnost Nichols Inst, San Juan Capistrano, CA USA. Loma Linda Univ, Med Ctr, Dept Internal Med, Loma Linda, CA USA. Loma Linda Univ, Med Ctr, Dept Pathol, Loma Linda, CA USA. RP LaFranchi, SH (reprint author), Oregon Hlth & Sci Univ, Dept Pediat, 707 SW Gaines Rd, Portland, OR 97239 USA. EM lafrancs@ohsu.edu NR 27 TC 50 Z9 58 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 2003 VL 143 IS 3 BP 296 EP 301 DI 10.1067/S0022-3476(03)00184-7 PG 6 WC Pediatrics SC Pediatrics GA 728GV UT WOS:000185710200007 PM 14517508 ER PT J AU Tarazi, FI Baldessarini, RJ Kula, NS Zhang, KH AF Tarazi, FI Baldessarini, RJ Kula, NS Zhang, KH TI Long-term effects of olanzapine, risperidone, and quetiapine on ionotropic glutamate receptor types: Implications for antipsychotic drug treatment SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID MESSENGER-RNA LEVELS; RAT-BRAIN; KAINATE RECEPTORS; AMPA RECEPTOR; ATYPICAL ANTIPSYCHOTICS; CAUDATE-PUTAMEN; EMERGING ROLE; CLOZAPINE; SCHIZOPHRENIA; HALOPERIDOL AB Levels of ionotropic glutamate (Glu) N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and kainic acid (KA) receptors in rat forebrain regions were compared by quantitative in vitro receptor autoradiography after continuous treatment for 28 days with the atypical antipsychotics olanzapine, risperidone, and quetiapine, or vehicle controls. All three treatments significantly decreased NMDA binding in caudate-putamen (CPu; by 30, 34, and 26%, respectively) but increased AMPA receptor levels in same region (by 22, 30, and 28%). Olanzapine and risperidone, but not quetiapine, also reduced NMDA receptor labeling in hippocampal CA1 (21 and 19%) and CA3 (23 and 22%) regions. KA receptors were unaltered by any treatment in the brain regions examined. These findings suggest that the antipsychotic effects of olanzapine and risperidone may be mediated in part by NMDA receptors in hippocampus, and perhaps AMPA receptors in CPu. The findings also support the hypothesis that down-regulation of NMDA receptors by atypical antipsychotic agents in CPu contributes to their low risk of extrapyramidal side effects. Inability of olanzapine, risperidone, and quetiapine to alter KA receptors suggests their minimal role in mediating the central nervous system actions of these drugs. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Tarazi, FI (reprint author), Harvard Univ, McLean Hosp, Sch Med, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. NR 51 TC 55 Z9 55 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2003 VL 306 IS 3 BP 1145 EP 1151 DI 10.1124/jpet.103.052597 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 712UU UT WOS:000184817400040 PM 12829726 ER PT J AU LeMarbre, G Stauber, S Khayat, RN Puleo, DS Skatrud, JB Morgan, BJ AF LeMarbre, G Stauber, S Khayat, RN Puleo, DS Skatrud, JB Morgan, BJ TI Baroreflex-induced sympathetic activation does not alter cerebrovascular CO2 responsiveness in humans SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID CEREBRAL BLOOD-FLOW; BODY NEGATIVE-PRESSURE; TRANSCRANIAL DOPPLER; ORTHOSTATIC STRESS; CARBON-DIOXIDE; NERVE ACTIVITY; UPRIGHT TILT; RESPONSES; BARORECEPTOR; CIRCULATION AB We investigated the effect of baroreflex-induced sympathetic activation, produced by lower body negative pressure (LBNP) at -40 mmHg, on cerebrovascular responsiveness to hyper- and hypocapnia in healthy humans. Transcranial Doppler ultrasound was used to measure blood flow velocity (CFV) in the middle cerebral artery during variations in end-tidal carbon dioxide pressure (PIT,11,)of +10, +5,0,-5, and -10 mmHg relative to eupnoea. The slopes of the linear relationships between PET,CO, and CFV were computed separately for hyper- and hypocapnia during the LBNP and no-LBNP conditions. LBNP decreased pulse pressure, but did not change mean arterial pressure. LBNP evoked an increase in ventilation that resulted in a 9 2 mmHg decrease in P-ET,P-CO2, which was corrected by CO2 supplementation of the inspired air. LBNP did not affect cerebrovascular CO2 response slopes during steady-state hypercapnia (3.14 +/- 0.24 vs. 2.96 +/- 0.26 cm s(-1) mmHg(-1)) or hypocapnia (1.31 +/- 0.18 vs. 1.32 +/- 0.19 cm s(-1) mmHg(-1)), or the CFV responses to voluntary apnoea (+51 +/- 19 vs. +50 +/- 18 %). Thus, cerebrovascular CO2 responsiveness was not altered by baroreflex-induced sympathetic activation. Our data challenge the concept that sympathetic activation restrains cerebrovascular responses to alterations in CO2 pressure. C1 Univ Wisconsin, Dept Orthopaed & Rehabil, Madison, WI 53706 USA. Univ Wisconsin, Dept Med, Madison, WI 53706 USA. Middleton Vet Adm Hosp, Madison, WI 53705 USA. RP Morgan, BJ (reprint author), Univ Wisconsin, Dept Orthopaed & Rehabil, 1300 Univ Ave,5173 MSC, Madison, WI 53706 USA. RI Khayat, Rami/E-3380-2011 NR 52 TC 43 Z9 43 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD SEP 1 PY 2003 VL 551 IS 2 BP 609 EP 616 DI 10.1113/jphysiol.2003.046987 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 727XK UT WOS:000185686000022 PM 12844511 ER PT J AU Baethge, C Gruschka, P Smolka, MN Berghofer, A Bschor, T Muller-Oerlinghausen, B Bauer, M AF Baethge, C Gruschka, P Smolka, MN Berghofer, A Bschor, T Muller-Oerlinghausen, B Bauer, M TI Effectiveness and outcome predictors of long-term lithium prophylaxis in unipolar major depressive disorder SO JOURNAL OF PSYCHIATRY & NEUROSCIENCE LA English DT Article DE depressive disorder; drug therapy, combination; lithium carbonate; treatment outcome ID MAINTENANCE TREATMENT; BIPOLAR DISORDER; RECURRENCE; MORTALITY; RECOVERY; ILLNESS; PATTERN AB Objective: To determine the effectiveness of lithium prophylaxis in unipolar major depressive disorder (MDD) and to identify predictors of outcome including comedication. Methods: In this long-term naturalistic study, clinical data from 55 patients with MDD (DSM-III-R) were collected prospectively in an outpatient clinic specializing in the treatment of affective disorders. Outcome measures: Change in hospital admission rate (number and duration) during prophylaxis compared with the period before prophylaxis, Morbidity-index during prophylaxis and time to first recurrence after initiation of lithium treatment. Results: During an average follow-up period of 6.7 years, a significant decline in the number of days spent in hospital (p < 0.001; 52 d/yr less; 95% CI 31-73 d) and a low Morbidity-index (mean 0.07) was observed. Only in 6 patients did medication have to be changed because of side-effects (n = 4) or a lack of efficacy (n = 2). None of the independent variables we analyzed proved to be important in predicting the outcome of lithium prophylaxis. Comedication was necessary in 21 patients. The overall outcome of their prophylactic treatment, however, did not differ from the group that did not receive comedication in the symptom-free intervals. Conclusions: The results of this study, with its long observation period and the inclusion of comedication as a confounding variable, indicate that lithium is a potent prophylactic agent for unipolar MDD in a naturalistic setting. In contrast to the findings of others, age was not associated with the outcome of prophylaxis, and latency did not predict outcome. Contrary to doubts that have been raised in recent years with regard to the effectiveness of lithium in everyday clinical practice, lithium appears to be a safe and potent alternative to antidepressants. C1 Massachusetts Gen Hosp, Mailman Res Ctr, McLean Div, Psychot Disorders Program, Belmont, MA 02478 USA. Harvard Univ, Consolidated Dept Psychiat, Cambridge, MA 02138 USA. Free Univ Berlin, Klinikum Benjamin Franklin, Dept Psychiat & Psychotherapy, D-1000 Berlin, Germany. Univ Heidelberg, Dept Psychiat, Heidelberg, Germany. Cent Inst Mental Hlth, Dept Addict Behav & Addict Med, D-6800 Mannheim, Germany. Humboldt Univ, Inst Social Med Epidemiol & Hlth Econ, Berlin, Germany. Tech Univ Dresden, Klinikum Carl Gustav Carus, Dept Psychiat & Psychotherapy, D-8027 Dresden, Germany. Drug Commiss German Med Assoc, Cologne, Germany. Humboldt Univ, Dept Psychiat & Psychotherapy, Berlin, Germany. RP Baethge, C (reprint author), Massachusetts Gen Hosp, Mailman Res Ctr, McLean Div, Psychot Disorders Program, 115 Mill St, Belmont, MA 02478 USA. RI Smolka, Michael/B-4865-2011 OI Smolka, Michael/0000-0001-5398-5569 NR 29 TC 16 Z9 16 U1 0 U2 1 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 1180-4882 J9 J PSYCHIATR NEUROSCI JI J. Psychiatry Neurosci. PD SEP PY 2003 VL 28 IS 5 BP 355 EP 361 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 723GE UT WOS:000185423700005 PM 14517579 ER PT J AU Pollack, MH Simon, NM Worthington, JJ Doyle, AL Peters, P Toshkov, F Otto, MW AF Pollack, MH Simon, NM Worthington, JJ Doyle, AL Peters, P Toshkov, F Otto, MW TI Combined paroxetine and clonazepam treatment strategies compared to paroxetine monotherapy for panic disorder SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Article DE clonazepam; combined treatment; panic disorder; paroxetine ID IMIPRAMINE; SCALE; ALPRAZOLAM AB Despite the widespread application of combined selective serotonin reuptake inhibitors (SSRI) and benzodiazepine treatment for panic disorder, there has been relatively little systematic assessment of the safety and efficacy of this therapeutic strategy. Although the limited number of studies to date suggest a more rapid onset of benefit with combined, treatment, this-study is the first to address the critical question of whether continued combined treatment confers superior efficacy. This study is a randomized, double-blind, three-arm study in patients with panic disorder (n = 60), comparing the efficacy and safety of paroxetine and placebo (PP), paroxetine coadministered with clonazepam followed by a tapered benzodiazepine discontinuation phase (PC-D), and ongoing combination treatment (PC-M). All treatment groups demonstrated significant improvement by endpoint. There was a significant advantage for the combined treatment groups early in treatment but, subsequently, outcome in all three groups was similar. A trend towards greater achievement of endpoint remission status for the PC-D group was attenuated when variability in baseline severity was considered.. The results of this study should be interpreted in the context of a relatively moderate sample size and higher rates of early dropout. Combined treatment with paroxetine and clonazepam resulted in more rapid response than with the SSRI alone, but there was no differential benefit beyond the initial few weeks of therapy. Initiating combined treatment followed by benzodiazepine taper after a few weeks may provide early benefit while avoiding the potential adverse consequences of long-term combination therapy. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Pollack, MH (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WAC-812,15 Parkman St, Boston, MA 02114 USA. FU NIMH NIH HHS [MH 01831] NR 23 TC 51 Z9 51 U1 1 U2 7 PU SAGE PUBLICATIONS LTD PI LONDON PA 6 BONHILL STREET, LONDON EC2A 4PU, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD SEP PY 2003 VL 17 IS 3 BP 276 EP 282 DI 10.1177/02698811030173009 PG 7 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 725HY UT WOS:000185539200009 PM 14513919 ER PT J AU Tohen, M Vieta, E Kettter, T Centorino, F Calabrese, J Sachs, G Bowden, C Risser, R Baker, RW Evans, AR Dube, S Tollefson, G McGee, D Breier, A AF Tohen, M Vieta, E Kettter, T Centorino, F Calabrese, J Sachs, G Bowden, C Risser, R Baker, RW Evans, AR Dube, S Tollefson, G McGee, D Breier, A TI Olanzapine and olanzapine-fluoxetine combination (OFC) in the treatment of bipolar depression SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT Summer Meeting of the British-Association-for-Psychopharmacology CY JUL 20-23, 2003 CL CAMBRIDGE, ENGLAND SP British Assoc Psychopharmacol C1 Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. Hosp Clin Barcelona, IDIBAPS, Bipolar Disorders Program, Barcelona, Spain. Stanford Univ, Dept Psychiat, Stanford, CA USA. Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78285 USA. Eli Lilly & Co, Basingstoke, Hants, England. RI Vieta, Eduard/I-6330-2013 OI Vieta, Eduard/0000-0002-0548-0053 NR 0 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 6 BONHILL STREET, LONDON EC2A 4PU, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD SEP PY 2003 VL 17 IS 3 SU S BP A23 EP A23 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 726WC UT WOS:000185623500090 ER PT J AU Sherman, SE Lanto, AB Nield, M Yano, EM AF Sherman, SE Lanto, AB Nield, M Yano, EM TI Smoking cessation care received by veterans with chronic obstructive pulmonary disease SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE chronic obstructive pulmonary disease; counseling; smoking cessation ID LUNG HEALTH; INTERVENTION; HABITS; BURDEN AB Smoking is the main cause of chronic obstructive pulmonary disease (COPD), and smoking cessation is the only effective intervention to slow its progression. We examined whether smokers with COPD received more cessation services than smokers without COPD. Current smokers from 18 Veterans Health Administration primary care clinics completed baseline and 12 month follow-up surveys (baseline n = 1,941; 12 month n = 1,080), composed of validated questions on smoking habits, history, and attitudes; health/functional status; and sociodemographics. Both at baseline and 12 month follow-up, smokers with COPD were more likely to report that they had been advised to quit, prescribed nicotine patches, or referred to a smoking cessation program within the last year. However, the rate of quitting smoking was the same for smokers with COPD and smokers without COPD. The increase in cessation services received by smokers with COPD was noted primarily among smokers not interested in quitting. New approaches may be required, particularly to help smokers not interested in quitting. C1 VA Greater Los Angles Healthcare Syst, Ctr Excellence Study Healthcare Provider Behavior, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Dept Med, Div Pulm & Crit Care, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. RP Sherman, SE (reprint author), VA Greater Los Angles Healthcare Syst, Ctr Excellence Study Healthcare Provider Behavior, 16111 Plummer St, Sepulveda, CA 91343 USA. NR 31 TC 13 Z9 14 U1 2 U2 4 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD SEP-OCT PY 2003 VL 40 IS 5 SU 2 BP 1 EP 12 PG 12 WC Rehabilitation SC Rehabilitation GA 737MC UT WOS:000186235500002 PM 15074449 ER PT J AU Kerns, RD Otis, J Rosenberg, R Reid, MC AF Kerns, RD Otis, J Rosenberg, R Reid, MC TI Veterans' reports of pain and associations with ratings of health, health-risk behaviors, affective distress, and use of the healthcare system SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE emotional distress; health-risk behaviors; health services use; pain; primary care ID RECEIVING PRIMARY-CARE; LOW-BACK-PAIN AB The improved management of pain among veterans seeking care in Veterans Health Administration (VHA) facilities has been established as a priority. This study documents the high prevalence of reports of pain among a convenience sample of 685 veterans seeking care in a VHA primary care setting. Also reported are associations of pain complaints with self-rated health, an index of emotional distress, health-risk behaviors such as tobacco and alcohol use, health-related concerns about diet and weight, and perceptions of the availability of social support. The relationship between the presence of pain and use of outpatient and inpatient medical and mental health services is also examined. Nearly 50% of the sample reported that they experience pain regularly and that they were concerned about this problem at the time of the index visit to their primary care provider. Persons acknowledging the presence of pain, relative to those not reporting pain, were younger, reported worsening health over the past year, had greater emotional distress, used tobacco, had diet and/or weight concerns, and were found to use more outpatient medical, but not inpatient medical or mental health services. Results support the goals of the VHA National Pain Management Strategy designed to reduce unnecessary pain and suffering among veterans receiving care in VHA facilities. C1 VA Connecticut Healthcare Syst, Psychol Serv 116B, West Haven, CT 06516 USA. VA Connecticut Healthcare Syst, Dept Vet Affairs, West Haven, CT 06516 USA. Yale Univ, New Haven, CT USA. VA Boston Healthcare Syst, Boston, MA USA. Pfizer Inc, Groton, CT USA. Cornell Univ Med Coll, New York, NY USA. RP Kerns, RD (reprint author), VA Connecticut Healthcare Syst, Psychol Serv 116B, West Haven, CT 06516 USA. EM robert.kerns@med.va.gov NR 22 TC 83 Z9 85 U1 0 U2 2 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD SEP-OCT PY 2003 VL 40 IS 5 BP 371 EP 379 PG 9 WC Rehabilitation SC Rehabilitation GA 736RH UT WOS:000186186600003 PM 15080222 ER PT J AU Otis, JD Keane, TM Kerns, RD AF Otis, JD Keane, TM Kerns, RD TI An examination of the relationship between chronic pain and post-traumatic stress disorder SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE anxiety; avoidance; chronic pain; post-traumatic stress disorder; vulnerability ID MOTOR-VEHICLE ACCIDENTS; CHRONIC BACK PAIN; CHRONIC MUSCULOSKELETAL PAIN; MALE VIETNAM VETERANS; ANXIETY SENSITIVITY; FIBROMYALGIA SYNDROME; MUTUAL MAINTENANCE; NATIONAL SAMPLE; FEAR-AVOIDANCE; SOCIAL SUPPORT AB Chronic pain and post-traumatic stress disorder (PTSD) are frequently observed within the Department of Veterans Affairs healthcare system and are often associated with a significant level of affective distress and physical disability. Clinical practice and research suggest that these two conditions co-occur at a high rate and may interact in such a way as to negatively impact the Course of either disorder; however, relatively little research has been conducted in this area. This review summarizes the current literature pertaining to the prevalence and development of chronic pain and PTSD. Research describing the comorbidity of both conditions is reviewed, and several theoretical models are presented to explain the mechanisms by which these two disorders may be maintained. Future directions for research and clinical implications are discussed. C1 VA Boston Healthcare Syst, Psychol Serv 116B, Boston, MA 02130 USA. VA Boston Healthcare Syst, Dept Vet Affairs, Boston, MA 02130 USA. Yale Univ, New Haven, CT USA. VA Connecticut Healthcare Syst, W Haven, CT USA. RP Otis, JD (reprint author), VA Boston Healthcare Syst, Psychol Serv 116B, 150 S Huntington Ave, Boston, MA 02130 USA. NR 73 TC 148 Z9 150 U1 3 U2 15 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD SEP-OCT PY 2003 VL 40 IS 5 BP 397 EP 405 PG 9 WC Rehabilitation SC Rehabilitation GA 736RH UT WOS:000186186600005 PM 15080224 ER PT J AU Rentschler, AJ Cooper, RA Blasch, B Boninger, ML AF Rentschler, AJ Cooper, RA Blasch, B Boninger, ML TI Intelligent walkers for the elderly: Performance and safety testing of VA-PAMAID robotic walker SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE engineering test; navigational assistance; obstacle avoidance; robotic walker; visual impairment ID FALLS AB A walker that could help navigate and avoid collisions with obstacles could help reduce health costs and increase the quality of care and independence of thousands of people. This study evaluated the safety and performance of the Veterans Affairs Personal Adaptive Mobility Aid (VA-PAMAID). We performed engineering tests on the VA-PAMAID to determine safety factors, including stability, energy consumption, fatigue life, and sensor and control malfunctions. The VA-PAMAID traveled 10.9 km on a full charge and avoided obstacles while traveling at a speed of up to 1.2 m/s. No failures occurred during static stability, climatic, or fatigue testing. Some problems were encountered during obstacle climbing and sensor and control testing. The VA-PAMAID has good range, has adequate reaction time, and is structurally sound. Clinical trials are planned to compare the device to other low-technical adaptive mobility devices. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Va Rehabil Res & Dev, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Phys Med & Rehabil & Bioengn, Pittsburgh, PA USA. Atlanta VA Med Ctr, VA Rehabil Res & Dev Ctr, Decatur, GA USA. RP VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Va Rehabil Res & Dev, 151-R1,7180 Highland Dr, Pittsburgh, PA 15206 USA. EM rcooper@pitt.edu OI Boninger, Michael/0000-0001-6966-919X NR 19 TC 47 Z9 51 U1 2 U2 4 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD SEP-OCT PY 2003 VL 40 IS 5 BP 423 EP 431 PG 9 WC Rehabilitation SC Rehabilitation GA 736RH UT WOS:000186186600008 PM 15080227 ER PT J AU Evans, CT Legro, MW Weaver, FM Goldstein, B AF Evans, CT Legro, MW Weaver, FM Goldstein, B TI Influenza vaccination among veterans with Spinal Cord Injury: Part 1. A survey of attitudes and behavior SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE spinal cord injuries; influenza; vaccination; immunization; veterans; health promotion; preventive medicine; paraplegia; tetraplegia; rehabilitation ID POPULATION; ADULTS; DEATH AB Background/Objective: Persons with spinal cord injury and disorders (SCID) are at increased risk of developing influenza, pneumonia, and ensuing complications. Influenza vaccine has been shown to be effective, yet vaccination rates have been low in this population. To improve these rates, barriers and facilitators to receiving influenza vaccine in this population were identified. Methods: A cross-sectional telephone survey was conducted with a convenience sample of patients at 13 Department of Veterans Affairs (VA) Spinal Cord Injury (SCI) Centers between September and November 2000. Survey questions assessed perceptions regarding the influenza vaccine. Results: Participants interviewed (N = 377) had a mean age of 58.6 years and were predominantly male and white. Most had had received the influenza vaccine at some time in the past; however, 35% had not received it in the previous year. The most common reason reported for not being vaccinated was the belief that it was not important. Those who knew the best time to be vaccinated were more likely to have been vaccinated the previous year (OR = 3.57, 95%, Cl: 2.12-6.01). Other predictors of vaccination included being married, being aged 65 and older, and being aware that the vaccine was a good way to prevent some pulmonary problems that can result from influenza. Conclusions: Barriers to vaccination include poor understanding of the seriousness of influenza and of the vulnerability of someone with SCID to respiratory complications. Availability of the influenza vaccine at VA facilities and knowledge of when to be vaccinated were facilitators. Providers should use every opportunity to vaccinate patients and provide education about the value of influenza vaccination and when to be vaccinated. C1 Edward J Hines Jr VA Hosp, Midw Ctr Hlth Serv & Policy Res, Dept Vet Affairs, Hines, IL 60141 USA. VA Puget Sound Hlth Care Syst, Spinal Cord Injury Qual Enhancement Res Initiat, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Spinal Cord Injury & Disorders Strateg Healthcare, Dept Vet Affairs, Seattle, WA USA. Northwestern Univ, Inst Hlth Serv Res & Policy Studies, Chicago, IL 60611 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Evans, CT (reprint author), Edward J Hines Jr VA Hosp, Midw Ctr Hlth Serv & Policy Res, Dept Vet Affairs, 151H,5th & Roosevelt Rd,POB 5000, Hines, IL 60141 USA. NR 16 TC 6 Z9 6 U1 1 U2 3 PU AMER PARAPLEGIA SOC PI JACKSON HWIGHTS PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD FAL PY 2003 VL 26 IS 3 BP 204 EP 209 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 739PJ UT WOS:000186355400004 PM 14997958 ER PT J AU Weaver, FM Goldstein, B Evans, CT Legro, MW LaVela, S Smith, B Miskevics, S Hammond, MC AF Weaver, FM Goldstein, B Evans, CT Legro, MW LaVela, S Smith, B Miskevics, S Hammond, MC TI Influenza vaccination among veterans with spinal cord injury: Part 2. Increasing vaccination rates SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE spinal cord injuries; influenza; vaccination; immunization; veterans; health promotion; preventive medicine; paraplegia; tetraplegia; rehabilitation ID RANDOMIZED CONTROLLED-TRIAL; MEDICAL OPINION LEADERS; IMMUNIZATION RATES; REMINDERS; PERFORMANCE; MORTALITY; DEATH; CARE; QUESTIONNAIRE; GUIDELINES AB Background/Objective: Respiratory complications are the leading cause of morbidity and mortality among individuals with spinal cord injury (SCI). Influenza vaccination is effective in reducing the likelihood of contracting influenza and of subsequent respiratory complications, hospitalizations, and deaths. Historically, vaccination rates for veterans with SCI treated in Veterans Affairs (VA) facilities have been low. The objective of this study was to increase vaccination rates in this population using a multipronged strategy. Methods: A quasi-experimental design involving 2,284 veterans treated at 8 VA SCI Centers was used. Patients at 4 centers received reminder letters and educational materials tailored to SCI. Provider education included mailed reminders and posters in SCI clinical areas. Clinical champions were identified at each site. Four other centers, matched to the study sites in program size and prior vaccination rates, served as comparison sites providing usual care. Vaccination rates were assessed using mailed surveys with telephone follow-up. Results: The influenza vaccination rate was significantly higher in the intervention group than in the comparison group (60.5% vs 54.3%; P = 0.01). Vaccine recipients were older than nonrecipients (mean age 60.8 vs 53.1 years; P < 0.0001). Reasons for not receiving a vaccination included refusal, feeling that being vaccinated was not worth the trouble, and not believing that the vaccine would prevent influenza. Conclusions: Use of low-cost mailed reminders and educational materials resulted in significantly higher vaccination rates. Further efforts to reach targeted subgroups of nonrecipients, such as patients who are younger or from an ethnic minority, are warranted. C1 Edward Hines Jr VA Hosp, Midw Ctr Hlth Serv & Policy Res 151H, Dept Vet Affairs, Hines, IL 60141 USA. Edward Hines Jr VA Hosp, SCI QUERI, Dept Vet Affairs, Hines, IL 60141 USA. Northwestern Univ, ISHRPS, Chicago, IL 60611 USA. VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Spinal Cord Injury & Disorders Strateg Healthcare, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Dept Vet Affairs, SCI QUERI, Seattle, WA USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Weaver, FM (reprint author), Edward Hines Jr VA Hosp, Midw Ctr Hlth Serv & Policy Res 151H, Dept Vet Affairs, 5th & Roosevelt Rd,POB 5000, Hines, IL 60141 USA. NR 43 TC 21 Z9 21 U1 0 U2 1 PU AMER PARAPLEGIA SOC PI JACKSON HWIGHTS PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD FAL PY 2003 VL 26 IS 3 BP 210 EP 218 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 739PJ UT WOS:000186355400005 PM 14997959 ER PT J AU Goldstein, B Hammond, MC AF Goldstein, B Hammond, MC TI Commentary - The importance of influenza vaccinations in persons with spinal cord injury and disease SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Editorial Material C1 VA Puget Sound Hlth Care Syst, SCI Hlth Care Grp, Seattle, WA USA. RP Goldstein, B (reprint author), VA Puget Sound Hlth Care Syst, SCI Hlth Care Grp, Seattle, WA USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU AMER PARAPLEGIA SOC PI JACKSON HWIGHTS PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD FAL PY 2003 VL 26 IS 3 BP 219 EP 220 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 739PJ UT WOS:000186355400006 PM 14997960 ER PT J AU Helkowski, WM Ditunno, JF Boninger, M AF Helkowski, WM Ditunno, JF Boninger, M TI Autonomic dysreflexia: Incidence in persons with neurologically complete and incomplete tetraplegia SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE autonomic dysreflexia; tetraplegia; spinal cord injuries; hypertension; rehabilitation ID SPINAL-CORD INJURY; HYPERREFLEXIA AB Background: Autonomic dysreflexia (AD) is a common problem in patients with spinal cord injury (SCI) above the T6 neurologic level and may cause serious medical complications if untreated. Previous studies have focused on patients with complete SCI. Design: Prospective analysis of a historic cohort. A retrospective review of a subset of the cohort also was performed. Objectives: To examine the percentage of persons with complete and incomplete tetraplegia who developed AD and determine whether patients with incomplete injuries were at risk for developing AD; and to study the onset of AD and determine the time period that patients are at risk for developing AD. Methods: Data were collected prospectively on 332 patients with tetraplegia to determine American Spinal Injury Association (ASIA) impairment score, neurologic level, presence of AD, and length of hospital stay. The charts of 34 patients who developed AD were then reviewed retrospectively for further data such as onset and contributing factors of AD. Also obtained were data from the National SCI Statistical Center database for comparison of percentage of patients with complete and incomplete injuries who developed AD. Results: Patients with motor-complete SCI (ASIA A or ASIA 13) had a higher percentage of AD (P = 0.001) during their initial hospitalization than did patients with motor-incomplete SCI. However, patients with motor-incomplete injuries also were at risk for developing AD. The onset of AD occurred between I and 6 months after injury. Conclusion: Patients with incomplete tetraplegia are at risk for developing AD. As hospital lengths of stay decrease, patients may be discharged before onset of symptoms. Patient and family education about AD is, therefore, increasingly important for all patients with tetraplegia. C1 Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. Thomas Jefferson Univ Hosp, Dept Rehabil Med, Philadelphia, PA 19107 USA. VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. RP Helkowski, WM (reprint author), Univ Pittsburgh, Dept Phys Med & Rehabil, 3471 5th Ave,201 Kaufman Bldg, Pittsburgh, PA 15260 USA. OI Boninger, Michael/0000-0001-6966-919X NR 12 TC 28 Z9 29 U1 0 U2 1 PU AMER PARAPLEGIA SOC PI JACKSON HWIGHTS PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD FAL PY 2003 VL 26 IS 3 BP 244 EP 247 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 739PJ UT WOS:000186355400012 PM 14997966 ER PT J AU Long, CJ Eddington, DK Colburn, HS Rabinowitz, WM AF Long, CJ Eddington, DK Colburn, HS Rabinowitz, WM TI Binaural sensitivity as a function of interaural electrode position with a bilateral cochlear implant user SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID COMPLEX WAVEFORMS; SPEECH-PERCEPTION; DISCRIMINATION; LATERALIZATION; NOISE; DELAY AB Experiments were conducted with a single, bilateral cochlear implant user to examine interaural level and time-delay cues that putatively underlie the design and efficacy of bilateral implant systems. The subject's two implants were of different types but custom equipment allowed presentation of controlled bilateral stimuli, particularly those with specified interaural time difference (ITD) and interaural level difference (ILD) cues. A lateralization task was used to measure the effect of these cues on the perceived location of the sensations elicited. For trains of fixed- amplitude, biphasic cur-rent pulses at 100 pps, the subject demonstrated sensitivity to an ITD of 300 mus, providing evidence of access to binaural information. The choice of bilateral electrode pair greatly influenced ITD sensitivity, suggesting that electrode pairings are likely to be an important consideration in the effort to provide binaural advantages. The selection of bilateral electrode pairs showing sensitivity to ITD was partially aided by comparisons of the pitch elicited by individual electrodes in each ear (when stimulated alone with fixed-amplitude current pulses at 813 pps): specifically, interaural electrodes with similar pitches were more likely (but not certain) to show ITD sensitivity. Significant changes in lateral position occurred with specific electrode pairs. With five bilateral electrode pairs of 14 tested, ITDs of 300 and 600 mus moved an auditory image significantly from right to left. With these same pairs, ILD changes of approximate to 11% of the dynamic range (in muApp) moved an auditory image from the far left to the far right-significantly farther than the nine pairs not showing significant ITD sensitivity. However, even these nine pairs did show response changes as a function of the interaural (or confounding monaural) level cue. Overall, insofar as the access to bilateral cues demonstrated herein generalizes to other subjects, it provides hope that the normal binaural advantages for speech recognition and sound localization can be made available to bilateral implant users. (C) 2003 Acoustical Society of America. C1 MIT, Div Hlth Sci & Technol, Speech & Hearing Sci Program, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Cochlear Implant Res Lab, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Boston Univ, Hearing Res Ctr, Dept Biomed Engn, Boston, MA 02215 USA. Bose Corp, Framingham, MA 01701 USA. RP Long, CJ (reprint author), MRC, CBU, 15 Chaucer Rd, Cambridge CB2 2EF, England. EM stoph@alum.mit.edu FU NIDCD NIH HHS [N01-DC-6-2100, T32 DC00038] NR 35 TC 71 Z9 74 U1 0 U2 2 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD SEP PY 2003 VL 114 IS 3 BP 1565 EP 1574 DI 10.1121/1.1603765 PG 10 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 720PQ UT WOS:000185269500037 PM 14514210 ER PT J AU Manne, S Duhamel, K Ostroff, J Parsons, S Martini, DR Williams, SE Mee, L Sexson, S Austin, J Winkel, G Boulad, F Redd, WH AF Manne, S Duhamel, K Ostroff, J Parsons, S Martini, DR Williams, SE Mee, L Sexson, S Austin, J Winkel, G Boulad, F Redd, WH TI Coping and the course of mother's depressive symptoms during and after pediatric bone marrow transplantation SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE coping; pediatric bone marrow transplantation; maternal adjustment; psychological distress ID STAGE BREAST-CANCER; PSYCHOLOGICAL DISTRESS; SOCIAL SUPPORT; INTERVENTION PROGRAM; CHILDHOOD-CANCER; BECK DEPRESSION; FOLLOW-UP; CHILDREN; PARENTS; LEUKEMIA AB Objective: To evaluate the role of maternal coping strategies in depressive symptoms experienced by mothers of children undergoing bone marrow transplantation (BMT). Method: A total of 207 mothers completed measures of coping and depressive symptoms at the time of the child's BMT, 3 and 6 months post-BMT The sample was collected between 1998 and 2002. The acceptance rate was 73%. The contribution of demographic, illness and treatment parameters, and mothers' concerns about the child were also evaluated. Growth curve modeling was used to evaluate the role of coping in the course of depressive symptoms. Both main effects and interactions of coping strategies with time of assessment were evaluated. Results: Acceptance and humor were associated with reductions in maternal depressive symptoms, and planning and alcohol/substance use were associated with increases in maternal depressive symptoms. Positive reframing, use of emotional support, and use of religion were associated with the course of depressive symptoms, but the magnitude of associations differed depending on the use of the coping strategies at the time of transplantation. Mothers' fears about the child also predicted depressive symptoms. Conclusions: Acceptance and humor may be targets for behavioral interventions to reduce mothers' depressive symptoms during and after pediatric BMT hospitalization. C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Mt Sinai Sch Med, Ruttenberg Canc Ctr, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Feinberg Sch Med, Childrens Mem Hosp, Evanston, IL 60208 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Childrens Healthcare Atlanta, Atlanta, GA USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. CUNY, Grad Ctr, New York, NY 10021 USA. RP Manne, S (reprint author), Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. OI Ostroff, Jamie/0000-0003-2671-5680 FU NIMH NIH HHS [MH 57738] NR 59 TC 23 Z9 23 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 2003 VL 42 IS 9 BP 1055 EP 1068 DI 10.1097/01.CHI.0000070248.24125.C0 PG 14 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 714PD UT WOS:000184921900009 PM 12960705 ER PT J AU McGinley-Smith, DE Tsao, SS AF McGinley-Smith, DE Tsao, SS TI Dermatoses from ticks SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Review ID MOUNTAIN-SPOTTED-FEVER; ACRODERMATITIS-CHRONICA-ATROPHICANS; HUMAN GRANULOCYTIC EHRLICHIOSIS; BORNE RELAPSING FEVER; BORRELIA-BURGDORFERI INFECTION; B-CELL LYMPHOMA; POLYMERASE-CHAIN-REACTION; SCLEROSUS-ET-ATROPHICUS; LONE-STAR TICK; NEW-YORK-STATE AB Ticks are ectoparasites that cause dermatologic disease directly by their bite and indirectly as vectors of bacterial, rickettsial, protozoal, and viral diseases. In North America, where ticks are the leading cause of vector-borne infection, dermatologists should recognize several tick species. Basic tick biology and identification will be reviewed. Tick bites cause a variety of acute and chronic skin lesions. The tick-borne diseases include Lyme disease, tick-borne relapsing fever, tularemia, babesiosis, Rocky Mountain spotted fever, other spotted fevers, ehrlichiosis, Colorado tick fever, and others. The epidemiology, clinical features, diagnosis, and treatment of these diseases are reviewed with an emphasis on cutaneous manifestations. Finally, the prevention of diseases caused by ticks is reviewed. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. RP Tsao, SS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 275 Cambridge St,Prof Off Bldg,Suite 501, Boston, MA 02114 USA. NR 385 TC 20 Z9 21 U1 0 U2 2 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 SEP PY 2003 VL 49 IS 3 BP 363 EP 392 DI 10.1067/S0190-9622(03)01868-1 PG 30 WC Dermatology SC Dermatology GA 716CV UT WOS:000185012000001 PM 12963900 ER PT J AU Aidlen, JT Nazarey, P Kling, D Kinane, B Donahoe, PK Schnitzer, JJ AF Aidlen, JT Nazarey, P Kling, D Kinane, B Donahoe, PK Schnitzer, JJ TI Terminal differentiation modulates nitrofen induced apoptosis SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 89th Annual Clinical Congress of the American-College-of-Surgeons CY OCT 19-23, 2003 CL CHICAGO, ILLINOIS SP Amer Coll Surg C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2003 VL 197 IS 3 SU S BP S49 EP S49 PG 1 WC Surgery SC Surgery GA 720EH UT WOS:000185248100118 ER PT J AU Black, J Al Badawi, H Casey, P Abbott, W LaMuraglia, G Watkins, M AF Black, J Al Badawi, H Casey, P Abbott, W LaMuraglia, G Watkins, M TI Acute limb ischemia produces unique systemic and local reponses prior to reperfusion SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 89th Annual Clinical Congress of the American-College-of-Surgeons CY OCT 19-23, 2003 CL CHICAGO, ILLINOIS SP Amer Coll Surg C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston VA Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2003 VL 197 IS 3 SU S BP S98 EP S98 PG 1 WC Surgery SC Surgery GA 720EH UT WOS:000185248100247 ER PT J AU Casey, PJ Black, JH Cambria, RP Albadawi, H Watkins, MT AF Casey, PJ Black, JH Cambria, RP Albadawi, H Watkins, MT TI PARP inhibitor PJ34 rescues neurologic function following thoracic aortic ischemia reperfusion SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 89th Annual Clinical Congress of the American-College-of-Surgeons CY OCT 19-23, 2003 CL CHICAGO, ILLINOIS SP Amer Coll Surg C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2003 VL 197 IS 3 SU S BP S97 EP S97 PG 1 WC Surgery SC Surgery GA 720EH UT WOS:000185248100243 ER PT J AU Flannery, JV Liu, R Ellison, B Houston, M Baldwin, A Adams, J Elliott, P Cusack, J AF Flannery, JV Liu, R Ellison, B Houston, M Baldwin, A Adams, J Elliott, P Cusack, J TI Schedule-dependent response to combination proteasome inhibition and CPT-11 treatment in colorectal xenografts SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 89th Annual Clinical Congress of the American-College-of-Surgeons CY OCT 19-23, 2003 CL CHICAGO, ILLINOIS SP Amer Coll Surg C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2003 VL 197 IS 3 SU S BP S81 EP S81 PG 1 WC Surgery SC Surgery GA 720EH UT WOS:000185248100203 ER PT J AU Johnston, DR Hoerbelt, R Shoji, T Mezrich, JD Houser, SL Allan, JS Ledgerwood, LG Hasse, RS Sachs, DH Madsen, JC AF Johnston, DR Hoerbelt, R Shoji, T Mezrich, JD Houser, SL Allan, JS Ledgerwood, LG Hasse, RS Sachs, DH Madsen, JC TI A novel technique of en-bloc vascularized thymus and heart transplantation abrogates cardiac allograft rejection SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 89th Annual Clinical Congress of the American-College-of-Surgeons CY OCT 19-23, 2003 CL CHICAGO, ILLINOIS SP Amer Coll Surg C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2003 VL 197 IS 3 SU S BP S88 EP S89 PG 2 WC Surgery SC Surgery GA 720EH UT WOS:000185248100223 ER PT J AU Malo, M Zhang, WY Abedrapo, M Henderson, J Siddique, A Chen, A Mozumder, M Hodin, R AF Malo, M Zhang, WY Abedrapo, M Henderson, J Siddique, A Chen, A Mozumder, M Hodin, R TI Multiple potential molecular targets for modulating thyroid hormone action SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 89th Annual Clinical Congress of the American-College-of-Surgeons CY OCT 19-23, 2003 CL CHICAGO, ILLINOIS SP Amer Coll Surg C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2003 VL 197 IS 3 SU S BP S7 EP S7 PG 1 WC Surgery SC Surgery GA 720EH UT WOS:000185248100003 ER PT J AU Vacanti, J Cheung, W Borenstein, J Kaazampur-Mofrad, M Shin, M Sevy, A Kulig, K AF Vacanti, J Cheung, W Borenstein, J Kaazampur-Mofrad, M Shin, M Sevy, A Kulig, K TI Hepatocyte and endothelial cell survival in a tissue engineered human liver device with its own vascular network SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 89th Annual Clinical Congress of the American-College-of-Surgeons CY OCT 19-23, 2003 CL CHICAGO, ILLINOIS SP Amer Coll Surg C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2003 VL 197 IS 3 SU S BP S86 EP S86 PG 1 WC Surgery SC Surgery GA 720EH UT WOS:000185248100216 ER PT J AU Westbrook, SD Paunovich, ED Freytes, CO AF Westbrook, SD Paunovich, ED Freytes, CO TI Adult hemopoietic stem cell transplantation SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; ORAL COMPLICATIONS; INFECTIONS; MANAGEMENT; MUCOSITIS; PATIENT; IMMUNOTHERAPY; CHEMOTHERAPY; MALIGNANCIES; RECIPIENTS AB Background. Hemopoietic stem cell transplantation, or HSCT, is an important tool in modern cancer treatment. Refinement of transplantation techniques and supportive care has resulted in increased posttranslation survival rates. Dental care is a key supportive element in both pretransplantation and posttransplantation care of this patient population. Methods. The authors provide an overview of HSCT transplantation, emphasizing the oral complications and required supportive dental care. Conclusions. It is critical that transplantation candidates undergo dental screenings and be treated adequately before transplantation, that their care be closely managed during the transplantation process, and that they be given dental support as soon as their recovery permits. Dentists should consult with the patient's oncologist or primary health provider to identify the appropriate timing and intensity of dental support. Clinical Implications. Because of improved transplantation survival rates, more patients may seek supportive outpatient dental care after transplantation, which requires special management considerations. Dental professionals need to be knowledgeable about modern HSCT. C1 S Texas Vet Hlth Care Syst, Clin Oral Hlth Care Program Geriatr & Extended Ca, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Adult Bone Marrow Transplant Program, San Antonio, TX USA. RP Westbrook, SD (reprint author), 13614 Inwood Pk, San Antonio, TX 78216 USA. NR 37 TC 1 Z9 3 U1 0 U2 1 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD SEP PY 2003 VL 134 IS 9 BP 1224 EP 1231 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 722XY UT WOS:000185404400022 PM 14528994 ER PT J AU Niederman, R AF Niederman, R TI Manual versus powered toothbrushes - The cochrane review SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article AB Background. In a report released in January 2003, The Cochrane Collaboration Oral Health Group provided a systematic review of the effectiveness of powered versus manual tooth-brushes, which generated much interest in the popular press. Methods. The Cochrane researchers developed and implemented search strategies for the Cochrane Oral Health Group's Trial Register, the Cochrane Central Register of Controlled Trials, MEDLINE and the Cumulative Index to Nursing and Allied Health Literature. They contacted manufacturers for additional information. Trials were selected if they met the following criteria compared power versus power versus manual design, drew participants from a general population without disabilities, provided data regarding plaque and gingivitis, and were at least 28 days in length. Reviewers evaluated only studies published in 2001 or earlier. Six reviewers from the Cochrane study independently extracted information in duplicate. Indexes for plaque and gingivitis were expressed as standardized values for data distillation. Data distillation was accomplished using a meta-analysis, with a mean difference between powered and manual toothbrushes serving as the measure of effectiveness. Results. The searches identified 354 trials, only 29 of which met the inclusion criteria. These trials involved about 2,500 subjects and provided data for meta-analysis. The results indicated that only the rotating oscillation toothbrush consistently provided a statistically significant, although modest clinical benefit over manual toothbrushes in reducing plaque and gingivitis. Conclusions and Clinical Implications. Some powered toothbrushes with a rotation-oscillation action achieve a significant, but modest, reduction in plaque and gingivitis compared with manual toothbrushes. C1 Forsyth Inst, DSM Forsyth Ctr Evidence Based Dent, Boston, MA 02115 USA. RP Niederman, R (reprint author), Forsyth Inst, DSM Forsyth Ctr Evidence Based Dent, 140 Fenway, Boston, MA 02115 USA. NR 7 TC 6 Z9 7 U1 7 U2 24 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD SEP PY 2003 VL 134 IS 9 BP 1240 EP 1244 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 722XY UT WOS:000185404400024 PM 14528996 ER PT J AU Bates-Jensen, BM Cadogan, M Jorge, J Schnelle, JE AF Bates-Jensen, BM Cadogan, M Jorge, J Schnelle, JE TI Standardized quality-assessment ulcer care in the nursing home SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE pressure ulcer care; quality indicators; quality assessment ID PRESSURE ULCERS; RISK AB OBJECTIVES: To demonstrate reliability and feasibility of a standardized protocol to assess and score quality indicators relevant to pressure ulcer (PU) care processes in nursing homes (NHs). DESIGN: Descriptive. SETTING: Eight NHs. PARTICIPANTS: One hundred ninety-one NH residents for whom the PU Resident Assessment Protocol of the Minimum Data Set was initiated. MEASUREMENTS: Nine quality indicators (two related to screening and prevention of PU, two focused on assessment, and five addressing management) were scored using medical record data, direct human observation, and wireless thigh monitor observation data. Feasibility and reliability of medical record, observation, and thigh monitor protocols were determined. RESULTS: The percentage of participants who passed each of the indicators, indicating care consistent with practice guidelines, ranged from 0% to 98% across all indicators. In general, participants in NHs passed fewer indicators and had more problems with medical record accuracy before a PU was detected (screening/prevention indicators) than they did once an ulcer was documented (assessment and management indicators). Reliability of the medical record protocol showed kappa statistics ranging from 0.689 to 1.00 and percentage agreement from 80% to 100%. Direct observation protocols yielded kappa statistics of 0.979 and 0.928. Thigh monitor protocols showed kappa statistics ranging from 0.609 to 0.842. Training was variable, with the observation protocol requiring 1 to 2 hours, medical records requiring joint review of 20 charts with average time to complete the review of 20 minutes, and the thigh monitor data requiring 1 week for training in data preparation and interpretation. CONCLUSION: The standardized quality assessment system generated scores for nine PU quality indicators with good reliability and provided explicit scoring rules that permit reproducible conclusions about PU care. The focus of the indicators on care processes that are under the control of NH staff made the protocol useful for external survey and internal quality improvement purposes, and the thigh monitor observational technology provided a method for monitoring repositioning care processes that were otherwise difficult to monitor and manage. C1 Univ Calif Los Angeles, Sch Med, Div Geriatr, Los Angeles, CA USA. Borun Ctr Gerontol Res & Jewish Home Aging, Reseda, CA USA. Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. Sepulveda Geriatr Res Educ & Clin Ctr, Greater Los Angeles Vet Affairs Healthcare Syst, Sepulveda, CA USA. RP Bates-Jensen, BM (reprint author), Univ Calif Los Angeles, Jewish Home Borun Ctr, 7150 Tampa Ave, Reseda, CA 91335 USA. NR 16 TC 13 Z9 13 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 SEP PY 2003 VL 51 IS 9 BP 1195 EP 1202 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 721NF UT WOS:000185321900001 ER PT J AU Bates-Jensen, BM Cadogan, M Osterweil, D Levy-Storms, L Jorge, J Al-Samarrai, N Grbic, V Schnelle, JF AF Bates-Jensen, BM Cadogan, M Osterweil, D Levy-Storms, L Jorge, J Al-Samarrai, N Grbic, V Schnelle, JF TI The minimum data set pressure ulcer indicator: Does it reflect differences in care processes related to pressure ulcer prevention and treatment in nursing homes? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE Minimum Data Set; pressure ulcer care; quality indicators ID VULNERABLE ELDERS; QUALITY AB OBJECTIVES: To determine whether nursing homes (NHs) that score in the extreme quartiles of pressure ulcer (PU) prevalence as reported on the Minimum Data Set (MDS) PU quality indicator provide different PU care. DESIGN: Descriptive, cohort. SETTING: Sixteen NHs. PARTICIPANTS: Three hundred twenty-nine NH residents at risk for PU development as determined by the PU Resident Assessment Protocol of the MDS. MEASUREMENTS: Sixteen care process quality indicators (10 specific to PU care processes, five related to nutrition, and one related to incontinence management) were scored using medical record data, direct human observation, interviews, and data from wireless thigh movement monitors. RESULTS: There were no differences between homes with low- and high-PU prevalence rates reported on the MDS PU quality indicator on most care processes. NHs with high PU prevalence rates used pressure-reduction surfaces more frequently and were better at documentation of four wound characteristics when PUs were present. No measure of PU care processes was better in low-PU NHs. Neither low- nor high-PU prevalence NHs routinely repositioned residents every 2 hours, even though 2-hour repositioning was documented in the medical record for nearly all residents. CONCLUSION: The assumption that homes with fewer PUs and thus low PU prevalence according to the MDS quality indicator are providing better PU care was not supported in this sample. NHs that scored low on the MDS PU quality indicator did not provide significantly better care than NHs that scored high. All NHs could improve PU prevention, as evidenced by the poor performance on prevention care processes by low- and high-PU NHs. The MDS PU quality indicator is not a useful measure of the quality of PU care in NHs and can be misleading if not presented with an explanation of the meaning of the indicator. C1 Univ Calif Los Angeles, Sch Med, Div Geriatr, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Borun Ctr Gerontol Res, Reseda, CA USA. Univ Calif Los Angeles, Los Angeles Jewish Home Aging, Reseda, CA USA. Sepulveda Geriatr Res Educ & Clin Ctr, Greater Los Angeles Vet Affairs Healthcare Syst, Sepulveda, CA USA. RP Bates-Jensen, BM (reprint author), Univ Calif Los Angeles, Jewish Home Borun Ctr, 7150 Tampa Ave, Reseda, CA 91335 USA. NR 19 TC 63 Z9 63 U1 3 U2 8 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2003 VL 51 IS 9 BP 1203 EP 1212 DI 10.1046/j.1532-5415.2003.51403.x PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 721NF UT WOS:000185321900002 PM 12919231 ER PT J AU Volicer, L Ganzini, L AF Volicer, L Ganzini, L TI Health professionals' views on standards for decision-making capacity regarding refusal of medical treatment in mild Alzheimer's disease SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE decision-making capacity; dementia; ethical standards ID INFORMED CONSENT; ASSESSMENT-TOOL; LEGAL STANDARD; COMPETENCE; CONSISTENCY; JUDGMENTS; PATIENT AB This study was designed to determine which elements professionals consider important for evaluation of decision-making capacity. Survey with a vignette case report of an individual with mild dementia was mailed to four groups of individuals: 1. members of the Academy of Psychosomatic Medicine, 2. chairs of Veterans Affairs (VA) Ethics Advisory Committees (EACs), 3. randomly selected geriatricians who were members of the Gerontological Society of America (GSA), and 4. randomly selected psychologists who were members of the GSA. Two hundred thirty-seven psychiatrists, 95 VA EAC chairs, 103 geriatricians, and 46 psychologists responded to this survey. The majority of the respondents endorsed all five basic elements as necessary for determination of decision-making capacity in the presented vignette, but only a minority of respondents endorsed all five basic elements, and a small proportion of respondents endorsed only one or two elements. The results indicate that physicians do not use uniform standards for assessment of decision-making capacity. C1 EN Rogers Mem Hosp, Ctr Geriatr Res Educ & Clin, Bedford, MA USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Volicer, L (reprint author), Edith Nourse Rogers Mem Vet Hosp, GRECC 182B, 200 Springs Rd, Bedford, MA 01730 USA. NR 17 TC 14 Z9 14 U1 0 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 SEP PY 2003 VL 51 IS 9 BP 1270 EP 1274 DI 10.1046/j.1532-5415.2003.51412.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 721NF UT WOS:000185321900011 PM 12919240 ER PT J AU Kaufman, JS O'Connor, TZ Zhang, JHY Cronin, RE Fiore, LD Ganz, MB Goldfarb, DS Peduzzi, PN AF Kaufman, JS O'Connor, TZ Zhang, JHY Cronin, RE Fiore, LD Ganz, MB Goldfarb, DS Peduzzi, PN CA Vet Affairs Cooperative Study Grp TI Randomized controlled trial of clopidogrel plus aspirin to prevent hemodialysis access graft thrombosis SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID VENOUS NEOINTIMAL HYPERPLASIA; MUSCLE CELL-PROLIFERATION; DOUBLE-BLIND; VASCULAR ACCESS; ARTERIOVENOUS-FISTULAS; RENAL-FAILURE; TICLOPIDINE; STENOSIS; SULFINPYRAZONE; COMPLICATIONS AB Thrombosis of hemodialysis vascular access grafts represents a major medical and economic burden. Experimental and clinical models suggest a role for antiplatelet agents in the prevention of thrombosis. The study was designed to determine the efficacy of the combination of aspirin and clopidogrel in the prevention of graft thrombosis. The study was a randomized, double-blind trial conducted at 30 hemodialysis units at Veterans Affairs medical centers. Participants undergoing hemodialysis with a polytetrafluoroethylene graft in the arm were randomized to receive either double placebos or aspirin (325 mg) and clopi-dogrel (75 mg) daily. Participants were to be monitored while receiving study medications for a minimum of 2 yr. The study was stopped after randomization of 200 participants, as recommended by the Data Safety and Monitoring Board because of a significantly increased risk of bleeding among the participants receiving aspirin and clopidogrel therapy. The cumulative incidence of bleeding events was significantly greater for those participants, compared with participants receiving placebos [hazard ratio, 1.98; 95% confidence interval (CI), 1. 19 to 3.28; P = 0.007]. Twenty-three participants in the placebo group and 44 participants in the active treatment group experienced a bleeding event (P = 0.006). There was no significant benefit of active treatment in the prevention of thrombosis (hazard ratio, 0.81; 95% CI, 0.47 to 1.40; P = 0.45), although there was a trend toward a benefit among participants who had not experienced previous graft thrombosis (hazard ratio, 0.52; 95% CI, 0.22 to 1.26; P = 0.14). In the hemodialysis population, therapy with aspirin and clopidogrel was associated with a significantly increased risk of bleeding and probably would not result in a reduced frequency of graft thrombosis. C1 Boston Univ, Sch Med, Dept Vet Affairs, Boston Healthcare Syst, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Coordinating Ctr, Cooperat Studies Program, Dept Vet Affairs, West Haven, CT USA. Vet Affairs N Texas Hlth Care Ctr, Dallas, TX USA. Cleveland Vet Affairs Med Ctr, Cleveland, OH USA. New York Vet Affairs Med Ctr, New York, NY USA. RP Kaufman, JS (reprint author), VA Boston Healthcare Syst, Renal Sect 111 RE, 150 S Huntington Ave, Boston, MA 02130 USA. NR 40 TC 122 Z9 131 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2003 VL 14 IS 9 BP 2313 EP 2321 DI 10.1097/01.ASN.0000081661.10246.33 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 716JR UT WOS:000185025500012 PM 12937308 ER PT J AU Stehman-Breen, CO Gillen, D Steffes, M Jacobs, DR Lewis, CE Kiefe, CI Siscovick, D AF Stehman-Breen, CO Gillen, D Steffes, M Jacobs, DR Lewis, CE Kiefe, CI Siscovick, D TI Racial differences in early-onset renal disease among young adults: The Coronary Artery Risk Development in Young Adults (CARDIA) Study SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION RATE; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; DIABETES-MELLITUS; SERUM CREATININE; QUALITY-CONTROL; CHOLESTEROL; RECRUITMENT; SEGREGATION; EXCRETION AB Although 11 million people in the United States have chronic renal insufficiency, little is known about ethnic/racial disparities for early-onset renal impairment. This study sought to determine whether there is an independent association between race/ethnicity and early-onset renal impairment and to identify other risk factors that might account for observed disparities. All Coronary Artery Risk Development in Young Adults subjects in which serum creatinine was measured at the year 15 examination were identified (n = 3554), excluding those who were pregnant at year 15, Potential risk factors at study entry (ages 18 to 30 yr, 1985 to 1986) included age, weight, gender, race/ethnicity, glucose, uric acid, and systolic BP. Renal impairment was defined as creatinine greater than or equal to1.5 mg/dl for men and greater than or equal to1.2 mg/dl for women at year 15 (ages 33 to 45 yr). Fifty-two (2.7%) women and 39 (2.4%) men had renal impairment at the year 15 examination. In bivariate analyses, the odds of renal impairment among black women was estimated to be 2.4-fold that of white women, and among black men, the odds of renal impairment were 9.0-fold that of white men. In multivariate analysis, the odds of an elevated creatinine among black women compared with white women reduced to a nonsignificant 1.5-fold, whereas among men, the odds of an elevated creatinine among blacks was 11.4-fold that of whites. Although adjustment for baseline glucose levels accounted for much of the association between ethnicity and elevated creatinine among women, adjustment for weight, systolic BP, uric acid, glucose, and socioeconomic status did not account for the association between ethnicity and renal impairment among men. The data suggest that there are ethnic differences in the development of early-onset renal dysfunction. Among women, these differences are modest and largely accounted for by differences in glucose levels early in adult life. Differences in race/ethnicity related risk of early-onset renal impairment are particularly large among men and are not accounted for by the metabolic or socioeconomic factors evaluated. C1 Seattle VA Med Ctr, Dept Med, Seattle, WA 98108 USA. Seattle VA Med Ctr, Dept Epidemiol, Seattle, WA 98108 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Publ Hlth, Dept Epidemiol, Minneapolis, MN 55455 USA. Univ Oslo, Inst Nutr Res, N-0316 Oslo, Norway. Univ Alabama, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. RP Stehman-Breen, CO (reprint author), Seattle VA Med Ctr, Dept Med, 1660 S Columbian Way,MS 111A, Seattle, WA 98108 USA. NR 30 TC 22 Z9 23 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2003 VL 14 IS 9 BP 2352 EP 2357 DI 10.1097/01.ASN.0000083392.11042.14 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 716JR UT WOS:000185025500017 PM 12937313 ER PT J AU Menke, TJ Giordano, TP Rabeneck, L AF Menke, TJ Giordano, TP Rabeneck, L TI Utilization of health care resources by HIV-infected white, African-American, and Hispanic men in the era before highly active antiretroviral therapy SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE HIV disease/AIDS; race; ethnic groups; health services; utilization; cohort studies ID UNITED-STATES; RACIAL-DIFFERENCES; DISEASE; ACCESS; ZIDOVUDINE; SERVICES; ADULTS; QUESTIONNAIRE; MEDICATIONS; VETERANS AB In the highly active antiretroviral therapy (HAART) era, U.S. African-American and Hispanic patients with HIV use HAART less, but emergency and inpatient services more, than white patients. We evaluated whether these patterns existed in the pre-HAART era. Data from prospective cohort studies of 462 male Veterans Affairs patients and 1,309 male patients from the AIDS Costs and Services Utilization Survey were combined. Resource utilization of white, African-American, and Hispanic men was compared. Compared to whites, African Americans were more likely to visit the emergency department and less likely to have mental health, home health, and dental visits; had fewer outpatient and substance abuse treatment visits; and had more inpatient nights. Hispanics were less likely to have mental health and home health visits, and had more inpatient nights. Whites used prescription drugs more than African Americans or Hispanics, but antiretrovirals were equally used. Lower access to HAART for African-American and Hispanic patients is a new phenomenon, not a continuation of pre-HAART patterns, while the undesirable patterns of emergency and outpatient provider resource utilization in the HAART era are a continuation of pre-HAART patterns. Undesirable resource utilization patterns by African-American and Hispanic populations need urgent attention. C1 Houston VA Med Ctr, Hlth Serv Res & Dev Serv, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. RP Giordano, TP (reprint author), Houston VA Med Ctr, Hlth Serv Res & Dev Serv, Houston Ctr Qual Care & Utilizat Studies, 152,2002 Holcombe Blvd, Houston, TX 77030 USA. EM tpg@bcm.tmc.edu FU NIAID NIH HHS [T32AI07456]; NIDDK NIH HHS [K24DK59318]; NIMH NIH HHS [K23MH67505] NR 37 TC 13 Z9 13 U1 0 U2 0 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD SEP PY 2003 VL 95 IS 9 BP 853 EP 861 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 836IH UT WOS:000222548600009 PM 14527053 ER PT J AU Webber, AP AF Webber, AP TI Recurrent cardiac failure of environmental origin SO JOURNAL OF THE ROYAL SOCIETY OF MEDICINE LA English DT Editorial Material ID CARBON-MONOXIDE C1 Univ Calif Los Angeles, Sch Med, Sepulveda, CA USA. GRECC, VA Greater Los Angeles, Sepulveda, CA USA. RP Webber, AP (reprint author), 10982 Roebling Ave,341 Westwood, Los Angeles, CA 90024 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0141-0768 J9 J ROY SOC MED JI J. R. Soc. Med. PD SEP PY 2003 VL 96 IS 9 BP 458 EP 459 DI 10.1258/jrsm.96.9.458 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 720RQ UT WOS:000185274100011 PM 12949204 ER PT J AU Gaissert, HA Grillo, HC Wright, CD Donahue, DM Wain, JC Mathisen, DJ AF Gaissert, HA Grillo, HC Wright, CD Donahue, DM Wain, JC Mathisen, DJ TI Complication of benign tracheobronchial strictures by self-expanding metal stents SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT Conference of the American-College-of-Chest-Physicians CY NOV 02-07, 2002 CL SAN DIEGO, CALIFORNIA SP Amer Coll Chest Physicians ID TRACHEAL STENOSIS; MANAGEMENT; AIRWAY AB Objectives: Self-expanding metal stents are used to palliate benign strictures. We examined the complications of this approach. Methods: Between 1997 and 2002, we observed recurrent airway obstruction and extension of benign inflammatory strictures after the placement of tracheobronchial Microvasive Ultraflex stents and Wallstents (Boston Scientific Corp, Natick, Mass), in 10 patients with postintubation strictures and 5 with other indications; all but 1 patient were referred to us. Patients with tracheal (9), subglottic (1), combined tracheal and subglottic (3), and bronchial (2) strictures had been treated with covered and uncovered Wallstents (6) and Microvasive Ultraflex stents (9). Results: After stent insertion, stricture and granulations within previously normal airway were seen in all patients. New subglottic strictures resulting from the stent caused hoarseness in 4 patients. A bronchoesophageal fistula was found in 1 patient at presentation and a tracheoesophageal fistula in another during extraction of a Wallstent. Primary surgical reconstruction, judged to have been feasible before wire stent insertion in 10 patients, was possible after stenting in only 7 and failed in 2. Palliative tubes were placed in 60% (9/15). Self-expanding metal stents may lengthen luminal damage, incite subglottic strictures, and cause esophagorespiratory fistula in inflammatory airway strictures. The injury is severe, occurs after a short duration of stenting, and precludes definitive surgical treatment or requires more extensive tracheal resection. Conclusion: The current generation of self-expanding metal stents should be avoided in benign strictures of trachea and bronchi. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Surg, Boston, MA 02114 USA. RP Gaissert, HA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Surg, Blake 1570,Fruit St, Boston, MA 02114 USA. NR 13 TC 80 Z9 100 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD SEP PY 2003 VL 126 IS 3 BP 744 EP 747 DI 10.1016/S0022-5223(03)00361-1 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 723DM UT WOS:000185417200023 PM 14502148 ER PT J AU Benacerraf, BR Bromley, BS Shipp, TD Laboda, L AF Benacerraf, BR Bromley, BS Shipp, TD Laboda, L TI The making of an advanced practice sonographer SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Diagnost Ultrasound Associates, Boston, MA USA. RP Benacerraf, BR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD SEP PY 2003 VL 22 IS 9 BP 865 EP 867 PG 3 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 718MN UT WOS:000185150700002 PM 14510257 ER PT J AU McDougal, WS AF McDougal, WS TI Lymphedema of the external genitalia SO JOURNAL OF UROLOGY LA English DT Review DE lymphedema; genitalia, male; transplants; reconstructive surgical procedure ID CONGENITAL LYMPHEDEMA; SURGICAL-TREATMENT; PENILE LYMPHEDEMA; RECONSTRUCTION; SCROTUM; ELEPHANTIASIS; ADOLESCENTS; MANAGEMENT; CHILDREN AB Purpose: This article presents a simple classification of lymphedema of the external genitalia, which is useful for selecting the appropriate therapy, and evaluates our experience with the various therapeutic options used to treat this disorder. Materials and Methods: The literature was reviewed and the records of patients treated for the disorder were analyzed. Results: A convenient classification of the disorder divides cases into congenital and acquired. Therapy is primarily dependent on whether the disease is self-limited and whether there has been any pathological change in the skin, lymphatics and subcutaneous tissue. For self-limited diseases in which no permanent pathological sequelae occur conservative therapy is appropriate. For most chronic conditions a surgical procedure is required. Excisional techniques are most effective for severe forms of the disease. In select cases subcutaneous tissue excision with preservation of the overlying skin is appropriate. However, for most patients excision of the skin and subcutaneous tissue with split-thickness grafting is most effective. Conclusions: When patients with lymphedema of the external genitalia require surgery and are properly selected for the appropriate procedure, the functional and cosmetic results are excellent and patient rehabilitation is likely. C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP McDougal, WS (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St, Boston, MA 02114 USA. NR 20 TC 32 Z9 33 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2003 VL 170 IS 3 BP 711 EP 716 DI 10.1097/01.ju.0000067625.45000.9e PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 712TN UT WOS:000184813400001 PM 12913680 ER PT J AU Cooperberg, MR Lubeck, DP Penson, DF Mehta, SS Carroll, PR Kane, CJ AF Cooperberg, MR Lubeck, DP Penson, DF Mehta, SS Carroll, PR Kane, CJ TI Sociodemographic and clinical risk characteristics of patients with prostate cancer within the veterans affairs health care system: Data from capsure SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; United States Department of Veterans Affairs; ethnicity ID RADICAL PROSTATECTOMY; SOCIOECONOMIC-STATUS; RACE AB Purpose: Veterans Affairs (VA) health care system investigators perform large clinical trials in prostate cancer treatment but potential differences between VA and other patient cohorts have not been explored systematically. Materials and Methods: Cancer of the Prostate Strategic Urologic Research Endeavor is an ongoing observational database of men with prostate cancer, comprising 7,202 patients treated at 35 sites across the United States. Three sites that together contribute 241 patients are VA medical centers. Demographic and clinical characteristics were compared between all VA and nonVA patients in the database and a multivariate model was used to explore the interactions between ethnicity and VA status for predicting clinical characteristics. Results: VA patients were 4 times as likely as nonVA patients to be black. They had lower income, less education and more co-morbidity at presentation (all comparisons p <0.0001). VA patients had higher risk disease. Mean serum prostate specific antigen at diagnosis was 20.1 vs 15.3 ng/ml for nonVA patients (p = 0.003). Mean Gleason score was 6.4 for VA patients vs 6.0 for nonVA patients (p <0.0001). Differing ethnic distributions explained the differences in prostate specific antigen between VA and nonVA patients. However, VA status, socioeconomic level and ethnicity independently predicted Gleason score. VA patients were more likely to undergo watchful waiting or primary hormonal therapy and less likely to receive definitive local treatment (p <0.0001). Conclusions: Significant sociodemographic and clinical differences exist between VA and nonVA patients, which should be borne in mind when extrapolating the results of VA clinical trials to the general population. These observations require validation in larger patient cohorts. C1 Univ Calif San Francisco, Dept Urol, Program Urol Oncol, Urol Outcomes Res Grp,Mt Zion Comprehens Canc Ctr, San Francisco, CA 94143 USA. Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Urol, Seattle, WA 98195 USA. TAP Pharmaceut Prod Inc, Lake Forest, IL USA. RP Kane, CJ (reprint author), Box 0738,400 Parnassus Ave, San Francisco, CA 94143 USA. RI Cooperberg, Matthew/B-3867-2008 FU PHS HHS [1P50 C 89520] NR 15 TC 35 Z9 35 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2003 VL 170 IS 3 BP 905 EP 908 DI 10.1097/01.ju.0000081200.63275.0b PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 712TN UT WOS:000184813400054 PM 12913727 ER PT J AU Holmberg, EB Doyle, P Perkell, JS Hammarberg, B Hillman, RE AF Holmberg, EB Doyle, P Perkell, JS Hammarberg, B Hillman, RE TI Aerodynamic and acoustic voice measurements of patients with vocal nodules: Variation in baseline and changes across voice therapy SO JOURNAL OF VOICE LA English DT Article DE objective measures; vocal nodules; voice aerodynamics; voice acoustics; voice therapy; treatment efficacy ID GLOTTAL AIR-FLOW; IMPACT STRESS; FRAMEWORK; PRESSURE; QUALITY; FEMALE AB An important clinical issue concerns the efficacy of current voice therapy approaches in treating voice disorders, such as vocal nodules. Much research focuses on finding reliable methods for documentation of treatment results. In this second treatment study of ten patients with vocal nodules, who participated in a behaviorally based voice therapy program, 11 aerodynamic (transglottal air pressure and glottal waveform) and acoustic (spl, f0, and spectrum slope) measures were used. Three pretherapy baseline assessments were carried out, followed by one assessment after each of five therapy phases. Measurements were made of two types of speech materials: Strings of repeated /pae/ syllables and sustained /ae/ phonations in two loudness conditions: comfortable loudness and loud voice. The data were normalized using z-scores, which were based on data from 22 normal subjects. The results showed that the aerodynamic measures reflected the presence of vocal pathology to a higher degree than did the acoustic spectral measures, and they should be useful in studies comparing nodule and normal voice production. Large individual session-to-session variation was found for all measures across pretherapy baseline recordings, which contributed to nonsignificant differences between baseline and therapy data. C1 Huddinge Univ Hosp, Karolinska Inst, Dept Logoped & Phoniatr, SE-14186 Stockholm, Sweden. Massachusetts Eye & Ear Infirm, Voice & Speech Lab, Boston, MA 02114 USA. MIT, Elect Res Lab, Speech Grp, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Holmberg, EB (reprint author), Huddinge Univ Hosp, Karolinska Inst, Dept Logoped & Phoniatr, SE-14186 Stockholm, Sweden. FU NIDCD NIH HHS [R01 DC00266-15] NR 36 TC 35 Z9 42 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0892-1997 J9 J VOICE JI J. Voice PD SEP PY 2003 VL 17 IS 3 BP 269 EP 282 DI 10.1067/S0892-1997(03)00076-6 PG 14 WC Otorhinolaryngology SC Otorhinolaryngology GA 721ER UT WOS:000185304500001 PM 14513951 ER PT J AU Flaherty, JH Stalvey, B Rubenstein, L AF Flaherty, JH Stalvey, B Rubenstein, L TI A consensus statement on nonemergent medical transportation services for older persons SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID CARE; HEALTH; DRIVERS; HOSPITALIZATION; INTERVENTION; COMMUNITY; FRAILTY; PROGRAM; ADULTS; MODEL C1 St Louis Univ, Med Ctr, Div Geriatr Med, St Louis, MO 63104 USA. St Louis VA Med Ctr, Ctr Geriatr Res Educ & Clin, St Louis, MO USA. Texas Dept Aging, Off Aging Policy & Informat, Austin, TX USA. Univ Calif Los Angeles, Greater Los Angeles VA Med Ctr, Ctr Geriatr Res Educ & Clin, Sepulveda, CA USA. Univ Calif Los Angeles, Multicampus Geriatr Program, Sepulveda, CA USA. RP Flaherty, JH (reprint author), St Louis Univ, Med Ctr, Div Geriatr Med, 1402 S Grand, St Louis, MO 63104 USA. NR 37 TC 2 Z9 2 U1 1 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 2003 VL 58 IS 9 BP 826 EP 831 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 729UL UT WOS:000185793100011 ER PT J AU Jenkins, AJ Lyons, TJ Zheng, DY Otvos, JD Lackland, DT McGee, D Garvey, WT Klein, RL AF Jenkins, AJ Lyons, TJ Zheng, DY Otvos, JD Lackland, DT McGee, D Garvey, WT Klein, RL CA DCCT EDIC Res Grp TI Lipoproteins in the DCCT/EDIC cohort: Associations with diabetic nephropathy SO KIDNEY INTERNATIONAL LA English DT Article DE diabetes mellitus; nephropathy; lipoproteins; NMR ID LOW-DENSITY-LIPOPROTEIN; IN-VITRO OXIDATION; RENAL-DISEASE; COMPLICATIONS TRIAL; IDDM PATIENTS; APOLIPOPROTEIN-B; BLOOD-PRESSURE; FOLLOW-UP; LDL; MICROALBUMINURIA AB Background. Lipoproteins may contribute to diabetic nephropathy. Nuclear magnetic resonance (NMR) can quantify subclasses and mean particle size of very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL), and LDL particle concentration. The relationship between detailed lipoprotein analyses and diabetic nephropathy is of interest. Methods. In a cross-sectional study, lipoproteins from 428 women and 540 men from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort were characterized by conventional lipid enzymology, NMR, apolipoprotein levels, and LDL oxidizibility. Linear regression was performed for each lipoprotein parameter versus log albumin excretion rate (AER), with and without covariates for age, diabetes duration, HbA(1c) , hypertension, body mass index, waist-hip ratio, and DCCT treatment group. Significance was taken at P < 0.05. Results. By multivariate analysis, conventional profile, total triglycerides, total- and LDL cholesterol, but not HDL cholesterol, were associated with AER. NMR-determined large, medium, and small VLDL were associated with AER in both genders (except large VLDL in women), and intermediate density lipoprotein (IDL) was associated with AER (men only). LDL particle concentration and ApoB were positively associated with AER (in men and in the total cohort), and there was a borderline inverse association between LDL diameter and AER in men. Small HDL was positively associated with AER and a borderline negative association was found for large HDL. No associations were found with ApoA1, Lp(a), or LDL oxidizibility. Conclusion. Potentially atherogenic lipoprotein profiles are associated with renal dysfunction in type 1 diabetes and further details are gained from NMR analysis. Longitudinal studies are needed to determine if dyslipoproteinemia can predict patients at risk of nephropathy, or if lipoprotein-related interventions retard nephropathy. C1 Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Biometry, Charleston, SC 29401 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. N Carolina State Univ, Raleigh, NC 27695 USA. RP Klein, RL (reprint author), Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, POB 250766,114 Doughty St, Charleston, SC 29401 USA. EM kleinrl@musc.edu FU NHLBI NIH HHS [P01 HL55782] NR 47 TC 107 Z9 112 U1 2 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2003 VL 64 IS 3 BP 817 EP 828 DI 10.1046/j.1523-1755.2003.00164.x PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 711GY UT WOS:000184732300006 PM 12911531 ER PT J AU Kramer, HJ Choi, HK Atkinson, K Stampfer, M Curhan, GC AF Kramer, HJ Choi, HK Atkinson, K Stampfer, M Curhan, GC TI The association between gout and nephrolithiasis in men: The Health Professionals' Follow-Up Study SO KIDNEY INTERNATIONAL LA English DT Article DE kidney stones; gout; epidemiology ID KIDNEY-STONES; RISK; HYPERTENSION; EPIDEMIOLOGY; PREVENTION; CALCIUM AB Approximately 10 million adults in the United States have experienced the passage of a kidney stone, and up to 5 million have been diagnosed with gout by a physician. Previous reports have suggested that gout increases the risk for the development of kidney stones, but there are no prospective data. We used data from a cohort of 51,529 male health care professionals to examine the independent association between gout and kidney stone disease. In a cross-sectional analysis of gout and kidney stone disease reported on the 1986 baseline questionnaire, the prevalence of kidney stone disease was almost twofold higher in men with history of gout compared to those without (15% vs. 8%). After adjusting for age and body mass index (BMI), a history of gout remained significantly associated with kidney stone disease (OR 1.88; 95% CI 1.68 to 2.11). We then prospectively examined the risk of incident kidney stones in men with and without a confirmed diagnosis of gout after excluding men who reported a history of kidney stone disease or gout on the baseline questionnaire. A confirmed diagnosis of gout increased the multivariate relative risk of incident kidney stones (RR 2.12; 95% CI 1.22 to 3.68). In contrast, a history of kidney stone disease was not associated with increased risk of gout (RR 1.05; 95% CI 0.54 to 2.07). In conclusion, a history of gout independently increases the risk for incident kidney stones in men. Physicians should provide dietary counseling, such as increasing fluid intake and decreasing salt consumption, to subjects with gout in addition to other risk factors, such as family history of kidney stones, in order to decrease the likelihood of stone formation. C1 Loyola Univ, Med Ctr, Dept Epidemiol & Prevent Med, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Med, Div Nephrol, Maywood, IL 60153 USA. Massachusetts Gen Hosp, Dept Med, Rheumatol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Gen Med Unit, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Curhan, GC (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. OI Kramer, Holly/0000-0002-6374-837X FU NIDDK NIH HHS [DK58573] NR 21 TC 59 Z9 62 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2003 VL 64 IS 3 BP 1022 EP 1026 DI 10.1046/j.1523-1755.2003.t01-2-00171.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 711GY UT WOS:000184732300027 PM 12911552 ER PT J AU Breitner, JCS AF Breitner, JCS TI NSAIDs and Alzheimer's disease: how far to generalise from trials? SO LANCET NEUROLOGY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; CACHE COUNTY; PLACEBO; WOMEN C1 VA Puget Sound Hlth Care Syst, GRECC S182, Seattle, WA 98108 USA. RP Breitner, JCS (reprint author), VA Puget Sound Hlth Care Syst, GRECC S182, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 7 TC 20 Z9 27 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD SEP PY 2003 VL 2 IS 9 BP 527 EP 527 DI 10.1016/S1474-4422(03)00498-8 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 717VT UT WOS:000185112000013 PM 12941571 ER PT J AU Metson, R AF Metson, R TI Symposium: Masters in otolaryngology - Update in rhinology SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Eastern Section of the Triological-Society CY JAN 25, 2003 CL BOSTON, MASSACHUSETTS SP Triol Soc, Eastern Sect ID ENDOSCOPIC SINUS SURGERY; ALLERGIC FUNGAL SINUSITIS; IMAGE-GUIDANCE SYSTEMS; TISSUE EOSINOPHILIA; CHRONIC RHINOSINUSITIS; SUPERIOR TURBINATE; MODIFIED LOTHROP; NASAL POLYPOSIS; SPHENOID SINUS; APOPTOSIS AB The past few years have witnessed several noteworthy advances in the field of rhinology in general and in the treatment of chronic sinusitis in particular. Many of these advances can be classified into three major trends: technology, techniques, and tissue eosinophilia. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Metson, R (reprint author), 0 Emerson Pl, Boston, MA 02114 USA. NR 42 TC 0 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD SEP PY 2003 VL 113 IS 9 BP 1466 EP 1469 DI 10.1097/00005537-200309000-00006 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 721AB UT WOS:000185293900006 PM 12972915 ER PT J AU Wiernik, PH Cassileth, PA Leong, T Hoagland, HC Bennett, JM Paietta, E Oken, MM AF Wiernik, PH Cassileth, PA Leong, T Hoagland, HC Bennett, JM Paietta, E Oken, MM TI A randomized trial of induction therapy (daunorubicin, vincristine, prednisone versus daunorubicin, vincristine, prednisone, cytarabine and 6-thioguanine) in adult acute lymphoblastic leukemia with long-term follow-up: An Eastern Cooperative Oncology Group study (E3486) SO LEUKEMIA & LYMPHOMA LA English DT Article DE randomized trial; ECOG group study; acute lymphoblastic leukemia; adult ALL; ALL ID ACUTE LYMPHOCYTIC-LEUKEMIA; INTENSIVE POSTREMISSION CHEMOTHERAPY; ACUTE MYELOID-LEUKEMIA; REGIMEN; INTENSIFICATION; ASPARAGINASE; EXPERIENCE; TOXICITY AB In this study of previously untreated adult acute lymphocytic leukemia (ALL) performed by the Eastern Cooperative Oncology Group, patients were randomized to induction therapy with either DVP (daunorubicin 45 mg/m(2) daily, days 1, 2 and 3; prednisone 60 mg/m(2) daily orally days 1-35; and vincristine 2 mg intravenously on days 1, 8, 15 and 22) or DATVP (daunorubicin 60 mg/m(2) daily, days 1, 2 and 3; cytarabine 25 mg/m(2) intravenous bolus followed by 200 mg/m(2) daily as a continuous infusion on days 1-5; 6-thioguanine 100 mg/m(2) orally every 12 h on days 1-5; vincristine 2 mg intravenously on days 1 and 8; and prednisone 60 mg/m(2)/day orally, days 1-7. Complete responders to both regimens received the same post-remission therapy, which consisted of a single course of cytarabine 3 gm/m(2) infused over 1 h every 12 h for 12 doses. One month later those patients still in remission received six cycles of consolidation therapy with MACHO (cyclophosphamide 650 mg/m(2), doxorubicin 40 mg/m(2) vincristine 2 mg all intravenously on day 1 with prednisone 100 mg/m(2) orally daily on days 1-5. Methotrexate 200 mg/m(2) intravenously and L-asparaginase 6000 U/m(2) were given on day 22 and each course was given every 5 weeks. A single dose of intrathecal methotrexate was also given with each MACHO course. There were 276 evaluable patients randomized in this study. Complete response rates were 71% for DVP and 58% for DATVP. Median durations of complete response were 5.5 and 6.8 months, respectively. Median survival of all randomized patients was 14.4 months in each group. DATVP was more toxic than DVP. Intensification of treatment for adults with ALL may not improve outcome. Progress in the treatment of adults with ALL will require the identification of new agents for this neoplasm. C1 New York Med Coll, OLM Canc Ctr, Bronx, NY 10466 USA. Univ Miami Sylvester, Ctr Comprehens Canc, Miami, FL 33152 USA. Dana farber Canc INst, Boston, MA USA. Mayo Clin, Ctr Canc, Rochester, NY USA. Univ Rochester, Ctr Canc, Rochester, NY USA. Virginia Piper Comprehens Canc Ctr, Minneapolis, MN USA. RP Wiernik, PH (reprint author), New York Med Coll, OLM Canc Ctr, 600 E 233rd St, Bronx, NY 10466 USA. FU NCI NIH HHS [CA 14958, CA 23318, CA 66636, CA91151, CA 11083, CA 21115, CA 13650] NR 23 TC 1 Z9 1 U1 0 U2 1 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 SEP PY 2003 VL 44 IS 9 BP 1515 EP 1521 DI 10.1080/1042819031000082975 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 698NX UT WOS:000184006600011 PM 14565653 ER PT J AU Sawafuji, K Miyakawa, Y Weisberg, E Griffin, JD Ikeda, Y Kizaki, M AF Sawafuji, K Miyakawa, Y Weisberg, E Griffin, JD Ikeda, Y Kizaki, M TI Aminopeptidase inhibitors inhibit proliferation and induce apoptosis of K562 and STI571-resistant K562 cell lines through the MAPK and GSK-3 beta pathways SO LEUKEMIA & LYMPHOMA LA English DT Article DE STI571; aminopeptidase inhibitors; drug resistance; CML ID CHRONIC MYELOID-LEUKEMIA; ABL TYROSINE KINASE; ACUTE NONLYMPHOCYTIC LEUKEMIA; GLYCOGEN-SYNTHASE KINASE-3; BESTATIN; UBENIMEX; RESISTANCE; DIFFERENTIATION; AMPLIFICATION; THERAPY AB A tyrosine kinase inhibitor, STI571, has been demonstrated to be effective for the treatment of chronic myelogenous leukemia (CML). STI571 inhibits tyrosine kinase activity of ABL and induces apoptosis of CML cells. However, drug resistance develops commonly in patients with blast phase CML, and has become a significant therapeutic problem. We examined the effects of aminopeptidase inhibitors on CML cell line (K562) and a STI571-resistant subline of K562. Ubenimex and the more potent aminopeptidase inhibitor, actinonin, inhibited proliferation of both K562 cells and STI571-resistant K562 cells and also induced their apoptosis in dose- and time-dependent manners. Ubenimex and actinonin induced the activation of caspase-3, and the induction of apoptosis was inhibited by pan-caspase inhibitor, indicating this apoptosis is caspase-dependent. We found that serine phosphorylation of both MAPK and glycogen synthase kinase-3beta were suppressed by aminopeptidase inhibitors in parent K562 and STI571-resistant K562 cells. The expression level of cyclin D1 protein was also reduced by ubenimex and actinonin in both cell lines. These results indicated STI571-resistance does not confer the cross-resistance to aminopeptidase inhibitors in K562 cells and revealed the new findings of aminopeptidase inhibitor-induced intracellular signaling pathways. C1 Keio Univ, Sch Med, Dept Internal Med, Div Hematol,Shinjuku Ku, Tokyo 1608582, Japan. Dana Farber Canc Ctr Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Miyakawa, Y (reprint author), Keio Univ, Sch Med, Dept Internal Med, Div Hematol,Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan. NR 25 TC 20 Z9 20 U1 0 U2 1 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 SEP PY 2003 VL 44 IS 11 BP 1987 EP 1996 DI 10.1080/1042819031000122033 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 726RJ UT WOS:000185612700020 PM 14738154 ER PT J AU Battle, TE Castro-Malaspina, H Gribben, JG Frank, DA AF Battle, TE Castro-Malaspina, H Gribben, JG Frank, DA TI Sustained complete remission of CLL associated with the use of a Chinese herbal extract: case report and mechanistic analysis SO LEUKEMIA RESEARCH LA English DT Article DE apoptosis; signal transduction; complementary therapy; non-Hodgkin's lymphoma; kinase; protein phosphorylation ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CANCER CELL-LINES; TEA POLYPHENOLS; INHIBITION; ACTIVATION; DOCETAXEL; APOPTOSIS; GROWTH; KINASE; BCL-2 AB We report the case of a man with chronic lymphocytic leukemia (CLL) who, in the absence of cytotoxic chemotherapy, began taking a Chinese herbal extract. Shortly thereafter, he experienced a steady decline of his lymphocytosis and adenopathy, and he remains in remission now over 10 years later. The herbal extract inhibited the survival of primary CLL cells under in vitro culture conditions. However, it did not inhibit the activation of Akt or MAP kinase, nor did it inhibit the serine phosphorylation of STAT L Thus, through an as yet unknown mechanism, this extract appears to exert pro-apoptotic effects in CLL. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. Mem Sloan Kettering Canc Ctr, New York, NY USA. RP Frank, DA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA93053, CA79547, CA 81534] NR 14 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD SEP PY 2003 VL 27 IS 9 BP 859 EP 863 DI 10.1016/S0145-2126(03)00009-2 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 692KB UT WOS:000183659300013 PM 12804645 ER PT J AU McGibbon, CA AF McGibbon, CA TI Inter-rater and intra-rater reliability of subchondral bone and cartilage thickness measurement from MRI SO MAGNETIC RESONANCE IMAGING LA English DT Article DE subchondral bone; articular cartilage; thickness; measurement reliability; magnetic resonance imaging ID PATELLOFEMORAL ARTICULAR-CARTILAGE; HYALINE CARTILAGE; 3-DIMENSIONAL ASSESSMENT; NONINVASIVE TECHNIQUE; COMPUTATIONAL METHOD; KNEE-JOINT; OSTEOARTHRITIS; REPRODUCIBILITY; ACCURACY; OPTIMIZATION AB MRI is often used to visualize and quantify the articular cartilage layer of load bearing joints affected by degenerative diseases, such as osteoarthritis (OA). Although the role played by the subchondral bone in the etiology and/or progression of OA may be important, the ability to visualize and quantify subchondral bone with MRI has received little attention. In this report we examined the inter-rater and intra-rater reliability of subchondral bone and cartilage thickness measurements from MR images of cadaver femoral head specimens. A 3D-SPGR pulse sequence tuned to eliminate chemical shift artifact through phase cancellation was used to image the specimens. Three raters manually segmented four specimens on two different occasions. Subchondral bone and cartilage thickness measurements were calculated from the segmented images. Inter-rater and intra-rater reliabilities were very high (>.98) for both cartilage and subchondral bone thickness measurements. We conclude that subchondral bone thickness can be measured as reliably as cartilage thickness from MR images. (C) 2003 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Biomot Lab, MGH Inst Hlth Profess, Dept Paediat Orthopaed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP McGibbon, CA (reprint author), Massachusetts Gen Hosp, Biomot Lab, MGH Inst Hlth Profess, Dept Paediat Orthopaed, Boston, MA 02114 USA. FU NIAMS NIH HHS [R01 AR45278] NR 44 TC 15 Z9 15 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD SEP PY 2003 VL 21 IS 7 BP 707 EP 714 DI 10.1016/S0730-725X(03)00107-3 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 733EW UT WOS:000185987800003 PM 14559334 ER PT J AU Krause, MHJ Kwong, KK Xiong, J Gragoudas, ES Young, LHY AF Krause, MHJ Kwong, KK Xiong, J Gragoudas, ES Young, LHY TI MRI of blood volume with MS 325 in experimental choroidal melanoma SO MAGNETIC RESONANCE IMAGING LA English DT Article DE nuclear magnetic resonance; melanoma; blood volume; choroid; neoplasms; pathology; physiopathology ID PHOTODYNAMIC THERAPY; SIMULATING LESIONS; 5-AMINOLEVULINIC ACID; INTRAOCULAR TUMORS; IMAGING EVALUATION; VASCULAR VOLUME; UVEAL MELANOMA; MURINE TUMOR; RABBIT MODEL; STEADY-STATE AB Functional magnetic resonance imaging (MRI) allows quantitative blood volume imaging in vivo at high tissue resolution. The purpose is to apply this technique for untreated and hyperthermia-treated experimental choroidal melanoma. MS 325 was used as new intravascular albumin-bound gadolinium-based contrast agent. Pigmented choroidal melanomas were established in albino rabbits. MRI was performed in 7 untreated eyes and 7 eyes treated with a Neodymium:Yttrium-Lanthanum-Fluoride-laser at 1047 nm. 3D-spoiled gradient echo pulse sequences were used to acquire T' weighted axial images. First, a set of images was collected without contrast agent. MS 325 was then injected i.v. and images were obtained within 12 min after injection. Signal intensities were measured within tumor, ciliary body, choroid, and iris and relative signal intensities were determined for these tissues in relation to vitreous. In untreated tumors, the relative signal intensity was higher after injection of MS 325 (5.61 + 0.70) than without MS 325 (2.90 + 0.33; p = 0.0002). In contrast, the relative signal intensity of treated tumors did not differ significantly before and after MS 325 (6.19 + 1.59 and 6.13 + 1.64). Histopathological sections indicated vascular occlusion in treated tumors. All other studied tissues of untreated and treated eyes showed a significant increase of relative signal intensities in the presence of MS 325. An animal model for the research on contrast agents in MRI is presented. Blood volume measurement with MS 325 was adapted for experimental choroidal melanomas. Reduced change of relative signal intensity indicates compromised blood volume after vascular occlusion in hyperthermia-treated melanoma. Further studies are needed to investigate whether this technique allows the evaluation of tumor viability following treatments. (C) 2003 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Charlestown, MA 02129 USA. RP Young, LHY (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. NR 47 TC 6 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD SEP PY 2003 VL 21 IS 7 BP 725 EP 732 DI 10.1016/S0730-725X(03)00100-0 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 733EW UT WOS:000185987800005 PM 14559336 ER PT J AU Taylor, JL Wu, CL Cory, D Gonzalez, RG Bielecki, A Cheng, LL AF Taylor, JL Wu, CL Cory, D Gonzalez, RG Bielecki, A Cheng, LL TI High-resolution magic angle spinning proton NMR analysis of human prostate tissue with slow spinning rates SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE HR-MAS; proton MRS; human prostate; slow spinning ID MAGNETIC-RESONANCE SPECTROSCOPY; H-1-NMR SPECTROSCOPY; SELECTIVE EXCITATION; TUMORS AB The development of high-resolution magic angle spinning (HR-MAS) NMR spectroscopy for intact tissue analysis and the correlations between the measured tissue metabolites and disease pathologies have inspired investigations of slow-spinning methodologies to maximize the protection of tissue pathology structures from HR-MAS centrifuging damage. Spinning sidebands produced by slow-rate spinning must be suppressed to prevent their complicating the spectral region of metabolites. Twenty-two human prostatectomy samples were analyzed on a 14.1T spectrometer, with HR-MAS spinning rates of 600 Hz, 700 Hz, and 3.0 kHz, a repetition time of 5 sec, and employing various rotor-synchronized suppression methods, including DANTE, WATER-GATE, TOSS, and PASS pulse sequences. Among them, DANTE, as the simplest scheme, has shown the most potential in suppression of tissue water signals and spinning sidebands, as well as in quantifying metabolic concentrations. (C) 2003 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. MIT, Dept Nucl Engn, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. MIT, Francis Bitter Natl Magnet Lab, Cambridge, MA 02139 USA. RP Cheng, LL (reprint author), CNY-7,149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA80901, CA77727]; NCRR NIH HHS [RR00995] NR 14 TC 57 Z9 59 U1 1 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD SEP PY 2003 VL 50 IS 3 BP 627 EP 632 DI 10.1002/mrm.10562 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 718YP UT WOS:000185174500023 PM 12939772 ER PT J AU Ellison, MA AF Ellison, MA TI Authoritative knowledge and single women's unintentional pregnancies, abortions, adoption, and single motherhood: Social stigma and structural violence SO MEDICAL ANTHROPOLOGY QUARTERLY LA English DT Article ID REPRODUCTION AB This article explores the sources of authoritative knowledge that shaped single, white, middle-class women's unintentional pregnancies and childbearing decisions throughout five reproductive eras. Women who terminated a pregnancy were most influenced by their own personal needs and circumstances. birth mothers' decisions were based on external sources of knowledge, such as their mothers, social workers, and social pressures. In contrast, single mothers based their decision on instincts and their religious or moral beliefs. Reproductive policies further constrained and significantly shaped women's experiences. The social stigma associated with these forms of stratified maternity suggests that categorizing pregnant women by their marital status, or births as out-of-wedlock, reproduces the structural violence implicit to normative models of female sexuality and maternity. This mixed-method study included focus groups to determine the kinds of knowledge women considered authoritative, a mailed survey to quantify these identified sources, and one-on-one interviews to explore outcomes in depth. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. RP Ellison, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. NR 79 TC 27 Z9 28 U1 3 U2 12 PU AMER ANTHROPOLOGICAL ASSOC PI ARLINGTON PA 4350 NORTH FAIRFAX DRIVE SUITE 640, ARLINGTON, VA 22203 USA SN 0745-5194 J9 MED ANTHROPOL Q JI Med. Anthropol. Q. PD SEP PY 2003 VL 17 IS 3 BP 322 EP 347 DI 10.1525/maq.2003.17.3.322 PG 26 WC Anthropology; Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Anthropology; Public, Environmental & Occupational Health; Biomedical Social Sciences GA 713YJ UT WOS:000184885300002 PM 12974201 ER PT J AU Beach, MC Asch, DA Jepson, C Hershey, JC Mohr, T McMorrow, S Ubel, PA AF Beach, MC Asch, DA Jepson, C Hershey, JC Mohr, T McMorrow, S Ubel, PA TI Public response to cost-quality tradeoffs in clinical decisions SO MEDICAL DECISION MAKING LA English DT Article DE decision making; public opinion; cost-benefit analysis; health care rationing ID MANAGED CARE; HEALTH-CARE; PHYSICIAN; CONTAINMENT; JUSTICE; LOYALTIES; MEDICINE; BEDSIDE; DUTIES; ETHICS AB Purpose. To explore public attitudes toward the incorporation of cost-effectiveness analysis into clinical decisions. Methods. The authors presented 781 jurors with a survey describing 1 of 6 clinical encounters in which a physician has to choose between cancer screening tests. They provided cost-effectiveness data for all tests, and in each scenario, the most effective test was more expensive. They instructed respondents to imagine that he or she was the physician in the scenario and asked them to choose which test to recommend and then explain their choice in an open-ended manner. The authors then qualitatively analyzed the responses by identifying themes and developed a coding scheme. Two authors separately coded the statements with high overall agreement (kappa = 0.76). Categories were not mutually exclusive. Results. Overall, 410 respondents (55%) chose the most expensive option, and 332 respondents (45%) choose a less expensive option. Explanatory comments were given by 82% respondents. Respondents who chose the most expensive test focused on the increased benefit (without directly acknowledging the additional cost) (39%), a general belief that life is more important than money (22%), the significance of cancer risk for the patient in the scenario (20%), the belief that the benefit of the test was worth the additional cost (8%), and personal anecdotes/preferences (6%). Of the respondents who chose the less expensive test, 40% indicated that they did not believe that the patient in the scenario was of significant risk for cancer, 13% indicated that they thought the less expensive test was adequate or not meaningfully different from the more expensive test, 12% thought the cost of the test was not worth the additional benefit, 9% indicated that the test was too expensive (without mention of additional benefit), and 7% responded that resources were limited. Conclusions. Public response to cost-quality tradeoffs is mixed. Although some respondents justified their decision based on the cost-effectiveness information provided, many focused instead on specific features of the scenario or on general beliefs about whether cost should be incorporated into clinical decisions. C1 Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD 21205 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. Philadelphia Hlth Management Corp, Philadelphia, PA USA. Urban Inst, Ctr Hlth Policy, Washington, DC 20037 USA. VA Ann Arbor Healthcare Syst, VA Hlth Serv, Res & Dev Ctr Excellence, Ann Arbor, MI USA. Univ Michigan, Div Gen Internal Med, Ann Arbor, MI 48109 USA. Program Improving Heath Care Decis Making, Ann Arbor, MI USA. RP Beach, MC (reprint author), Johns Hopkins Univ, Sch Med, Div Gen Internal Med, 1830 E Monument St,Room 8016, Baltimore, MD 21205 USA. OI Asch, David/0000-0002-7970-286X FU NCI NIH HHS [R01-CA78052-01]; NIMHD NIH HHS [L60 MD000303, L60 MD000303-01, L60 MD000303-02] NR 28 TC 5 Z9 5 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD SEP-OCT PY 2003 VL 23 IS 5 BP 369 EP 378 DI 10.1177/0272989X03256882 PG 10 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 724RK UT WOS:000185500400002 PM 14570295 ER PT J AU Mrus, JM Yi, MS Freedberg, KA Wu, AW Zackin, R Gorski, H Tsevat, J AF Mrus, JM Yi, MS Freedberg, KA Wu, AW Zackin, R Gorski, H Tsevat, J TI Utilities derived from visual analog scale scores in patients with HIV/AIDS SO MEDICAL DECISION MAKING LA English DT Article DE HIV; AIDS; quality of life ID HUMAN-IMMUNODEFICIENCY-VIRUS; QUALITY-OF-LIFE; HIV-INFECTED ADULTS; HEALTH STATE UTILITIES; COST-EFFECTIVENESS; ANTIRETROVIRAL THERAPY; PREFERENCES; SIMULATION; FOUNDATION; DISEASE AB Background. Visual analog scale (VAS) scores are used as global quality-of-life indicators and, unlike true utilities (which assess the desirability of health states v. an external metric), are often collected in HIV-related clinical trials. The purpose of this study was to derive and evaluate transformations relating aggregate VAS scores to utilities for current health in patients with HIV/AIDS. Methods.. HIV-specific transformations were developed using linear and nonlinear regression to attain models that best fit mean VAS and standard gamble (SG) utility values directly derived from 299 patients with HIV/AIDS participating in a multicenter study of health values. The authors evaluated the transformations using VAS and SG utility values derived directly from patients in other HIV/AIDS studies. Derived transformations were also compared with published transformations. Results. A simple linear transformation was derived (u = 0.44v + 0.49), as was the exponent for a curvilinear model (u = 1 - [1 - v](1.6)), where u = the sample mean utility and v the sample mean VAS score. The curvilinear transformation predicted values within 0.10 of the actual SG utility in 5 of 8 estimates and within 0.05 in 3 of 8 estimates (absolute error ranged from 0.01 to +0.21). The linear transformation performed somewhat better, predicting within 0.10 of the actual SG value in 6 of 8 cases and within 0.05 in 5 of 8 estimates (absolute error ranged from -0.05 to +0.13). An alternative linear model (u = v + 0.018) derived from the literature performed similarly to our linear model (7 of 8 predictions within 0.10, 1 of 8 estimates within 0.05, and absolute error ranging from -0.15 to +0.10), whereas an alternative published curvilinear model (u. = 1 - [1 - v](2.3)) performed the least well (2 of 8 estimates within 0.10 of the actual values and no estimates within 0.05). Conclusions. Predicted utilities are a reasonable alternative for use in HIV/AIDS decision analyses and cost-effectiveness analyses. Linear transformations performed better than curvilinear transformations in this context and can be used to convert aggregate VAS scores to aggregate SG values in large HIV/AIDS studies that collect VAS data but not utilities. C1 Univ Cincinnati, Med Ctr, Div Gen Internal Med, Dept Internal Med, Cincinnati, OH 45267 USA. Univ Cincinnati, Med Ctr, Inst Hlth Policy & Hlth Serv Res, Cincinnati, OH 45267 USA. Cincinnati VA Med Ctr, Hlth Serv Res & Dev, Cincinnati, OH USA. Univ Cincinnati, Med Ctr, Dept Pediat, Cincinnati, OH 45267 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Cambridge, MA 02138 USA. Johns Hopkins Univ, Dept Hlth Policy & Management, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD 21218 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Cambridge, MA 02138 USA. RP Mrus, JM (reprint author), Univ Cincinnati, Med Ctr, Div Gen Internal Med, Dept Internal Med, POB 670535, Cincinnati, OH 45267 USA. FU NCCIH NIH HHS [R01 AT001147, R01 AT01147-01]; NIAID NIH HHS [AI25897, AI27668, AI38855, AI42006, R01 AI042006, U01 AI025897, U01 AI027668, U01 AI038855, U01 AI038858, U01AI38858] NR 33 TC 20 Z9 20 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD SEP-OCT PY 2003 VL 23 IS 5 BP 414 EP 421 DI 10.1177/0272989X03256884 PG 8 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 724RK UT WOS:000185500400006 PM 14570299 ER PT J AU Baron, J Asch, DA Fagerlin, A Jepson, C Loewenstein, G Riis, J Stineman, MG Ubel, PA AF Baron, J Asch, DA Fagerlin, A Jepson, C Loewenstein, G Riis, J Stineman, MG Ubel, PA TI Effect of assessment method on the discrepancy between judgments of health disorders people have and do not have: A Web study SO MEDICAL DECISION MAKING LA English DT Article DE adaptation; utility assessment; response shift; focusing illusion ID QUALITY-OF-LIFE; RESPONSE SHIFT; PREFERENCES; UTILITY; CHEMOTHERAPY; EXPERIENCE; PERCEPTION; VALUATION; STATES; CANCER AB Three experiments on the World Wide Web asked subjects to rate the severity of common health disorders such as acne or arthritis. People who had a disorder ("Haves") tended to rate it as less severe than people who did not have it ("Not-haves"). Two explanations of this Have versus Not-have discrepancy were rejected. By one account, people change their reference point when they rate a disorder that they have. More precise reference points would, on this account, reduce the discrepancy, but, if anything, the discrepancy was larger. By another account, people who do not have the disorder focus on attributes that are most affected by it, and the discrepancy should decrease when people make ratings on several attributes. Again, if anything, the discrepancy increased when ratings were on separate attributes (combined by a weighted average). The discrepancy varied in size and direction across disorders. Subjects also thought that they would be less affected than others. C1 Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Rehabil Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Vet Affairs Ann Arbor Healthcare Syst, Vet Adm Hlth Serv Res & Dev Ctr Excellence, Ann Arbor, MI USA. Univ Michigan, Div Gen Internal Med, Program Improving Hlth Care Decis, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. Carnegie Mellon Univ, Dept Social & Decis Sci, Pittsburgh, PA 15213 USA. RP Baron, J (reprint author), Univ Penn, Dept Psychol, 3815 Walnut St, Philadelphia, PA 19104 USA. OI Asch, David/0000-0002-7970-286X FU NIA NIH HHS [AG16258] NR 26 TC 33 Z9 33 U1 4 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD SEP-OCT PY 2003 VL 23 IS 5 BP 422 EP 434 DI 10.1177/0272989X03257277 PG 13 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 724RK UT WOS:000185500400007 PM 14570300 ER PT J AU Rider, EA Longmaid, HE AF Rider, EA Longmaid, HE TI A model for merging residency programmes during health care consolidations: a course for success SO MEDICAL EDUCATION LA English DT Article DE education medical; continuing, organisation and administration; internship and residency, organisation and administration; health faculty merger, methods; interprofessional relations; communication ID MERGER AB Introduction As health care delivery systems experience economic and competitive challenges, institutional mergers have become a means for economic survival. Academic hospital mergers are well chronicled, yet little has been written about postgraduate, or residency, training programme mergers and their human and programmatic consequences. Mergers present opportunities to strengthen and redesign residency programmes, but risks include programme disruption, resident and faculty morale, and housestaff and faculty recruitment and retention. Mergers can cause a sense of disequilibrium, influencing resident and staff perceptions of job security, commitment to teaching, and even the viability of the residency programme. Objective We describe a process for the survival and successful merging of existing residency training programmes in the context of larger health care mergers. People, management, and communication skills are critical for leaders of the change process. We offer approaches and guidelines for leaders and others who are involved health care and residency training programme mergers. Awareness and understanding of systems issues and human factors improve the likelihood of success. Although our guidelines are intended primarily for residency programme mergers, they are equally applicable to mergers of health care institutions. Conclusion Successful residency training programme mergers require a carefully planned and executed series of actions that minimise disruptions. Effective communication on all levels is key. Success is associated with effective leadership, good communication skills, an open process with physician input, attention to institutional cultures, and a relatively short timetable. Most important is the continuous involvement, input, and creation of the programme by those most affected. C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Off Educ Dev, Boston, MA 02115 USA. MassGen Hosp Children, Div Gen Pediat, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Milton Hosp, Boston, MA USA. RP Rider, EA (reprint author), Harvard Univ, Sch Med, Off Educ Dev, 260 Longwood Ave,MEC 384, Boston, MA 02115 USA. NR 25 TC 3 Z9 4 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0308-0110 J9 MED EDUC JI Med. Educ. PD SEP PY 2003 VL 37 IS 9 BP 794 EP 801 DI 10.1046/j.1365-2923.2003.01599.x PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 717WH UT WOS:000185113400011 PM 12950943 ER PT J AU Kerdok, AE Cotin, SM Ottensmeyer, MP Galea, AM Howe, RD Dawson, SL AF Kerdok, AE Cotin, SM Ottensmeyer, MP Galea, AM Howe, RD Dawson, SL TI Truth cube: Establishing physical standards for soft tissue simulation SO MEDICAL IMAGE ANALYSIS LA English DT Article DE physical standard; real-time models; model validation; soft tissue mechanics; surgical simulation ID ENDOSCOPIC SURGERY; VIRTUAL-REALITY AB Accurate real-time models of soft tissue behavior are key elements in medical simulation systems. The need for fast computation in these simulations, however, often requires simplifications that limit deformation accuracy. Validation of these simplified models remains a challenge. Currently, real-time modeling is at best validated against finite element models that have their own intrinsic limitations. This study develops a physical standard to validate real-time soft tissue deformation models. We took CT images of a cube of silicone rubber with a pattern of embedded Teflon spheres that underwent uniaxial compression and spherical indentation tests. The known material properties, geometry and controlled boundary conditions resulted in a complete set of volumetric displacement data. The results were compared to a finite element model analysis of identical situations. This work has served as a proof of concept for a robust physical standard for use in validating soft tissue models. A web site has been created to provide access to our database: http://biorobotics.harvard.edu/truthcube/ (soon to be http://www.truthcube.org). (C) 2003 Elsevier B.V. All rights reserved. C1 Harvard Univ, Div Engn & Appl Sci, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, CIMIT Simulat Grp, Boston, MA 02114 USA. RP 29 Oxford St,Pierce Hall, Cambridge, MA 02138 USA. EM kerdok@fas.harvard.edu NR 10 TC 78 Z9 82 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1361-8415 EI 1361-8423 J9 MED IMAGE ANAL JI Med. Image Anal. PD SEP PY 2003 VL 7 IS 3 BP 283 EP 291 DI 10.1016/S1361-8415(03)00008-2 PG 9 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 723MC UT WOS:000185435300006 PM 12946469 ER PT J AU Thieke, C Bortfeld, T Niemierko, A Nill, S AF Thieke, C Bortfeld, T Niemierko, A Nill, S TI From physical dose constraints to equivalent uniform dose constraints in inverse radiotherapy planning SO MEDICAL PHYSICS LA English DT Article DE equivalent uniform dose; inverse planning; optimization constraints; projection onto convex sets ID CONVEX-SETS; RADIATION-THERAPY; OPTIMIZATION; DISTRIBUTIONS; PROJECTIONS AB Optimization algorithms in inverse radiotherapy planning need information about the desired dose distribution. Usually the planner defines physical dose constraints for each structure of the treatment plan, either in form of minimum and maximum doses or as dose-volume constraints. The concept of equivalent uniform dose (EUD) was designed to describe dose distributions with a higher clinical relevance. In this paper, we present a method to consider the EUD as an optimization constraint by using the method of projections onto convex sets (POCS). In each iteration of the optimization loop, for the actual dose distribution of an organ that violates an EUD constraint a new dose distribution is calculated that satisfies the EUD constraint, leading to voxel-based physical dose constraints. The new dose distribution is found by projecting the current one onto the convex set of all dose distributions fulfilling the EUD constraint. The algorithm is easy to integrate into existing inverse planning systems, and it allows the planner to choose between physical and EUD constraints separately for each structure. A clinical case of a head and neck tumor is optimized using three different sets of constraints: physical constraints for all structures, physical constraints for the target and EUD constraints for the organs at risk, and EUD constraints for all structures. The results show that the POCS method converges stable and given EUD constraints are reached closely. (C) 2003 American Association of Physicists in Medicine. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Deutsch Krebsforschungszentrum, Dept Phys Med, Heidelberg, Germany. RP Thieke, C (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. FU NCI NIH HHS [CA 50628] NR 21 TC 63 Z9 67 U1 3 U2 4 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD SEP PY 2003 VL 30 IS 9 BP 2332 EP 2339 DI 10.1118/1.1598852 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 722MJ UT WOS:000185379100010 PM 14528955 ER PT J AU Shifren, JL AF Shifren, JL TI Is there a role for testosterone therapy in premenopausal women? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID DEHYDROEPIANDROSTERONE REPLACEMENT; ANDROGEN C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Shifren, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD SEP-OCT PY 2003 VL 10 IS 5 BP 383 EP 384 DI 10.1097/01.GME.0000089029.10080.D9 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 721XE UT WOS:000185343100001 PM 14501596 ER PT J AU Miller, KK AF Miller, KK TI Does nutritional deprivation produce irreversible damage to the reproductive system? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID ANOREXIA-NERVOSA; NEUROENDOCRINE; LEPTIN C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Neuroendocrine Unit, Boston, MA 02114 USA. RP Miller, KK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Neuroendocrine Unit, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD SEP-OCT PY 2003 VL 10 IS 5 BP 385 EP 386 DI 10.1097/01.GME.0000088006.36340.41 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 721XE UT WOS:000185343100002 PM 14501597 ER PT J AU Abdul-Karim, MA Al-Kofahi, K Brown, EB Jain, RK Roysam, B AF Abdul-Karim, MA Al-Kofahi, K Brown, EB Jain, RK Roysam, B TI Automated tracing and change analysis of angiogenic vasculature from in vivo multiphoton confocal image time series SO MICROVASCULAR RESEARCH LA English DT Article DE in vivo change analysis; angiogenesis; tumor vasculature; vasculature tracing; vasculature segmentation; automated morphometry; multiphoton microscopy ID CHICK CHORIOALLANTOIC MEMBRANE; ENDOTHELIAL GROWTH-FACTOR; 3-DIMENSIONAL ANALYSIS; MICROVESSEL DENSITY; TUMOR ANGIOGENESIS; BREAST-CANCER; QUANTITATION; QUANTIFICATION; MICROSCOPY; ARCHITECTURE AB Automated methods are described for tracing and analysis of changes in angiogenic vasculature imaged by a multiphoton laser-scanning confocal microscope. Utilizing chronic animal window models, time series of in vivo 3-D images were acquired on approximately the same target volume of the same specimen while undergoing angiogenic change (typically every 24 h for 7 days). Objective, precise, 3-D, rapid, and fully automated vessel morphometry was performed using an adaptive tracing algorithm that is based on a generalized irregular cylinder model of the vasculature. This algorithm was found to be not only adaptive enough for tracing angiogenic vasculature, but also very efficient in its use of computer memory, and fast, taking less than 1 min to trace a 768 X 512 X 32, 8-bit/pixel 3-D image stack on a Dell Pentium III 1-GHz computer. The automatically traced centerlines were manually validated on six image stacks and the average spatial error was measured to be 2 pixels, with an average concordance of 81% between manual and automated traces on a voxel basis. The tracing output includes geometrical statistics of traced vasculature and serves as the basis of statistical change analysis. The computer methods described here are designed to be scalable to much larger hypothesis testing studies involving quantitative measurements of tumor angiogenesis, gene expression relative to known vascular structures, and impact of drug delivery. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Rensselaer Polytech Inst, ECSE Dept, Troy, NY 12180 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Roysam, B (reprint author), Rensselaer Polytech Inst, ECSE Dept, Troy, NY 12180 USA. FU NCI NIH HHS [P01CA80124, R24CA85140] NR 41 TC 36 Z9 37 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD SEP PY 2003 VL 66 IS 2 BP 113 EP 125 DI 10.1016/S0026-2862(03)00039-6 PG 13 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 716VK UT WOS:000185050100005 PM 12935769 ER PT J AU Caselli, A Uccioli, L Khaodhiar, L Veves, A AF Caselli, A Uccioli, L Khaodhiar, L Veves, A TI Local anesthesia reduces the maximal skin vasodilation during iontophoresis of sodium nitroprusside and heating SO MICROVASCULAR RESEARCH LA English DT Article DE laser Doppler; skin; microcirculation; endothelial function; vascular reactivity; smooth muscle cell ID DIABETIC PERIPHERAL NEUROPATHY; REFLEX-RELATED VASODILATION; BLOOD-FLOW; NITRIC-OXIDE; MICROCIRCULATION; ACETYLCHOLINE; MECHANISMS; RESPONSES; ASPIRIN; HUMANS AB Aim. To evaluate the effect of local anesthesia on the skin vasodilation induced by the iontophoresis of sodium nitroprusside and heating. Methods. Skin vascular reactivity, in response to iontophoresis of sodium nitroprusside (SNP), was evaluated at the forearm and foot in 13 neuropathic diabetic (DN) and 11 nonneuropathic diabetic (D) patients and 9 healthy, nondiabetic subjects who served as controls (C). The direct (DI) and nerve axon reflex-related (N-V) vasodilation were measured by using two single-point laser Doppler probes. The vasodilation in response to local warming was also assessed. A topical anesthetic was applied on the contralateral forearm and foot and all the measurements were repeated. Results. Dermal anesthesia resulted in a reduction of the direct vasodilation to SNP at the forearm [C: 58.1 +/- 16, D: 60.6 +/- 11%, and DN: 48.3 +/- 37% (postanesthesia percentage of reduction; mean +/- SEM), P < 0.01] and at the foot in all three groups (D: 38.5 +/- 12%, P < 0.01; C: 27.2 +/- 14% and DN: 11.3 +/- 17.5%, P = NS). The N-V related vasodilation was very low before and did not change after local anesthesia. The postanesthesia hyperemic response to warming was significantly reduced at low temperatures but did not change at 44degreesC. Conclusion. The sodium nitroprusside-related vasodilation is reduced after local anesthesia in a similar way in healthy subjects and diabetic patients with and without neuropathy. The response to heating is also reduced at low temperatures. This indicates a stabilizing effect of local anesthesia on the smooth muscle cell. (C) 2003 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med,Joslin Beth Israel Deaconess Foot Ctr, Beth Israel Deaconess Med Ctr, Microcirculat Lab,Dept Surg, Boston, MA 02215 USA. Univ Roma Tor Vergata, Dept Internal Med, Rome, Italy. RP Veves, A (reprint author), Harvard Univ, Sch Med,Joslin Beth Israel Deaconess Foot Ctr, Beth Israel Deaconess Med Ctr, Microcirculat Lab,Dept Surg, Palmer 317,West Campus,1 Deaconess Rd, Boston, MA 02215 USA. NR 21 TC 11 Z9 12 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 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD SEP PY 2003 VL 66 IS 2 BP 134 EP 139 DI 10.1016/S0026-2862(03)00053-0 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 716VK UT WOS:000185050100007 PM 12935771 ER PT J AU Dong, Q Kirley, S Rueda, B Zhao, C Zukerberg, L Oliva, E AF Dong, Q Kirley, S Rueda, B Zhao, C Zukerberg, L Oliva, E TI Loss of cables, a novel gene on chromosome 18q, in ovarian cancer SO MODERN PATHOLOGY LA English DT Article DE cables; ovarian cancer; ovary; tumorigenesis ID CARCINOMA; P53; PHOSPHORYLATION; TUMORS; COLON; DCC AB Cables, a cyclin-dependent kinase (cdk) interacting protein, has recently been identified and mapped to human chromosome 18q11. Cables appears to be primarily involved in cell cycle regulation and cell proliferation. Overexpression of Cables in Hela and other cell lines inhibits cell proliferation and tumor formation. We hypothesize that loss of Cables expression is associated with ovarian cancer. To test our hypothesis, we examined Cables expression in the four most common subtypes of ovarian carcinomas: serous, endometrioid, mucinous, and clear cell. In addition, mucinous and serous borderline tumors were also included. Loss of Cables expression was observed at high frequency in ovarian serous (I I of 14 cases, 79%) and endometrioid (5 of 10 cases, 50%) carcinomas. In contrast, strong Cables staining was detected in all clear cell carcinomas (10 cases) and mucinous tumors (5 carcinomas and 5 borderline tumors). The majority of serous borderline tumors (I I of 14 cases, 79%) showed positive Cables staining, with the rest showing focal loss of Cables expression. Furthermore, RT-PCR revealed the lack of Cables mRNA in a human ovarian cancer xenograft. No correlation was noted between loss of Cables and histologic grade, tumor stage, and survival. In conclusion, our results indicate that loss of Cables is common in ovarian serous and endometrioid carcinomas and imply that Cables may be involved in the pathogenesis of these two types of ovarian carcinomas. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Oliva, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 251A, Boston, MA 02114 USA. NR 20 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 2003 VL 16 IS 9 BP 863 EP 868 DI 10.1097/01.MP.0000084434.88269.0A PG 6 WC Pathology SC Pathology GA 725QG UT WOS:000185553400004 PM 13679449 ER PT J AU Chaudhri, B del Monte, F Hajjar, RJ Harding, SE AF Chaudhri, B del Monte, F Hajjar, RJ Harding, SE TI Contractile effects of adenovirally-mediated increases in SERCA2a activity: A comparison between adult rat and rabbit ventricular myocytes SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE myocyte; gene therapy; SERCA2a; phospholamban; rat; rabbit ID SARCOPLASMIC-RETICULUM CA2+-ATPASE; GENE-TRANSFER; TRANSGENIC MICE; HEART-FAILURE; OVEREXPRESSION; PHOSPHOLAMBAN; RESTORATION; RELAXATION; TRANSIENTS; EXCHANGE AB Adenoviral vectors have been successfully used to increase the activity of the sarcoplasmic reticulum Ca2+-ATPase in adult ventricular myocytes and to produce functional improvements in contractility in vivo and in vitro. While in vivo experiments are often performed in rat, in vitro manipulation of myocytes has been confined to rabbit and human cells. In the present study we make quantitative comparisons between cultured adult rat and rabbit myocytes in their responses to SERCA2a overexpression using adenoviral vectors. We also compare the strategy of SERCA2a overexpression with that of phospholamban down-regulation, using adenovirus carrying antisense message, as a means to increase SERCA2a activity and enhance contraction and relaxation. Adult myocytes were cultured for 48 h with either vector, and contraction assessed in 2 mM Ca2+, 37degreesC, at a range of stimulation frequencies. Contraction amplitude was enhanced to a similar degree in either rat or rabbit myocytes at most stimulation frequencies, with SERCA2a overexpression and phospholamban down-regulation approximately equally effective. The maximum effect of either vector was less than that of beta-adrenoceptor agonists. Relaxation was accelerated in rabbit myocytes more strongly than in rat. Phospholamban antisense was slightly less effective than SERCA2a overexpression on relaxation times in rabbit. Increasing stimulation frequency also accelerated relaxation in rat myocytes: this effect was greater than, and additive with, that of SERCA2a overexpression. We conclude that, despite some species-dependent modification, the effects of increased SERCA2a activity are broadly similar in rat and rabbit. Both SERCA2a overexpression and phospholamban down-regulation are effective strategies, and neither appears to produce supraphysiological stimulatory effects on contraction or relaxation. C1 Univ London Imperial Coll Sci Technol & Med, Fac Med, Natl Heart & Lung Inst, London SW3 6LY, England. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Harding, SE (reprint author), Univ London Imperial Coll Sci Technol & Med, Fac Med, Natl Heart & Lung Inst, Dovehouse St, London SW3 6LY, England. NR 23 TC 8 Z9 8 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD SEP PY 2003 VL 251 IS 1-2 BP 103 EP 109 DI 10.1023/A:1025442201851 PG 7 WC Cell Biology SC Cell Biology GA 715EW UT WOS:000184958400016 PM 14575311 ER PT J AU Wang, XZ Grammatikakis, N Siganou, A Calderwood, SK AF Wang, XZ Grammatikakis, N Siganou, A Calderwood, SK TI Regulation of molecular chaperone gene transcription involves the serine phosphorylation, 14-3-3 epsilon binding, and cytoplasmic sequestration of heat shock factor 1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; C-FOS GENE; DNA-BINDING; FACTOR-I; NUCLEAR-LOCALIZATION; HSF1 ACTIVATION; STRESS; CELLS; HSP70; EXPRESSION AB Heat shock factor 1 (HSF1) regulates the transcription of molecular chaperone hsp genes. However, the cellular control mechanisms that regulate HSF1 activity are not well understood. In this study, we have demonstrated for the first time that human HSF1 binds to the essential cell signaling protein 14-3-3epsilon. Binding of HSF1 to 14-3-3epsilon occurs in cells in which extracellular signal regulated kinase (ERK) is activated and blockade of the ERK pathway by treatment with the specific ERK pathway inhibitor PD98059 in vivo strongly suppresses the binding. We previously showed that ERK1 phosphorylates HSF1 on serine 307 and leads to secondary phosphorylation by glycogen synthase kinase 3 (GSK3) on serine 303 within the regulatory domain and that these phosphorylation events repress HSF1. We show here that HSF1 binding to 14-3-3epsilon requires HSF1 phosphorylation on serines 303 and 307. Furthermore, the serine phosphorylation-dependent binding of HSF1 to 14-3-3epsilon results in the transcriptional repression of HSF1 and its sequestration in the cytoplasm. Leptomycin B, a specific inhibitor of nuclear export receptor CRM1, was found to reverse the cytoplasmic sequestration of HSF1 mediated by 14-3-3epsilon, suggesting that CRM1/14-3-3epsilon directed nuclear export plays a major role in repression of HSF1 by the ERK/GSK3/14-3-3epsilon pathway. Our experiments indicate a novel pathway for HSF1 regulation and suggest a mechanism for suppression of its activity during cellular proliferation. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Calderwood, SK (reprint author), Boston Univ, Sch Med, Ctr Mol Stress Response, 650 Albany St,X300, Boston, MA 02118 USA. FU NCI NIH HHS [CA31303, CA47407, CA50642, CA77465, R01 CA047407, R01 CA077465] NR 59 TC 61 Z9 64 U1 0 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 SEP PY 2003 VL 23 IS 17 BP 6013 EP 6026 DI 10.1128/MCB.23.17.6013-6026.2003 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 713FP UT WOS:000184846700006 PM 12917326 ER PT J AU Cheng, WH von Kobbe, C Opresko, PL Fields, KM Ren, J Kufe, D Bohr, VA AF Cheng, WH von Kobbe, C Opresko, PL Fields, KM Ren, J Kufe, D Bohr, VA TI Werner syndrome protein phosphorylation by Abl tyrosine kinase regulates its activity and distribution SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DNA-DAMAGING AGENTS; C-ABL; FUNCTIONAL INTERACTION; APOPTOTIC RESPONSE; IONIZING-RADIATION; INDUCE APOPTOSIS; NUCLEAR FOCI; HELICASE; COMPLEX; CELLS AB The Werner syndrome protein (WRN) is a caretaker of the human genome, and the Abl kinase is a regulator of the DNA damage response. Aberrant DNA repair has been linked to the development of cancer. Here, we have identified a direct binding between WRN and c-Abl in vitro via the N-terminal and central regions of WRN and the Src homology domain 3 of c-Abl. After bleomycin treatment in culture, WRN and c-Abl are dissociated and followed by an Abl kinase-dependent WRN relocalization to the nucleoplasm. WRN is a substrate of c-Abl in vitro and in vivo. WRN is tyrosine phosphorylated either transiently by treatment of HeLa cells with bleomycin or constitutively in cells from chronic myeloid leukemia (CML) patients, and these phosphorylations are prevented by treatment with the Abl kinase inhibitor STI-571. Tyrosine phosphorylation of WRN results in inhibition of both WRN exonuclease and helicase activities. Furthermore, anti-WRN immunoprecipitates from CML cells treated with STI-571 show increased 3'-->5' exonuclease activity. These findings suggest a novel signaling pathway by which c-Abl mediates WRN nuclear localization and catalytic activities in response to DNA damage. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Opresko, Patricia/0000-0002-6470-2189 FU NCI NIH HHS [CA 29431, R01 CA029431] NR 57 TC 52 Z9 53 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2003 VL 23 IS 18 BP 6385 EP 6395 DI 10.1128/MCB.23.18.6385-6395.2003 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 717RM UT WOS:000185103900005 PM 12944467 ER PT J AU Costigan, M Samad, TA Allchorne, A Lanoue, C Tate, S Woolf, CJ AF Costigan, M Samad, TA Allchorne, A Lanoue, C Tate, S Woolf, CJ TI High basal expression and injury-induced down regulation of two regulator of G-protein signaling transcripts, RGS3 and RGS4 in primary sensory neurons SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID ROOT GANGLION NEURONS; NERVE INJURY; SODIUM-CHANNELS; MESSENGER-RNA; PERIPHERAL AXOTOMY; PAIN; SURVIVAL; RECEPTOR; SYSTEM; BRAIN AB The regulators of G-protein signaling (RGS) proteins are a family of intracellular modulators of G-protein coupled receptor (GPCR) sensitivity. They act as GTPase accelerating proteins returning the Galpha subunit back to an inactive latent state. We find that RGS3 and RGS4 are constitutively expressed at high levels in C-fiber primary sensory neurons in the adult rat dorsal root ganglion (DRG) and transection of the sciatic nerve results in a substantial down regulation of these transcripts. RGS4 mRNA is expressed only in GDNF-responsive neurons and GDNF supports the expression of this transcript in primary DRG cultures. A PDZ domain containing subtype of RGS3 is the most abundant and regulated form of this protein within the DRG. Decreased levels of RGS3 and RGS4 in injured sensory neurons is likely to result in an increased GPCR sensitivity, and therefore contribute to alterations in cellular function seen after such lesions. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. GlaxoSmithKline Res & Dev, Mol Pharmacol, Stevenage SG1 2NY, Herts, England. RP Costigan, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, 13th St,Bldg 149,4309, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS 39518, NS 38253] NR 32 TC 14 Z9 15 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 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD SEP PY 2003 VL 24 IS 1 BP 106 EP 116 DI 10.1016/S1044-7431(03)00135-0 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 729VV UT WOS:000185796500009 PM 14550772 ER PT J AU Shammas, MA Reis, RJS Akiyama, M Koley, H Chauhan, D Hideshima, T Goyal, RK Hurley, LH Anderson, KC Munshi, NC AF Shammas, MA Reis, RJS Akiyama, M Koley, H Chauhan, D Hideshima, T Goyal, RK Hurley, LH Anderson, KC Munshi, NC TI Telomerase inhibition and cell growth arrest by G-quadruplex interactive agent in multiple myeloma SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID HUMAN TUMOR-CELLS; HEMATOPOIETIC-CELLS; HUMAN FIBROBLASTS; WILD-TYPE; IN-VIVO; CANCER; APOPTOSIS; LENGTH; RNA; DNA AB Objective: The aim of this study was to test the efficacy of telomerase inhibitor (TMPyP4 [tetra(N-methyl-4-pyridyl)-porphyrin chloride]; a G-quadruplex-intercalating porphyrin) as a potential therapeutic agent for multiple myeloma. Materials and Methods: We studied telomere length, telomerase activity, and effect of telomerase inhibition in multiple myeloma cells. Several myeloma cell lines were analyzed for telomerase activity, telomere length, and gene expression. Three myeloma cell lines (U266, ARH77, and ARD) were treated with TMPyP4 for 3-4 weeks. Viable cell number was assessed by trypan blue exclusion, and nature of cell death was determined by annexin labeling and/or DNA fragmentation. In situ oligo ligation technique was used to identify specific DNase I-type DNA cleavage. Results: We report high telomerase activity and shortened telomeres in myeloma cells compared to normal B cells. We have also observed inhibition of telomerase activity, reduction in telomere length, and decline of myeloma cell growth, as measured by trypan blue dye exclusion, following exposure to TMPyP4. Exposure to porphyrin reduced telomerase activity of U266, ARH77, and ARD myeloma cells by 98%, 92%, and 99%, respectively. Exposure to porphyrin had no effect on viability for the first 14 days, followed by death of 75-90% of cells over the next 2 weeks. The nature of cell death was apoptotic, as determined by annexin and DNA nick labeling. Majority of cells showed DNA fragmentation specific to caspase-3-activated DNase I. Conclusions: These results demonstrate anti-proliferative activity of G-quadruplex-intercalating agents, and suggest telomerase as an important therapeutic target for myeloma therapy. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Boston VA Hlth Care Syst, W Roxbury, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Arkansas Med Sci, Dept Geriatr, Little Rock, AR USA. Univ Arkansas Med Sci, Dept Biochem, Little Rock, AR USA. Univ Arkansas Med Sci, Dept Biol Mol, Little Rock, AR USA. Univ Arkansas Med Sci, Little Rock, AR USA. Cent Arkansas Vet Hlth Care Syst, Little Rock, AR USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. Univ Arizona, Coll Pharm, Tucson, AZ USA. RP Munshi, NC (reprint author), Dana Farber Canc Inst, 44 Binney St M557, Boston, MA 02115 USA. RI Shmookler Reis, Robert/C-4112-2009 NR 43 TC 80 Z9 81 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD SEP PY 2003 VL 2 IS 9 BP 825 EP 833 PG 9 WC Oncology SC Oncology GA 723PH UT WOS:000185440400001 PM 14555701 ER PT J AU Dick, FA Dyson, N AF Dick, FA Dyson, N TI pRB contains an E2F1-specific binding domain that allows E2F1-induced apoptosis to be regulated separately from other E2Factivities SO MOLECULAR CELL LA English DT Article ID S-PHASE ENTRY; TRANSCRIPTION FACTOR E2F-1; RETINOBLASTOMA TUMOR-SUPPRESSOR; CELL-CYCLE; DNA-DAMAGE; GROWTH SUPPRESSION; IN-VIVO; FAMILIAL RETINOBLASTOMA; INCOMPLETE PENETRANCE; HISTONE DEACETYLASE AB The interaction between pRB and E2F is critical for control of the cell cycle and apoptosis. Here we report that pRB contains two distinct E2F binding sites. The previously identified E2F binding site on pRB is necessary for stable association with E2Fs on DNA. A second E2F interaction site is located entirely within the C-terminal domain of pRB and is specific for E2F1. E2F1/pRB complexes formed through this site have low affinity for DNA, but the interaction is sufficient for pRB to regulate E2F1-induced apoptosis, and E2F1 loses the ability to interact with this site following DNA damage. These results show that pRB interacts with individual E2F proteins in different ways and suggest that pRB's regulation of E2F1-induced apoptosis is physically separable from its transcriptional control of other E2F proteins. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Dyson, N (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [R01 CA 64402] NR 61 TC 96 Z9 97 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD SEP PY 2003 VL 12 IS 3 BP 639 EP 649 DI 10.1016/S1097-2765(03)00344-7 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 726RV UT WOS:000185613800013 PM 14527410 ER PT J AU Avni, D Yang, H Martelli, F Hofmann, F ElShamy, WM Ganesan, S Scully, R Livingston, DM AF Avni, D Yang, H Martelli, F Hofmann, F ElShamy, WM Ganesan, S Scully, R Livingston, DM TI Active localization of the retinoblastoma protein in chromatin and its response to S phase DNA damage SO MOLECULAR CELL LA English DT Article ID ORIGIN RECOGNITION COMPLEX; SMALL-T-ANTIGEN; SIMIAN-VIRUS-40 SMALL-T; REPLICATION INITIATION SITES; CELL-CYCLE PROGRESSION; EPSTEIN-BARR-VIRUS/; DEPENDENT MANNER; MAMMALIAN-CELLS; GENE PROMOTER; INHIBITION AB The Rb protein suppresses development of an abnormal state of endoreduplication arising after S phase DNA damage. In diploid, S phase cells, the activity of protein phosphatase 2A (PP2A) licenses the stable association of un(der)phosphorylated Rb with chromatin. After damage, chromatin-associated pRb is attracted to certain chromosomal replication initiation sites in the order in which they normally fire. Like S phase DNA damage in Rb-/- cells, specific interruption of PP2A function in irradiated, S phase wt cells also elicited a state of endoreduplication. Thus, PP2A normally licenses the recruitment of Rb to chromatin sites in S phase from which, after DNA damage, it relocalizes to selected replication control sites and suppresses abnormal, postdamage rereplicative activity. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Canc Biol Program, Boston, MA 02115 USA. RP Livingston, DM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. RI Scully, Ralph/F-5008-2013; OI Martelli, Fabio/0000-0002-8624-7738 FU NCI NIH HHS [K01 CA079576] NR 52 TC 78 Z9 81 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD SEP PY 2003 VL 12 IS 3 BP 735 EP 746 DI 10.1016/S1097-2765(03)00355-1 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 726RV UT WOS:000185613800021 PM 14527418 ER PT J AU Fleming, JC Tartaglini, E Kawatsuji, R Yao, D Fujiwara, Y Bednarski, JJ Fleming, MD Neufeld, EJ AF Fleming, JC Tartaglini, E Kawatsuji, R Yao, D Fujiwara, Y Bednarski, JJ Fleming, MD Neufeld, EJ TI Male infertility and thiamine-dependent erythroid hypoplasia in mice lacking thiamine transporter Slc19a2 SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE thiamine transport; spermatogenesis; vitamin B1; reticulocytopenia; TRMA; erythroid hypoplasia; Slc19a2 ID RESPONSIVE MEGALOBLASTIC-ANEMIA; DIABETES-MELLITUS; GENE; MOUSE; DEAFNESS; ENCODES; MUTATIONS; FAMILY; MEMBER AB Thiamine-responsive megaloblastic anemia with diabetes and deafness (TRMA) is an autosomal recessive disease caused by mutations in the high-affinity thiamine transporter gene SLC19A2. To study the role of thiamine transport in the pathophysiology of TRMA syndrome and of each of the component disorders, we created a targeted disruption of the Slc19a2 gene in mice. Slc19a2 -/- mice are viable and females are fertile. Male -/- mice on a pure 129/Sv background are infertile with small testes (testis/body weight = 0.13 +/- 0.04 knockout vs. 0.35 +/- 0.05 wild type, P < 0.000005). The lack of developing germ cells beyond primary spermatocytes suggests an arrest in spermatogenesis prior to meiosis II. Nuclear chromatin changes indicative of apoptosis are present. No mature sperm are found in the tubules or epididymis. This phenotype suggests a previously unknown role for thiamine transport in spermatogenesis and male fertility. Sle19a2 -/- mice on a pure 129/Sv background develop reticulocytopenia after two weeks on thiamine-depleted chow with a virtual absence of reticulocytes in the peripheral blood (0.12% knockout vs. 2.58% wild type, P = 0.0079). Few erythroid precursors are found in the bone marrow. Contrary to human TRMA syndrome, we see no evidence of megaloblastosis or ringed sideroblasts in the bone marrow of Slc19a2 -/- mice in thiamine-replete or thiamine-deficient dietary states. Phenotypic differences between TRMA patients and Slc19a2 -/- mice might be explained by dissimilar tissue expression patterns of the transporter, as well as by differing metabolic needs and possible different species-specific contributions of the related thiamine transporter Slc19a3. (C) 2003 Elsevier Inc. All rights reserved. C1 Childrens Hosp, Dana Farber Canc Inst, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Neufeld, EJ (reprint author), Childrens Hosp, Dana Farber Canc Inst, Div Hematol, 300 Longwood Ave, Boston, MA 02115 USA. RI Neufeld, Ellis/F-9331-2011 FU NHLBI NIH HHS [HL/DC66182, K24HL04184, T32HL07574]; NICHD NIH HHS [P30-HD18655]; NIDDK NIH HHS [K01 DK064203] NR 22 TC 15 Z9 16 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2003 VL 80 IS 1-2 BP 234 EP 241 DI 10.1016/S1096-7192(03)00141-0 PG 8 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 738TU UT WOS:000186304600021 PM 14567973 ER PT J AU Sadallah, S Heim, M Hess, C Klimkait, T Dopler, N Schifferli, JA AF Sadallah, S Heim, M Hess, C Klimkait, T Dopler, N Schifferli, JA TI No association of HCV with erythrocytes in vivo SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 9th European Meeting on Complement in Human Disease CY SEP 06-09, 2003 CL TRIESTE, ITALY DE immune complexes; HCV C1 Univ Basel Hosp, Res Dept, CH-4031 Basel, Switzerland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. Univ Basel, Inst Microbiol, Basel, Switzerland. RI Klimkait, Thomas/A-1057-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD SEP PY 2003 VL 40 IS 2-4 BP 212 EP 212 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 715MJ UT WOS:000184975900099 ER PT J AU Hao, SL Mata, M Wolfe, D Huang, SH Glorioso, JC Fink, DJ AF Hao, SL Mata, M Wolfe, D Huang, SH Glorioso, JC Fink, DJ TI HSV-mediated gene transfer of the glial cell-derived neurotrophic factor provides an antiallodynic effect on neuropathic pain SO MOLECULAR THERAPY LA English DT Article DE gene therapy; pain; HSV; GDNF ID FOS-LIKE IMMUNOREACTIVITY; NERVE GROWTH-FACTOR; SPINAL-CORD NEURONS; DORSAL-HORN; SENSORY NEURONS; SCIATIC-NERVE; DRG NEURONS; PERIPHERAL NEUROPATHIES; FACTOR GDNF; RAT AB Neuropathic pain is a difficult clinical problem that is often refractory to medical management. Glial-derived neurotrophic factor (GDNF) administered intrathecally has been shown to prevent or reduce pain in an animal model of neuropathic pain, but cannot be delivered in the required doses to treat human pain. We have previously demonstrated that peripheral subcutaneous inoculation of a replication-incompetent herpes simplex virus (HSV)-based vector can be used to transduce neurons of the dorsal root ganglion. To examine whether HSV-mediated expression of GDNF could be used to ameliorate neuropathic pain, we constructed a replication-incompetent HSV vector expressing GDNF. Subcutaneous inoculation of the vector I week after spinal nerve ligation resulted in a continuous antiallodynic effect that was maintained for 3-4 weeks. Reinoculation of the vector reestablished the antiallodynic effect with a magnitude that was at least equivalent to the initial effect. Vector-mediated GDNF expression blocked the nonnoxious touch-induced increase in c-fos expression in dorsal horn characteristic of the painful state. Gene transfer to produce a trophic factor offers a novel approach to the treatment of neuropathic pain that may be appropriate for human therapy. C1 VA Pittsburgh Healthcare Syst, Dept Neurol, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Mol Genet & Biochem, Pittsburgh, PA 15260 USA. RP Fink, DJ (reprint author), VA Pittsburgh Healthcare Syst, Dept Neurol, S-520 BST200 Lothrop St, Pittsburgh, PA 15213 USA. NR 59 TC 60 Z9 68 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD SEP PY 2003 VL 8 IS 3 BP 367 EP 375 DI 10.1016/S1525-0016(03)00185-0 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 719HG UT WOS:000185197100005 PM 12946309 ER PT J AU Andersson, G Denaro, M Johnson, K Morgan, P Sullivan, A Houser, S Patience, C White-Scharf, ME Down, JD AF Andersson, G Denaro, M Johnson, K Morgan, P Sullivan, A Houser, S Patience, C White-Scharf, ME Down, JD TI Engraftment of retroviral EGFP-transduced bone marrow in mice prevents rejection of EGFP-transgenic skin grafts SO MOLECULAR THERAPY LA English DT Article DE bone marrow transplantation; transgene immunogenicity; retrovirus vector; EGFP; molecular chimerism; immunological tolerance ID GREEN FLUORESCENT PROTEIN; IN-VIVO PERSISTENCE; T-CELL TOLERANCE; HEMATOPOIETIC-CELLS; IMMUNE-RESPONSES; GENE-TRANSFER; STEM-CELLS; TRANSPLANTATION TOLERANCE; MIXED CHIMERISM; EXPRESSION AB We have investigated whether a state of tolerance toward EGFP-expressing skin tissue can be induced by prior establishment of EGFP molecular chimerism by transplant of gene-transduced bone marrow in mice. Irradiated (10 Gy) C57BL/6J mice were transplanted with bone marrow cells transduced with two different retroviral vectors encoding EGFP. EGFP-transduced, mock-transduced, and age-matched control mice received skin grafts from both C57BL/6 EGFP-transgenic (B6-EGFP. Tg) and MHC-mismatched B10.A donor mice at 8, 29, or 39 weeks after bone marrow transplantation. Although 14 of 17 control mice rejected EGFP.Tg skin grafts within 100 days, 24 of 25 mice receiving EGFP-expressing bone marrow cells accepted their B6-EGFP.Tg grafts out to 200 days after skin grafting, including animals with undetectable levels of EGFP expression in blood cells. The EGFP-transduced animals rejected third-party grafts from MHC-mismatched mice within 20 days, indicating that acceptance of the EGFP-expressing skin grafts was the result of the induction of specific and operational immune tolerance. Thus, our data indicate that (a) EGFP-expressing tissue elicits an immunological rejection in C57BL/6 mice and (b) tolerance can be induced by engrafting relatively small numbers of EGFP-transduced hematopoietic cells. These experiments utilizing EGFP as an immunogen point to the wider therapeutic potential of employing transplantation of gene-transduced hematopoietic cells for establishing immunological tolerance and thereby preventing rejection of gene-corrected cells and tissues. C1 BioTransplant Inc, Boston, MA 02129 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Patience, C (reprint author), BioTransplant Inc, Charlestown Navy Yard,300 Technol Sq,7th Floor, Boston, MA 02129 USA. NR 36 TC 25 Z9 26 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 1525-0016 J9 MOL THER JI Mol. Ther. PD SEP PY 2003 VL 8 IS 3 BP 385 EP 391 DI 10.1016/S1525-0016(03)00210-7 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 719HG UT WOS:000185197100007 PM 12946311 ER PT J AU Schwarzschild, MA Chen, JF Tennis, M Messing, S Kamp, C Ascherio, A Holloway, RG Marek, K Tanner, CM McDermott, M Lang, AE AF Schwarzschild, MA Chen, JF Tennis, M Messing, S Kamp, C Ascherio, A Holloway, RG Marek, K Tanner, CM McDermott, M Lang, AE CA Parkinson Study Grp TI Relating caffeine consumption to Parkinson's disease progression and dyskinesias development SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 17th Annual Symposium on Etiology, Pathogenesis, and Treatment of Parkinssons Disease and Other Movement Disorders CY OCT 19, 2003 CL SAN FRANCISCO, CALIFORNIA SP Parkinson Study Grp, Huntington Study Grp, Dystonia Study Grp, Myoclonus Study Grp, Tourettes Syndrome Study Grp, Cooperat Ataxia Grp, Movement Disorder Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Univ Rochester, Rochester, NY USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Inst Neurodegenerat Disorders, New Haven, CT USA. Parkinsons Inst, Sunnyvale, CA USA. Univ Toronto, Toronto, ON, Canada. NR 0 TC 6 Z9 6 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 2003 VL 18 IS 9 BP 1082 EP 1083 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 723PF UT WOS:000185440200027 ER PT J AU Cudkowicz, M AF Cudkowicz, M CA Huntington Study Grp TI Minocycline safety and tolerability in Huntington's disease SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 17th Annual Symposium on Etiology, Pathogenesis, and Treatment of Parkinssons Disease and Other Movement Disorders CY OCT 19, 2003 CL SAN FRANCISCO, CALIFORNIA SP Parkinson Study Grp, Huntington Study Grp, Dystonia Study Grp, Myoclonus Study Grp, Tourettes Syndrome Study Grp, Cooperat Ataxia Grp, Movement Disorder Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 2003 VL 18 IS 9 BP 1084 EP 1085 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 723PF UT WOS:000185440200033 ER PT J AU Martin, CH Aifantis, I Scimone, ML von Andrian, UH Reizis, B von Boehmer, H Gounari, F AF Martin, CH Aifantis, I Scimone, ML von Andrian, UH Reizis, B von Boehmer, H Gounari, F TI Efficient thymic immigration of B220(+) lymphoid-restricted bone marrow cells with T precursor potential SO NATURE IMMUNOLOGY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; PROGENITOR CELLS; LINEAGE; EXPRESSION; MICE; LYMPHOPOIESIS; NOTCH1; FATE; GENE; DIFFERENTIATION AB Using a human CD25 reporter transgene controlled by regulatory sequences from the gene encoding pre-T cell receptor alpha, we identified a common lymphocyte precursor (CLP-2) population that, in contrast to the previously identified CLP-1 population, was c-Kit(-)B220(+). In short-term culture, the CLP-2 could be derived from the CLP-1 subset, and contained cells that in clonogenic assays were assessed to be bipotent precursors of T and B cells. Intravenous injection of bone marrow cells yielded a selective accumulation of CLP-2 thymic immigrants that in thymic organ culture generated mature alphabeta T cells. Although the CLP-2 subset may represent the most differentiated population with T cell potential before commitment to the B cell lineage, other subsets of thymic immigrants capable of generating T cells may exist. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Univ Chicago, Dept Med, Rheumatol Sect, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, 44 Binney St, Boston, MA 02115 USA. RI von Andrian, Ulrich/A-5775-2008; OI Reizis, Boris/0000-0003-1140-7853 FU PHS HHS [R01A145846, R01A147281] NR 35 TC 162 Z9 165 U1 0 U2 6 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 SEP PY 2003 VL 4 IS 9 BP 866 EP 873 DI 10.1038/ni965 PG 8 WC Immunology SC Immunology GA 715YN UT WOS:000185002200013 PM 12925850 ER PT J AU Taupin, D Podolsky, DK AF Taupin, D Podolsky, DK TI Trefoil factors: Initiators of mucosal healing SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID EPIDERMAL GROWTH-FACTOR; PANCREATIC SPASMOLYTIC POLYPEPTIDE; EPITHELIAL-CELL MIGRATION; HUMAN GASTRIC ADENOCARCINOMA; INFLAMMATORY-BOWEL-DISEASE; COLON-CARCINOMA CELLS; TGF-BETA RECEPTOR; TRANSCRIPTION FACTOR; GENE-EXPRESSION; ACID-SECRETION AB Maintaining the integrity of the gastrointestinal tract, despite the continual presence of microbial flora and injurious agents, is essential. Epithelial continuity depends on a family of small, yet abundant, secreted proteins - the trefoil factors (TFFs). TFFs protect mucous epithelia from a range of insults and contribute to mucosal repair, although the signalling events that mediate these responses are only partially understood. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Canberra Hosp, Canberra, ACT, Australia. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. NR 142 TC 318 Z9 338 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD SEP PY 2003 VL 4 IS 9 BP 721 EP U3 DI 10.1038/nrm1203 PG 14 WC Cell Biology SC Cell Biology GA 716ZW UT WOS:000185061500015 PM 14506475 ER PT J AU Siegle, GJ Steinhauer, SR Stenger, VA Konecky, R Carter, CS AF Siegle, GJ Steinhauer, SR Stenger, VA Konecky, R Carter, CS TI Use of concurrent pupil dilation assessment to inform interpretation and analysis of fMRI data SO NEUROIMAGE LA English DT Article ID PREFRONTAL CORTEX INVOLVEMENT; WORKING-MEMORY; EMOTIONAL INFORMATION; BRAIN ACTIVATION; TASK; LOAD; RESPONSES; MAINTENANCE; PERFORMANCE; COMPONENTS AB Potential contributions of concurrently acquired pupil dilation data to functional magnetic resonance imaging (fMRI) experiments were examined. Sixteen healthy participants completed a working memory task (digit sorting) during measurement of pupil dilation outside the fMRI environment and during concurrent 3T fMRI assessment. Pupil dilation increased parametrically with task difficulty inside and outside the scanner, on a similar time course, suggesting that task demand was similar in both environments. The time course of pupil dilation during digit sorting was similar to the time course of the fMRI signal in the middle frontal gyrus, suggesting that middle-frontal gyrus activity indexed the engagement working memory processes. Incorporating individual differences in pupil dilation improved the sensitivity and specificity of general linear modeling analyses of activity in the middle frontal gyrus, above and beyond standard analytic techniques. Results suggest concurrent pupil dilation during fMRI assessment can help to (1) specify whether task demand is the same inside and outside the fMRI environment, (2) resolve the extent to which fMRI signals reflect different aspects of event-related designs, and (3) explain variation in fMRI data due to individual differences in information processing. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Siegle, GJ (reprint author), Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA. FU NIMH NIH HHS [MH64159-01, MH55762, MH60473] NR 35 TC 84 Z9 85 U1 2 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2003 VL 20 IS 1 BP 114 EP 124 DI 10.1016/S1053-8119(03)00298-2 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 728ZN UT WOS:000185746400010 PM 14527574 ER PT J AU Jasdzewski, G Strangman, G Wagner, J Kwong, KK Poldrack, RA Boas, DA AF Jasdzewski, G Strangman, G Wagner, J Kwong, KK Poldrack, RA Boas, DA TI Differences in the hemodynamic response to event-related motor and visual paradigms as measured by near-infrared spectroscopy SO NEUROIMAGE LA English DT Article ID CEREBRAL OXYGENATION CHANGES; EARLY NEGATIVE RESPONSE; FOCAL BRAIN ACTIVATION; HEMOGLOBIN CONCENTRATION; SENSORY STIMULATION; BLOOD OXYGENATION; WAVELENGTH DEPENDENCE; FUNCTIONAL ACTIVATION; OPTICAL SPECTROSCOPY; IMAGING SPECTROSCOPY AB Several current brain imaging techniques rest on the assumption of a tight coupling between neural activity and hemodynamic response. The nature of this neurovascular coupling, however, is not completely understood. There is some evidence for a decoupling of these processes at the onset of neural activity, which manifests itself as a momentary increase in the relative concentration of deoxyhemoglobin (HbR). The existence of this early component of the hemodynamic response function, however, is controversial, as it is inconsistently found. Near infrared spectroscopy (NIRS) allows quantification of levels of oxyhemoglobin (HbO(2)) and HbR during task performance in humans. We acquired NIRS data during performance of simple motor and visual tasks, using rapid-presentation event-related paradigms. Our results demonstrate that rapid, event-related NIRS can provide robust estimates of the hemodynamic response without artifacts due to low-frequency signal components, unlike data from blocked designs. In both the motor and visual data the onset of the increase in HbO(2) occurs before HbR decreases, and there is a poststimulus undershoot. Our results also show that total blood volume (HbT) drops before HbO(2) and undershoots baseline, raising a new issue for neurovascular models. We did not find early deoxygenation in the motor data using physiologically plausible values for the differential pathlength factor, but did find one in the visual data. We suggest that this difference, which is consistent with functional magnetic resonance imaging (fMRI) data, may be attributable to different capillary transit times in these cortices. (C) 2003 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula M Martinos Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neural Syst Grp, Charlestown, MA 02129 USA. Harvard Mit Div Hlth Sci & Technol, Charlestown, MA 02129 USA. RP Jasdzewski, G (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula M Martinos Ctr, 149 13th St, Charlestown, MA 02129 USA. FU NCRR NIH HHS [P41-RR14075]; NINDS NIH HHS [R29-NS38842] NR 68 TC 134 Z9 137 U1 2 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2003 VL 20 IS 1 BP 479 EP 488 DI 10.1016/S1053-8119(03)00311-2 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 728ZN UT WOS:000185746400044 PM 14527608 ER PT J AU Kennedy, DN AF Kennedy, DN TI Share and share alike SO NEUROINFORMATICS LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Kennedy, DN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1539-2791 J9 NEUROINFORMATICS JI Neuroinformatics PD FAL PY 2003 VL 1 IS 3 BP 211 EP 213 DI 10.1385/NI:1:3:211 PG 3 WC Computer Science, Interdisciplinary Applications; Neurosciences SC Computer Science; Neurosciences & Neurology GA 735CN UT WOS:000186095000001 PM 15046244 ER PT J AU Gardner, D Toga, AW Ascoli, GA Beatty, JT Brinkley, JF Dale, AM Fox, PT Gardner, EP George, JS Goddard, N Harris, KM Herskovits, EH Hines, ML Jacobs, GA Jacobs, RE Jones, EG Kennedy, DN Kimberg, DY Mazziotta, JC Miller, PL Mori, S Mountain, DC Reiss, AL Rosen, GD Rottenberg, DA Shepherd, GM Smalheiser, NR Smith, KP Strachan, T Van Essen, DC Williams, RW Wong, STC AF Gardner, D Toga, AW Ascoli, GA Beatty, JT Brinkley, JF Dale, AM Fox, PT Gardner, EP George, JS Goddard, N Harris, KM Herskovits, EH Hines, ML Jacobs, GA Jacobs, RE Jones, EG Kennedy, DN Kimberg, DY Mazziotta, JC Miller, PL Mori, S Mountain, DC Reiss, AL Rosen, GD Rottenberg, DA Shepherd, GM Smalheiser, NR Smith, KP Strachan, T Van Essen, DC Williams, RW Wong, STC TI Towards effective and rewarding data sharing SO NEUROINFORMATICS LA English DT Editorial Material C1 Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, Lab Neuroinformat, New York, NY 10021 USA. Univ Calif Los Angeles, Sch Med, Lab Neuroimaging, Los Angeles, CA 90025 USA. George Mason Univ, Krasnow Inst Adv Study, Computat Neuroanat Grp, Fairfax, VA 22030 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA. MIT, NMR Ctr, Cambridge, MA 02139 USA. Univ Texas, Hlth Sci Ctr, Res Imaging Res Ctr, San Antonio, TX 78229 USA. NYU, Sch Med, Dept Physiol & Neurosci, New York, NY 10016 USA. Los Alamos Natl Lab, Biophys Grp, Los Alamos, NM 87544 USA. Univ Edinburgh, Div Informat, Edinburgh EH1 2QL, Midlothian, Scotland. Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA. Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21287 USA. Montana State Univ, Dept Neurosci & Cell Biol, Bozeman, MT 59717 USA. CALTECH, Pasadena, CA 91125 USA. Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Univ Calif Los Angeles, Sch Med, Brain Mapping Ctr, Los Angeles, CA 90024 USA. Yale Univ, Sch Med, Ctr Med Informat, New Haven, CT 06520 USA. Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. Stanford Univ, Dept Child & Adolescent Psychiat, Stanford, CA 94305 USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Univ Minnesota, VA Med Ctr 127, Dept Neurol & Radiol, Minneapolis, MN 55417 USA. Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06520 USA. Univ Illinois, Inst Psychiat, Chicago, IL 60612 USA. Mitre Corp, Mclean, VA 22102 USA. Inst Human Genet, Int Ctr Life, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England. Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. Univ Tennessee, Ctr Hlth Sci, Dept Anat & Neurobiol, Ctr Genomics & Bioinformat, Memphis, TN 38163 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94131 USA. RP Gardner, D (reprint author), Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, Lab Neuroinformat, New York, NY 10021 USA. RI Kimberg, Daniel/D-1164-2009; Dale, Anders/A-5180-2010; Fox, Peter/B-4725-2010; OI Fox, Peter/0000-0002-0465-2028; Rosen, Glenn/0000-0001-8281-5446; Williams, Robert/0000-0001-8924-4447 NR 4 TC 52 Z9 52 U1 0 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1539-2791 J9 NEUROINFORMATICS JI Neuroinformatics PD FAL PY 2003 VL 1 IS 3 BP 289 EP 295 DI 10.1385/NI:1:3:289 PG 7 WC Computer Science, Interdisciplinary Applications; Neurosciences SC Computer Science; Neurosciences & Neurology GA 735CN UT WOS:000186095000007 PM 15046250 ER PT J AU Raskind, MA AF Raskind, MA TI Update on Alzheimer drugs (galantamine) SO NEUROLOGIST LA English DT Article DE cholinesterase inhibitor; galantamine; Alzheimer disease ID NICOTINIC ACETYLCHOLINE-RECEPTORS; PLACEBO-CONTROLLED TRIAL; VASCULAR DEMENTIA; HEALTH ECONOMICS; BINDING-SITES; DISEASE; GALANTHAMINE; INHIBITION; MODULATION; TACRINE AB Background: Deficient cholinergic function contributes to the cognitive and behavioral signs and symptoms of Alzheimer disease (AD). A successful treatment approach in AD has been the enhancement of cholinergic function by cholinesterase inhibitors. Review Summary: Galantamine is a cholinesterase inhibitor and allosteric modulating ligand at nicotinic cholinergic receptors. Galantamine 24 mg/d has been demonstrated consistently effective compared with placebo for the cognitive, functional, and behavioral aspects of Alzheimer's disease in large multicenter trials. Cognition and function on average are preserved for 12 months in Alzheimer disease patients receiving galantamine. It is safe and very well tolerated when dosage is escalated gradually. Conclusions: Galantamine is a valuable addition to agents available for the pharmacologic treatment of AD. C1 Univ Washington, Alzheimers Dis Res Ctr, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Raskind, MA (reprint author), VA Puget Sound Hlth Care Syst Mental Illness Res, 116MI-RECC,1660 S Columbia Way, Seattle, WA 98108 USA. NR 42 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1074-7931 J9 NEUROLOGIST JI Neurologist PD SEP PY 2003 VL 9 IS 5 BP 235 EP 240 DI 10.1097/01.nrl.0000087722.46430.c4 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 726ZJ UT WOS:000185631200004 PM 12971834 ER PT J AU Gould, GG Pardon, MC Morilak, DA Frazer, A AF Gould, GG Pardon, MC Morilak, DA Frazer, A TI Regulatory effects of reboxetine treatment alone, or following paroxetine treatment, on brain noradrenergic and serotonergic systems SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE antidepressants; reboxetine; norepinephrine transporter; quantitative autoradiography; serotonin transporter; paroxetine ID MESSENGER-RNA EXPRESSION; TYROSINE-HYDROXYLASE; LOCUS-COERULEUS; RAT-BRAIN; EXTRACELLULAR NORADRENALINE; QUANTITATIVE AUTORADIOGRAPHY; ANTIDEPRESSANT TREATMENTS; REUPTAKE INHIBITORS; BETA-ADRENOCEPTORS; MAJOR DEPRESSION AB When patients do not respond to an initial antidepressant, one clinical approach is to switch to an agent in a different pharmacological class. However, few studies have examined the neurochemical consequences of this practice. To study this, we examined changes in binding sites in rat brain for norepinephrine (NET) and serotonin transporters (SERT), alpha(1), alpha(2), and beta(1) adrenergic receptors after chronic administration of paroxetine (PRX), reboxetine (RBX), or PRX followed by RBX. We also examined the effects of these treatments on mRNA expression for tyrosine hydroxylase (TH). RBX treatment for 3 weeks reduced NET binding significantly, by similar to40% in terminal field areas, and 6 weeks of RBX reduced it even more, by similar to60%. RBX treatment for 3 and 6 weeks reduced beta(1) adrenergic receptor-binding sites equally, by 50-60%. At no time did RBX treatment reduce SERT-binding sites. PRX treatment had no effect on beta(1) adrenergic or NET-binding sites, but reduced SERT-binding sites by 75-80%. Neither treatment altered mRNA for TH, alpha(1), or alpha(2) adrenergic receptor-binding sites. When 3 weeks of RBX treatment followed 3 weeks of PRX treatment, NET-binding sites were reduced to the same extent as measured after 6 weeks of RBX treatment alone, indicating that PRX pretreatment may have 'primed' the subsequent regulatory effect of RBX on the NET. Thus, pretreatment of rats with PRX actually enhanced at least one regulatory effect of RBX treatment on the noradrenergic system, and did not interfere with any other pharmacological effect caused by RBX treatment. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Gould, GG (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, MC 7764,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. OI Pardon, Marie-Christine/0000-0003-4737-9479; Gould, Georgianna/0000-0002-5470-8763 FU NIMH NIH HHS [MH57001] NR 39 TC 25 Z9 25 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 2003 VL 28 IS 9 BP 1633 EP 1641 DI 10.1038/sj.npp.1300236 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 717HX UT WOS:000185083900010 PM 12825093 ER PT J AU Weber, DC Chan, AW Bussiere, MR Harsh, GR Ancukiewicz, M Barker, FG Thornton, AT Martuza, RL Nadol, JB Chapman, PH Loeffler, JS AF Weber, DC Chan, AW Bussiere, MR Harsh, GR Ancukiewicz, M Barker, FG Thornton, AT Martuza, RL Nadol, JB Chapman, PH Loeffler, JS TI Proton beam radiosurgery for vestibular schwannoma: Tumor control and cranial nerve toxicity SO NEUROSURGERY LA English DT Article DE acoustic neuroma; cranial nerve toxicity; proton therapy; stereotactic radiosurgery; vestibular schwannoma ID FRACTIONATED STEREOTACTIC RADIOTHERAPY; RELATIVE BIOLOGICAL EFFECTIVENESS; LARGE ANIMAL-MODEL; ACOUSTIC NEUROMA; HEARING PRESERVATION; DOSE DISTRIBUTIONS; RADIATION-THERAPY; COMPLICATIONS; MANAGEMENT; NEURINOMAS AB OBJECTIVE: We sought to determine the tumor control rate and cranial nerve function outcomes in patients with vestibular schwannomas who were treated with proton beam stereotactic radiosurgery. METHODS: Between November 1992 and August 2000, 88 patients with vestibular schwannomas were treated at the Harvard Cyclotron Laboratory with proton beam stereotactic radiosurgery in which two to four convergent fixed beams of 160-MeV protons were applied. The median transverse diameter was 16 mm (range, 2.5-35 mm), and the median tumor volume was 1.4 cm(3) (range, 0.1-15.9 cm(3)). Surgical resection had been performed previously in 15 patients (17%). Facial nerve function (House-Brackmann Grade 1) and trigeminal nerve function were in 79 patients (89.8%). Eight patients (9%) had good or excellent hearing (Gardner-Robertson [GR] Grade 1), and 13 patients (15%) had serviceable hearing (GR Grade 2). A median dose of 12 cobalt Gray equivalents (range, 10-18 cobalt Gray equivalents) was prescribed to the 70 to 108% isodose lines (median, 70%). The median follow-up period Was 38.7 months (range, 12-102.6 mo). RESULTS: The actuarial 2- and 5-year tumor control rates were 95.3% (95% confidence interval [CI], 90.9-99.9%) and 93.6% (95% CI, 88.3-99.3%). Salvage radio-surgery was performed in one patient 32.5 months after treatment, and a craniotomy was required 19.1 months after treatment in another patient with hemorrhage in the vicinity of a stable tumor. Three patients (3.4%) underwent shunting for hydrocephalus, and a subsequent partial resection was performed in one of these patients. The actuarial 5-year cumulative radiological reduction rate was 94.7% (95%, CI, 81.2-98.3%). Of the 21 patients (24%) with functional hearing (GR Grade 1 or 2), 7 (33.3%) retained serviceable hearing ability (GR Grade 2). Actuarial 5-year normal facial and trigeminal nerve function preservation: rates were 91.1% (95% CI, 85-97.6%) and 89.4% (95% CI, 82-96.7%). Univariate analysis revealed that prescribed dose,(P = 0.005), maximum dose (P = 0.006), and the inhomogeneity coefficient (P = 0.03) were associated with a significant risk of long-term facial neuropathy. No other cranial nerve deficits or cancer relapses were observed. CONCLUSION: Proton beam stereotactic radiosurgery has been shown to be an effective means of tumor control. A high radiological response rate was observed. Excellent facial and trigeminal nerve function preservation rates were achieved. A reduced prescribed dose is associated with a significant decrease in facial neuropathy. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA USA. RP Weber, DC (reprint author), Paul Scherrer Inst, Strahlmed Abt, CH-5232 Villigen, PSI, Switzerland. NR 48 TC 52 Z9 53 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD SEP PY 2003 VL 53 IS 3 BP 577 EP 586 DI 10.1227/01.NEU.0000079369.59219.C0 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 718AL UT WOS:000185122900011 PM 12943574 ER PT J AU Hord, ED Cohen, SP Cosgrove, GR Ahmed, SU Vallejo, R Chang, YC Stojanovic, MP AF Hord, ED Cohen, SP Cosgrove, GR Ahmed, SU Vallejo, R Chang, YC Stojanovic, MP TI The predictive value of sympathetic block for the success of spinal cord stimulation SO NEUROSURGERY LA English DT Article DE causalgia; complex regional region pain syndrome; reflex sympathetic dystrophy; spinal cord stimulation; sympathetic block ID REGIONAL PAIN SYNDROME; IASP DIAGNOSTIC-CRITERIA; SUBSTANCE-P; DYSTROPHY; MECHANISMS; MANAGEMENT; RELIEF; EXPERIENCE; RESPONSES; NEURONS AB Objective: The purpose of this study was to assess the predictive value of response to sympathetic blockade (SB) on the success rate of spinal cord stimulation (SCS) in patients with complex regional pain syndrome. Methods: We performed a retrospective study on 23 patients with complex regional pain syndrome who underwent both SB and subsequent SCS trials in the past 3 years at the Massachusetts General Hospital Pain Center, Boston, MA, and Walter Reed Army Medical Center, Washington, DC. Fifteen of these patients underwent permanent placement of an SCS device, and pain relief at 1- and 9-month follow up was recorded. Results: Among the 23 patients included in the study, those having transient pain relief with SB were more likely to have a positive SCS trial: all 13 with positive SB had good pain relief during the trial, compared with only 3 of the 10 with negative SB (100% versus 30%, p < 0.001). Among the 10 patients with negative SB, 7 noted poor pain relief during the trial despite adequate coverage, and they did not undergo placement of a permanent device. Among the patients who underwent permanent placement of the SCS device, those who received good pain relief with SB were more likely to have greater than 50% pain relief at 1 month follow-up (100% versus 33%, p = 0.029) and 9-month follow-up (87.5% versus 33.3%, P = 0.15). Conclusion: We conclude that patients with good response to SB before SCS are more likely to have a positive response during their SCS trial and long-term pain relief after placement of permanent SCS device. C1 Massachusetts Gen Hosp, MGH Pain Ctr, Intervent Pain Program, Dept Anesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, MGH Pain Ctr, Intervent Pain Program, Dept Crit Care & Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Uniformed Serv Univ Hlth Sci, Walter Reed Army Med Ctr, Pain Management Ctr, Dept Anesthesia, Washington, DC USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, MGH Pain Ctr, Dept Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. RP Hord, ED (reprint author), Massachusetts Gen Hosp, MGH Pain Ctr, Intervent Pain Program, Dept Anesthesia, WACC-324,15 Parkman St, Boston, MA 02114 USA. NR 33 TC 14 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD SEP PY 2003 VL 53 IS 3 BP 626 EP 632 DI 10.1227/01.NEU.0000080061.26321.8D PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 718AL UT WOS:000185122900021 PM 12943579 ER PT J AU Ogilvy, CS Ogilvy, BW Sztramski, P AF Ogilvy, CS Ogilvy, BW Sztramski, P TI An easy-to-use intraoperative digital videography, still photography, and X-ray-capture system SO NEUROSURGERY LA English DT Article DE data acquisition; digital photography; intraoperative videography AB OBJECTIVE: The goal was to evaluate an easy-to-construct digital system for documentation of intraoperative still and motion photography. In addition, the management of pre- and postoperative images was considered. METHODS: A Macintosh system (both hardware and software) is described in detail, as are techniques and use. RESULTS: The system has proved to be easy to use. It is user-friendly and makes it possible to rapidly edit and store data from preoperative studies, as well as intraoperative videography and still photography. The cost is minimal, compared with other commercially available systems. CONCLUSION: Digital videography and still photography can easily be accomplished with minimal modifications to existing hardware and software systems. Patient x-rays can also be incorporated into this system, for easy retrieval. C1 Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ogilvy, CS (reprint author), VBK710,55 Fruit St, Boston, MA 02114 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD SEP PY 2003 VL 53 IS 3 BP 781 EP 783 DI 10.1227/01.NEU.0000080082.92588.CE PG 3 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 718AL UT WOS:000185122900057 PM 12943597 ER PT J AU Monzillo, LU Hamdy, O Horton, ES Ledbury, S Mullooly, C Jarema, C Porter, S Ovalle, K Moussa, A Mantzoros, CS AF Monzillo, LU Hamdy, O Horton, ES Ledbury, S Mullooly, C Jarema, C Porter, S Ovalle, K Moussa, A Mantzoros, CS TI Effect of lifestyle modification on adipokine levels in obese subjects with insulin resistance SO OBESITY RESEARCH LA English DT Article DE adipose tissue; cytokines; weight loss ID TUMOR-NECROSIS-FACTOR; C-REACTIVE PROTEIN; SUBCUTANEOUS ADIPOSE-TISSUE; TYPE-2 DIABETES-MELLITUS; WEIGHT-LOSS; FACTOR-ALPHA; INTERLEUKIN-6; WOMEN; REDUCTION; DISEASE AB Objective: To study the effect of weight loss in response to a lifestyle modification program on the circulating levels of adipose tissue derived cytokines (adipokines) in obese individuals with insulin resistance. Research Methods and Procedures: Twenty-four insulin-resistant obese subjects with varying degrees of glucose tolerance completed a 6-month program consisting of combined hypocaloric diet and moderate physical activity. Adipokines [leptin, adiponectin, resistin, tumor necrosis factor-a (TNF-alpha), interleukin-6 (IL-6)] and highly sensitive C-reactive protein were measured before and after the intervention. Insulin sensitivity index was evaluated by the frequently sampled intravenous glucose tolerance test. Results: Participants had a 6.9 +/- 0.1 kg average weight loss, with a significant improvement in sensitivity index and reduction in plasma leptin (27.8 +/- 3 vs. 23.6 +/- 3 ng/mL, p = 0.01) and IL-6 (2.75 +/- 1.51 vs. 2.3 +/- 0.91 pg/mL, p = 0.012). TNF-alpha levels tended to decrease (2.3 +/- 0.2 vs. 1.9 +/- 0.1 pg/mL, p = 0.059). Adiponectin increased significantly only among diabetic subjects. The reductions in leptin were correlated with the decreases in BMI (r = 0.464, p < 0.05) and with changes in highly sensitive C-reactive protein (r = 0.466, p < 0.05). Discussion: Weight reduction in obese individuals with insulin resistance was associated with a significant decrease in leptin and IL-6 and a tendency toward a decrease in circulating TNF-alpha, whereas adiponectin was increased only in diabetic subjects. Further studies are needed to elucidate the relationship between changes of adipokines and the health benefits of weight loss. C1 Harvard Univ, Sch Med, Clin Res Ctr, Joslin Diabet Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Div Endocrinol, Boston, MA 02115 USA. RP Mantzoros, CS (reprint author), 99 Brookline Ave, Boston, MA 02215 USA. FU NCRR NIH HHS [RR 01032]; PHS HHS [R01 58785] NR 31 TC 248 Z9 261 U1 2 U2 9 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 SEP PY 2003 VL 11 IS 9 BP 1048 EP 1054 DI 10.1038/oby.2003.144 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 723MN UT WOS:000185436300004 PM 12972674 ER PT J AU Yao, L Baltatzis, S Zafirakis, P Livir-Rallatos, C Voudouri, A Markomichelakis, NN Zhao, TZ Foster, CS AF Yao, L Baltatzis, S Zafirakis, P Livir-Rallatos, C Voudouri, A Markomichelakis, NN Zhao, TZ Foster, CS TI Human mast cell subtypes in conjunctiva of patients with atopic keratoconjunctivitis, ocular cicatricial pemphigoid and Stevens-Johnson syndrome SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article ID HUMAN T-MAST; FIBROBLAST PROLIFERATION; QUANTITATIVE-ANALYSIS; MONOCLONAL-ANTIBODY; FIXATION TECHNIQUES; TRYPTASE; CHYMASE; HETEROGENEITY; PHENOTYPE; EXPRESSION AB Purpose: Investigate mast cell (MCs) subtypes in atopic keratoconjunctivitis (AKC), ocular cicatrical pemphigoid (OCP), and Stevens-Johnson Syndrome (SJS). Methods: MCs subtypes were determined by immunohistochemistry of conjunctiva (obtained from 34 patients - 9 AKC, 9 OCP, 9 SJS and 7 normal) using monoclonal antibodies directed against chymase (MCc) and tryptase (MCT). Double staining was used to distinguish MCS as positive for both chymase and tryptase (MCTc). Results: The number of MCs was significantly increased in AKC, OCP and SJS patients, compared to normal subjects. MCc were especially high in AKC, and moderately high in OCR MC,and MCTC were similar in each disease group. Conclusions: While the AKC findings were not surprising, the result in OCP and SJS suggests that MCs play an underappreciated role in the inflammatory process of these disorders. Disparate proportions of MCS subtypes in these diseases may imply differential functions of MCs in these disorders. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Immunol & Uveitis Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Hilles Immunol Lab,Dept Ophthalmol, Boston, MA 02114 USA. Gen Hosp, Athens Med Sch, Dept Ophthalmol, Athens, Greece. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. NR 40 TC 6 Z9 8 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD SEP PY 2003 VL 11 IS 3 BP 211 EP 222 DI 10.1076/ocii.11.3.211.17353 PG 12 WC Ophthalmology SC Ophthalmology GA 755EU UT WOS:000187391400006 PM 14566647 ER PT J AU Powell, SN Kachnic, LA AF Powell, SN Kachnic, LA TI Roles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and the cellular response to ionizing radiation SO ONCOGENE LA English DT Article DE breast cancer; BRCA genes; tumor suppressor genes; DNA repair; ionizing radiation; homologous recombination; DNA replication ID FAMILIAL BREAST-CANCER; TRANSCRIPTION-COUPLED REPAIR; SUSCEPTIBILITY GENE BRCA1; POLYMERASE-II HOLOENZYME; OVARIAN-CANCER; DAMAGE RESPONSE; CHROMOSOMAL BREAKS; DIRECTED REPAIR; PROTEIN-KINASE; S-PHASE AB Inheritance of one defective copy of either of the two breast cancer susceptibility genes, BRCA1 and BRCA2, predisposes individuals to breast and ovarian cancers. Current progress in determining the function of these genes suggests that they participate in a common pathway to facilitate orderly homologous recombination and thereby maintain genomic integrity. As a consequence of this defect in homologous recombination, tumors that arise in BRCA carriers are likely to be more sensitive to ionizing radiation. This review summarizes recent investigations about the nature of the defect in DNA repair, and highlights the unanswered questions about the tumor suppressor paradox of BRCA genes. The unsolved mystery is the other genetic changes that must occur to turn a BRCA-deficient cell from a nonviable cell into a tumor cell capable of endless growth. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Boston Med Ctr, Dept Radiat Oncol, Boston, MA USA. RP Powell, SN (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 302,100 Blossom St, Boston, MA 02114 USA. NR 76 TC 154 Z9 159 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 1 PY 2003 VL 22 IS 37 BP 5784 EP 5791 DI 10.1038/sj.onc.1206678 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 717JV UT WOS:000185086100006 PM 12947386 ER PT J AU Latina, MA Gulati, V AF Latina, MA Gulati, V TI A modification of the ahmed valve for tight places SO OPHTHALMIC SURGERY LASERS & IMAGING LA English DT Article ID TUBE SHUNT; GLAUCOMA AB The availability of adequate conjunctival tissue is essential for successful implantation of glaucoma valves. This report describes a technique to place a trimmed Ahmed valve in an eye with limited subconjunctival space due to systemic disease and multiple previous surgical procedures, including a scleral buckle. Successful lowering of intraocular pressure was obtained with the technique during the follow-up period. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Latina, MA (reprint author), 20 Pond Dr,Suite 203, Reading, MA 01867 USA. NR 3 TC 3 Z9 4 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1082-3069 J9 OPHTHALMIC SUR LA IM JI Ophthalmic Surg. Lasers Imaging PD SEP-OCT PY 2003 VL 34 IS 5 BP 396 EP 397 PG 2 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 719YG UT WOS:000185232200008 PM 14509464 ER PT J AU Seddon, JM Sharma, S Chong, S Hutchinson, A Allikmets, R Adelman, RA AF Seddon, JM Sharma, S Chong, S Hutchinson, A Allikmets, R Adelman, RA TI Phenotype and genotype correlations in two best families SO OPHTHALMOLOGY LA English DT Article ID BEST-DISEASE GENE; MACULAR DYSTROPHY; VITELLIFORM DYSTROPHY; DEGENERATION AB Objective: To evaluate mutations in the Best mascular dystrophy (VMD2) gene in two families with Best disease and to describe the phenotype-genotype correlations of genetically determined affected and unaffected individuals. Design: Family genetic study. Participants: Two families with Best disease were identified, and family members were evaluated by ophthalmologic examination or fundus photography to assess their phenotype. All affected patients and some of the unaffected family members had a blood sample drawn, and the DNA was analyzed for mutations in the VMD2 gene. Main Outcome Measures: Twenty-one subjects in the two pedigrees with Best disease were studied. One amino acid-changing mutation in the VMD2 gene was found to segregate independently in each family (P297S or E300D, respectively). Results: Eleven individuals had some evidence of maculopathy, including retinal pigment epithelial changes, drusen, pigment epithelial irregularities, or cicatricial changes. Ten of these 11 patients (91%) with maculopathy had a mutation in the VMD2 gene, of whom 8 were clinically diagnosed as having Best disease and 2 were diagnosed as having possible Best maculopathy. The one patient without a mutation in the VMD2 gene had age-related macular degeneration (AMD). Ten family members did not have evidence of maculopathy, of whom 6 had no mutation in the VMD2 gene. Four family members (2 in each pedigree) had mutations in the VMD2 gene, abnormal electro-oculogram (EOG) results, but normal maculae at age 40 or older. Of the 7 individuals with no mutation in the VMD2 gene, 6 were phenotypically normal and the other had late-onset visual loss resulting from AMD. Conclusions: All family members with maculopathy consistent with Best disease (n = 10) had an amino acid-changing mutation in the VMD2 gene. Four individuals who did not have maculopathy, but did have an abnormal EOG, also had mutations in the VMD2 gene. The presence of a VMD2 mutation is associated with abnormal retinal function, which can occur in the absence of phenotypic manifestation of macular disease. (C) 2003 by the American Academy of Ophthalmology. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Epidemiol Unit,Dept Ophthalmol, Boston, MA 02114 USA. Queens Univ, Kingston, ON, Canada. Columbia Univ, Dept Ophthalmol, New York, NY USA. Columbia Univ, Dept Pathol, New York, NY USA. Yale Univ, Ctr Eye, New Haven, CT USA. RP Seddon, JM (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Epidemiol Unit,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY11309, EY13435] NR 16 TC 26 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD SEP PY 2003 VL 110 IS 9 BP 1724 EP 1731 DI 10.1016/S0161-6420(03)00575-X PG 8 WC Ophthalmology SC Ophthalmology GA 715BG UT WOS:000184950200011 PM 13129869 ER PT J AU Kiss, S Letko, E Qamruddin, S Baltatzis, S Foster, CS AF Kiss, S Letko, E Qamruddin, S Baltatzis, S Foster, CS TI Long-term progression, prognosis, and treatment of patients with recurrent ocular manifestations of Reiter's syndrome SO OPHTHALMOLOGY LA English DT Article ID REACTIVE ARTHRITIS; CLINICAL-FEATURES; UVEITIS; SPONDYLARTHROPATHIES; PERSPECTIVE; DIAGNOSIS; DISORDERS AB Purpose: To investigate the spectrum of ocular involvement, to examine the clinical outcome, and to analyze the influence of treatment in patients with chronic ocular manifestations of Reiter's syndrome (RS) referred to a tertiary care ocular immunology service. Design: Retrospective, noncomparative, interventional case series. Participants: Twenty-five patients with RS evaluated at the Ocular Immunology and Uveitis Service of the Massachusetts Eye and Ear Infirmary from 1981 through 2001. Methods: Charts of patients were reviewed and data on age, gender, follow-up time, ocular symptoms, extraocular involvement, ocular complications, therapy, and visual acuities were recorded. Main Outcome Measures: Visual acuity, ocular complications, disease progression, clinical outcome, and systemic treatment. Results: Twenty-five patients (20 male and 5 female) diagnosed with RS, with a mean age at presentation to our service of 37 years, were studied. The mean follow-up was 48.5 months. Eighty-five percent of patients tested were positive for human leukocyte antigen B27. Sixty-four percent of patients had a positive family history. All patients had oligoarthritis and enthesitis, most commonly affecting the back (56%), Achilles tendon (52%), and sacroiliac joint (24%). Eighty percent had a history of infection, most frequently urethritis (68%). Forty-four percent had a history of mucocutaneous lesions. All patients demonstrated ocular involvement at the time of diagnosis (68% with unilateral and 32% with bilateral disease), 84% had evidence of uveitis, 3% had scleritis, 2% had conjunctivitis, and 1% had pars planitis and iridocyclitis. During follow-up, the ocular complications included conjunctivitis (96%), anterior uveitis (92%), posterior uveitis (64%), keratitis (64%), cataract (56%), intermediate uveitis (40%), scleritis (28%), cystoid macular edema (28%), papillitis (16%), and glaucoma (16%). Systemic treatment for ocular inflammation was initiated in all patients. Ninety-six percent were treated with nonsteroidal anti-inflammatory agents. Eighty-eight percent were treated with corticosteroids, 64% requiring systemic prednisone. Immunosuppressive therapy was initiated in 52% of patients, with all receiving methotrexate. Seven patients required more than one immunosuppressive agent. The mean initial visual acuity was 20/25 in the right eye and 20/30 in the left eye. The mean final visual acuity was 20/25 in the right eye and 20/25 in the left eye. Conclusions: Reiter's syndrome may be associated with chronic recurrent ocular inflammation. Systemic therapy (including immunosuppressive treatment) typically is required to control the ocular inflammation and to prevent progressive visual loss. (C) 2003 by the American Academy of Ophthalmology. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Immunol & Uveities Serv, Boston, MA USA. RP Foster, CS (reprint author), Massachusetts Eye & Ear Infirm, Serv Immunol, 243 Charles St, Boston, MA 02114 USA. NR 24 TC 14 Z9 18 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD SEP PY 2003 VL 110 IS 9 BP 1764 EP 1769 DI 10.1016/S0161-6420(03)00620-1 PG 6 WC Ophthalmology SC Ophthalmology GA 715BG UT WOS:000184950200017 PM 13129875 ER PT J AU Schulz, RB Ripoll, J Ntziachristos, V AF Schulz, RB Ripoll, J Ntziachristos, V TI Noncontact optical tomography of turbid media SO OPTICS LETTERS LA English DT Article ID APPROXIMATION AB Optical tomography of turbid media has so far been limited by systems that require fixed geometries or measurements employing fibers. We present a system that records noncontact optical measurements from diffuse media of arbitrary shapes and retrieves the three-dimensional surface information of the diffuse medium. We further present a novel method of combining this composite data set and obtain accurate fluorescence reconstructions. This approach offers significant experimental simplicity and yields high-information-content datasets. The performance of this novel tomographic approach is demonstrated with experimental reconstructions of phantoms. (C) 2003 Optical Society of America. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Lab Bioopt & Mol Imaging, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Schulz, RB (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Lab Bioopt & Mol Imaging, Bldg 149,13th St,Suite 5209, Charlestown, MA 02129 USA. 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 8 TC 93 Z9 95 U1 1 U2 6 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 SEP PY 2003 VL 28 IS 18 BP 1701 EP 1703 DI 10.1364/OL.28.001701 PG 3 WC Optics SC Optics GA 717VR UT WOS:000185111900028 PM 13677542 ER PT J AU Chen, CY Halpin, C Rauch, SD AF Chen, CY Halpin, C Rauch, SD TI Oral steroid treatment of sudden sensorineural hearing loss: A ten year retrospective analysis SO OTOLOGY & NEUROTOLOGY LA English DT Article DE sudden sensorineural hearing loss; steroids ID INNER-EAR; DEAFNESS; INFECTION; PATHOLOGY; CARBOGEN; THERAPY AB Objective: To describe ten years of experience with Sudden Sensorineural Hearing Loss and compare the outcomes with and without treatment with oral corticosteroids. Study Design: Retrospective review of medical records. Setting: Large specialty hospital, Department of Otolaryngology. Patients: Patients presenting with sudden onset (72 hours) unilateral sensorineural hearing loss, with no evidence of Meniere's Disease, acoustic injury, retrocochlear disease, and other specifiable disorders. Interventions: The majority of patients received a standard course of oral corticosteroids (Prednisone 60mg and taper). A smaller group declined treatment. Main Outcome Measures: Recovery of hearing sensitivity was measured using standard audiometry and reported as change in Pure Tone Average. Word recognition scores were also analyzed. Results: When severe-to-profound cases are analyzed, a significant improvement (p < .01) in Pure Tone Average is seen in cases treated with steroids versus those untreated. When milder cases are included, a statistical floor effect prevents differentiation of these groups. Word recognition scores were significantly improved (p < .05) in the treated group. Conclusions: Application of steroid medication significantly improves the recovery outcomes in cases of Severe Sudden Sensorineural Hearing Loss. C1 Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. Chang Gung Mem Hosp, Dept Otolaryngol, Chilung, Taiwan. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Rauch, SD (reprint author), Massachusetts Eye & Ear Infirm, Dept Audiol, 243 Charles St, Boston, MA 02114 USA. NR 40 TC 73 Z9 91 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD SEP PY 2003 VL 24 IS 5 BP 728 EP 733 DI 10.1097/00129492-200309000-00006 PG 6 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 722LZ UT WOS:000185377400006 PM 14501447 ER PT J AU Lim, G Sung, B Ji, RR Mao, JR AF Lim, G Sung, B Ji, RR Mao, JR TI Upregulation of spinal cannabinoid-1-receptors following nerve injury enhances the effects of Win 55,212-2 on neuropathic pain behaviors in rats SO PAIN LA English DT Article DE neuropathic pain; allodynia; hyperalgesia; cannabinoid receptor; nerve injury; tyrosine kinase; mitogen-activated protein kinase; Win 55,212-2 ID CANNABINOID CB1 RECEPTORS; PLACEBO-CONTROLLED TRIAL; DORSAL-ROOT GANGLIA; PROTEIN-KINASE-C; NEUROTROPHIC FACTOR; POSTHERPETIC NEURALGIA; PHOSPHATIDYLINOSITOL 3-KINASE; MORPHINE-TOLERANCE; DIABETIC NEUROPATHY; IDIOPATHIC FORMS AB Exogenous cannabinoids are effective in attenuating neuropathic pain behaviors induced by peripheral nerve injury. but the mechanisms of their effectiveness remain unclear. Here we examined the expression of spinal cannabinoid-1-receptors (CB1Rs) following chronic constriction sciatic nerve injury (CCI) and its relation to the effects of a CBR agonist (Win 55,212-2) on neuropathic pain in rats. CCI induced a time-dependent upregulation of spinal CB1Rs primarily within the ipsilateral Superficial spinal cord dorsal horn as revealed by both Western blot and immunohistochemistry. This CCI-induced CB1R upregulation was at least in part mediated through tyrosine kinase receptors (Trk), because intrathecal treatment with the Trk inhibitor K252a (1 mug) for postoperative days 1-6 significantly reduced the CB1R Upregulation in CCI rats. At the intracellular level, the mitogen-activated protein kinase (ERK-MAPK) inhibitor PD98059 (1 mug) prevented, while the protein kinase C inhibitor chelerythrine (10 mug) partially reduced, the CCI-induced CB1R upregulation when each agent was administered intrathecally for postoperative days 1-6. Importantly, the CCI-induced upregulation of spinal CB1Rs enhanced the effects of Win 55,212-2 on both thermal hyperalgesia and mechanical allodynia, since inhibition of the CB1R upregulation by PD98059 resulted in a significant reduction of the effects of Win 55,212-2 in CCI rats. These results indicate that upregulation of spinal CBIRs following peripheral nerve injury may contribute to the therapeutic effects of exogenous cannabinoids oil neuropathic pain. (C) 2003 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,MGH Pain Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02114 USA. RP Mao, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,MGH Pain Ctr, WACC 324,15 Parkman St, Boston, MA 02114 USA. OI Ji, Ru-Rong/0000-0002-9355-3688 FU NIDA NIH HHS [DA08835]; NINDS NIH HHS [R01 NS040698, R01 NS42661] NR 92 TC 94 Z9 99 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD SEP PY 2003 VL 105 IS 1-2 BP 275 EP 283 DI 10.1016/S0304-3959(03)00242-2 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 729AB UT WOS:000185747600033 PM 14499445 ER PT J AU Reid, MC Otis, J Barry, LC Kerns, RD AF Reid, MC Otis, J Barry, LC Kerns, RD TI Cognitive-behavioral therapy for chronic low back pain in older persons: A preliminary study SO PAIN MEDICINE LA English DT Article DE chronic low back pain; cognitive-behavioral therapy; older persons ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MUSCULOSKELETAL PAIN; HIP FRACTURE; DISABILITY; PREVALENCE; ARTHRITIS; COMMUNITY; ELDERLY/; ADULTS; HEALTH AB Objective. To determine the feasibility and potential efficacy of providing cognitive-behavioral therapy (CBT) to older persons with chronic low back pain (CLBP). Methods. This was an uncontrolled pilot study conducted at a senior housing center (SHC) in New Haven, Connecticut. Fourteen SHC residents aged 65 years and older who were cognitively intact (Mini Mental State Examination score greater than or equal to24) and had CLBP were recruited for the study. CBT was administered in 10 weekly individual sessions. Participants were phoned 5 days on average after each session (range: 3-7 days) to determine their comprehension and perceived usefulness of the CBT materials and adherence with the assigned homework exercises. Using standardized measures, we determined participants' levels of pain intensity, pain-related disability, and physical and social activity at baseline, and at 2 and 24 weeks posttreatment. Results. Participants had a mean age of 77.4 (+/-7.9 SD) years and were mostly female (86%). Thirteen (93%) participants completed all 10 sessions. Comprehension of CBT, defined as self-reported understanding of the materials presented each week, exceeded 97%. The perceived usefulness of each treatment session was assessed on a 0-10 scale, and the mean ratings for the sessions ranged from 7.5-9.4. The mean number of days that participants practiced the homework exercises each week varied from 1.8 to 4.0. Significant reductions (P < 0.01) in participants' pain intensity and pain-related disability scores were found at the 2-week posttreatment (vs pretreatment) assessment. These treatment effects waned over time, but did not return to pretreatment levels at 24 weeks. Participants' physical and social activity levels did not change. Conclusions. CBT is a feasible treatment for cognitively intact, older persons with CLBP, and may be efficacious as well. C1 Cornell Univ, Weill Med Coll, Div Geriatr & Gerontol, New York, NY 10021 USA. Boston VA Healthcare Syst, Dept Psychol, Boston, MA USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Psychol, New Haven, CT 06510 USA. VA Connecticut Healthcare Syst, Dept Psychol, West Haven, CT USA. RP Reid, MC (reprint author), Cornell Univ, Weill Med Coll, Div Geriatr & Gerontol, 525 E 68th St,Box 39, New York, NY 10021 USA. NR 30 TC 29 Z9 29 U1 3 U2 7 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD SEP PY 2003 VL 4 IS 3 BP 223 EP 230 DI 10.1046/j.1526-4637.2003.03030.x PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 721ZX UT WOS:000185349300004 PM 12974821 ER PT J AU Piraino, B Bernardini, J Florio, T Fried, L AF Piraino, B Bernardini, J Florio, T Fried, L TI Staphylococcus aureus prophylaxis and trends in gram-negative infections in peritoneal dialysis patients SO PERITONEAL DIALYSIS INTERNATIONAL LA English DT Article; Proceedings Paper CT 22nd Annual Conference on Dialysis CY MAR 04-06, 2002 CL TAMPA, FLORIDA DE Staphylococcus aureus; Pseudomonas aeruginosa; peritonitis; exit-site infection; mupirocin; gram-negative infection; prophylaxis ID EXIT-SITE INFECTION; MUPIROCIN OINTMENT; NASAL CARRIAGE; CAPD AB Objective: To examine gram-negative exit-site infection and peritonitis rates before and after the implementation of Staphylococcus aureus prophylaxis in peritoneal dialysis (PD) patients. Design: Prospective data collection with periodic implementation of protocols to decrease infection rates in two PD programs. Patients: 663 incident patients on PD. Interventions: Implementation of S. aureus prophylaxis, beginning in 1990. Main Outcome Measures: Rates of S. aureus, gram-negative, and Pseudomonas aeruginosa exit-site infections and peritonitis. Results: Staphylococcus aureus exit-site infection and peritonitis rates fluctuated without significant trends during the first decade (without prophylaxis), then began to decline during the 1990s subsequent to implementation of prophylaxis, reaching levels of 0.02/year at risk and zero in the year 2000. Gram-negative infections fell toward the end of the 1980s, due probably to the implementation of better connectology. However, there have been no significant changes for the past 6 years. There was little change in P. aeruginosa infections over the entire time period. Pseudomonas aeruginosa is now the most common cause of catheter infection and catheter-related peritonitis. Conclusions: Prophylaxis against S. aureus is highly effective in reducing the rate of S. aureus infections but has no effect on gram-negative infections. Pseudomonas aeruginosa is now the most serious cause of catheter-related peritonitis. C1 Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. RP Piraino, B (reprint author), Suite 200,3504 5th Ave, Pittsburgh, PA 15213 USA. OI Piraino, Beth/0000-0001-5061-0841 NR 17 TC 43 Z9 44 U1 0 U2 0 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 0896-8608 J9 PERITON DIALYSIS INT JI Perit. Dial. Int. PD SEP-OCT PY 2003 VL 23 IS 5 BP 456 EP 459 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 735NQ UT WOS:000186121800009 PM 14604197 ER PT J AU O'Neill, J Siembieda, DW Crawford, KC Halgren, E Fisher, A Fitten, LJ AF O'Neill, J Siembieda, DW Crawford, KC Halgren, E Fisher, A Fitten, LJ TI Reduction in distractibility with AF102B and THA in the macaque SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE AF102B; THA; muscarinic agonists; cholinesterase inhibitors; distractibility; monkeys ID VISUAL ATTENTIONAL TASK; ALZHEIMERS-DISEASE; CHOLINESTERASE-INHIBITORS; MUSCARINIC AGONISTS; CHOLINERGIC SYSTEM; RECEPTOR AGONISTS; AGE-DIFFERENCES; RHESUS-MONKEYS; DOUBLE-BLIND; M1 AGONISTS AB Distractibility in primates may be influenced by central cholinergic systems. Two cholinomimetics, the m-1 muscarinic agonist (+/-)-cis-2-methyl-spiro(1,3-oxathiolane-5,3')quinuclidine (AF102B, civemeline) and the cholinesterase inhibitor tetrahydroaminoacridine (THA, tacrine), were compared to vehicle controls for effects on distractibility in an automated visuospatial attention task. The task required visual pursuit of a moving target amongst distractor stimuli that acted to impair performance and was executed by seven healthy adult bonnet macaque monkeys. Task accuracy and reaction time were measured 1.5 h after systemic administration of each substance. For the sevensubject group at individually titrated best doses, accuracy increased significantly relative to vehicle for both drugs. Reaction time at best dose decreased for both drugs, but not significantly. Muscarinic agonists and cholinesterase inhibitors may reduce distractibility in primates. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, Neuropsychiat Inst, Los Angeles, CA 90024 USA. DVAMC W Los Angeles, Los Angeles, CA 90073 USA. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Israel Inst Biol Res, Ness Ziona, Israel. DVAMC Sepulveda, North Hills, CA 91343 USA. RP O'Neill, J (reprint author), Univ Calif Los Angeles, Neuropsychiat Inst, 47-417A,760 Westwood Plaza, Los Angeles, CA 90024 USA. NR 51 TC 5 Z9 6 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD SEP PY 2003 VL 76 IS 2 BP 301 EP 306 DI 10.1016/j.pbb.2003.08.006 PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 743AL UT WOS:000186550200011 PM 14592682 ER PT J AU Kollias, N Baqer, A Sadiq, I Gillies, R Ou-Yang, H AF Kollias, N Baqer, A Sadiq, I Gillies, R Ou-Yang, H TI Measurement of solar UVB variations by polysulphone film SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID ULTRAVIOLET-RADIATION; DOSIMETERS; SPECTRA AB Sheets of polysulphone film have been extensively used as detectors to monitor solar UVB radiation. The advantages of polysulphone detectors are that they are small in size, they have good thermal stability and they are sensitive to UVB radiation. The principal disadvantage of polysulphone detectors is that their spectral sensitivity includes part of the short-wavelength UVA. In this study, we investigate the spectral sensitivity of the polysulphone detector with a series of monochromatic (+/-2 nm) excitations. We then compare the polysulphone-effective solar radiation with the erythemally effective solar radiation by comparing solar UVB data obtained with polysulphone films with those obtained with a spectroradiometer. From polysulphone data on the seasonal variation of solar UVB radiation, we estimate the corresponding fluctuations of the absorption of the ozone layer. We show that the spectral sensitivity of the polysulphone film is closer to the erythema action spectrum than that indicated by earlier data and that polysulphone detectors can be used to predict the erythema risk of solar UVB. Measurements on solar UVB with polysulphone films and with a spectroradiometer were found to be strongly correlated (R-2 > 0.95). Finally, polysulphone-based measurements provide a good measure of the fluctuations of the stratospheric ozone layer. C1 Johnson & Johnson Consumer Prod Worldwide, Skillman, NJ USA. Al Sabah Hosp, Minist Publ Hlth, Kuwait, Kuwait. SKIN Inc, Conshohocken, PA USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Ou-Yang, H (reprint author), Unilever Res, 45 River Rd, Edgewater, NJ 07010 USA. NR 14 TC 12 Z9 12 U1 0 U2 4 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD SEP PY 2003 VL 78 IS 3 BP 220 EP 224 DI 10.1562/0031-8655(2003)078<0220:MOSUVB>2.0.CO;2 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 722KG UT WOS:000185370600002 PM 14556306 ER PT J AU Kothari, DH Haley, SM Gill-Body, KM Dumas, HM AF Kothari, DH Haley, SM Gill-Body, KM Dumas, HM TI Measuring functional change in children with Acquired Brain Injury (ABI): Comparison of generic and ABI-specific scales using the Pediatric Evaluation of Disability Inventory (PEDI) SO PHYSICAL THERAPY LA English DT Article DE item response theory; outcome measurement; pediatric brain injury; Pediatric Evaluation of Disability Inventory; Rasch measurement ID RASCH ANALYSIS; ASSUMPTIONS; PERFORMANCE; INTERVAL; MODEL; LEVEL; PF-10 AB Background and Purpose. The Pediatric Evaluation of Disability Inventory (PEDI) subscales are hierarchic in nature, with item placements within each subscale reflecting the general order of skill attainment in children without disabilities. The purpose of this study was to determine whether a hierarchical subscale developed in this study for children with acquired brain injuries (ABIs) corresponds to the generic PEDI subscales, and, if not, whether condition-specific (ABI-specific) PEDI subscales are more sensitive for measuring change. Subjects. Eighty-seven children and adolescents (mean age=9.2 years, SD=5.2, range=1-20) with ABI during inpatient rehabilitation admissions were included. Methods. Data were collected by retrospective chart review. Rasch one-parameter analyses were conducted to construct the ABI-specific PEDI scale focusing on the Mobility and Self-care domains (content areas) only. Each domain consists of a Functional Skills subscale and a Caregiver Assistance subscale. Thus, in all, 4 scales were constructed within the ABI-specific PEDI scale. Differences in item hierarchies and sensitivity between generic and ABI-specific PEDI subscales for each domain were then examined. Results. Both generic and ABI-specific PEDI scales were sensitive for measuring functional changes during inpatient rehabilitation hospitalization. Even though the generic and ABI-specific item hierarchies differed substantially, only one of the 4 ABI-specific PEDI subscales (Caregiver Assistance Self-care subscale) was more sensitive for measuring change than the generic PEDI scale. Discussion and Conclusion. The ABI-specific scales added relatively little improvement in sensitivity compared with the generic PEDI scales of the Mobility and Self-care domains. Thus, for group analyses, the authors recommend use of the generic PEDI subscales for children with ABI. Future work with ABI-specific subscales may improve the physical therapist's ability to describe an individual's pattern of functional recovery. C1 VA Rehabil Res & Dev Ctr, Palo Alto, CA 94304 USA. Boston Univ, Sargent Coll Hlth & Rehabil Sci, Boston, MA 02215 USA. Massachusetts Gen Hosp, MGH Inst Hlth Prof, Phys Therapy Serv, Boston, MA USA. Franciscan Childrens Hosp, Res Ctr Children Special Hlth Care Needs, Boston, MA USA. Rehabil Ctr, Boston, MA USA. RP Kothari, DH (reprint author), VA Rehabil Res & Dev Ctr, Bldg 51,3801 Miranda Ave, Palo Alto, CA 94304 USA. EM dhara@rrdmail.stanford.edu NR 30 TC 29 Z9 29 U1 1 U2 2 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD SEP PY 2003 VL 83 IS 9 BP 776 EP 785 PG 10 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA 805XO UT WOS:000220399200001 PM 12940765 ER PT J AU Jette, DU Bacon, K Batty, C Carlson, M Ferland, A Hemingway, RD Hill, JC Ogilvie, L Volk, D AF Jette, DU Bacon, K Batty, C Carlson, M Ferland, A Hemingway, RD Hill, JC Ogilvie, L Volk, D TI Evidence-based practice: Beliefs, attitudes, knowledge, and behaviors of physical therapists SO PHYSICAL THERAPY LA English DT Article DE evidence-based practice; physical therapy; professional role behaviors ID EVIDENCE-BASED MEDICINE; GENERAL-PRACTITIONERS; CLINICAL-PRACTICE; IMPLEMENT EVIDENCE; PATIENT-CARE; BARRIERS; GUIDELINES; AWARENESS; SHOULDER AB Background and Purpose. Little research has been done regarding the attitudes and behaviors of physical therapists relative to the use of evidence in practice. The purposes of this study were to describe the beliefs, attitudes, knowledge, and behaviors of physical therapist members of the American Physical Therapy Association (APTA) as they relate to evidence-based practice (EBP) and to generate hypotheses about the relationship between these attributes and personal And practice characteristics of the respondents. Methods. A survey of a random sample of physical therapist members of A-PTA resulted in a 48.8% return rate and a sample of 488 that was fairly representative of the national membership. Participants completed a questionnaire designed to determine beliefs, attitudes, knowledge, and behaviors regarding EBP, as well as demographic information about themselves and their practice settings. Responses were summarized for each item, and logistic regression analyses were used to examine relationships among variables. Results. Respondents agreed that the use of evidence in practice was necessary, that the literature was helpful in their practices, and that quality of patient care was better when evidence was used. Training, familiarity with and confidence in search strategies, use of databases, and critical appraisal tended to be associated with younger therapists with fewer years since they were licensed. Seventeen percent of the respondents stated they read fewer than 2 articles in a typical month, and one quarter of the respondents stated they used literature in their clinical decision making less than twice per month. The majority of the respondents had access to online information, although more had access at home than at work. According to the respondents, the primary barrier to implementing EBP was lack of time. Discussion and Conclusion. Physical therapists stated they had a positive attitude about EBP and were interested in learning or improving), the skills necessary to implement EBP. They noted that they needed to increase the use of evidence in their daily practice. C1 Simmons Coll, Phys Therapy Program, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Bellingham Phys Therapy, Bellingham, WA USA. Physicians Phys Therapy, Phoenix, AZ USA. Somerville Hosp, Somerville, MA USA. Harvard Univ, HealthSouth Braintree Rehabil Ctr, Cambridge, MA 02138 USA. Shaughnessy Kaplan Rehabil Hosp, Salem, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jette, DU (reprint author), Simmons Coll, Phys Therapy Program, 300 The Fenway, Boston, MA 02115 USA. EM diane.jette@simmons.edu NR 26 TC 213 Z9 222 U1 2 U2 17 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD SEP PY 2003 VL 83 IS 9 BP 786 EP 805 PG 20 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA 805XO UT WOS:000220399200002 PM 12940766 ER PT J AU Kim, HJ Lee, SR Moon, KD AF Kim, HJ Lee, SR Moon, KD TI Ether fraction of methanol extracts of Gastrodia elata, medicinal herb protects against neuronal cell damage after transient global ischemia in gerbils SO PHYTOTHERAPY RESEARCH LA English DT Article DE Gastrodia elata; global brain ischemia; hippocampus; neuroprotection ID RADICAL SCAVENGING ACTIVITIES; CEREBRAL-ISCHEMIA; DNA FRAGMENTATION; RAT-BRAIN; GLUTAMATE; ANTIOXIDANT; HIPPOCAMPUS; APOPTOSIS; BL.; NEUROTOXICITY AB Gastrodia elata (GE), a medicinal herb, has been used traditionally for the treatment of convulsive diseases such as epilepsy in oriental countries including South Korea and still occupies an important place in traditional medicine in Asia. We designed this study to examine whether the ether fraction of methanol extracts (EFME) of GE protects the hippocampal neuronal damage induced by transient global ischemia in a gerbil model. Gerbils were treated with the EFME of GE (2011 or 500 mg/kg per day, p.o.) for 14 days before brain ischemia. The lower dose of EFME of GE failed to attenuate the hippocampal neuronal damage in the CA1 region. However, the higher dose of EFME of GE attenuated the hippocampal neuronal damage in the CA1 region. The present results show that the EFME of GE has a protective effect against neuronal damage following global ischemia in gerbils. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Kyungpook Natl Univ, Dept Food Sci & Technol, Taegu 702701, South Korea. Keimyung Univ, Dept Pharmacol, Taegu 700310, South Korea. RP Lee, SR (reprint author), Harvard Univ, Massachusetts Gen Hosp East, Sch Med, Dept Neurol & Radiol,Neuroprotect Res Lab, 149, Charlestown, MA 02129 USA. NR 22 TC 46 Z9 51 U1 0 U2 7 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0951-418X J9 PHYTOTHER RES JI Phytother. Res. PD SEP PY 2003 VL 17 IS 8 BP 909 EP 912 DI 10.1002/ptr.1246 PG 4 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 724WJ UT WOS:000185509400009 PM 13680822 ER PT J AU Chang, EL Bernardino, CR Rubin, PAD AF Chang, EL Bernardino, CR Rubin, PAD TI Transcaruncular orbital decompression for management of compressive optic neuropathy in thyroid-related orbitopathy SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID GRAVES OPHTHALMOPATHY; EYE DISEASE; FOLLOW-UP; RADIOTHERAPY; THERAPY; APEX AB This study was conducted to assess the outcome of transcaruncular orbital decompression to treat compressive optic neuropathy in thyroid-related orbitopathy. It involved a retrospective, noncomparative case series of 18 eyes of 10 consecutive patients with documented vision loss secondary to thyroid-related orbitopathy. Bony decompression of the orbital apex was performed via a transcaruncular approach. Main outcome measures were visual acuity, color vision, presence of diplopia, and reduction of exophthalmos. Of 18 eyes, 16 (89 percent) had improved visual acuity after the operation. One eye had no improvement and one had worsening of vision in the setting of diabetic retinopathy. Color vision was improved in 12 eyes (67 percent). Five of the patients did not have diplopia before the operation; none of these patients developed double vision after intervention. Exophthalmos was decreased by an average of 2.6 mm. The authors conclude that transcaruncular orbital decompression for compressive optic neuropathy in thyroid-related orbitopathy is successful in restoring visual function. Compared with other approaches used for decompression surgery, the transcaruncular approach offers direct access to the medial wall and orbital apex without a cutaneous incision or disruption of the medial canthus. In addition, this approach allows a controlled, graded removal of the ethmoidal air cells and reduced recovery time. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalm Plast Orbital & Cosmet Surg, Boston, MA 02114 USA. RP Rubin, PAD (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalm Plast Orbital & Cosmet Surg, 243 Charles St, Boston, MA 02114 USA. NR 23 TC 27 Z9 28 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD SEP 1 PY 2003 VL 112 IS 3 BP 739 EP 747 DI 10.1097/01.PRS.0000069708.70121.67 PG 9 WC Surgery SC Surgery GA 713VB UT WOS:000184877700004 PM 12960854 ER PT J AU Sorensen, G Emmons, K Hunt, MK Barbeau, E Goldman, R Peterson, K Kuntz, K Stoddard, A Berkman, L AF Sorensen, G Emmons, K Hunt, MK Barbeau, E Goldman, R Peterson, K Kuntz, K Stoddard, A Berkman, L TI Model for incorporating social context in health behavior interventions: applications for cancer prevention for working-class, multiethnic populations SO PREVENTIVE MEDICINE LA English DT Review DE cancer prevention; health promotion; nutrition; physical activity; health disparities; health inequalities ID COLON-CANCER; PHYSICAL-ACTIVITY; UNITED-STATES; PUBLIC-HEALTH; URBAN POPULATIONS; MULTIVITAMIN USE; LIFE-STYLE; RISK; PROMOTION; WOMEN AB Background. This article proposes a conceptual framework for addressing social contextual factors in cancer prevention interventions, and describes work that operationalizes this model in interventions for working class, multiethnic populations. Methods. The Harvard Cancer Prevention Program Project includes three studies: (1) an intervention study in 25 small businesses; (2) an intervention study in 10 health centers; and (3) a computer simulation modeling project that translates risk factor modifications into gains in life expectancy and number of cancers averted. The conceptual framework guiding this work articulates pathways by which social context may influence health behaviors, and is used to frame the interventions and guide evaluation design. Results. Social contextual factors cut across multiple levels of influence, and include individual factors (e.g., material circumstances, psychosocial factors), interpersonal factors (e.g., social ties, roles/responsibilities, social norms), organizational factors (e.g., work organization, access to health care), and neighborhood/community factors (e.g., safety, access to grocery stores). Social context is shaped by sociodemographic characteristics (e.g., social class, race/ethnicity, gender, age, language) that impact day-to-day realities. Conclusions. By illuminating the pathways by which social contextual factors influence health behaviors, it will be possible to enhance the effectiveness of interventions aimed at reducing social inequalities in risk behaviors. (C) 2003 American Health Foundation and Elsevier Science (USA). All rights reserved. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Brown Univ, Ctr Primary Care & Prevent, Pawtucket, RI USA. Univ Massachusetts, Sch Publ Hlth, Amherst, MA 01003 USA. RP Sorensen, G (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St Room SM-258, Boston, MA 02115 USA. FU NCI NIH HHS [P01 CA 75308] NR 106 TC 117 Z9 118 U1 0 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP PY 2003 VL 37 IS 3 BP 188 EP 197 DI 10.1016/S0091-7435(03)00111-7 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 711VG UT WOS:000184761300002 PM 12914824 ER PT J AU Achenbach, S Hoffmann, U Ferencik, M Wicky, S Brady, TJ AF Achenbach, S Hoffmann, U Ferencik, M Wicky, S Brady, TJ TI Tomographic coronary angiography by EBCT and MDCT SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review ID SPIRAL COMPUTED-TOMOGRAPHY; ELECTRON-BEAM CT; ARTERY BYPASS GRAFTS; HEART-RATE; NONINVASIVE DETECTION; IMAGE QUALITY; LEFT MAIN; STENOSES; RECONSTRUCTION; VISUALIZATION C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Achenbach, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 100 Charles River Plaza,Suite 400, Boston, MA 02114 USA. NR 56 TC 13 Z9 14 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 0033-0620 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD SEP-OCT PY 2003 VL 46 IS 2 BP 185 EP 195 DI 10.1016/S0033-0620(03)00086-0 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 725EZ UT WOS:000185532000007 PM 14505291 ER PT J AU Murthy, S Marcelli, M Weigel, NL AF Murthy, S Marcelli, M Weigel, NL TI Stable expression of full length human androgen receptor in PC-3 prostate cancer cells enhances sensitivity to retinoic acid but not to I alpha,25-dihydroxyvitamin D-3 SO PROSTATE LA English DT Article DE prostate cancer; vitamin D; androgen receptor; PC-3 cells; retinoids ID VITAMIN-D; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; 1,25-DIHYDROXYVITAMIN D-3; 9-CIS-RETINOIC ACID; LNCAP CELLS; 24-HYDROXYLASE ACTIVITY; GROWTH-INHIBITION; LINE LNCAP; IN-VITRO; PROLIFERATION AB BACKGROUND. PC-3 prostate cancer cell growth is inhibited by 1alpha,25-dihydroxyvitamin D-3 (1,25 D) and retinoids, but not to the same extent as the androgen receptor (AR) positive LNCaP prostate cancer cells. Previous reports suggest a role for AR in growth inhibition of LNCaP cells by 1,25 D and retinoids. PC-3 cells do not express AR. We therefore asked whether re-expression of AR would enhance the response of PC-3 cells to 1,25 D and retinoids. METHODS. PC-3 cells were stably transfected with wild type human AR cDNA. Pooled cells expressing AR protein at levels comparable to LNCaP cells were used to analyze response to 1,25 D, retinoids, androgens, and anti-androgens. RESULTS. AR re-expression in PC-3 cells restored response to androgens and anti-androgens, but growth inhibition by 1,25 D was not significantly altered. However, cells were sensitized to low levels of retinoids, and, in contrast to the parental PC-3 cells, sub-optimal levels of 1,25 D and retinoids caused additive growth inhibition. CONCLUSIONS. Restoring AR expression and activity in PC-3 cells results in enhanced sensitivity to low levels of retinoids while the response to 1,25 D remains unaltered. Thus, the involvement of AR in prostate cancer growth inhibition by 1,25 D appears to be cell line specific. Prostate 56: 293-304, 2003. (C) 2003 Wiley-Liss, Inc. C1 Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. RP Weigel, NL (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, 1 Baylor Plaza, Houston, TX 77030 USA. FU NCI NIH HHS [R01 CA 75337] NR 40 TC 10 Z9 10 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 0270-4137 J9 PROSTATE JI Prostate PD SEP PY 2003 VL 56 IS 4 BP 293 EP 304 DI 10.1002/pros.10261 PG 12 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 711LJ UT WOS:000184741800008 PM 12858358 ER PT J AU Nonacs, R Cohen, LS AF Nonacs, R Cohen, LS TI Assessment and treatment of depression during pregnancy: an update SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID PAROXETINE WITHDRAWAL SYNDROME; SEROTONIN REUPTAKE INHIBITORS; EXPOSED IN-UTERO; INFANT DEVELOPMENT; BIRTH OUTCOMES; MATERNAL CLOMIPRAMINE; POSTNATAL DEPRESSION; PSYCHIATRIC-ILLNESS; FLUOXETINE EXPOSURE; DRUG-USE AB Mood disorders are twice as common in women as compared with men and frequently cluster during the childbearing years. With significant data supporting the effectiveness and tolerability of pharmacologic treatments to treat a spectrum of psychiatric disorders, growing numbers of women are treated with psychotropic medications during their reproductive years. In this article, we review the available information on antidepressant medication use during pregnancy and provide guidelines for the treatment of depression in pregnant women. C1 Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, Clin Psychopharmacol Unit, Dept Psychiat, Boston, MA 02114 USA. RP Nonacs, R (reprint author), Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, Clin Psychopharmacol Unit, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. NR 85 TC 41 Z9 45 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD SEP PY 2003 VL 26 IS 3 BP 547 EP + DI 10.1016/S0193-953X(03)00046-7 PG 17 WC Psychiatry SC Psychiatry GA 726NP UT WOS:000185606000003 PM 14563097 ER PT J AU Joffe, H Soares, CN Cohen, LS AF Joffe, H Soares, CN Cohen, LS TI Assessment and treatment of hot flushes and menopausal mood disturbance SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID HORMONE REPLACEMENT THERAPY; QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; BREAST-CANCER SURVIVORS; FOLLICLE-STIMULATING-HORMONE; CEREBRAL-BLOOD-FLOW; POSTMENOPAUSAL WOMEN; ESTROGEN REPLACEMENT; PERIMENOPAUSAL WOMEN; DOUBLE-BLIND AB Recent reports on hormone replacement therapy (HRT) by the Women's Health Initiative (WHI) have changed the risk-benefit ratio on HRT use for millions of women. Whereas HRT was used previously for treatment of hot flushes and for prevention of cardiovascular disease and osteoporosis, the WHI reports have narrowed the primary use of HRT to menopausal symptom management. This review discusses emerging trends in the assessment and treatment of hot flushes, mood disturbance, and other neuropsychological symptoms that occur in menopausal women. Though HRT remains the mainstay of treatment for symptomatic menopausal women, alternative treatment strategies are being explored, including several major classes of psychoactive medications. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Perinatal & Reprod Psychiat Clin Re, Boston, MA 02114 USA. RP Joffe, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Perinatal & Reprod Psychiat Clin Re, 15 Parkman St,WACC, Boston, MA 02114 USA. NR 117 TC 38 Z9 42 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 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD SEP PY 2003 VL 26 IS 3 BP 563 EP + DI 10.1016/S0193-953X(03)00045-5 PG 20 WC Psychiatry SC Psychiatry GA 726NP UT WOS:000185606000004 PM 14563098 ER PT J AU Crowley, JJ Oslin, DW Patkar, AA Gottheil, E DeMaria, PA O'Brien, CP Berrettini, WH Grice, DE AF Crowley, JJ Oslin, DW Patkar, AA Gottheil, E DeMaria, PA O'Brien, CP Berrettini, WH Grice, DE TI A genetic association study of the mu opioid receptor and severe opioid dependence SO PSYCHIATRIC GENETICS LA English DT Article DE opioid dependence; substance dependence; genetics; mu opioid receptor gene; OPRM1; single nucleotide polymorphism; association study; heroin ID CONTROLLING MORPHINE PREFERENCE; SINGLE-NUCLEOTIDE POLYMORPHISM; SUBSTANCE DEPENDENCE; ALCOHOL DEPENDENCE; ABUSE; ADDICTION; WITHDRAWAL; VARIANTS; BINDING; OPIATES AB Objectives Twin, family and adoption studies have suggested that vulnerability to opioid dependence may be a partially inherited trait (Cadoret et al., 1986; Merikangas et al., 1998; Tsuang et al., 1998, 2001). Studies using animal models also support a role for genetic factors in opioid dependence, and point to a locus of major effect on mouse chromosome 10 (Berrettini et al., 1994; Alexander et al., 1996), which harbors the mu opioid receptor gene (Mor1) (Kozak et aL, 1994). The gene encoding the human mu opioid receptor (OPRM1) is thus an obvious candidate gene for contributing to opioid dependence. A recent report (Hoehe et al., 2000) found a significant association between a specific combination of OPRM1 single nucleotide polymorphisms (SNPs) and substance dependence. Methods In the current study, we genotyped 213 subjects with severe opioid dependence (89 African-Americans, 124 European-Americans) and 196 carefully screened 'super-control' subjects (96 African-Americans, 100 European-Americans) at five SNPs residing in the OPRM1 gene. The polymorphisms include three in the promoter region (T(-1793)A, T-1699 insertion and A(-1320)G) and two in exon 1 (C+17T [Ala6Val] and A(+118)G [Asp40Asn]). Results Statistical analysis of the allele frequency differences between opioid-dependent and control subjects for each of the polymorphisms studied yielded P values in the range of 0.444-1.000. Haplotype analysis failed to identify any specific combination of SNPs associated with the phenotype. Conclusions Despite reasonable statistical power we found no evidence of association between the five mu opioid receptor polymorphisms studied and severe opioid dependence in our sample. There were, however, significant allele frequency differences between African-Americans and European-Americans for all five polymorphisms, irrespective of drug-dependent status. Linkage disequilibrium analysis of the African-American genotypes indicated linkage disequilibrium (P<0.0001) across the five-polymorphism, 1911 base pair region. In addition, only four haplotypes of these five polymorphisms are predicted to exist in African-Americans. (C) 2003 Lippincott Williams Wilkins. C1 Univ Penn, Dept Pharmacol, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Psychiat & Human Behav, Philadelphia, PA 19107 USA. MIRECC, Vet Affairs Med Ctr, Philadelphia, PA USA. OI Crowley, James/0000-0001-9051-1557 FU NIDA NIH HHS [R01 DA 11835, K08 DA 00340, K12 DA 00357, K12 DA000357, P60 DA 05186-16]; NIGMS NIH HHS [T32 GM 008076-17] NR 30 TC 83 Z9 87 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8829 J9 PSYCHIAT GENET JI Psychiatr. Genet. PD SEP PY 2003 VL 13 IS 3 BP 169 EP 173 DI 10.1097/01.ypg.0000071762.90004.45 PG 5 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 718MH UT WOS:000185150200006 PM 12960749 ER PT J AU Cook, JM Ruzek, JI Cassidy, E AF Cook, JM Ruzek, JI Cassidy, E TI Possible association of posttraumatic stress disorder with cognitive impairment among older adults SO PSYCHIATRIC SERVICES LA English DT Editorial Material ID MENTAL-HEALTH-SERVICES; DEMENTIA; SURVIVORS; SYMPTOMS; VETERANS; MEMORY; SERIES C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Palo Alto Hlth Care Syst Natl Ctr PTSD, Dept Vet Affairs, Palo Alto, CA USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. RP Cook, JM (reprint author), Univ Penn, Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM cook_j@mail.trc.upenn.edu NR 20 TC 7 Z9 7 U1 0 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2003 VL 54 IS 9 BP 1223 EP 1225 DI 10.1176/appi.ps.54.9.1223 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 839BQ UT WOS:000222758700007 PM 12954937 ER PT J AU Weilburg, JB O'Leary, KM Meigs, JB Hennen, J Stafford, RS AF Weilburg, JB O'Leary, KM Meigs, JB Hennen, J Stafford, RS TI Evaluation of the adequacy of outpatient antidepressant treatment SO PSYCHIATRIC SERVICES LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Psychiatric-Association CY MAY 18-23, 2002 CL Philadelphia, PA SP Amer Psychiatr Assoc ID SEROTONIN REUPTAKE INHIBITORS; TREATING MAJOR DEPRESSION; PRIMARY-CARE PRACTICE; TRICYCLIC ANTIDEPRESSANTS; COLLABORATIVE CARE; CLINICAL-PRACTICE; MENTAL-DISORDERS; TRIAL; GUIDELINES; OUTCOMES AB Objective: Most studies evaluating the adequacy of antidepressant treatment have focused on the relatively small segment of the medicated population with a diagnosis of depression. This study assessed the rates and determinants of the adequacy of antidepressant treatment among all outpatients who receive antidepressants. Methods: A retrospective analysis was conducted using pharmacy claims made by patients with a primary care physician in a managed care plan at an academic medical center from 1996 through 1999. Adequate antidepressant treatment was defined as prescription of the lowest likely effective dosage of an antidepressant for at least 90 consecutive days. Data for a total of 15,476 records and 1,550 patients were available. Results: Overall, 46 percent of the patients receiving antidepressants received minimally adequate treatment. The rates of adequate treatment were significantly higher among patients whose antidepressant prescriptions were written by both primary care physicians and psychiatrists than among patients whose antidepressants were prescribed solely by primary care physicians (61 percent versus 31 percent). Patients who had trials of SSRIs had significantly higher rates of treatment adequacy than those who had trials of tricyclic antidepressants but not SSRIs (51 percent compared with 27 percent) or trials with other antidepressants only (24 percent). Conclusions: Pharmacy claims from all patients receiving antidepressants indicate that these drugs are prescribed in ways that are unlikely to be fully effective across the broad spectrum of patients. Adequate antidepressant treatment trials were most likely when psychiatrists collaborated with primary care physicians or other specialists and when SSRIs were used. C1 Massachusetts Gen Hosp, Dept Psychiat, Wang Ambulatory Care Ctr, Boston, MA 02144 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA USA. McLean Hosp, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA USA. Stanford Ctr Res Dis Prevent, Palo Alto, CA 94304 USA. RP Weilburg, JB (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Wang Ambulatory Care Ctr, Room 815,55 Fruit St, Boston, MA 02144 USA. EM jweilburg@partners.org NR 38 TC 67 Z9 67 U1 0 U2 2 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2003 VL 54 IS 9 BP 1233 EP 1239 DI 10.1176/appi.ps.54.9.1233 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 839BQ UT WOS:000222758700009 PM 12954939 ER PT J AU Shaner, A Eckman, L Roberts, LJ Fuller, T AF Shaner, A Eckman, L Roberts, LJ Fuller, T TI Feasibility of a skills training approach to reduce substance dependence among individuals with schizophrenia SO PSYCHIATRIC SERVICES LA English DT Article AB A novel treatment for persons who have both schizophrenia and substance abuse was evaluated by incorporating cognitive-behavioral drug relapse prevention strategies, into a skills training method originally developed to teach social and independent living skills to patients with schizophrenia. Thirty-four of 56 patients completed treatment and a three-month follow-up assessment. Participants learned substance abuse management skills and reported that they found the treatment relevant, useful, and satisfying, and their drug use decreased. Improvements were noted in medication adherence, Psychiatric symptoms, and quality of life. This manual-driven therapy may play an important role in the treatment of substance abuse among patients with schizophrenia. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Dept Vet Affairs Puget Sound Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. RP Shaner, A (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,116A, Los Angeles, CA 90073 USA. EM andrew.shaner@med.va.gov FU NIDA NIH HHS [R01 DA 09436] NR 10 TC 19 Z9 19 U1 1 U2 4 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2003 VL 54 IS 9 BP 1287 EP 1289 DI 10.1176/appi.ps.54.9.1287 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 839BQ UT WOS:000222758700018 PM 12954948 ER PT J AU Schwartz, C Meisenhelder, JB Ma, YS Reed, C AF Schwartz, C Meisenhelder, JB Ma, YS Reed, C TI Altruistic social interest behaviors are associated with better mental health SO PSYCHOSOMATIC MEDICINE LA English DT Article DE social interest; altruism; social support; mental health; physical health; spirituality; stress; response shift ID MEDICAL OUTCOMES; NATIONAL SAMPLE; RESPONSE SHIFT; SUPPORT; STRESS; RELIABILITY; PREDICTION; VALIDITY; RELIGION; MODELS AB Objective: This study investigated whether altruistic social interest behaviors such as engaging in helping others were associated with better physical and mental health in a stratified random sample of 2016 members of the Presbyterian Church throughout the United States. Methods: Mailed questionnaires evaluated giving and receiving help, prayer activities, positive and negative religious coping, and self-reported physical and mental health. Results: Multivariate regression analysis revealed no association between giving or receiving help and physical functioning, although the sample was highly skewed toward high physical functioning. Both helping others and receiving help were significant predictors of mental health, after adjusting for age, gender, stressful life events, income, general health, positive and negative religious coping, and asking God for healing (R-2 = .27). Giving help was a more important predictor of better reported mental health than receiving help, and feeling overwhelmed by others' demands was an independent predictor of worse mental health in the adjusted model. Significant predictors of giving help included endorsing more prayer activities, higher satisfaction with prayer life, engaging in positive religious coping, age, female gender, and being a church elder. Frequency of prayer and negative religious coping were not related to giving help. Conclusions: Helping others is associated with higher levels of mental health, above and beyond the benefits of receiving help and other known psychospiritual, stress, and demographic factors. The links between these findings and response shift theory are discussed, and implications for clinical interventions and future research are described. C1 Univ Massachusetts, Sch Med, Dept Med, Div Prevent & Behav Med, Worcester, MA 01605 USA. Massachusetts Gen Hosp, MGH Inst Hlth Profess, Charlestown, MA USA. RP Schwartz, C (reprint author), 31 Mitchell Rd, Concord, MA 01742 USA. OI Ma, Yunsheng/0000-0003-2317-3716 NR 49 TC 97 Z9 100 U1 3 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD SEP-OCT PY 2003 VL 65 IS 5 BP 778 EP 785 DI 10.1097/01.PSY.0000079378.39062.D4 PG 8 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 727QQ UT WOS:000185670300009 PM 14508020 ER PT J AU Huffman, JC Stern, TA Harley, RM Lundy, NA AF Huffman, JC Stern, TA Harley, RM Lundy, NA TI The use of DBT skills in the treatment of difficult patients in the general hospital SO PSYCHOSOMATICS LA English DT Article ID BORDERLINE PERSONALITY-DISORDER; DIALECTICAL BEHAVIOR-THERAPY; MANAGEMENT; CARE; SUGGESTIONS; DIAGNOSIS; ILLNESS C1 Massachusetts Gen Hosp, Psychiat Consultat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Psychiat Consultat Serv, 55 Fruit St,Warren 605, Boston, MA 02114 USA. NR 24 TC 6 Z9 6 U1 1 U2 3 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SEP-OCT PY 2003 VL 44 IS 5 BP 421 EP 429 DI 10.1176/appi.psy.44.5.421 PG 9 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 717HF UT WOS:000185081100011 PM 12954919 ER PT J AU Wittram, C Mark, EJ McLoud, TC AF Wittram, C Mark, EJ McLoud, TC TI CT-Histologic correlation of the ATS/ERS 2002 classification of idiopathic interstitial pneumonias SO RADIOGRAPHICS LA English DT Article; Proceedings Paper CT 88th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY DEC 01-06, 2002 CL CHICAGO, ILLINOIS SP Radiol Soc N Amer DE bronchiolitis obliterans organizing pneumonia; 60.79; lung CT 60.12118; lung interstitial disease 60.79; pneumonia acute interstitial 60.7921; pneumonia desquamative interstitial 60.793 pneumonia lymphocytic interstitial 60.795; pneumonia nonspecific interstitial and; fibrosis; 60.795 pneumonia usual interstitial 60.792 ID THIN-SECTION CT; OBLITERANS ORGANIZING PNEUMONIA; HIGH-RESOLUTION CT; CRYPTOGENIC FIBROSING ALVEOLITIS; LUNG-DISEASE; PULMONARY FIBROSIS; RESPIRATORY BRONCHIOLITIS; DIFFERENTIAL-DIAGNOSIS; CLINICAL-SIGNIFICANCE; FEATURES AB The American Thoracic Society and the European Respiratory Society 2002 classification defines the histologic patterns that provide the basis for a clinico-radiologic-pathologic diagnosis of an idiopathic interstitial pneumonia. Idiopathic pulmonary fibrosis is the clinical term for usual interstitial pneumonia, the characteristic histologic pattern is interstitial fibrosis with temporal heterogeneity, and the radiologic pattern is basal and subpleural areas of ground-glass and reticular attenuation and honeycomb pattern. Nonspecific interstitial pneumonia has cellular or fibrosing patterns of chronic inflammation with temporal homogeneity; the radiologic pattern is subpleural and basal areas of ground-glass and reticular attenuation. Lymphoid interstitial pneumonia results from lymphocyte interstitial infiltration; CT demonstrates ground-glass attenuation and nodular interlobular septal thickening. Respiratory bronchiolitis-associated interstitial lung disease is characterized by bronchiolocentric alveolar macrophage accumulation; CT shows centrilobular ground-glass attenuation. Desquamative interstitial pneumonia is characterized by alveolar macrophage accumulation with predominantly lower zone ground-glass attenuation seen on CT scans. Cryptogenic organizing pneumonia is characterized radiologically by peribronchial ground-glass attenuation and subpleural consolidation. Acute interstitial pneumonia is the clinical term for idiopathic diffuse alveolar damage; the exudative phase is characterized radiologically by diffuse ground-glass attenuation and dependent consolidation, with the additional feature of lung architectural distortion in the organizing phase. Ideally, diagnosis of an idiopathic interstitial pneumonia should be rendered only after all clinico-radiologic-pathologic data have been reviewed. (C)RSNA, 2003. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Wittram, C (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Fonders Bldg 202, Boston, MA 02114 USA. NR 54 TC 24 Z9 31 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP-OCT PY 2003 VL 23 IS 5 BP 1057 EP 1071 DI 10.1148/rg.235035702 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 721TR UT WOS:000185333900001 PM 12975500 ER PT J AU Titton, RL Gervais, DA Hahn, PF Harisinghani, MG Arellano, RS Mueller, PR AF Titton, RL Gervais, DA Hahn, PF Harisinghani, MG Arellano, RS Mueller, PR TI Urine leaks and urinomas: Diagnosis and imaging-guided intervention SO RADIOGRAPHICS LA English DT Article; Proceedings Paper CT 88th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY DEC 01-06, 2002 CL CHICAGO, ILLINOIS SP Radiol Soc N Amer DE genitourinary system, infection; genitourinary system, injuries; surgery, complications; ureter, stenosis or obstruction; urine, extravasation; urinoma ID URETERAL INJURIES; RENAL TRAUMA; MANAGEMENT AB Urine leaks from the kidney, ureter, bladder, and urethra most commonly result from trauma. Urinomas may be occult initially and may lead to complications such as abscess formation and electrolyte imbalances if not promptly diagnosed and appropriately managed. Radiologists play a key role in diagnosing urine leaks and determining their cause and extent. Contrast material-enhanced computed tomography (CT) with delayed imaging, CT cystography, and retrograde urethrography are the diagnostic imaging studies of choice. Studies such as intravenous pyelography, antegrade and retrograde pyelography, renal scintigraphy, and imaging-guided needle aspiration may play complementary diagnostic roles. In some instances, the role of the radiologist ends with the diagnosis of urine leaks, after which patients are treated conservatively or perhaps surgically. Uncomplicated renal urine leaks, extraperitoneal urinary bladder rupture, and type 1 urethral injuries are generally managed conservatively. Urine leaks that require more extensive, imaging-guided treatment can usually be managed safely and effectively with a combination of percutaneous urinoma drainage catheters, percutaneous nephrostomy catheters, ureteral stents, and bladder drainage. In the appropriate setting, use of these management options may reduce urinoma-related complications and limit or totally eliminate the need for urologic surgery. (C)RSNA, 2003. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Gervais, DA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. NR 15 TC 73 Z9 78 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP-OCT PY 2003 VL 23 IS 5 BP 1133 EP 1147 DI 10.1148/rg.235035029 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 721TR UT WOS:000185333900006 PM 12975505 ER PT J AU Maher, MM McNamara, AM MacEneaney, PM Sheehan, SJ Malone, DE AF Maher, MM McNamara, AM MacEneaney, PM Sheehan, SJ Malone, DE TI Abdominal aortic aneurysms: Elective endovascular repair versus conventional surgery - Evaluation with evidence-based medicine techniques SO RADIOLOGY LA English DT Article DE aneurysm, abdominal; aneurysm, surgery; aorta, grafts and prostheses; aorta, interventional procedures; technology assessment ID OPEN SURGICAL REPAIR; LIFE TABLE METHOD; USERS GUIDES; INTERVENTIONAL RADIOLOGY; COST-EFFECTIVENESS; CLINICAL-PRACTICE; AAA TREATMENT; HELP ME; MIDTERM; ARTICLE AB Purpose: To use evidence-based techniques to compare elective open surgical repair of abdominal aortic aneurysms with endovascular repair by means of stent placement. Materials and Methods: A focused clinical question formed the basis of a literature search. Evidence-based criteria were used to appraise and assign a "level of evidence" to retrieved articles. The following data were determined from the best studies: systemic, local, and/or vascular complications; graft failure rates; blood loss; mortality; length of intensive care and/or hospital stay; mid- and long-term outcomes; cost of endovascular repair versus that of surgery; and eligibility for endovascular repair. Absolute risk reductions and/or increases and numbers needed to treat or harm were calculated. Results: The best current evidence came from 22 studies, which showed that there is slight, if any, difference between mortality rates of endovascular repair and surgery. Hospital and/or intensive care stay is shorter, blood loss less, and systemic complications fewer (numbers needed to treat, two to 12) with endovascular repair. Some authors reported a significant increase in local and/or vascular complications with endovascular repair (numbers needed to harm, two to six). Graft failure is significantly more common with endovascular repair (numbers needed to harm four), and substantive adjunctive interventions are needed. Endovascular repair is more expensive than surgery. Conclusion: Elective endovascular repair has short-term benefits compared with surgery. There is slight, if any, difference in mortality. Endovascular repair costs more than surgery. At follow-up, surgical grafts performed better. (C) RSNA, 2003. C1 St Vincents Univ Hosp, Dept Radiol, Dublin 4, Ireland. Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. St Vincents Univ Hosp, Dept Vasc Surg, Dublin 4, Ireland. RP Malone, DE (reprint author), St Vincents Univ Hosp, Dept Radiol, Elm Pk, Dublin 4, Ireland. NR 74 TC 30 Z9 30 U1 1 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 2003 VL 228 IS 3 BP 647 EP 658 DI 10.1148/radiol.2283012185 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 715HT UT WOS:000184966400011 PM 12869684 ER PT J AU Stahl, JE Furie, KL Gleason, S Gazelle, GS AF Stahl, JE Furie, KL Gleason, S Gazelle, GS TI Stroke: Effect of implementing an evaluation and treatment protocol compliant with NINDS recommendations SO RADIOLOGY LA English DT Article DE brain, infarction; cost-effectiveness; economics, medical; radiology and radiologists, socioeconomic issues; tissue plasminogen activator (TPA) ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN-ACTIVATOR; QUALITY-OF-LIFE; RANDOMIZED CONTROLLED TRIAL; COST-EFFECTIVENESS ANALYSIS; AMERICAN-HEART-ASSOCIATION; HEALTH-CARE-PROFESSIONALS; SPECIAL-WRITING-GROUP; THROMBOLYTIC THERAPY; INTRACRANIAL ANEURYSMS AB Purpose: To evaluate-relative to routine clinical practice-the potential cost-effectiveness of implementing a strategy compliant with National Institute of Neurological Disorders and Stroke (NINDS) recommendations for care of patients presenting with signs and symptoms of acute ischemic stroke. Materials and Methods: A discrete-event simulation model of the process of stroke care from symptom onset through administration of tissue plasminogen activator (tPA) was constructed. A literature review was performed to determine process times, performance of computed tomography (CT), health outcomes, and cost estimates. The following were compared: (a) a "base-case" strategy determined on the basis of findings in the literature and (b) a NINDS-compliant strategy (ie, evaluation by emergency physician in less than 10 minutes, interpretation of CT scans within 45 minutes, and administration of tPA within I hour after presentation). Strategies were compared with regard to cost and effectiveness. Sensitivity analyses were performed for all relevant cost, timing, and resource parameters. Outcomes of concern were quality-adjusted life years and number of patients treated within a 3-hour therapeutic window. Results: The NINDS-compliant strategy resulted in an average quality-adjusted life years value of 3.64, versus 3.63 for the base case, at an approximate cost of $434 per patient. The NINDS-compliant strategy increased the proportion of treatable patients from 1.4% to 3.7% and remained cost-effective for expenditures of up to $450 per patient. Assuming base-case parameters are used, increasing the number of CT scanners from two to eight raised the proportion of treatable patients to 1.5%. Increasing the number of available neurologists from four to eight raised the proportion to 1.44%. Reducing the time from stroke onset to emergency department arrival by 30 minutes raised the proportion to up to 7.7%. Conclusion: Applying NINDS recommendations is potentially cost-effective, although reducing the time from stroke onset to emergency department arrival may be even more so. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Trinity Coll, Dept Econ, Hartford, CT 06106 USA. RP Stahl, JE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Zero Emerson Bldg,Suite 2H, Boston, MA 02114 USA. RI bashzar, salman/R-5748-2016 NR 80 TC 41 Z9 41 U1 1 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 2003 VL 228 IS 3 BP 659 EP 668 DI 10.1148/radiol.2283021557 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 715HT UT WOS:000184966400012 PM 12954888 ER PT J AU Harisinghani, MG Gervais, DA Maher, MM Cho, CH Hahn, PF Varghese, J Mueller, PR AF Harisinghani, MG Gervais, DA Maher, MM Cho, CH Hahn, PF Varghese, J Mueller, PR TI Transgluteal approach for percutaneous drainage of deep pelvic abscesses: 154 cases SO RADIOLOGY LA English DT Article; Proceedings Paper CT 87th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 25-30, 2001 CL CHICAGO, ILLINOIS SP Radiol Soc N Amer DE abscess, percutaneous drainage; pelvic organs, abscess; pelvic organs, interventional procedures ID 250 ABDOMINAL ABSCESSES; FLUID COLLECTIONS AB PURPOSE: To assess the effectiveness of a computed tomographic (CT) image-guided transgluteal approach for percutaneous drainage of deep pelvic abscesses as an alternative to surgical drainage. MATERIALS AND METHODS: The medical records of 140 patients who underwent percutaneous CT-guided transgluteal drainage of 154 deep pelvic abscesses were reviewed to determine the origins, location, and size of the abscesses; volume of initial aspirate; organisms identified in fluid culture; duration of catheter drainage; incidence of catheter-related pain and procedure-related complications; and short- and long-term outcomes. The resultant data were analyzed with a Fisher exact test for difference in the incidence of postprocedural catheter-site pain between transpiriformis and infrapiriformis approaches. RESULTS: The origins of the pelvic abscesses included postoperative fluid collection (n = 115), perforating appendicitis (n = 6), diverticulitis (n = 16), tubo-ovarian inflammation (n = 5), Crohn disease (n = 10), and internal bowel fistula due to irradiation (n = 2). The abscesses were 4-12 cm in diameter. The volume of the aspirate was 5-310 mL. Laboratory cultures of the aspirate grew mixed flora, but the organism most frequently isolated was Escherichia coli. Catheters were removed after a mean of 8 days. In 134 (96%) of 140 patients, there was complete resolution of the abscess following transgluteal drainage, without subsequent surgery. In six of 140 (4%) patients, incomplete resolution necessitated subsequent surgery for postoperative fluid collection (n = 3), diverticulitis (n = 2), or perforating appendicitis (n = 1). Complications of transgluteal drainage were rare and included hemorrhage in three (2%) of the 140 patients. There was no procedure-related mortality. A transpiriformis approach was significantly more likely to be associated with postprocedural pain (P < .001) than was an infrapiriformis approach. CONCLUSION: Percutaneous CT-guided transgluteal drainage is a safe and effective alternative to surgery for deep pelvic abscesses. Major complications are rare. (C) RSNA, 2003. C1 Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Harisinghani, MG (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. NR 15 TC 55 Z9 58 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 2003 VL 228 IS 3 BP 701 EP 705 DI 10.1148/radiol.2283020924 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 715HT UT WOS:000184966400017 PM 12881584 ER PT J AU Anzai, Y Piccoli, CW Outwater, EK Stanford, W Bluemke, DA Nurenberg, P Saini, S Maravilla, KR Feldman, DE Schmiedl, UP Brunberg, JA Francis, IR Harms, SE Som, PM Tempany, CM AF Anzai, Y Piccoli, CW Outwater, EK Stanford, W Bluemke, DA Nurenberg, P Saini, S Maravilla, KR Feldman, DE Schmiedl, UP Brunberg, JA Francis, IR Harms, SE Som, PM Tempany, CM TI Evaluation of neck and body metastases to nodes with ferumoxtran 10-enhanced MR imaging: Phase III safety and efficacy study SO RADIOLOGY LA English DT Article DE contrast media; iron; lymphatic system, MR; lymphatic system, neoplasms; magnetic resonance (MR), contrast enhancement ID SUPERPARAMAGNETIC IRON-OXIDE; MULTICENTER CLINICAL-TRIAL; MEDIASTINAL LYMPH-NODES; SQUAMOUS-CELL CARCINOMA; CONTRAST AGENT; NODAL METASTASES; SELECTIVE NECK; LYMPHOGRAPHY; PARTICLES; NANOPARTICLES AB PURPOSE: To determine the safety and efficacy of ferumoxtran 10-enhanced magnetic resonance (MR) imaging for diagnosis of metastases to lymph nodes and the clinical usefulness of ferumoxtran 10 in nodal staging. MATERIALS AND METHODS: One hundred fifty-two patients were injected with ferumoxtran 10. Readers independently evaluated precontrast MR images by using node size criteria and subjective assessment of other imaging features. Ferumoxtran 10-enhanced MR images were evaluated alone and paired with precontrast images for comparison. The diagnostic performances of precontrast MR size criteria and postcontrast MR imaging were evaluated with receiver operating characteristic (ROC) analysis. Lymph node signal intensity was correlated with histopathologic findings. MR imaging and histopathologic nodal stages were compared. RESULTS: Node-level sensitivity, specificity, and accuracy of precontrast MR imaging were 54%, 82%, and 68%, respectively, with node size criterion alone; 91%, 51%, and 71%, respectively, with subjective reader assessment; 85%, 85%, and 85%, respectively, with postcontrast MR imaging alone; and 83%, 77%, and 80%, respectively, with paired pre- and postcontrast MR imaging. Compared with size criteria, subjective reader assessment had higher sensitivity but substantially lower specificity. Areas under the ROC curve for pre- and postcontrast MR imaging were 0.76 and 0.83, respectively. Nonmetastatic nodes had significantly lower signal intensity than metastatic nodes on postcontrast T2-weighted MR images (P <.001). Postcontrast nodal staging was significantly more accurate than precontrast nodal staging (P <.01). Headache, back pain, vasodilatation, and urticaria each occurred in 6% of patients. CONCLUSION: Ferumoxtran 10-enhanced MR imaging was safe and effective and facilitated improved diagnostic performance. Use of iron oxide-enhanced MR imaging increased the positive predictive value by 20% and the accuracy by 14% compared with reader assessment. Differentiating patients with no nodal metastatic involvement was more reliable with ferumoxtran 10-enhanced MR imaging than with precontrast MR imaging. C1 Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Univ Texas, SW Med Sch, Dallas, TX 75230 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Michigan, Ctr Med, Ann Arbor, MI 48109 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, New York, NY USA. Mt Sinai Hosp, New York, NY 10029 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Robert Wood Johnson Univ Hosp, New Brunswick, NJ USA. Illinois Masonic Med Ctr, Chicago, IL 60657 USA. Stanford Univ, Ctr Med, Stanford, CA 94305 USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Univ N Carolina, Sch Med, Chapel Hill, NC 27514 USA. Univ Florida, Coll Med, Gainesville, FL 32610 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. Cooper Univ Med Ctr, Camden, NJ USA. Washington Univ, Sch Med, Edward Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. Adv Magnet, Cambridge, MA USA. Bracco Diagnost, Princeton, NJ USA. Dana Farber Canc Inst, Gillette Ctr Womens Canc, Boston, MA 02115 USA. Lahey Clin Fdn, Burlington, MA 01805 USA. Univ Alabama, Birmingham, AL 35294 USA. RP Anzai, Y (reprint author), Univ Washington, Sch Med, Dept Radiol, Box 357115,1959 NE Pacific St, Seattle, WA 98195 USA. OI Bluemke, David/0000-0002-8323-8086 NR 32 TC 155 Z9 158 U1 1 U2 6 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 2003 VL 228 IS 3 BP 777 EP 788 DI 10.1148/radiol.2283020892 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 715HT UT WOS:000184966400027 PM 12954896 ER PT J AU Gulliford, S Jiang, S Rowbottom, C Come, D Shirato, H Webb, S AF Gulliford, S Jiang, S Rowbottom, C Come, D Shirato, H Webb, S TI An adaptive method for predicting respiratory-induced motion in lung tumours using an artificial neural network SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 7th Biennial Meeting on Physics and Radiation Technology for Clinical Radiotherapy CY SEP 13-18, 2003 CL Geneva, SWITZERLAND SP ESTRO C1 Ipswich Hosp, Suffolk Oncol Ctr, Ipswich, Suffolk, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. Christie Hosp NHS Trust, N Western Med Phys Dept, Manchester M20 4BX, Lancs, England. Univ Reading, Dept Comp Sci, Reading, Berks, England. Hokkaido Univ, Sch Med, Dept Radiol, Sapporo, Hokkaido 060, Japan. Royal Marsden NHS Trust, Joint Dept Phys, London, England. RI Shirato, Hiroki/A-7068-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD SEP PY 2003 VL 68 SU 1 BP S55 EP S55 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 879IA UT WOS:000225708400155 ER PT J AU Kuefer, KH Monz, M Scherrer, A Alonso, F Trinkaus, H Bortfeld, T Thieke, C AF Kuefer, KH Monz, M Scherrer, A Alonso, F Trinkaus, H Bortfeld, T Thieke, C TI Real-time inverse planning using a precomputed multi-criteria plan database SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 7th Biennial Meeting on Physics and Radiation Technology for Clinical Radiotherapy CY SEP 13-18, 2003 CL Geneva, SWITZERLAND SP ESTRO C1 Fraunhofer ITWM, Kaiserslautern, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. DKFZ, Heidelberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD SEP PY 2003 VL 68 SU 1 BP S76 EP S76 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 879IA UT WOS:000225708400214 ER PT J AU Paganetti, H Suit, HD AF Paganetti, H Suit, HD TI Significance of RBE variations in proton therapy SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 7th Biennial Meeting on Physics and Radiation Technology for Clinical Radiotherapy CY SEP 13-18, 2003 CL Geneva, SWITZERLAND SP ESTRO C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD SEP PY 2003 VL 68 SU 1 BP S80 EP S80 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 879IA UT WOS:000225708400225 ER PT J AU Thieke, C Bortfeld, T Kuefer, KH AF Thieke, C Bortfeld, T Kuefer, KH TI New optimization concepts in inverse treatment planning SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 7th Biennial Meeting on Physics and Radiation Technology for Clinical Radiotherapy CY SEP 13-18, 2003 CL Geneva, SWITZERLAND SP ESTRO C1 Deutsch Krebsforschungszentrum, Dept Med Phys, D-6900 Heidelberg, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. Fraunhofer Inst Ind Math, Dept Optimizat, Kaiserslautern, Germany. NR 0 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD SEP PY 2003 VL 68 SU 1 BP S2 EP S2 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 879IA UT WOS:000225708400008 ER PT J AU Thieke, C Bortfeld, T Niemierko, A Kuefer, KH Nill, S AF Thieke, C Bortfeld, T Niemierko, A Kuefer, KH Nill, S TI Multicriteria optimization in inverse radiotherapy planning SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 7th Biennial Meeting on Physics and Radiation Technology for Clinical Radiotherapy CY SEP 13-18, 2003 CL Geneva, SWITZERLAND SP ESTRO C1 Deutsch Krebsforschungszentrum, Dept Phys Med, D-6900 Heidelberg, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. Fraunhofer Inst Ind Math, Dept Optimizat, Kaiserslautern, Germany. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD SEP PY 2003 VL 68 SU 1 BP S44 EP S44 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 879IA UT WOS:000225708400126 ER PT J AU McKeever, VM Huff, ME AF McKeever, VM Huff, ME TI A diathesis-stress model of posttraumatic stress disorder: Ecological, biological, and residual stress pathways SO REVIEW OF GENERAL PSYCHOLOGY LA English DT Article ID CHILD SEXUAL ABUSE; VIETNAM VETERANS; HIPPOCAMPAL VOLUME; PHYSICAL ABUSE; RISK FACTOR; COMBAT EXPERIENCE; CAUSAL MODEL; DEPRESSION; PTSD; VICTIMIZATION AB The symptoms captured within the contemporary diagnostic definition of posttraumatic stress disorder (PTSD) have been studied for more than 100 years. Yet, even with increasingly advanced discoveries regarding the etiology of PTSD, a comprehensive and up-to-date etiological model that incorporates both medical and psychological research has not been described and systematically studied. The diathesis-stress model proposed here consolidates existing medical and psychological research data on etiological factors associated with PTSD into 3 causal pathways: residual stress, ecological, and biological. In combination, these pathways illuminate how PTSD might develop and who might be at higher risk for developing the disorder. Research and treatment implications related to the diathesis-stress model are discussed. C1 VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. Univ Oregon, Counseling Psychol & Human Serv, Eugene, OR 97403 USA. RP McKeever, VM (reprint author), VAMC, Natl Ctr PTSD, 116B-3,150 S Huntington Ave, Boston, MA 02130 USA. EM Victoria.McKeever@med.va.gov NR 69 TC 36 Z9 36 U1 3 U2 14 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1089-2680 J9 REV GEN PSYCHOL JI Rev. Gen. Psychol. PD SEP PY 2003 VL 7 IS 3 BP 237 EP 250 DI 10.1037/1089-2680.7.3.237 PG 14 WC Psychology, Multidisciplinary SC Psychology GA 721TN UT WOS:000185333600002 ER PT J AU Rull, M Clayburne, G Sieck, M Schumacher, HR AF Rull, M Clayburne, G Sieck, M Schumacher, HR TI Intra-articular corticosteroid preparations: different characteristics and their effect during inflammation induced by monosodium urate crystals in the rat subcutaneous air pouch SO RHEUMATOLOGY LA English DT Article DE corticosteroids; betamethasone; prednisolone; triamcinolone; rat air pouch; monosodium urate crystals; inflammation; tophi ID TRIAMCINOLONE HEXACETONIDE; SYNOVIAL-FLUID; INJECTION; OSTEOARTHRITIS; HYDROCORTISONE; OSTEONECROSIS; INVIVO; KNEE AB Objective. To examine the effects of three commonly used intra-articular depot corticosteroid preparations tested in a rat air pouch model and their effect against monosodium urate (MSU) crystal-induced inflammation. Rheumatologists use intra-articular corticosteroid preparations to relieve pain and inflammation of acute monoarthritis without really knowing their effects on the synovial fluid and membrane or the differences between distinct preparations. This work compares the effect of three commonly used corticosteroid preparations in vivo, showing that they behave differently. Methods. A subcutaneous air pouch was formed in male Sprague-Dawley rats. A first group of 6-day-old air pouches were injected with 10 ml of 6 mg/ml normal saline solution, 6 mg/ml betamethasone containing both depot betamethasone acetate and soluble betamethasone phosphate (Celestone) in 9 ml of normal saline solution, 20 mg/ml of prednisolone tebutate (Hydeltra) in 9 ml of normal saline solution or 20 mg/ml of triamcinolone hexacetonide (Aristospan) in 9 ml of normal saline solution. A second group (group 2) of air pouches were injected with 15 mg of synthetic MSU crystals and 24 h later they were reinjected with 1 ml of the same three corticosteroid suspensions. For each condition four rats were killed at 6, 24, 48 h and 7 days. Pouch fluid and tissue were analysed. Results. In the first 6 h after normal saline solution or corticosteroid injection into the air pouch there were mildly increased leucocyte counts in the air pouch fluid. Betamethasone-injected pouches showed no cells in the fluid after 6 h and no crystals after 24 h, triamcinolone-injected pouches still showed rare cells at 7 days. Both triamcinolone and prednisolone crystals persisted in higher numbers and lasted longer in the fluid than did betamethasone (P<0.05). In group 2 MSU crystal phagocytosis in the fluid was decreased in the betamethasone- (P<0.01), prednisolone- (P<0.003) and triamcinolone- (P<0.006) injected pouches when compared with the MSU crystal-injected pouches alone. Pouches injected with MSU crystals alone showed the most intense tissue inflammation at all times. After MSU, betamethasone-injected pouches had a rapid but mild decrease in the number of lining cells and inflammation. In contrast, triamcinolone- and prednisolone-injected pouches showed a very thin tissue with few or no vessels and almost no inflammation at 7 days. The pouches injected with MSU crystals and any of the corticoid preparations had three times more tophus-like structures and persistent crystals identified than the ones injected with MSU crystals alone. Conclusion. Each of the corticosteroid preparations by themselves produced very mild transient inflammation. The betamethasone preparation with a soluble steroid component had a quicker but milder anti-inflammatory effect on MSU crystal-induced inflammation. In contrast to the doses used, prednisolone tebutate and triamcinolone hexacetonide preparations dramatically suppressed urate crystal-induced inflammation at 7 days, but both produced atrophy and necrosis of the membrane, yielding a very thin membrane with almost no vessels. When used for MSU crystal-induced inflammation these corticosteroid preparations suppressed some aspects of inflammation but may actually promote the persistence of MSU crystals and the formation of tophi. C1 Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Philadelphia, PA 19104 USA. RP Schumacher, HR (reprint author), VAMC Arthrit Res 151K, Univ & Woodland & Ave, Philadelphia, PA 19104 USA. NR 24 TC 18 Z9 22 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD SEP PY 2003 VL 42 IS 9 BP 1093 EP 1100 DI 10.1093/rheumatology/keg305 PG 8 WC Rheumatology SC Rheumatology GA 714QA UT WOS:000184923900013 PM 12777646 ER PT J AU Kirchhoff, CH Kremer, B von Below, SH Kyrein, HJ Mosges, R AF Kirchhoff, CH Kremer, B von Below, SH Kyrein, HJ Mosges, R TI Effects of dimethindene maleate nasal spray on the quality of life in seasonal allergic rhinitis SO RHINOLOGY LA English DT Article DE allergic rhinitis; antihistamine; dimethindene; quality of life ID FLUTICASONE PROPIONATE; HEALTH-STATUS; ANTIHISTAMINES; EFFICACY; RHINOCONJUNCTIVITIS; CORTICOSTEROIDS; LEVOCABASTINE; QUESTIONNAIRE; IMPAIRMENT; LORATADINE AB Objective: To determine if the HI-receptor antagonist dimethindene maleate (DMM), topically applied, is able to improve the quality of life (QoL) in patients with seasonal allergic rhinitis better than placebo. Methods: The study was a multi-centre, randomised, placebo-controlled, double-blinded phase III trial including 157 patients. Two parallel groups received either DMM nasal spray or placebo for 2 weeks. Patients answered 5 QoL questionnaires (Rhinoconjunctivitis QoL Questionnaire (LQ-AR), Munich Life Dimension List (MLDL), Profile of Mood States (POMS), 2 Visual Analogue Scales (VAS-QoL, VAS-GES)) on days 1, 4, 8, and 15. Results: QoL improved significantly in all scales and groups. Statistically significant differences between groups were achieved in the sub-scales LQ-AR Eye Symptoms and Daily Activities, MLDL Total, POMS Depression and Energy, VAS-QoL and VAS-General Health. All differences favoured the DMM group and were present initially but disappeared in visit 4, except MLDL Total and POMS Energy. Almost all other scores had a better tendency of DMM. Conclusion: A significant improvement of QoL was found in both groups. Only weak differences between groups (in favour of DMM) were found. There are several reasons explaining this outcome, mainly the rainy weather during the study period (mean weather index 10-20% less sunny than in previous seasons). C1 Univ Cologne, Inst Med Stat Informat & Epidemiol, D-50924 Cologne, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA USA. Univ Hosp Maastricht, Dept Otorhinolaryngol Head & Neck Surg, Maastricht, Netherlands. Novartis Consumer Hlth, Munich, Germany. RP Mosges, R (reprint author), Univ Cologne, Inst Med Stat Informat & Epidemiol, D-50924 Cologne, Germany. NR 39 TC 1 Z9 1 U1 0 U2 0 PU INT RHINOLOGIC SOC PI UTRECHT PA UNIV MEDICAL CENTER UTRECHT, RM G05 127, DEPT OTORHINOL, HEIDELBERGLAAN 100, 3584 CX UTRECHT, NETHERLANDS SN 0300-0729 J9 RHINOLOGY JI Rhinology PD SEP PY 2003 VL 41 IS 3 BP 159 EP 166 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA 746ZX UT WOS:000186781500005 PM 14579656 ER PT J AU Michaels, PJ Fishbein, MC Colvin, RB AF Michaels, PJ Fishbein, MC Colvin, RB TI Humoral rejection of human organ transplants SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Review ID RENAL-ALLOGRAFT REJECTION; CORONARY-ARTERY-DISEASE; ANTI-HLA ANTIBODIES; DONOR LIVER-TRANSPLANTATION; PORCINE ENDOTHELIAL-CELLS; ACUTE VASCULAR REJECTION; HUMAN CARDIAC ALLOGRAFTS; C4D COMPLEMENT FRAGMENT; CLASS-I MOLECULES; HEART-TRANSPLANTATION AB Although T-cell mediated rejection has remained the most common form of acute rejection, Immoral rejection now accounts for a substantial fraction in patients with kidney or heart allografts, and probably causes the majority of acute graft losses. The frequency, variously estimated at 20-30%, is attributed to improved methods of detection, including staining for C4d in tissues, which is more sensitive and specific than histological features. Detection of circulating anti-donor reactive antibody (usually to donor HLA antigens) confirms the diagnosis. The clinico-pathological entity of acute humoral rejection is well accepted in kidney and increasingly in heart transplantation. Recent evidence points to a new category of chronic humoral rejection, which accounts for about 60% of chronic rejection of kidneys. Importantly, the hallmark of Immoral rejection, C4d, can be detected in the grafts before development of histological evidence of chronic rejection. Humoral rejection is generally not responsive to the usual anti-T cell immunosuppressive agents, but small, non-controlled trials suggest humoral rejection can be reversed with plasmapheresis, intravenous immunoglobulin, anti-CD20 and other treatments, all of which deserve formal clinical evaluation. Prophylaxis for chronic rejection is expected to require donor-specific serological monitoring and protocol biopsies. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Univ Calif Los Angeles, Ctr Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. RP Colvin, RB (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 225, Boston, MA 02114 USA. NR 122 TC 95 Z9 110 U1 1 U2 10 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PD SEP PY 2003 VL 25 IS 2 BP 119 EP 140 DI 10.1007/s00281-003-0139-x PG 22 WC Immunology; Pathology SC Immunology; Pathology GA 726LB UT WOS:000185599600003 PM 12955463 ER PT J AU Abdollahi, A Lipson, K Han, X Krempien, R Trinh, T Weber, KJ Hahnfeldt, P Hlatky, L Howlett, AR Debus, J Huber, PE AF Abdollahi, A Lipson, K Han, X Krempien, R Trinh, T Weber, KJ Hahnfeldt, P Hlatky, L Howlett, AR Debus, J Huber, PE TI SU5416 and SU6668 attenuate the angiogenic effects of radiation-induced tumor cell growth factor production and amplify the direct anti-endothelial action of radiation in vitro SO STRAHLENTHERAPIE UND ONKOLOGIE LA English DT Meeting Abstract CT 9th Congress of the Deutschen-Gesellschaft-fur-Radioonkologie CY 2003 CL ESSEN, GERMANY SP Deutschen Gesellsh Radioonkologie C1 Univ Heidelberg, Strahlenklin DKFZ, Heidelberg, Germany. Sugen Inc, San Francisco, CA USA. Harvard Univ, Sch Med, DFCI, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0179-7158 J9 STRAHLENTHER ONKOL JI Strahlenther. Onkol. PD SEP PY 2003 VL 179 IS 9 BP 658 EP 658 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 720VW UT WOS:000185281400020 ER PT J AU Schmahmann, JD AF Schmahmann, JD TI Vascular syndromes of the thalamus SO STROKE LA English DT Review DE cerebral cortex; cognition; diaschisis; language; memory; thalamus ID ARTERY TERRITORY INFARCTION; TRANSIENT GLOBAL AMNESIA; POSTERIOR COMMUNICATING ARTERY; SUPERIOR TEMPORAL SULCUS; MEDIAL PULVINAR NUCLEUS; PSYCHIC SELF-ACTIVATION; RHESUS-MONKEY; CORTICOTHALAMIC CONNECTIONS; PREFRONTAL CORTEX; MACACA-FASCICULARIS AB Background-This article reviews the anatomy, connections, and functions of the thalamic nuclei, their vascular supply, and the clinical syndromes that result from thalamic infarction. Summary of Review-Thalamic nuclei are composed of 5 major functional classes: reticular and intralaminar nuclei that subserve arousal and nociception; sensory nuclei in all major domains; effector nuclei concerned with motor function and aspects of language; associative nuclei that participate in high-level cognitive functions; and limbic nuclei concerned with mood and motivation. Vascular lesions destroy these nuclei in different combinations and produce sensorimotor and behavioral syndromes depending on which nuclei are involved. Tuberothalamic territory strokes produce impairments of arousal and orientation, learning and memory, personality, and executive function; superimposition of temporally unrelated information; and emotional facial paresis. Paramedian infarcts cause decreased arousal, particularly if the lesion is bilateral, and impaired learning and memory. Autobiographical memory impairment and executive failure result from lesions in either of these vascular territories. Language deficits result from left paramedian lesions and from left tuberothalamic lesions that include the ventrolateral nucleus. Right thalamic lesions in both these vascular territories produce visual-spatial deficits, including hemispatial neglect. Inferolateral territory strokes produce contralateral hemisensory loss, hemiparesis and hemiataxia, and pain syndromes that are more common after right thalamic lesions. Posterior choroidal lesions result in visual field deficits, variable sensory loss, weakness, dystonia, tremors, and occasionally amnesia and language impairment. Conclusions-These vascular syndromes reflect the reciprocal cerebral cortical-thalamic connections that have been interrupted and provide insights into the functional properties of the thalamus. C1 Massachusetts Gen Hosp, Dept Neurol, VBK 915, Boston, MA 02114 USA. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol, VBK 915, Fruit St, Boston, MA 02114 USA. NR 140 TC 272 Z9 287 U1 3 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2003 VL 34 IS 9 BP 2264 EP 2278 DI 10.1161/01.STR.0000087786.38997.9E PG 15 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 718FW UT WOS:000185135300056 PM 12933968 ER PT J AU Marino, M Lisi, S Pinchera, A Marcocci, C Menconi, F Morabito, E Macchia, M Sellari-Franceschini, S McCluskey, RT Chiovato, L AF Marino, M Lisi, S Pinchera, A Marcocci, C Menconi, F Morabito, E Macchia, M Sellari-Franceschini, S McCluskey, RT Chiovato, L TI Glycosaminoglycans provide a binding site for thyroglobulin in orbital tissues of patients with thyroid-associated ophthalmopathy SO THYROID LA English DT Article ID GRAVES-OPHTHALMOPATHY; THYROTROPIN RECEPTOR; RAT THYROGLOBULIN; MEGALIN GP330; EYE DISEASE; HYPERTHYROIDISM; IDENTIFICATION; PATHOGENESIS; EXPRESSION; THERAPY AB The presence of thyroglobulin (Tg) in orbital tissues of patients with thyroid-associated ophthalmopathy (TAO) supports a role of Tg in TAO pathogenesis. To search for Tg-binding sites in orbital tissues, because Tg is a heparin-binding protein, we investigated its binding to glycosaminoglycans (GAGs) that are abundant in orbital tissues: chondroitin sulfate B (CSB) and C (CSC) and hyaluronic acid (HA). Both in solid phase and solution phase assays purified human Tg bound to GAGs. In solid-phase assays, binding was increased by coincubation with heparin or GAGs in solution, or with an antibody against a Tg heparin-binding sequence (Arg2489-Glu2503), possibly suggesting crosslinking of Tg molecules induced by GAGs or by the presumably bivalent antibody. Orbital tissue extracts from TAO patients that contained Tg were subjected to high-salt treatment, which resulted in separation of Tg from GAGs, as observed by column chromatography. After separation from GAGs. the Tg in orbital tissue extracts acquired the ability to bind to immobilized CSB, and heparin enhanced binding, resembling the findings with purified human Tg. Therefore, we conclude that GAGs provide binding sites for Tg in orbital tissues, which may explain the presence of Tg in orbital tissues of patients with TAO. C1 Univ Pisa, Dept Endocrinol, I-56124 Pisa, Italy. Univ Pisa, Dept Chem, I-56124 Pisa, Italy. Univ Pisa, Dept Neurosci, I-56124 Pisa, Italy. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Pavia, IRCCS, Endocrine Unit, Salvatore Maugeri Fdn, I-27100 Pavia, Italy. RP Marino, M (reprint author), Univ Pisa, Dept Endocrinol, Via Paradisa 2f, I-56124 Pisa, Italy. NR 24 TC 8 Z9 8 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD SEP PY 2003 VL 13 IS 9 BP 851 EP 859 DI 10.1089/105072503322401041 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 729KW UT WOS:000185773300004 PM 14588099 ER PT J AU Rigotti, NA Regan, S Moran, SE Wechsler, H AF Rigotti, NA Regan, S Moran, SE Wechsler, H TI Students' opinion of tobacco control policies recommended for US colleges: a national survey SO TOBACCO CONTROL LA English DT Article ID BINGE-DRINKING; CIGARETTE USE; YOUNG-ADULTS; HEALTH; ALCOHOL C1 Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Cambridge, MA 02138 USA. RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU NHLBI NIH HHS [K24-HL04440] NR 21 TC 40 Z9 40 U1 0 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PD SEP PY 2003 VL 12 IS 3 BP 251 EP 256 DI 10.1136/tc.12.3.251 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 741ZR UT WOS:000186490700012 PM 12958381 ER PT J AU Huang, WY Kruskall, M Uhl, L Shaz, BH AF Huang, WY Kruskall, M Uhl, L Shaz, BH TI The use of recombinant activated factor VII in three patients with central nervous system hemorrhages associated with factor VIII deficiency SO TRANSFUSION LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-of-Blood-Banks CY NOV 01-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Blood Banks C1 BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2003 VL 43 IS 9 SU S BP 5A EP 5A PG 1 WC Hematology SC Hematology GA 716TT UT WOS:000185045700016 ER PT J AU Dzik, WH AF Dzik, WH TI Emily Cooley Lecture 2002: Transfusion safety in the hospital SO TRANSFUSION LA English DT Editorial Material ID PATHOLOGISTS Q-PROBES; NEW-YORK-STATE; ERRORS; PERFORMANCE; GUIDELINES; SURGERY; AUDIT; CELL C1 Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. RP Dzik, WH (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, JJ-224,55 Fruit St, Boston, MA 02114 USA. NR 27 TC 85 Z9 87 U1 0 U2 1 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2003 VL 43 IS 9 BP 1190 EP 1199 DI 10.1046/j.1537-2995.2003.00523.x PG 10 WC Hematology SC Hematology GA 713KD UT WOS:000184855900003 PM 12919420 ER PT J AU Moberg, KH Hariharan, IK AF Moberg, KH Hariharan, IK TI Big things from a little RNA SO TRENDS IN CELL BIOLOGY LA English DT Article ID CAENORHABDITIS-ELEGANS/; CELL-PROLIFERATION; DROSOPHILA; APOPTOSIS; REAPER; HID; GENE; DEGRADATION; MICRORNA; DIAP1 AB In a recent study, Brennecke and colleagues show that bantam, a previously elusive Drosophila gene that promotes tissue growth, encodes a microRNA. The bantam microRNA regulates cell number in vivo and inhibits cell death by binding to the mRNA of the pro-apoptotic gene hid. These findings demonstrate that a single, tiny Drosophila RNA can regulate organ and organism size and link the nascent field of microRNA function to the study of pathways that coordinate cell death, cell growth and cell proliferation during the development of metazoan organisms. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. RP Hariharan, IK (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13 St, Boston, MA 02129 USA. NR 21 TC 6 Z9 9 U1 0 U2 4 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 SEP PY 2003 VL 13 IS 9 BP 455 EP 457 DI 10.1016/S0962-8924(03)00168-5 PG 3 WC Cell Biology SC Cell Biology GA 721HU UT WOS:000185311600003 PM 12946623 ER PT J AU Lieberman, J Song, E Lee, SK Shankar, P AF Lieberman, J Song, E Lee, SK Shankar, P TI Interfering with disease: opportunities and roadblocks to harnessing RNA interference SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID DOUBLE-STRANDED-RNA; HEPATITIS-B-VIRUS; SHORT HAIRPIN RNAS; MAMMALIAN-CELLS; GENE-EXPRESSION; HIV-1 INFECTION; MESSENGER-RNA; DIRECTED INHIBITION; FUNCTIONAL-ANATOMY; SYNTHETIC SIRNAS AB RNA interference (RNAi) is an evolutionarily conserved mechanism for silencing gene expression by targeted degradation of mRNA. Short double-stranded RNAs, known as small interfering RNAs (siRNA), are incorporated into an RNA-induced silencing complex that directs degradation of RNA containing a homologous sequence. RNAi has been shown to work in mammalian cells, and can inhibit viral infection and control tumor cell growth in vitro. Recently, it has been shown that intravenous injection of siRNA or of plasmids expressing sequences processed to siRNA can protect mice from autoimmune and viral hepatitis. RNAi could provide an exciting new therapeutic modality for treating infection, cancer, neurodegenerative disease and other illnesses. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015 NR 94 TC 81 Z9 86 U1 1 U2 4 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 SEP PY 2003 VL 9 IS 9 BP 397 EP 403 DI 10.1016/S1471-4914(03)00143-6 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 726BK UT WOS:000185578000006 PM 13129706 ER PT J AU Conde, FA Aronson, WJ AF Conde, FA Aronson, WJ TI Risk factors for male osteoporosis SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE androgen deprivation therapy; prostate cancer; osteoporosis; orchiectomy; gonadotropin-releasing hormone agonists ID ANDROGEN DEPRIVATION THERAPY; BONE-MINERAL DENSITY; PROSTATE-CANCER; ELDERLY-MEN; HORMONE AGONISTS; HIP FRACTURE; WOMEN; CARCINOMA; DETERMINANTS; ORCHIECTOMY AB Hypogonadism from long-term androgen deprivation therapy (ADT), either by bilateral orchiectomy or administration of gonadotropin-releasing hormone (GnRH) agonists, causes significant and accelerated bone loss that may increase the risk of bone fractures in men with prostate cancer. Recent reports, as well as new data from our institution, have shown a high prevalence of pre-existing osteopenia and osteoporosis in men with prostate cancer before receiving ADT, and this is of great concern because of the risk of further bone loss during ADT. Data from these studies suggest the urgent need for clinical guidelines for screening, prevention, and treatment of these cases. This article reviews the prevalence and risk factors associated with osteoporosis in men and addresses risk factors in men with prostate cancer not receiving ADT. Considerations for the patient selection and timing of bone densitometry will also be discussed. (C) 2003 Elsevier Inc. All rights reserved. C1 W Los Angeles VA Healthcare Ctr, Dept Nursing, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. RP Aronson, WJ (reprint author), W Los Angeles VA Healthcare Ctr, Dept Nursing, Los Angeles, CA USA. NR 39 TC 17 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN O I JI Urol. Oncol.-Semin. Orig. Investig. PD SEP-OCT PY 2003 VL 21 IS 5 BP 380 EP 383 DI 10.1016/S1078-1439(03)00109-1 PG 4 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 755UT UT WOS:000187430400013 PM 14670549 ER PT J AU Sanghani, MV Schultz, D Tempany, CM Titelbaum, D Renshaw, AA Loffredo, M Cote, K McMahon, B D'Amico, AV AF Sanghani, MV Schultz, D Tempany, CM Titelbaum, D Renshaw, AA Loffredo, M Cote, K McMahon, B D'Amico, AV TI Quantifying the change in endorectal magnetic resonance imaging-defined tumor volume during neoadjuvant androgen suppression therapy in patients with prostate cancer SO UROLOGY LA English DT Article ID TRANSRECTAL ULTRASOUND; COIL; CARCINOMA; MORPHOLOGY; PREDICTOR; TRIAL AB Objectives. To quantify the changes seen in the endorectal magnetic resonance imaging (erMRI)-defined prostate volume, predominant tumor volume, and secondary tumor volume during neoadjuvant total androgen suppression (TAS). Methods. Between July 1997 and April 2001, 152 consecutive patients with clinical Stage T1b-T3cNXMO prostate cancer were treated with 6 months of TAS and external beam radiotherapy. erMRI was conducted before and after 2 months of neoadjuvant TAS. The median values and percentage of changes in the erMRI-measured prostate volume and primary and secondary tumor volumes during neoadjuvant TAS were calculated and compared, using the Wilcoxon matched-pairs signed-rank method, for the patients overall and stratified by pretreatment risk group. Results. All patients had a significant decline in their erMRI-defined median prostate volume (36.6 versus 25.7 cm(3), P < 0.0001) during 2 months of neoadjuvant TAS. The median primary tumor volume decreased significantly in the intermediate-risk (0.77 versus 0.52 cm(3), P < 0.0001) and high-risk (2.48 versus 0.83 cm(3), P < 0.0001) patients. The median secondary tumor volume approached a significant decline in only the high-risk patients (0.45 versus 0.31 cm(3), p = 0.15). Fourteen percent of patients had an increase in their primary tumor volume during neoadjuvant TAS. Conclusions. The erMRI-defined primary and secondary tumor volumes generally decreased in the study population during neoadjuvant TAS. However, 14% of patients had an increase in their primary tumor volume during androgen suppression therapy. The clinical significance of this awaits further study. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Millersville Univ Pennsylvania, Dept Math, Millersville, PA 17551 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Shields MRI, Dept Radiol, Fall River, MA USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,Lower Level 2, Boston, MA 02115 USA. NR 21 TC 12 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 0090-4295 J9 UROLOGY JI Urology PD SEP PY 2003 VL 62 IS 3 BP 487 EP 491 DI 10.1016/S0090-4295(03)00463-1 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 720CA UT WOS:000185242700023 PM 12946752 ER PT J AU Koch, M Pancera, M Kwong, PD Kolchinsky, P Grundner, C Wang, LP Hendrickson, WA Sodroski, J Wyatt, R AF Koch, M Pancera, M Kwong, PD Kolchinsky, P Grundner, C Wang, LP Hendrickson, WA Sodroski, J Wyatt, R TI Structure-based, targeted deglycosylation of HIV-1 gp120 and effects on neutralization sensitivity and antibody recognition SO VIROLOGY LA English DT Article DE HIV-1; exterior envelope glycoprotein; structure; deglycosylation; neutralization; antibody binding; correlation ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 ENVELOPE GLYCOPROTEIN; N-LINKED OLIGOSACCHARIDE; SOLUBLE CD4 BINDING; MONOCLONAL-ANTIBODIES; V3 LOOP; CHEMOKINE RECEPTORS; ATOMIC-STRUCTURE; VARIABLE LOOPS; RESISTANCE AB The human immunodeficiency virus (HIV-1) exterior envelope glycoprotein, gpl20, mediates receptor binding and is the major target for neutralizing antibodies. Primary HIV-1 isolates are characteristically more resistant to broadly neutralizing antibodies, although the structural basis for this resistance remains obscure. Most broadly neutralizing antibodies are directed against functionally conserved gp120 regions involved in binding to either the primary virus receptor, CD4, or the viral coreceptor molecules that normally function as chemokine receptors. These antibodies are known as CD4 binding site (CD4BS) and CD4-induced (CD4i) antibodies, respectively. Inspection of the gp120 crystal structure reveals that although the receptor-binding regions lack glycosylation, sugar moieties lie proximal to both receptor-binding sites on gp120 and thus in proximity to both the CD4BS and the CD4i epitopes. In this study, guided by the X-ray crystal structure of gp 120, we deleted four N-linked glycosylation sites that flank the receptor-binding regions. We examined the effects of selected changes on the sensitivity of two prototypic HIV-1 primary isolates to neutralization by antibodies. Surprisingly, removal of a single N-linked glycosylation site at the base of the gp120 third variable region (V3 loop) increased the sensitivity of the primary viruses to neutralization by CD4BS antibodies. Envelope glycoprotein oligomers on the cell surface derived from the V3 glycan-deficient virus were better recognized by a CD4BS antibody and a V3 loop antibody than were the wild-type glycoproteins. Absence of all four glycosylation sites rendered a primary isolate sensitive to CD4i antibody-mediated neutralization. Thus, carbohydrates that flank receptor-binding regions on gp120 protect primary HIV-1 isolates from antibody-mediated neutralization. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NIH, Vaccine Res Ctr, Virol Lab, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Wyatt, R (reprint author), NIH, Vaccine Res Ctr, Virol Lab, Bldg 40,Room 4512, Bethesda, MD 20892 USA. FU NIAID NIH HHS [1 R21 AI-44328-02, 5 R21 AI-44328-02] NR 63 TC 135 Z9 139 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 1 PY 2003 VL 313 IS 2 BP 387 EP 400 DI 10.1016/S0042-6822(03)00294-0 PG 14 WC Virology SC Virology GA 720LC UT WOS:000185261400006 PM 12954207 ER PT J AU Chakravarti, A Zhai, GG AF Chakravarti, A Zhai, GG TI Molecular and genetic prognostic factors of prostate cancer SO WORLD JOURNAL OF UROLOGY LA English DT Review DE prostate cancer; radiotherapy; prognosis; molecular/genetic biomarkers; cell cycle; apoptosis angiogenesis; signal transduction; invasion/adhesion; tumor suppressor genes ID PREDICT PATHOLOGICAL STAGE; ENDOTHELIAL GROWTH-FACTOR; P53 PROTEIN ACCUMULATION; DISEASE-FREE SURVIVAL; DNA-PLOIDY ANALYSIS; CATHEPSIN-D LEVELS; E-CADHERIN; CELL-DEATH; RADIATION-THERAPY; SYNDECAN-1 EXPRESSION AB Prostate cancer is the most commonly diagnosed cancer in Western males, responsible for 3% of all deaths in men over 55 years of age and second only to lung cancer as a cause of cancer death. Biomarkers have become an important diagnostic tool in prostate cancer. The discovery of the serum marker prostate-specific antigen (PSA) significantly facilitated the detection and management of prostate cancer. As we enter into the post-genomics era, novel biomarkers of prostate cancer of therapeutic significance will invariably emerge. Here we review a series of existing and emerging molecular-based prognostic markers particularly with radiotherapy. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Chakravarti, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. NR 122 TC 11 Z9 11 U1 1 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0724-4983 J9 WORLD J UROL JI World J. Urol. PD SEP PY 2003 VL 21 IS 4 BP 265 EP 274 DI 10.1007/s00345-003-0362-z PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 726ML UT WOS:000185602800009 PM 12910365 ER PT J AU Cooper, DKC AF Cooper, DKC TI Porcine red blood cells as a source of blood transfusion in humans SO XENOTRANSPLANTATION LA English DT Editorial Material ID N-GLYCOLYLNEURAMINIC ACID; ALPHA-GALACTOSYL EXPRESSION; HUMAN NATURAL ANTIBODIES; HUMAN SERUM; ANTIGENS; XENOTRANSPLANTATION; ERYTHROCYTES; XENOANTIGENS; DETERMINANT; HEMOGLOBIN C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 31 TC 12 Z9 13 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2003 VL 10 IS 5 BP 384 EP 386 DI 10.1034/j.1399-3089.2003.00092.x PG 3 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 717FB UT WOS:000185074800002 PM 12950981 ER PT J AU Yamamoto, S Cooper, DKC AF Yamamoto, S Cooper, DKC TI An investigation of the effect of thalidomide on anti-gal antibody production in baboons SO XENOTRANSPLANTATION LA English DT Article DE anti-Gal antibody; mixed lymphocyte reaction; plasma cells; T cells; thalidomide; xenotransplantation ID MULTIPLE-MYELOMA; TRANSPLANTATION; BLOOD; COMBINATION; REJECTION; DEPLETION; THERAPY; CELLS AB Previous data suggest that natural anti-Galalpha1,3Gal (Gal) antibody (Ab) is produced by mature plasma cells. As thalidomide is effectively used in the treatment of patients with multiple myeloma, its effect on natural anti-Gal Ab production has been assessed in two baboons. During a 10-week course of thalidomide administration ( until it reached toxic levels in one baboon), there was no major reduction in Ab levels or in their rate of return after a course of extracorporeal immunoadsorption. A significant reduction of CD3+ cells (75%), and particularly of CD4+ cells (65 to 95%), was measured in the blood by flow cytometry. This was associated with general hyporesponsiveness on mixed lymphocyte reactivity in one baboon, but not in the other. Thalidomide would appear to have little effect on the production of natural Ab, but these observations lend some support to previous work by others indicating that thalidomide may suppress the cellular response to an allograft or xenograft. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149,13th St, Boston, MA 02129 USA. FU PHS HHS [1PO1 A145897] NR 23 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2003 VL 10 IS 5 BP 470 EP 474 DI 10.1034/j.1399-3089.2003.00064.x PG 5 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 717FB UT WOS:000185074800011 PM 12950990 ER PT J AU Yamada, K Yazawa, K Kamono, C Shimizu, A Moran, S Nuhn, M Teranishi, K Vagefi, P Prather, R Forsberg, EJ Hawley, R Schuurman, HJ Awwad, M Greenstein, J Fishman, J Cooper, DKC Sykes, M Sachs, DH Yamada, K AF Yamada, K Yazawa, K Kamono, C Shimizu, A Moran, S Nuhn, M Teranishi, K Vagefi, P Prather, R Forsberg, EJ Hawley, R Schuurman, HJ Awwad, M Greenstein, J Fishman, J Cooper, DKC Sykes, M Sachs, DH Yamada, K TI An initial report of alpha-Gal deficient pig-to-baboon renal xenotransplantation: Evidence for the benefit of co-transplanting vascularized donor thymic tissue SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT 7th Congress of the International-Xenotransplantation-Association CY 2003 CL GLASGOW, SCOTLAND SP Int Xenotransplantat Assoc C1 Transplantat Biol Res Ctr, Charlestown, MA USA. Immerge BioTherapeut Inc, Charlestown, MA USA. Univ Missouri, Columbia, MO 65211 USA. Infigen Inc, De Forest, WI USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2003 VL 10 IS 5 BP 480 EP 480 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 717FB UT WOS:000185074800016 ER PT J AU Houser, SL Kuwaki, K Knosalla, C Dor, FJMF Gollackner, B Cheng, J Schuurmann, HJ Cooper, DKC AF Houser, SL Kuwaki, K Knosalla, C Dor, FJMF Gollackner, B Cheng, J Schuurmann, HJ Cooper, DKC TI Thrombotic microangiopathy and necrosis in pig-to-baboon cardiac xenografts SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT 7th Congress of the International-Xenotransplantation-Association CY 2003 CL GLASGOW, SCOTLAND SP Int Xenotransplantat Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Transplantat Biol Res Ctr, Charlestown, MA USA. Immerge BioTherapeut Inc, Charlestown, MA USA. Massachusetts Gen Hosp, TBRC, Boston, MA 02114 USA. RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2003 VL 10 IS 5 BP 481 EP 481 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 717FB UT WOS:000185074800020 ER PT J AU Koulmanda, M Papas, KK Qipo, A Wu, H Smith, RN Weir, GC Auchincloss, H Colton, CK AF Koulmanda, M Papas, KK Qipo, A Wu, H Smith, RN Weir, GC Auchincloss, H Colton, CK TI Islet oxygen consumption rate as a predictor of in vivo efficacy post-transplantation SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT 7th Congress of the International-Xenotransplantation-Association CY 2003 CL GLASGOW, SCOTLAND SP Int Xenotransplantat Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2003 VL 10 IS 5 BP 484 EP 484 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 717FB UT WOS:000185074800033 ER PT J AU Shimizu, A Yamada, K Barth, RN Cheng, J Yamamoto, S Kamano, C Yazawa, K Schuurman, HJ Sachs, DH Colvin, RB AF Shimizu, A Yamada, K Barth, RN Cheng, J Yamamoto, S Kamano, C Yazawa, K Schuurman, HJ Sachs, DH Colvin, RB TI Progressive acute humoral xenograft rejection is characterized by microangiopathic glomerulopathy in pig to baboon kidney xenografts SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT 7th Congress of the International-Xenotransplantation-Association CY 2003 CL GLASGOW, SCOTLAND SP Int Xenotransplantat Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Immerge BioTherapeut, Charlestown, MA USA. RI Barth, Rolf/B-2542-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2003 VL 10 IS 5 BP 489 EP 489 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 717FB UT WOS:000185074800054 ER PT J AU Patience, C Wood, J Quinn, G Suling, K Cina, R Huang, C Scobie, L Onions, D Fishman, J Schuurman, HJ AF Patience, C Wood, J Quinn, G Suling, K Cina, R Huang, C Scobie, L Onions, D Fishman, J Schuurman, HJ TI The human-tropic PERV transmission phenotype of miniature swine is determined by exogenous virus SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT 7th Congress of the International-Xenotransplantation-Association CY 2003 CL GLASGOW, SCOTLAND SP Int Xenotransplantat Assoc C1 Immerge BioTherapeut Inc, Charlestown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2003 VL 10 IS 5 BP 491 EP 491 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 717FB UT WOS:000185074800061 ER PT J AU Koulmanda, M Qipo, A Smith, RN Auchincloss, H AF Koulmanda, M Qipo, A Smith, RN Auchincloss, H TI Xenograft survival of human and pig islet transplants in nonobese diabetic (NOD) mice SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT 7th Congress of the International-Xenotransplantation-Association CY 2003 CL GLASGOW, SCOTLAND SP Int Xenotransplantat Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2003 VL 10 IS 5 BP 517 EP 517 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 717FB UT WOS:000185074800161 ER PT J AU Kuwaki, K Tseng, YL Dor, FJMF Houser, S Prabharasuth, D Alt, A Hawley, R Prather, R Forsberg, EJ Shimizu, A Yamada, K Sachs, DH Schuurman, HJ Awwad, M Cooper, DKC AF Kuwaki, K Tseng, YL Dor, FJMF Houser, S Prabharasuth, D Alt, A Hawley, R Prather, R Forsberg, EJ Shimizu, A Yamada, K Sachs, DH Schuurman, HJ Awwad, M Cooper, DKC TI Initial results of xenotransplantation (Tx) in baboons using hearts from 1,3-galactosyltransferase gene-knockout (GT-KO) pigs SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT 7th Congress of the International-Xenotransplantation-Association CY 2003 CL GLASGOW, SCOTLAND SP Int Xenotransplantat Assoc C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Immerge BioTherapeut Inc, Charlestown, MA USA. Univ Missouri, Columbia, MO 65211 USA. Infingen Inc, De Forest, WI USA. RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2003 VL 10 IS 5 BP 526 EP 526 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 717FB UT WOS:000185074800198 ER PT J AU Kuwaki, K Knosalla, C Dor, FJMF Tseng, YL Gollackner, B Houser, S Cooper, DKC AF Kuwaki, K Knosalla, C Dor, FJMF Tseng, YL Gollackner, B Houser, S Cooper, DKC TI Troponin-T levels as a predictor of graft dysfunction in pig-to-baboon heterotopic heart transplantation SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT 7th Congress of the International-Xenotransplantation-Association CY 2003 CL GLASGOW, SCOTLAND SP Int Xenotransplantat Assoc C1 Transplantat Biol Res Ctr, Charlestown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2003 VL 10 IS 5 BP 527 EP 527 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 717FB UT WOS:000185074800200 ER PT J AU Surman, OS Hertl, M AF Surman, OS Hertl, M TI Liver donation: donor safety comes first SO LANCET LA English DT Editorial Material ID TRANSPLANTATION C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Serv, Boston, MA 02114 USA. RP Surman, OS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 10 TC 21 Z9 22 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD AUG 30 PY 2003 VL 362 IS 9385 BP 674 EP 675 DI 10.1016/S0140-6736(03)14239-0 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 716NH UT WOS:000185034800002 PM 12957084 ER PT J AU Hisamatsu, T Suzuki, M Podolsky, DK AF Hisamatsu, T Suzuki, M Podolsky, DK TI Interferon-gamma augments CARD4/NOD1 gene and protein expression through interferon regulatory factor-1 in intestinal epithelial cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; INFLAMMATORY-BOWEL-DISEASE; INVASIVE SHIGELLA-FLEXNERI; FAMILY-MEMBER; TNF-ALPHA; ACTIVATION; NOD2; BACTERIAL; TRANSCRIPTION; RECOGNITION AB Although intestinal epithelial cells appear to be functionally hyporesponsive to normal intestinal flora, human intestinal epithelial cells can respond to enteroinvasive bacteria and induce an inflammatory response. This initial inflammatory response leads to the recruitment of polymorphonuclear leukocytes to the affected site in vitro and in vivo. CARD4/NOD1 is a potential cytosolic receptor for peptidoglycan in mammalian cells that resembles pathogen-resistant proteins of plants. In this context, CARD4/NOD1 is a candidate for a recognition protein of intracellular bacteria or peptidoglycan in intestinal epithelial cells. In this study, we demonstrate that CARD4/NOD1 is constitutively expressed in intestinal epithelial cell lines and isolated primary intestinal epithelial cells. Interferon-gamma (IFNgamma), which is a potent pro-inflammatory cytokine in intestinal mucosal inflammation, activates CARD4/NOD1 mRNA transcription in a time- and dose-dependent manner and results in augmentation of CARD4/NOD1 protein in SW480 cells. Promoter analysis of CARD4/NOD1 indicates that interferon regulatory factor-1 (IRF-1) binding motif (-791 to -782) is essential for the effect of IFNgamma. Nuclear extracts from SW480 cells treated with IFNgamma show specific binding of oligonucleotides corresponding to this IRF-1-binding motif, which was supershifted by anti-IRF-1 antibody in electrophoretic mobility shift assay. Overexpression of IRF-1 protein activates the CARD4/NOD1 promoter but not the deletion mutant of the IRF-1-binding site in a co-transfection assay of IRF-1 expression plasmid with CARD4/NOD1 promoter. These studies suggest that the Th1 cytokine, IFNgamma, activates CARD4/NOD1 transcription and regulate innate immune mechanisms in the condition of intestinal mucosal inflammation. C1 Massachusetts Gen Hosp, Dept Med, Ctr Study Inflammatory Bowel Dis, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Dept Med, Ctr Study Inflammatory Bowel Dis, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK41557, DK43351, DK53304] NR 32 TC 67 Z9 70 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 29 PY 2003 VL 278 IS 35 BP 32962 EP 32968 DI 10.1074/jbc.M304355200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 714FN UT WOS:000184901800059 PM 12813035 ER PT J AU Entingh, AJ Taniguchi, CM Kahn, CR AF Entingh, AJ Taniguchi, CM Kahn, CR TI Bi-directional regulation of brown fat adipogenesis by the insulin receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR-I; PANCREATIC BETA-CELLS; MESSENGER-RNA; GENE-EXPRESSION; ADIPOCYTE DIFFERENTIATION; 3T3-L1 PREADIPOCYTES; GLUCOSE-UPTAKE; KNOCKOUT; FETAL; STIMULATION AB Insulin is a potent inducer of adipogenesis, and differentiation of adipocytes requires many components of the insulin signaling pathway, including the insulin receptor substrate IRS-1 and phosphatidylinositol 3-kinase (PI3K). Brown pre-adipocytes in culture exhibit low levels of insulin receptor (IR), and during differentiation there is both an increase in total IR levels and a shift in the alternatively spliced forms of IR from the A isoform (-exon 11) to the B isoform (+exon 11). Brown pre-adipocyte cell lines from insulin receptor-deficient mice exhibit dramatically impaired differentiation and an inability to regulate alternative splicing of the insulin receptor. Surprisingly, re-expression of either splice isoform of IR in the IR-deficient cells fails to rescue differentiation in these cells. Likewise, overexpression of IR in control IR1ox cells also results in inhibition of differentiation and a failure to accumulate expression of the adipogenic markers peroxisome proliferator-activated receptor gamma, Glut4, and fatty acid synthase, although cells overexpressing IR retain the ability to activate PI3K and down-regulate mitogen-activated protein kinase ( MAPK) phosphorylation. Thus, differentiation of brown adipocytes requires a timed and regulated expression of IR, and either the absence or overabundance of insulin receptors in these cells dramatically inhibits differentiation. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Cellular & Mol Physiol, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Cellular & Mol Physiol, 1 Joslin Pl, Boston, MA 02215 USA. NR 34 TC 47 Z9 48 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 29 PY 2003 VL 278 IS 35 BP 33377 EP 33383 DI 10.1074/jbc.M303056200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 714FN UT WOS:000184901800109 PM 12807888 ER PT J AU Lee, JT AF Lee, JT TI Functional intergenic transcription: a case study of the X-inactivation centre SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT Discussion Meeting of the Royal-Society on Epigenesis Versus Preformation during Mammalian Development CY FEB 19-20, 2003 CL ROYAL SOC, LONDON, ENGLAND HO ROYAL SOC DE non-coding RNA; intergenic transcription; Xite; Xist; Tsix; X inactivation ID DROSOPHILA BITHORAX COMPLEX; EMBRYONIC STEM-CELLS; ENHANCER-BLOCKING ACTIVITY; CLASS SWITCH RECOMBINATION; BETA-GLOBIN LOCUS; CHROMOSOME-INACTIVATION; XIST GENE; H19 GENE; TSIX; MOUSE AB Long known to be riddled with repetitive elements and regarded as 'junk', intergenic regions in the mammalian genome now appear to be more than incidental spacers between coding sequences. Here, I review the example of Xite, an intergenic region at the X-inactivation centre which was recently shown to regulate the X-chromosome choice decision. Xite contains a series of DNaseI-hypersensitive sites and harbours two intergenic transcription start sites. These intergenic transcription elements act at the onset of X-chromosome inactivation (XCI) to bias the selection of the active X. It has been proposed that Xite acts in cis on Tsix by promoting its persistence during XCI. Xite has also been proposed to be a candidate for the X-controlling element, a naturally occurring modifier of XCI ratios in mice and possibly also in humans. It seems likely that intergenic transcription will turn out to be a widespread phenomenon in mammals and that, more importantly, it will emerge as a significant regulatory mechanism for the expression of coding sequences. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. EM lee@frodo.mgh.harvard.edu NR 60 TC 5 Z9 5 U1 0 U2 0 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T R SOC B JI Philos. Trans. R. Soc. B-Biol. Sci. PD AUG 29 PY 2003 VL 358 IS 1436 BP 1417 EP 1423 DI 10.1098/rstb.2003.1328 PG 7 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 715CE UT WOS:000184952300020 PM 14511490 ER PT J AU Borsook, D Becerra, L AF Borsook, D Becerra, L TI Pain imaging: future applications to integrative clinical and basic neurobiology SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE fMRI; pain; analgesia; analgesics; drug discovery; brain maps ID POSITRON EMISSION TOMOGRAPHY; ANTERIOR CINGULATE CORTEX; PRIMARY SENSORY NEURONS; PHANTOM-LIMB PAIN; PRIMARY SOMATOSENSORY CORTEX; CHRONIC NEUROPATHIC PAIN; CERVICAL-SPINAL-CORD; HUMAN BRAIN ACTIVITY; CEREBRAL BLOOD-FLOW; FOS-LIKE PROTEIN AB We have entered a new era in understanding CNS circuitry involved in acute and chronic pain. The ability to objectively measure a pain or analgesic state of the brain using non-invasive methods that define neural activation provides the possibility for top-down approaches to drug discovery. These brain maps represent the specific brain state. In the future, correlations with such states and behavioral, genetic, epigenetic or other chemical markers may help define specific diagnostic tools and novel approaches to drug discovery. (C) 2003 Published by Elsevier B.V. C1 Descartes Therapeut Inc, Cambridge, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. RP Borsook, D (reprint author), Descartes Therapeut Inc, 790 Mem Dr,Suite 104, Cambridge, MA USA. NR 204 TC 12 Z9 12 U1 1 U2 5 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 AUG 28 PY 2003 VL 55 IS 8 BP 967 EP 986 DI 10.1016/S0169-409X(03)00099-1 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 719DU UT WOS:000185189000005 PM 12935940 ER PT J AU Zeitels, SM Healy, GB AF Zeitels, SM Healy, GB TI Medical progress: Laryngology and phonosurgery SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID VOCAL CORD PARALYSIS; DYE-LASER TREATMENT; ADDUCTOR SPASMODIC DYSPHONIA; LARYNGOTRACHEAL RECONSTRUCTION; MEDIALIZATION LARYNGOPLASTY; MICROLARYNGOSCOPIC SURGERY; LARYNGEAL PAPILLOMAS; CLINICAL EXPERIENCE; ARYTENOID ADDUCTION; GLOTTIC CANCER C1 Massachusetts Eye & Ear Infirm, Div Laryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Childrens Hosp, Dept Otolaryngol & Commun Disorders, Boston, MA 02115 USA. RP Zeitels, SM (reprint author), Massachusetts Eye & Ear Infirm, Div Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 93 TC 41 Z9 44 U1 0 U2 5 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 28 PY 2003 VL 349 IS 9 BP 882 EP 892 DI 10.1056/NEJMra035148 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 715JM UT WOS:000184968400011 PM 12944575 ER PT J AU Fernandez-del Castillo, CF Sahani, DV Brugge, WR Harris, NL Warshaw, AL Lauwers, GY Carter, EL AF Fernandez-del Castillo, CF Sahani, DV Brugge, WR Harris, NL Warshaw, AL Lauwers, GY Carter, EL TI A man with recurrent epigastric pain and elevated amylase levels - Lymphoplasmacytic sclerosing pancreatitis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID AUTOIMMUNE-RELATED PANCREATITIS; INFLAMMATORY PSEUDOTUMOR; STEROID-THERAPY; NATURAL-HISTORY; CHOLANGITIS; CLASSIFICATION; MUTATIONS; FIBROSIS; VARIANT; GENE C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Fernandez-del Castillo, CF (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 29 TC 15 Z9 18 U1 1 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 AUG 28 PY 2003 VL 349 IS 9 BP 893 EP 901 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 715JM UT WOS:000184968400012 PM 12944576 ER PT J AU Campagna, JA Miller, KW Forman, SA AF Campagna, JA Miller, KW Forman, SA TI Mechanisms of actions of inhaled anesthetics (vol 348, pg 2110, 2003) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Correction ID CHANNELS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Campagna, JA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 4 TC 3 Z9 3 U1 1 U2 13 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 AUG 28 PY 2003 VL 349 IS 9 BP 910 EP 910 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 715JM UT WOS:000184968400022 ER PT J AU Rosen, T AF Rosen, T TI Update on genital lesions SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID EXTRAMAMMARY PAGETS-DISEASE; CLINICAL-DIAGNOSIS; ANOGENITAL WARTS; LICHEN-SCLEROSUS; EARLY SYPHILIS; ULCER DISEASE; VITILIGO; HERPES; CREAM; VIRUS C1 Baylor Coll Med, Houston Vet Adm Med Ctr, Dermatol Serv, Houston, TX 77005 USA. RP Rosen, T (reprint author), Baylor Coll Med, Houston Vet Adm Med Ctr, Dermatol Serv, 2815 Plumb, Houston, TX 77005 USA. OI Rosen, Ted/0000-0002-5946-5529 NR 33 TC 10 Z9 10 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 27 PY 2003 VL 290 IS 8 BP 1001 EP 1005 DI 10.1001/jama.290.8.1001 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 715FA UT WOS:000184958900002 PM 12941660 ER PT J AU Wang, TJ Massaro, JM Levy, D Vasan, RS Wolf, PA D'Agostino, RB Larson, MG Kannel, WB Benjamin, EJ AF Wang, TJ Massaro, JM Levy, D Vasan, RS Wolf, PA D'Agostino, RB Larson, MG Kannel, WB Benjamin, EJ TI A risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community - The Framingham Heart Study SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RANDOMIZED CONTROLLED TRIALS; LEFT-VENTRICULAR HYPERTROPHY; ANTITHROMBOTIC THERAPY; ELDERLY POPULATION; CLINICAL-TRIALS; ISCHEMIC STROKE; ASPIRIN THERAPY; ANTICOAGULATION; PREVENTION; THROMBOEMBOLISM AB Context Prior risk stratification schemes for atrial fibrillation (AF) have been based on randomized trial cohorts or Medicare administrative databases, have included patients with established AF, and have focused on stroke as the principal outcome. Objective To derive risk scores for stroke alone and stroke or death in community-based individuals with new-onset AF. Design, Setting, and Participants Prospective, community-based, observational cohort in Framingham, Mass. We identified 868 participants with new-onset AF, 705 of whom were not treated with warfarin at baseline. Risk scores for stroke (ischemic or hemorrhagic) and stroke or death were developed with censoring when warfarin initiation occurred during follow-up. Event rates were examined in low-risk individuals, as defined by the risk score and 4 previously published risk schemes. Main Outcome Measures Stroke and the combination of stroke or death. Results During a mean follow-up of 4.0 years free of warfarin use, stroke alone occurred in 83 participants and stroke or death occurred in 382 participants. A risk score for stroke was derived that included the following risk predictors: advancing age, female sex, increasing systolic blood pressure, prior stroke or transient ischemic attack, and diabetes. With the risk score, 14.3% of the cohort had a predicted 5-year stroke rate less than or equal to7.5% (average annual rate less than or equal to1.5%), and 30.6% of the cohort had a predicted 5-year stroke rate less than or equal to10% (average annual rate less than or equal to2%). Actual stroke rates in these low-risk groups were 1.1 and 1.5 per 100 person-years, respectively. Previous risk schemes classified 6.4% to 17.3% of subjects as low risk, with actual stroke rates of 0.9 to 2.3 per 100 person-years. A risk score for stroke or death is also presented. Conclusion These risk scores can be used to estimate the absolute risk of an adverse event in individuals with AF, which may be helpful in counseling patients and making treatment decisions. C1 Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiol, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Epidemiol, Boston, MA 02215 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Div Cardiol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA. RP Benjamin, EJ (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [1K24-HL-04334, K23 HL074077-01, N01-HC-25195]; NINDS NIH HHS [5R01-NS-17950] NR 44 TC 401 Z9 411 U1 0 U2 15 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 27 PY 2003 VL 290 IS 8 BP 1049 EP 1056 DI 10.1001/jama.290.8.1049 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 715FA UT WOS:000184958900023 PM 12941677 ER PT J AU Antin, JH AF Antin, JH TI A 41-year-old woman with chronic myelogenous leukemia SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CHRONIC MYELOID-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; TYROSINE KINASE INHIBITOR; CHRONIC GRANULOCYTIC-LEUKEMIA; CYTOGENETIC CLONAL EVOLUTION; IMATINIB MESYLATE THERAPY; POLYMERASE-CHAIN-REACTION; 1ST CHRONIC PHASE; BCR-ABL C1 Dana Farber Canc Inst, Dept Med Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Antin, JH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Stem Cell Transplantat Program, 44 Binney St, Boston, MA 02115 USA. NR 66 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 27 PY 2003 VL 290 IS 8 BP 1083 EP 1090 DI 10.1001/jama.290.8.1083 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 715FA UT WOS:000184958900028 PM 12941682 ER PT J AU Borsook, D DaSilva, AFM Ploghaus, A Becerra, L AF Borsook, D DaSilva, AFM Ploghaus, A Becerra, L TI Specific and somatotopic functional magnetic resonance imaging activation in the trigeminal ganglion by brush and noxious heat SO JOURNAL OF NEUROSCIENCE LA English DT Article DE trigeminal ganglion; human; fMRI; pain; brush; heat ID POLYMODAL NOCICEPTORS; PAIN; NERVE; OXYGENATION; NEURONS; FMRI; AFFERENTS; ANATOMY; MONKEY; CELLS AB We used functional magnetic resonance imaging (fMRI) to assess activation in the trigeminal ganglion during innocuous mechanical (brush) and noxious thermal (46degreesC) stimulation of the face within the receptive fields of each of the three divisions of the trigeminal nerve in healthy volunteers. For both stimulus types, we observed signal changes only in the ipsilateral ganglion, and activation occurred somatotopically, as predicted by the known anatomical segregation of the neurons comprising the ophthalmic (V1), maxillary (V2), and mandibular (V3) divisions of the nerve. Signal decreased after brush stimuli and increased after the application of noxious heat. The abilities to detect somatotopic activation within the ganglion and to segregate non-noxious mechanical from noxious thermal stimuli suggest that fMRI will be valuable for measuring changes in the trigeminal ganglion in human models of neuropathic pain and in the clinical condition itself and may also be useful in the evaluation of pain therapies. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Radiol,Athinoula Martinos NMR Ctr, Ctr Pain Funct Neuroimaging & Therapy Res, Boston, MA 02129 USA. RP Borsook, D (reprint author), Descartes Therapeut Inc, 790 Mem Dr, Cambridge, MA 02139 USA. NR 32 TC 40 Z9 40 U1 2 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 27 PY 2003 VL 23 IS 21 BP 7897 EP 7903 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 715YH UT WOS:000185001700022 PM 12944520 ER PT J AU Perez, JM Simeone, FJ Saeki, Y Josephson, L Weissleder, R AF Perez, JM Simeone, FJ Saeki, Y Josephson, L Weissleder, R TI Viral-induced self-assembly of magnetic nanoparticles allows the detection of viral particles in biological media SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID BUILDING-BLOCKS; NMR; VIRUS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02129 USA. RP Perez, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, 149 13th St, Boston, MA 02129 USA. NR 12 TC 329 Z9 343 U1 6 U2 53 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD AUG 27 PY 2003 VL 125 IS 34 BP 10192 EP 10193 DI 10.1021/ja036409g PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 714ND UT WOS:000184919600023 PM 12926940 ER PT J AU Mezrich, JD Yamada, K Lee, RS Mawulawde, K Benjamin, LC Schwarze, ML Maloney, ME Amoah, HC Houser, SL Sachs, DH Madsen, JC AF Mezrich, JD Yamada, K Lee, RS Mawulawde, K Benjamin, LC Schwarze, ML Maloney, ME Amoah, HC Houser, SL Sachs, DH Madsen, JC TI Induction of tolerance to heart transplants by simultaneous cotransplantation of donor kidneys may depend on a radiation-sensitive renal-cell population SO TRANSPLANTATION LA English DT Article ID CARDIAC ALLOGRAFT VASCULOPATHY; MAJOR HISTOCOMPATIBILITY COMPLEX; MINIATURE SWINE; PERIPHERAL TOLERANCE; IMMUNE-MECHANISMS; TIME-COURSE; MODEL; MAINTENANCE; PREVENTION AB Background. To determine the mechanism by which cotransplantation of a donor kidney and heart allograft induces tolerance to both organs in miniature swine, we examined the renal elements responsible for tolerance induction. Methods. Recipients received 12 days of cyclosporine, and transplants were performed across a major histocompatibility complex (MHC) class I mismatch. Group 1 animals received heart transplants (n=5); group 2 animals received heart and kidney allografts with no other manipulation (n=4); group 3 animals received heart transplants and donor-specific renal parenchymal cells (n=4); group 4 animals received heart and kidney allografts from lethally irradiated donors (n=7); group 5 animals received irradiated hearts and nonirradiated kidneys (n=2); group 6 animals received nonirradiated hearts and peripheral blood leukocytes from swine MHC matched to recipients and becoming tolerant to donor antigen (n=2); group 7 animals received nonirradiated hearts and donor-specific peripheral blood monocyte cells (PBMC) (n=2). Results. Animals in group 1 developed vasculopathy and fulminant rejection by day 55. Animals in group 2 never developed vascular lesions. Parenchymal kidney cell infusion (group 3) did not prolong cardiac survival. Animals in group 4 developed arteriopathy by postoperative day (POD) 28. Group 5 recipients accepted allografts without vascular lesions. Adoptive transfer of leukocytes from tolerant swine (group 6) prolonged cardiac graft survival as much as 123 days, whereas donor PBMC infusion (group 7) did not affect cardiac survival or development of arteriopathy. Conclusions. Radiosensitive elements in kidney allograft may be responsible for tolerance induction and prevention of chronic vascular lesions in recipients of simultaneous heart and kidney allografts. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Massachusetts Gen Hosp, Dept Surg, EDR 105, Boston, MA 02114 USA. FU NHLBI NIH HHS [P01 HL18646-24, R01 HL54211-05] NR 26 TC 27 Z9 28 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 AUG 27 PY 2003 VL 76 IS 4 BP 625 EP 631 DI 10.1097/01.TP.0000079926.80833.42 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 718FU UT WOS:000185135100001 PM 12973099 ER PT J AU Makhlouf, L Duvivier-Kali, VF Bonner-Weir, S Dieperink, H Weir, GC Sayegh, MH AF Makhlouf, L Duvivier-Kali, VF Bonner-Weir, S Dieperink, H Weir, GC Sayegh, MH TI Importance of hyperglycemia on the primary function of allogeneic islet transplants SO TRANSPLANTATION LA English DT Article ID RAT ISLETS; KIDNEY CAPSULE; BLOOD-FLOW; BETA; LANGERHANS; ALLOGRAFTS; SURVIVAL; NONFUNCTION; REJECTION; HYPOXIA AB Background. Hyperglycemia has been shown to influence primary function of islet isografts. In this study, we investigated the influence of hyperglycemia on primary function of allogeneic islets transplanted into spontaneously diabetic recipients (NOD) or streptozotocin-induced diabetic mice (BALB/c). Methods. Mice with moderate, severe, or very severe hyperglycemia underwent transplantation with a marginal number of islets (350 into BALB/c mice and 700 into NOD mice). To prevent the alloimmune response, we used blockade of CD28:B7 and CD40L:CD40 costimulatory signaling pathways to determine the effect of hyperglycemia alone. Blood glucose levels of the mice were monitored after transplantation, and the grafts were assessed morphologically. Results. Transplantation of allogeneic islets into moderately hyperglycemic BALB/c mice or severely diabetic NOD mice normalized the blood glucose levels in all mice within 3 days after transplantation, demonstrating the primary function of the graft. However, primary nonfunction was observed in all animals when islet transplantation was performed into severely diabetic BALB/c mice or very severely diabetic NOD mice. When mice were treated with costimulation blockade, reversal of diabetes was observed in severely diabetic BALB/c mice 15 days after transplantation, showing that the islets could adapt to the environment and function. However, transplantation of islets into NOD mice with very severe diabetes treated with costimulation blockade did not reverse diabetes, showing that even in the absence of alloimmune responses and given an adaptation period, the islets could not function. Conclusions. This study demonstrates that severe hyperglycemia impairs islet allograft function in BALB/c and NOD mice and that successful islet allotransplantation depends on the degree of hyperglycemia in the recipient. C1 Harvard Univ, Sch Med, Lab Immunogenet & Transplantat, Renal Div,Dept Med,Brigham & Womens Hosp, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02115 USA. RP Sayegh, MH (reprint author), Harvard Univ, Sch Med, Lab Immunogenet & Transplantat, Renal Div,Dept Med,Brigham & Womens Hosp, Boston, MA 02215 USA. FU NIAID NIH HHS [P01 AI-41521]; NIDDK NIH HHS [R01 DK-50657] NR 34 TC 24 Z9 25 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD AUG 27 PY 2003 VL 76 IS 4 BP 657 EP 664 DI 10.1097/01.TP0000080881.75767.0E PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 718FU UT WOS:000185135100008 PM 12973104 ER PT J AU Koulmanda, M Qipo, A Smith, RN Kawai, T O'Neil, J Koyama, I Weir, G Auchincloss, H Strom, TB AF Koulmanda, M Qipo, A Smith, RN Kawai, T O'Neil, J Koyama, I Weir, G Auchincloss, H Strom, TB TI Islet allograft survival in diabetic monkeys after anti-CD154, DST, and sirolimus treatment SO TRANSPLANTATION LA English DT Meeting Abstract CT 9th Congress of the International-Pancreas-and-Islet-Transplant-Association CY JUL 08-11, 2003 CL DUBLIN, IRELAND SP Int Pancreas & Islet Transplant Assoc C1 Massachusetts Gen Hosp, Islet Transplantat Lab, Transplantat Unit, 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD AUG 27 PY 2003 VL 76 IS 4 SU S MA 101 BP S51 EP S51 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 718FV UT WOS:000185135200100 ER PT J AU Wijkstrom, M Kirchhof, N Clemmings, S Nakano, M Ansite, J Zhang, HJ Mueller, NJ Awwad, M Fishman, JA Schuurman, HJ Hering, BJ AF Wijkstrom, M Kirchhof, N Clemmings, S Nakano, M Ansite, J Zhang, HJ Mueller, NJ Awwad, M Fishman, JA Schuurman, HJ Hering, BJ TI Prolonged pig islet xenograft survival and function in cynomolgus monkeys immunosuppressed with basiliximab, RAD, and FTY720 SO TRANSPLANTATION LA English DT Meeting Abstract CT 9th Congress of the International-Pancreas-and-Islet-Transplant-Association CY JUL 08-11, 2003 CL DUBLIN, IRELAND SP Int Pancreas & Islet Transplant Assoc C1 Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA. Immerge BioTherapeut, Charlestown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Mueller, Nicolas/B-6864-2013 OI Mueller, Nicolas/0000-0002-1059-3191 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD AUG 27 PY 2003 VL 76 IS 4 SU S MA 75 BP S43 EP S43 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 718FV UT WOS:000185135200075 ER PT J AU Chen, EW Canto, JG Parsons, LS Peterson, ED Littrell, KA Every, NR Gibson, CM Hochman, JS Ohman, EM Cheeks, M Barron, HV AF Chen, EW Canto, JG Parsons, LS Peterson, ED Littrell, KA Every, NR Gibson, CM Hochman, JS Ohman, EM Cheeks, M Barron, HV CA Investigators Natl Registry Myocar TI Relation between hospital intra-aortic balloon counterpulsation volume and mortality in acute myocardial infarction complicated by cardiogenic shock SO CIRCULATION LA English DT Article DE mortality; balloon; myocardial infarction; shock; epidemiology ID PRACTICE GUIDELINES COMMITTEE; ASSOCIATION TASK-FORCE; ONE-YEAR SURVIVAL; GUSTO-I TRIAL; CORONARY ANGIOPLASTY; EARLY REVASCULARIZATION; AORTIC COUNTERPULSATION; ACC/AHA GUIDELINES; CLINICAL OUTCOMES; NATIONAL REGISTRY AB Background - Increasing evidence suggests an inverse relationship between outcome and the total number of invasive cardiac procedures performed at a given hospital. The purpose of the present study was to determine if a similar relationship exists between the number of intra-aortic balloon counterpulsation ( IABP) procedures performed at a given hospital per year and the in-hospital mortality rate of patients with acute myocardial infarction complicated by cardiogenic shock. Methods and Results - We analyzed data of 12 730 patients at 750 hospitals enrolled in the National Registry of Myocardial Infarction 2 from 1994 to 1998. The hospitals were divided into tertiles ( low -, intermediate -, and high - IABP volume hospitals) according to the number of IABPs performed at the given hospital per year. The median number of IABPs performed per hospital per year was 3.4, 12.7, and 37.4 IABPs at low-, intermediate-, and high-volume hospitals, respectively. Of those patients who underwent IABP, there were only minor differences in baseline patient characteristics between the 3 groups. Crude mortality rate decreased with increasing IABP volume: 65.4%, lowest volume tertile; 54.1%, intermediate volume tertile; and 50.6%, highest volume tertile ( P for trend < 0.001). This mortality difference represented 150 fewer deaths per 1000 patients treated at the high IABP hospitals. In the multivariate analysis, high hospital IABP volume for patients with acute myocardial infarction was associated with lower mortality ( OR = 0.71, 95% CI = 0.56 to 0.90), independent of baseline patient characteristics, hospital factors, treatment, and procedures such as PTCA. Conclusions - Among the myocardial infarction patients with cardiogenic shock who underwent IABP placement, mortality rate was significantly lower at high - IABP volume hospitals compared with low - IABP volume hospitals. C1 Permanente Med Grp Inc, Dept Med, Div Cardiol, Richmond, CA 94801 USA. Univ Calif San Francisco, Div Cardiol, San Francisco, CA 94143 USA. Univ Alabama, Chest Pain Ctr, Birmingham, AL USA. Univ Alabama, Ctr Outcomes & Effectiveness Res & Educ, Birmingham, AL USA. Ovat Res Grp, Seattle, WA USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Genentech Inc, Dept Med Affairs, San Francisco, CA 94080 USA. VA Puget Sound Healthcare Syst, NW HSR&D Field Program, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. NYU, Sch Med, Div Cardiol, New York, NY USA. Univ N Carolina, Dept Med, Div Cardiol, Chapel Hill, NC USA. RP Chen, EW (reprint author), Permanente Med Grp Inc, Dept Med, Div Cardiol, 901 Nevin Ave, Richmond, CA 94801 USA. NR 30 TC 74 Z9 91 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 26 PY 2003 VL 108 IS 8 BP 951 EP 957 DI 10.1161/01.CIR.000008508.59734.E4 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 715DH UT WOS:000184954900011 PM 12912817 ER PT J AU Wang, TJ Evans, JC Benjamin, EJ Levy, D LeRoy, EC Vasan, RS AF Wang, TJ Evans, JC Benjamin, EJ Levy, D LeRoy, EC Vasan, RS TI Natural history of asymptomatic left ventricular systolic dysfunction in the community SO CIRCULATION LA English DT Article DE heart failure; ventricular dysfunction; echocardiography ID CONGESTIVE-HEART-FAILURE; MYOCARDIAL-INFARCTION; EJECTION FRACTION; CLINICAL IMPLICATIONS; URBAN-POPULATION; MORTALITY; SURVIVAL; DISEASE AB Background - Information is limited regarding the rates of progression to congestive heart failure (CHF) and death in individuals with asymptomatic left ventricular systolic dysfunction (ALVD). We sought to characterize the natural history of ALVD, by studying unselected individuals with this condition in the community. Methods and Results - We studied 4257 participants ( 1860 men) from the Framingham Study who underwent routine echocardiography. The prevalence of ALVD ( visually estimated ejection fraction [EF] less than or equal to 50% without a history of CHF) was 6.0% in men and 0.8% in women. During up to 12 years of follow-up, rates of CHF among subjects with normal left ventricular systolic function ( EF > 50%, n = 4128) and ALVD ( n = 129) were 0.7 and 5.8 per 100 person-years, respectively. After adjustment for cardiovascular disease risk factors, ALVD was associated with a hazards ratio (HR) for CHF of 4.7 (95% CI 2.7 to 8.1), compared with individuals without ALVD. An elevated risk of CHF after ALVD was observed even in individuals without prior myocardial infarction or valvular disease, with an adjusted HR of 6.5 ( CI 3.1 to 13.5). Mild ALVD ( EF 40% to 50%, n = 78) and moderate-to-severe ALVD ( EF < 40%, n = 51) were associated with adjusted HRs for CHF of 3.3 ( CI 1.7 to 6.6) and 7.8 ( CI 3.9 to 15.6), respectively. ALVD was also associated with an increased mortality risk ( adjusted HR 1.6, CI 1.1 to 2.4). The median survival of ALVD subjects was 7.1 years. Conclusion - Individuals with ALVD in the community are at high risk of CHF and death, even when only mild impairment of EF is present. Additional studies are needed to define optimal therapy for mild ALVD. C1 Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Boston Med Ctr, Cardiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston Med Ctr, Dept Med, Boston, MA 02118 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [K23 HL-074077-01, K24 HL-04334-01A1, N01-HC-25195]; NINDS NIH HHS [5R01-NS-17950] NR 21 TC 255 Z9 261 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 26 PY 2003 VL 108 IS 8 BP 977 EP 982 DI 10.1161/01.CIR.0000085166.44904.79 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 715DH UT WOS:000184954900015 PM 12912813 ER PT J AU Hoffmann, U Brady, TJ Muller, J AF Hoffmann, U Brady, TJ Muller, J TI Use of new Imaging techniques to screen for coronary artery disease SO CIRCULATION LA English DT Article C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Integrat Med & Technol, Boston, MA 02114 USA. RP Hoffmann, U (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Integrat Med & Technol, 100 Charles River Plaza,Suite 400, Boston, MA 02114 USA. NR 0 TC 21 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 26 PY 2003 VL 108 IS 8 BP E50 EP E53 DI 10.1161/01.CIR.0000085363.88377.F2 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 715DH UT WOS:000184954900024 PM 12939244 ER PT J AU Irizarry, MC Hyman, BT AF Irizarry, MC Hyman, BT TI Brain isoprostanes - A marker of lipid peroxidation and oxidative stress in AD SO NEUROLOGY LA English DT Editorial Material ID ALZHEIMERS-DISEASE; IN-VIVO; F-2-ISOPROSTANES; ANTIOXIDANTS C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Irizarry, MC (reprint author), Massachusetts Gen Hosp E, Ctr Agin, Alzheimer Dis Res Unit, Bldg 114,Room 2010, Charlestown, MA 02129 USA. NR 12 TC 5 Z9 5 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 26 PY 2003 VL 61 IS 4 BP 436 EP 437 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 715CX UT WOS:000184953900003 PM 12939413 ER PT J AU Cudkowicz, ME Shefner, JM Schoenfeld, DA Brown, RH Johnson, H Qureshi, M Jacobs, M Rothstein, JD Appel, SH Pascuzzi, RM Heiman-Patterson, TD Donofrio, PD David, WS Russell, JA Tandan, R Pioro, EP Felice, KJ Rosenfeld, J Mandler, RN Sachs, GM Bradley, WG Raynor, EM Baquis, GD Belsh, JM Novella, S Goldstein, J Hulihan, J AF Cudkowicz, ME Shefner, JM Schoenfeld, DA Brown, RH Johnson, H Qureshi, M Jacobs, M Rothstein, JD Appel, SH Pascuzzi, RM Heiman-Patterson, TD Donofrio, PD David, WS Russell, JA Tandan, R Pioro, EP Felice, KJ Rosenfeld, J Mandler, RN Sachs, GM Bradley, WG Raynor, EM Baquis, GD Belsh, JM Novella, S Goldstein, J Hulihan, J CA NE ALS Consortium TI A randomized, placebo-controlled trial of topiramate in amyotrophic lateral sclerosis SO NEUROLOGY LA English DT Article ID MOTOR-NEURON DISEASE; SPINAL-CORD; GLUTAMATE; GABAPENTIN; TRANSPORT; RECOVERY; MUSCLE; RAT AB Objective: To determine if long-term topiramate therapy is safe and slows disease progression in patients with ALS. Methods: A double-blind, placebo-controlled, multicenter randomized clinical trial was conducted. Participants with ALS (n = 296) were randomized (2: 1) to receive topiramate ( maximum tolerated dose up to 800 mg/day) or placebo for 12 months. The primary outcome measure was the rate of change in upper extremity motor function as measured by the maximum voluntary isometric contraction (MVIC) strength of eight arm muscle groups. Secondary endpoints included safety and the rate of decline of forced vital capacity (FVC), grip strength, ALS functional rating scale (ALSFRS), and survival. Results: Patients treated with topiramate showed a faster decrease in arm strength (33.3%) during 12 months (0.0997 vs 0.0748 unit decline/month, p = 0.012). Topiramate did not significantly alter the decline in FVC and ALSFRS or affect survival. Topiramate was associated with an increased frequency of anorexia, depression, diarrhea, ecchymosis, nausea, kidney calculus, paresthesia, taste perversion, thinking abnormalities, weight loss, and abnormal blood clotting (pulmonary embolism and deep venous thrombosis). Conclusions: At the dose studied, topiramate did not have a beneficial effect for patients with ALS. High-dose topiramate treatment was associated with a faster rate of decline in muscle strength as measured by MVIC and with an increased risk for several adverse events in patients with ALS. Given the lack of efficacy and large number of adverse effects, further studies of topiramate at a dose of 800 mg or maximum tolerated dose up to 800 mg/day are not warranted. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Trials Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Biostat Ctr, Boston, MA USA. Upstate Med Univ, Dept Neurol, Syracuse, NY USA. Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Indiana Univ, Dept Neurol, Indianapolis, IN 46204 USA. MCP Hahnemann, Dept Neurol, Philadelphia, PA USA. Wake Forest Univ, Sch Med, Dept Neurol, Winston Salem, NC 27109 USA. Hennepin Cty Med Ctr, Dept Neurol, Minneapolis, MN 55415 USA. Lahey Clin Med Ctr, Dept Neurol, Burlington, MA 01803 USA. Univ Vermont, Coll Med, Dept Neurol, Burlington, VT USA. Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA. Univ Connecticut, Ctr Hlth, Dept Neurol, Farmington, CT USA. Carolinas Med Syst, Dept Neurol, Charlotte, NC USA. George Washington Univ Hosp, Dept Neurol, Washington, DC USA. Rhode Isl Hosp, Dept Neurol, Providence, RI USA. Univ Miami, Sch Med, Dept Neurol, Miami, FL USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Baystate Med Ctr, Dept Neurol, Springfield, MA USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, New Brunswick, NJ 08903 USA. Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. Ortho McNeil Pharmaceut Corp, Raritan, NJ USA. RP Cudkowicz, ME (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Trials Unit, 15 Parkman St,WACC 836, Boston, MA 02114 USA. RI rothstein, jeffrey/C-9470-2013 FU NCRR NIH HHS [M01RR00109, M01RR06192, M01RR07122, RR01032, RR01066]; NINDS NIH HHS [1R01NS39988, 5K08NS01896] NR 29 TC 139 Z9 143 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 26 PY 2003 VL 61 IS 4 BP 456 EP 464 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 715CX UT WOS:000184953900007 PM 12939417 ER PT J AU Silbert, LC Quinn, JF Moore, MM Corbridge, E Ball, MJ Murdoch, G Sexton, G Kaye, JA AF Silbert, LC Quinn, JF Moore, MM Corbridge, E Ball, MJ Murdoch, G Sexton, G Kaye, JA TI Changes in premorbid brain volume predict Alzheimer's disease pathology SO NEUROLOGY LA English DT Article ID HIPPOCAMPAL-FORMATION; TEMPORAL-LOBE; OLDEST-OLD; NEUROPATHOLOGY; DEMENTIA; SEVERITY; DURATION AB Objective: To assess whether changes in antemortem MRI brain volume measurements are valid predictors of subsequent Alzheimer disease (AD) pathology. Methods: Thirty-nine subjects, 15 nondemented and 24 with cognitive impairment, were followed until death. Regional postmortem measures of senile plaque (SP) and neurofibrillary tangle (NFT) severity were examined in relationship to cross-sectional and longitudinal volumetric measurements obtained from antemortem MRI. Results: Total brain volume change over time was related to the accumulation of cortical NFT. The rate of ventricular CSF volume increase was related to both cortical NFT and SP. The last hippocampal volume prior to death was related to hippocampal NFT burden; the rate of hippocampal volume atrophy was not related to hippocampal NFT pathology. These significant relationships continue to exist when all nondemented subjects are excluded from analysis. In subjects with cognitive impairment, the best predictor of cortical NFT and SP is the rate of ventricular volume increase. Excluding subjects with long duration between MRI and death did not appreciably alter results. Conclusions: MRI volumes measured over time are valid biomarkers of pathologic progression of AD across a range of antemortem clinical states. The rate of ventricular volume enlargement can be used to monitor disease progression or response to treatment in future clinical trials that are targeted at NFT and SP pathology. C1 Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Med & Preventat Med, Portland, OR USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Silbert, LC (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, CR-131,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. OI Kaye, Jeffrey/0000-0002-9971-3478 FU NCRR NIH HHS [M01 RR00334]; NIA NIH HHS [AG 08073] NR 27 TC 143 Z9 145 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 26 PY 2003 VL 61 IS 4 BP 487 EP 492 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 715CX UT WOS:000184953900012 PM 12939422 ER PT J AU Geng, Y Yu, QY Sicinska, E Das, M Schneider, JE Bhattacharya, S Rideout, WM Bronson, RT Gardner, H Sicinski, P AF Geng, Y Yu, QY Sicinska, E Das, M Schneider, JE Bhattacharya, S Rideout, WM Bronson, RT Gardner, H Sicinski, P TI Cyclin E ablation in the mouse SO CELL LA English DT Article ID MINICHROMOSOME MAINTENANCE PROTEINS; HISTONE GENE-TRANSCRIPTION; CELL-FREE SYSTEM; S-PHASE; DROSOPHILA EMBRYOGENESIS; RETINOBLASTOMA PROTEIN; DNA-REPLICATION; HUMAN CANCERS; COMPLEX; CDK2 AB E type cyclins (E1 and E2) are believed to drive cell entry into the S phase. It is widely assumed that the two E type cyclins are critically required for proliferation of all cell types. Here, we demonstrate that E type cyclins are largely dispensable for mouse development. However, endoreplication of trophoblast giant cells and megakaryocytes is severely impaired in the absence of cyclin E. Cyclin E-deficient cells proliferate actively under conditions of continuous cell cycling but are unable to reenter the cell cycle from the quiescent Go state. Molecular analyses revealed that cells lacking cyclin E fail to normally incorporate MCM proteins into DNA replication origins during G(0)-->S progression. We also found that cyclin E-deficient cells are relatively resistant to oncogenic transformation. These findings define a molecular function for E type cyclins in cell cycle reentry and reveal a differential requirement for cyclin E in normal versus oncogenic proliferation. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Oxford, Dept Cardiovasc Med, Oxford OX3 7BN, England. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Tufts Univ, Sch Vet Med, North Grafton, MA 01536 USA. Tufts Univ, Sch Vet Med, North Grafton, MA 01536 USA. Biogen Inc, Cambridge, MA 02142 USA. RP Sicinski, P (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RI Bhattacharya, Shoumo/F-4127-2010 FU NCI NIH HHS [CA83688, CA85296] NR 53 TC 466 Z9 473 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD AUG 22 PY 2003 VL 114 IS 4 BP 431 EP 443 DI 10.1016/S0092-8674(03)00645-7 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 714TD UT WOS:000184928800007 PM 12941272 ER PT J AU Harvey, KF Pfleger, CM Hariharan, IK AF Harvey, KF Pfleger, CM Hariharan, IK TI The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis SO CELL LA English DT Article ID PROTEIN-KINASE; REGULATING APOPTOSIS; TNF SUPERFAMILY; IMAGINAL DISC; JNK PATHWAY; DEGRADATION; REAPER; DIAP1; GENE; GRIM AB Establishing and maintaining homeostasis is critical to the well-being of an organism and is determined by the balance of cell proliferation and death. Two genes that function together to regulate growth, proliferation, and apoptosis in Drosophila are warts (wts), encoding a serine/threonine kinase, and salvador (sav), encoding a WW domain containing Wts-interacting protein. However, the mechanisms by which sav and wts regulate growth and apoptosis are not well understood. Here, we describe mutations in hippo (hpo), which encodes a protein kinase most related to mammalian Mst1 and Mst2. Like wts and sav, hpo mutations result in increased tissue growth and impaired apoptosis characterized by elevated levels of the cell cycle regulator cyclin E and apoptosis inhibitor DIAP1. Hpo, Sav, and Wts interact physically and functionally, and regulate DIAP1 levels, likely by Hpo-mediated phosphorylation and subsequent degradation. Thus, Hpo links Sav and Wts to a key regulator of apoptosis. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Hariharan, IK (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA95281]; NIGMS NIH HHS [GM61672] NR 40 TC 442 Z9 455 U1 5 U2 36 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD AUG 22 PY 2003 VL 114 IS 4 BP 457 EP 467 DI 10.1016/S0092-8674(03)00557-9 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 714TD UT WOS:000184928800009 PM 12941274 ER PT J AU Jiang, ZY He, ZH King, BL Kuroki, T Opland, DM Suzuma, K Suzuma, I Ueki, K Kulkarni, RN Khan, CR King, GL AF Jiang, ZY He, ZH King, BL Kuroki, T Opland, DM Suzuma, K Suzuma, I Ueki, K Kulkarni, RN Khan, CR King, GL TI Characterization of multiple signaling pathways of insulin in the regulation of vascular endothelial growth factor expression in vascular cells and angiogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMOOTH-MUSCLE-CELLS; PROTEIN-KINASE-B; GLUCOSE-TRANSPORT; DIABETIC-RETINOPATHY; CELLULAR MECHANISMS; GENE-EXPRESSION; POTENTIAL ROLE; NITRIC-OXIDE; VEGF; ACTIVATION AB The effects of insulin on vascular endothelial growth factor (VEGF) expression in cultured vascular cells and in angiogenesis were characterized. Insulin increased VEGF mRNA levels in mouse aortic smooth muscle cells from 10(-9) to 10(-7) M with an initial peak of 3.7-fold increases at 1 h and a second peak of 2.8-fold after 12 h. The first peak of VEGF expression was inhibited by LY294002, an inhibitor of phosphatidylinositol (PI)3-kinase, and by the overexpression of dominant negative forms of p85 subunit of PI 3-kinase or Akt. Inhibitors of MEK kinase, PD98059, or overexpression of dominant negative forms of Ras was ineffective. In contrast, the chronic effect of insulin on VEGF expression was partially inhibited by both LY294002 or PD98059 as well as by the overexpression of dominant negatives of PI 3-kinase or Ras. The importance of PI 3-kinase-Akt pathway on VEGF expression was confirmed in mouse aortic smooth muscle cells isolated from insulin receptor substrate -1 knockout (IRS-1(-/-)) mice that showed parallel reductions of 46-49% in insulin-stimulated VEGF expression and PI 3-kinase-Akt activation. Insulin-induced activation of PI 3-kinase-Akt on hypoxia-induced VEGF expression and neovascularization was reduced by 40% in the retina of neonatal hypoxia model using IRS-1(-/-) mice. Thus, unlike other cells, insulin can regulate VEGF expression by both IRS-1/PI 3-kinase-Akt cascade and Ras-MAPK pathways in aortic smooth muscle cells. The in vivo results provide direct evidence that insulin can modulate hypoxia-induced angiogenesis via reduction in VEGF expression in vivo. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [R01 DK53105] NR 41 TC 60 Z9 66 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 22 PY 2003 VL 278 IS 34 BP 31964 EP 31971 DI 10.1074/jbc.M303314200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 712DP UT WOS:000184782100065 PM 12775712 ER PT J AU Leopold, JA Walker, J Scribner, AW Voetsch, B Zhang, YY Loscalzo, AJ Stanton, RC Loscalzo, J AF Leopold, JA Walker, J Scribner, AW Voetsch, B Zhang, YY Loscalzo, AJ Stanton, RC Loscalzo, J TI Glucose-6-phosphate dehydrogenase modulates vascular endothelial growth factor-mediated angiogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NITRIC-OXIDE SYNTHASE; LINKED GLUCOSE-6-PHOSPHATE-DEHYDROGENASE; CELL-GROWTH; INHIBITION; PHOSPHORYLATION; OVEREXPRESSION; EXPRESSION; DEFICIENCY; GENERATION; ACTIVATION AB Glucose-6-phosphate dehydrogenase (G6PD), the first enzyme of the pentose phosphate pathway, is the principal intracellular source of NADPH. NADPH is utilized as a cofactor by vascular endothelial cell nitric-oxide synthase (eNOS) to generate nitric oxide (NO.). To determine whether G6PD modulates NO.-mediated angiogenesis, we decreased G6PD expression in bovine aortic endothelial cells using an antisense oligodeoxynucleotide to G6PD or increased G6PD expression by adenoviral gene transfer, and we examined vascular endothelial growth factor (VEGF)-stimulated endothelial cell proliferation, migration, and capillary-like tube formation. Deficient G6PD activity was associated with a significant decrease in endothelial cell proliferation, migration, and tube formation, whereas increased G6PD activity promoted these processes. VEGF-stimulated eNOS activity and NO. production were decreased significantly in endothelial cells with deficient G6PD activity and enhanced in G6PD-overexpressing cells. In addition, G6PD-deficient cells demonstrated decreased tyrosine phosphorylation of the VEGF receptor Flk-1/ KDR, Akt, and eNOS compared with cells with normal G6PD activity, whereas overexpression of G6PD enhanced phosphorylation of Flk-1/KDR, Akt, and eNOS. In the Pretsch mouse, a murine model of G6PD deficiency, vessel outgrowth from thoracic aorta segments was impaired compared with C3H wild-type mice. In an in vivo Matrigel angiogenesis assay, cell migration into the plugs was inhibited significantly in G6PD-deficient mice compared with wild-type mice, and gene transfer of G6PD restored the wild-type phenotype in G6PD-deficient mice. These findings demonstrate that G6PD modulates angiogenesis and may represent a novel angiogenic regulator. C1 Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Leopold, JA (reprint author), Boston Univ, Sch Med, Whitaker Cardiovasc Inst, 700 Albany St,CABR W-507, Boston, MA 02118 USA. FU NHLBI NIH HHS [HL04399, HL58976, HL61795, P50 HL55993] NR 28 TC 68 Z9 74 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 22 PY 2003 VL 278 IS 34 BP 32100 EP 32106 DI 10.1074/jbc.M301293200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 712DP UT WOS:000184782100081 PM 12777375 ER PT J AU Danial, NN Gramm, CF Scorrano, L Zhang, CY Krauss, S Ranger, AM Datta, SR Greenberg, ME Licklider, LJ Lowell, BB Gygi, SP Korsmeyer, SJ AF Danial, NN Gramm, CF Scorrano, L Zhang, CY Krauss, S Ranger, AM Datta, SR Greenberg, ME Licklider, LJ Lowell, BB Gygi, SP Korsmeyer, SJ TI BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis SO NATURE LA English DT Article ID ALDRICH-SYNDROME PROTEIN; GLUCOSE-HOMEOSTASIS; CELL-SURVIVAL; TOM COMPLEX; PHOSPHORYLATION; GROWTH; DEATH; GENE; BETA; CHROMATOGRAPHY AB Glycolysis and apoptosis are considered major but independent pathways that are critical for cell survival(1-4). The activity of BAD, a pro-apoptotic BCL-2 family member, is regulated by phosphorylation in response to growth/survival factors(5-8). Here we undertook a proteomic analysis to assess whether BAD might also participate in mitochondrial physiology. In liver mitochondria, BAD resides in a functional holoenzyme complex together with protein kinase A(7) and protein phosphatase 1 (PP1) catalytic units(9), Wiskott-Aldrich family member WAVE-1 as an A kinase anchoring protein(10), and glucokinase (hexokinase IV)(11). BAD is required to assemble the complex in that Bad-deficient hepatocytes lack this complex, resulting in diminished mitochondria-based glucokinase activity and blunted mitochondrial respiration in response to glucose. Glucose deprivation results in dephosphorylation of BAD, and BAD-dependent cell death. Moreover, the phosphorylation status of BAD helps regulate glucokinase activity. Mice deficient for BAD or bearing a non-phosphorylatable BAD(3SA) mutant(12) display abnormal glucose homeostasis including profound defects in glucose tolerance. This combination of proteomics, genetics and physiology indicates an unanticipated role for BAD in integrating pathways of glucose metabolism and apoptosis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Neurobiol,Div Neurosci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Taplin Biol Mass Spectrometry Facil, Boston, MA 02115 USA. RP Korsmeyer, SJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, 44 Binney St, Boston, MA 02115 USA. RI Scorrano, Luca/A-6652-2008 OI Scorrano, Luca/0000-0002-8515-8928 NR 30 TC 437 Z9 454 U1 2 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 21 PY 2003 VL 424 IS 6951 BP 952 EP 956 DI 10.1038/nature01825 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 713EH UT WOS:000184843600044 PM 12931191 ER PT J AU Takagi, J Yang, YT Liu, JH Wang, JH Springer, TA AF Takagi, J Yang, YT Liu, JH Wang, JH Springer, TA TI Complex between nidogen and laminin fragments reveals a paradigmatic beta-propeller interface SO NATURE LA English DT Article ID BASEMENT-MEMBRANE FORMATION; RECEPTOR-RELATED PROTEIN-5; EGF-LIKE MOTIF; GAMMA-1 CHAIN; BINDING-SITE; BONE-DENSITY; MODULE; GENE; PROTEOGLYCAN; LIPOPROTEIN AB Basement membranes are fundamental to tissue organization and physiology in all metazoans. The interaction between laminin and nidogen is crucial to the assembly of basement membranes(1-4). The structure of the interacting domains reveals a six-bladed Tyr-Trp-Thr-Asp (YWTD) beta-propeller domain in nidogen bound to laminin epidermal-growth-factor-like (LE) modules III3-5 in laminin (LE3-5). Laminin LE module 4 binds to an amphitheatre-shaped surface on the pseudo-6-fold axis of the beta-propeller, and LE module 3 binds over its rim. A Phe residue that shutters the water-filled central aperture of the beta-propeller, the rigidity of the amphitheatre, and high shape complementarity enable the construction of an evolutionarily conserved binding surface for LE4 of unprecedentedly high affinity for its small size(5). Hypermorphic mutations in the Wnt co-receptor LRP5 (refs 6-9) suggest that a similar YWTD beta-propeller interface is used to bind ligands that function in developmental pathways. A related interface, but shifted off-centre from the pseudo-6-fold axis and lacking the shutter over the central aperture, is used in the low-density lipoprotein receptor for an intramolecular interaction that is regulated by pH in receptor recycling(10). C1 Ctr Blood Res, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wang, JH (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. NR 30 TC 92 Z9 94 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 21 PY 2003 VL 424 IS 6951 BP 969 EP 974 DI 10.1038/nature01873 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 713EH UT WOS:000184843600048 PM 12931195 ER PT J AU Crumpacker, CS Gonzalez, RG Makar, RS Harris, NL AF Crumpacker, CS Gonzalez, RG Makar, RS Harris, NL TI Case 26-2003: A 50-year-old Colombian man with fever and seizures - Encephalitis due to herpes simplex virus type 1 infection. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID POLYMERASE CHAIN-REACTION; CEREBROSPINAL-FLUID; DIAGNOSIS; ACYCLOVIR; VIDARABINE C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Infect Dis, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Crumpacker, CS (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Infect Dis, Boston, MA 02215 USA. NR 14 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 AUG 21 PY 2003 VL 349 IS 8 BP 789 EP 796 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 713EE UT WOS:000184843300011 PM 12930932 ER PT J AU Won, JS Im, YB Key, L Singh, I Singh, AK AF Won, JS Im, YB Key, L Singh, I Singh, AK TI The involvement of glucose metabolism in the regulation of inducible nitric oxide synthase gene expression in glial cells: possible role of glucose-6-phosphate dehydrogenase and CCAAT/enhancing binding protein SO JOURNAL OF NEUROSCIENCE LA English DT Article DE C/EBP; astrocytes; glucose; G6PD; iNOS; NADPH; NF-kappa B; nitric oxide ID SMOOTH-MUSCLE-CELLS; COLONIC ADENOCARCINOMA CELLS; TRANSIENT FOCAL ISCHEMIA; FACTOR-KAPPA-B; CEREBRAL INFARCTION; MESANGIAL CELLS; BRAIN INJURY; RAT; INHIBITION; DEHYDROEPIANDROSTERONE AB In rat glial cells the lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) gene expression was enhanced by extracellular glucose concentration in a dose-dependent manner. On the other hand, 2-deoxy-D-glucose decreased the LPS-induced iNOS gene expression even in the presence of glucose (6 gm/l), suggesting that glucose metabolism is linked to the regulation of iNOS gene expression. The intracellular NADPH/NADP(+) directly correlated with the extracellular glucose concentration, and the reduction of NADPH generation via a block of glucose-6-phosphate dehydrogenase (G6PD) by treatment with dehydroepiandrosterone or the antisense DNA oligomer of G6PD mRNA resulted in the inhibition of iNOS gene expression. Gel shift assays showed that CAAT/enhancing binding protein (C/EBP), rather than AP-1 or NF-kappaB, correlated better with a glucose-dependent increase in iNOS gene expression. The induction of C/EBP DNA binding activity by LPS and glucose was attributable mainly to the increase in C/EBP-delta protein. The cotransfection with wild-type C/EBP-delta increased the iNOS promoter activity to the level achieved with a higher glucose concentration in the presence of LPS. Therefore, our results suggest that C/EBP-delta may be a critical mediator in glucose-mediated regulation of iNOS gene expression. C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol, Charleston, SC 29425 USA. Ralph Johnson Vet Affairs Med Ctr, Lab Med Serv, Charleston, SC 29425 USA. RP Singh, AK (reprint author), Med Univ S Carolina, Dept Pediat, Clin Sci Bldg,Room 316,171 Ashley Ave, Charleston, SC 29425 USA. FU NINDS NIH HHS [NS-22576, NS-37766, NS-34741, NS-40810] NR 44 TC 32 Z9 32 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 20 PY 2003 VL 23 IS 20 BP 7470 EP 7478 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 713HX UT WOS:000184852600003 PM 12930785 ER PT J AU Tawakol, A Muller, J AF Tawakol, A Muller, J TI An Angioscopic view of the effect of statin therapy on coronary artery plaques SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID INTRAVASCULAR ULTRASOUND; CARDIOVASCULAR-DISEASE; PREVENTION; PREDICTION; THROMBOSIS; DISRUPTION; TRIGGERS; RUPTURE; ANGINA C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02138 USA. RP Tawakol, A (reprint author), Massachusetts Gen Hosp, Div Cardiol, VBK 301,55 Fruit St, Boston, MA 02114 USA. NR 24 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG 20 PY 2003 VL 42 IS 4 BP 687 EP 689 DI 10.1016/S0735-1097(03)00771-X PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 712DB UT WOS:000184780600016 PM 12932602 ER PT J AU Wong, KK DePinho, RA AF Wong, KK DePinho, RA TI Walking the telomere plank into cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID MYELODYSPLASTIC SYNDROMES; T-CELLS; HEPATOCELLULAR-CARCINOMA; ULCERATIVE-COLITIS; IONIZING-RADIATION; IN-VIVO; LENGTH; DYSFUNCTION; REDUCTION; CARCINOGENESIS C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,M413, Boston, MA 02115 USA. OI wong, kwok kin/0000-0001-6323-235X NR 39 TC 7 Z9 7 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 20 PY 2003 VL 95 IS 16 BP 1184 EP 1186 DI 10.1093/jnci/djg028 PG 3 WC Oncology SC Oncology GA 713FD UT WOS:000184845700002 PM 12928335 ER PT J AU Kerlikowske, K Smith-Bindman, R Ljung, BM Grady, D AF Kerlikowske, K Smith-Bindman, R Ljung, BM Grady, D TI Evaluation of abnormal mammography results and palpable breast abnormalities SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID FINE-NEEDLE ASPIRATION; PROBABLY BENIGN LESIONS; FOLLOW-UP MAMMOGRAPHY; MULTICENTER CLINICAL-TRIAL; SCREENING MAMMOGRAPHY; CORE-NEEDLE; DIAGNOSTIC-ACCURACY; PHYSICAL-EXAMINATION; HISTOPATHOLOGIC CORRELATION; CYTOLOGIC EXAMINATION AB Background: Because approximately 1 in 10 women with a breast lump or abnormal mammography result will have breast cancer, a series of decisions must be taken by a primary care practitioner to exclude or establish a diagnosis of breast cancer among these women. Purpose: To determine the most accurate and least invasive means to evaluate an abnormal mammography result and a palpable breast abnormality. Data Source: MEDLINE search (January 1966 to March 2003) for articles and reviews describing the accuracy of clinical examination, biopsy procedures, and radiographic examination for patients with abnormal mammography results or palpable breast abnormalities. Study Selection: The authors reviewed abstracts and selected articles that provided relevant primary data. Studies were included if 1) mammography, fine-needle aspiration biopsy, or core-needle biopsy was performed before a definitive diagnosis was obtained; 2) the study sample included 100 or more women; and 3) breast cancer status was determined from histopathology review of excisional biopsy specimens, from linkage with a state cancer registry or the Surveillance, Epidemiology, and End Results program, or from clinical follow-up of 95% or more of the study sample. Data Extraction: One investigator abstracted results. Methods were evaluated for major potential biases, but methodologic scoring was not performed. Data Synthesis: Likelihood ratios for first screening mammography were 0.1 for the Breast Imaging Reporting and Data System (BI-RADS) assessment category "negative or benign finding," 1.2 for "probably benign finding," 7 for "need additional imaging evaluation," 125 for "suspicious abnormality," and 2200 for "highly suggestive of malignancy." For fine-needle aspiration biopsy of a palpable lump performed by formally trained physicians, the likelihood ratio was infinity for an assessment of "malignant," 2.6 for "atypical/suspicious," and 0.02 for "benign." When diagnostic mammography was used to evaluate a palpable lump or nonpalpable breast abnormality, the positive likelihood ratios were 5.6 and 9.4, and the negative likelihood ratios were 0.15 and 0.19, respectively. Conclusions: Women whose screening mammography results are interpreted as "suspicious abnormality" or "highly suggestive of malignancy" have a high risk for breast cancer and should undergo core-needle biopsy or needle localization with surgical biopsy. Women whose screening mammography results are interpreted as "need additional imaging evaluation" have a moderate risk for breast cancer and should undergo diagnostic mammography or ultrasonography to decide whether a nonpalpable breast lesion should be biopsied. Women whose screening mammography results are interpreted as "probably benign finding" have a low risk for breast cancer and can undergo follow-up mammography in 6 months. Either fine-needle aspiration biopsy or ultrasonography is recommended as the first diagnostic test of a palpable breast abnormality to distinguish simple cysts from solid masses. Fine-needle aspiration biopsy also allows characterization of a solid mass. Diagnostic mammography does not help determine whether a palpable breast mass should be biopsied and should not affect the decision to perform a biopsy. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Kerlikowske, K (reprint author), San Francisco Vet Affairs Med Ctr, Gen Internal Med Sect, 111A1,4150 Clement St, San Francisco, CA 94121 USA. FU NCI NIH HHS [P50 CA58207, U01CA63740] NR 96 TC 68 Z9 73 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 19 PY 2003 VL 139 IS 4 BP 274 EP 284 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 712JY UT WOS:000184795600006 PM 12965983 ER PT J AU Jensen, DM Geffen, D AF Jensen, DM Geffen, D TI Treatment of patients at high risk for recurrent bleeding from a peptic ulcer SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID UPPER GASTROINTESTINAL HEMORRHAGE; ENDOSCOPIC TREATMENT; THERAPY; COAGULATION C1 Vet Affairs Greater Los Angeles Healthcare Ctr, CURE, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, CURE, Los Angeles, CA 90073 USA. RP Jensen, DM (reprint author), Vet Affairs Greater Los Angeles Healthcare Ctr, CURE, 11301 Wilshire Blvd,Bldg 115,Room 318, Los Angeles, CA 90073 USA. NR 15 TC 9 Z9 10 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 19 PY 2003 VL 139 IS 4 BP 294 EP 295 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 712JY UT WOS:000184795600008 PM 12965985 ER PT J AU Hak, AE Stampfer, MJ Campos, H Sesso, HD Gaziano, JM Willett, W Ma, J AF Hak, AE Stampfer, MJ Campos, H Sesso, HD Gaziano, JM Willett, W Ma, J TI Plasma Carotenoids and Tocopherols and risk of myocardial infarction in a low-risk population of US male physicians SO CIRCULATION LA English DT Article DE antioxidants; cardiovascular diseases; plasma; myocardial infarction ID CORONARY HEART-DISEASE; FOOD FREQUENCY QUESTIONNAIRE; LOW-DENSITY-LIPOPROTEIN; VITAMIN-E CONSUMPTION; BETA-CAROTENE; ALPHA-TOCOPHEROL; CARDIOVASCULAR-DISEASE; ANTIOXIDANT VITAMINS; POSTMENOPAUSAL WOMEN; LUNG-CANCER AB Background-Increased intake of carotenoids and vitamin E may protect against myocardial infarction (MI). However, prospective data on blood levels of carotenoids other than beta-carotene and vitamin E (tocopherol) and risk of MI are sparse. Methods and Results-We conducted a prospective, nested case-control analysis among male physicians without prior history of cardiovascular disease who were followed for up to 13 years in the Physicians' Health Study. Samples from 531 physicians diagnosed with MI were analyzed together with samples from paired control subjects, matched for age and smoking, for 5 major carotenoids (alpha- and beta-carotene, beta-cryptoxanthin, lutein, and lycopene), retinol, and alpha- and gamma-tocopherol. Overall, we found no evidence for a protective effect against MI for higher baseline plasma levels of retinol or any of the carotenoids measured. Among current and former smokers but not among never-smokers, higher baseline plasma levels of beta-carotene tended to be associated with lower risk (P for interaction=0.02). Men with higher plasma levels of gamma-tocopherol tended to have an increased risk of MI (P for trend=0.01). Conclusions-These prospective data do not support an overall protective relation between plasma carotenoids or tocopherols and future MI risk among men without a history of prior cardiovascular disease. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. VA Boston Healthcare Syst, Boston, MA USA. Erasmus Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. Erasmus Med Ctr, Dept Biostat, Rotterdam, Netherlands. Erasmus Med Ctr, Dept Internal Med, Rotterdam, Netherlands. RP Ma, J (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA097193, CA42182, CA90598, CA78293, CA58684] NR 35 TC 55 Z9 57 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 19 PY 2003 VL 108 IS 7 BP 802 EP 807 DI 10.1161/01.CIR.0000084546.82738.89 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 712VA UT WOS:000184818000006 PM 12900344 ER PT J AU Jiao, JW Kaur, N Lu, B Reeves, SA Halvorsen, SW AF Jiao, JW Kaur, N Lu, B Reeves, SA Halvorsen, SW TI Initiation and maintenance of CNTF-Jak/STAT signaling in neurons is blocked by protein tyrosine phosphatase inhibitors SO MOLECULAR BRAIN RESEARCH LA English DT Article DE cytokine; tyrosine phosphorylation; neuroblastoma; tyrosine kinase; gp130; interferon-gamma ID CILIARY NEUROTROPHIC FACTOR; JAK-STAT PATHWAYS; GENE-EXPRESSION; NEUROBLASTOMA-CELLS; NERVOUS-SYSTEM; SYMPATHETIC NEURONS; RECEPTOR COMPONENT; NEGATIVE REGULATOR; GANGLION NEURONS; ACTIVATION AB Cytokines, including interferon-gamma and ciliary neurotrophic factor (CNTF), act in common through tyrosine kinase-based Jak/STAT signaling pathways. We found that activation of the Jak/STAT pathway by both interferon-gamma and CNTF in nerve cells was rapidly terminated by tyrosine phosphatase inhibitors. Exposure of human neuroblastoma cells, BE(2)-C, first to tyrosine phosphatase inhibitors (either phenylarsine oxide or PTP inhibitor-2) prevented Jak1, STAT1 and STAT3 activation elicited subsequently by either CNTF or interferon-gamma. In contrast, exposure of these cells to phosphatase inhibitors after initial stimulation by CNTF or interferon-gamma prevented the normal time-dependent decrease of total cellular phosphotyrosine-STAT levels as expected, while excluding already formed phosphotyrosine-STAT from the nucleus. Thus, treatment of nerve cells with a tyrosine phosphatase inhibitor blocked nuclear signal transduction. A similar inhibition of CNTF-Jak/STAT signaling was observed following tyrosine phosphatase inhibition in SH-SY5Y human neuroblastoma cells, HMN-1 mouse motor neuron-neuroblastoma hybrid cells, HepG2 human hepatoma cells and embryonic chick ciliary ganglion and retinal neurons. Expression of dominant-negative forms of the tyrosine phosphatases, SHP-1 and/or SHP-2, in BE(2)-C cells had no effect on CNTF activation of STAT or on the ability of phosphatase inhibitors to block signaling. Further, results from H-35 cells expressing gp130 receptor subunits lacking functional SHP-2 binding sites revealed normal cytokine activation of Jak and STAT that was inhibited by phosphatase inhibitors. These findings suggest a critical control for regulating the initiation of Jak/STAT signaling requiring tyrosine phosphatase activity. (C) 2003 Elsevier B.V. All rights reserved. C1 SUNY Buffalo, Dept Pharmacol & Toxicol, Sch Med & Biomed Sci, Buffalo, NY 14214 USA. Massachusetts Gen Hosp, CNS Signaling Lab, Charlestown, MA USA. RP Halvorsen, SW (reprint author), SUNY Buffalo, Dept Pharmacol & Toxicol, Sch Med & Biomed Sci, 102 Farber Hall, Buffalo, NY 14214 USA. NR 61 TC 11 Z9 11 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD AUG 19 PY 2003 VL 116 IS 1-2 BP 135 EP 146 DI 10.1016/S0169-328X(03)00286-9 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 723QZ UT WOS:000185444200015 ER PT J AU Arai, T Kasper, JS Skaar, JR Ali, SH Takahashi, C DeCaprio, JA AF Arai, T Kasper, JS Skaar, JR Ali, SH Takahashi, C DeCaprio, JA TI Targeted disruption of p185/Cul7 gene results in abnormal vascular morphogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID F-BOX PROTEINS; UBIQUITIN-LIGASE COMPLEX; CYCLIN-E; CELL-CYCLE; MUSCLE ATROPHY; S-PHASE; SCF; PROTEOLYSIS; FAMILY; DEGRADATION AB Cul1, a member of the cullin ubiquitin ligase family, forms a multiprotein complex known as SCF and plays an essential role in numerous cellular and biological activities. A Cull homologue, p185 (Cul7), has been isolated as an simian virus 40 large T antigen-binding protein. To understand the physiological role of p185, we generated mice lacking p185. p185(-/-) embryos are runted and die immediately after birth because of respiratory distress. Dermal and hypodermal hemorrhage is detected in mutant embryos at late gestational stage. p185(-/-) placentas show defects in the differentiation of the trophoblast lineage with an abnormal vascular structure. We demonstrate that p185 forms an SCF-like complex with Skp1, Rbx1, Fbw6 (Fbx29), and FAP68 (FAP48, glomulin). FAP68 has recently been identified as a gene responsible for familial glomuvenous malformation. These results suggest that p185 forms a multiprotein complex and plays an important role in vascular morphogenesis. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP DeCaprio, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA 093804, R01 CA093804] NR 40 TC 76 Z9 84 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 19 PY 2003 VL 100 IS 17 BP 9855 EP 9860 DI 10.1073/pnas.1733908100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 714QY UT WOS:000184926000042 PM 12904573 ER PT J AU Lee, AH Iwakoshi, NN Anderson, KC Glimcher, LH AF Lee, AH Iwakoshi, NN Anderson, KC Glimcher, LH TI Proteasome inhibitors disrupt the unfolded protein response in myeloma cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GLUCOSE-REGULATED PROTEINS; TRANSCRIPTION FACTOR XBP-1; RETICULUM STRESS-RESPONSE; ENDOPLASMIC-RETICULUM; ER STRESS; MULTIPLE-MYELOMA; MESSENGER-RNA; MOLECULAR-MECHANISMS; INDUCED APOPTOSIS; MAMMALIAN-CELLS AB Novel agents that target the proteasome, a proteolytic complex responsible for the degradation of ubiquitinated proteins, have demonstrated remarkable therapeutic efficacy in multiple myeloma, a plasma cell malignancy. However, the mechanism by which these compounds act remains unknown. A signaling pathway called the unfolded protein response (UPR) allows cells to handle the proper folding of proteins. The transcription factor XBP-1, a regulator of the UPR, is also required for plasma cell differentiation, suggesting a link between the UPR and plasma cell differentiation. Here we show that proteasome inhibitors target XBP-1 and the UPR in myeloma cells. Proteasome inhibitors suppress the activity of the translumenal endoplasmic reticulum endoribonuclease/kinase, IRE1alpha, to impair the generation of the active, spliced XBP-1 species and simultaneously stabilize the unspliced species that acts as a dominant negative. Myeloma cells rendered functionally deficient in XBP-1 undergo increased apoptosis in response to endoplasmic reticulum stress. Identification of compounds that target the activity of IRE1alpha/XBP-1 may yield novel therapies for the treatment of multiple myeloma and other malignancies that rely on an intact UPR. C1 Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Glimcher, LH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. FU NIAID NIH HHS [AI 32412, R01 AI032412] NR 48 TC 375 Z9 387 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 AUG 19 PY 2003 VL 100 IS 17 BP 9946 EP 9951 DI 10.1073/pnas.1334037100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 714QY UT WOS:000184926000059 PM 12902539 ER PT J AU Kraemer, BC Zhang, B Leverenz, JB Thomas, JH Trojanowski, JQ Schellenberg, GD AF Kraemer, BC Zhang, B Leverenz, JB Thomas, JH Trojanowski, JQ Schellenberg, GD TI Neurodegeneration and defective neurotransmission in a Caenorhabditis elegans model of tauopathy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MULTIPLE SYSTEM TAUOPATHY; TAU TRANSGENIC MICE; C-ELEGANS; FRONTOTEMPORAL DEMENTIA; NEUROFIBRILLARY TANGLES; PRESENILE-DEMENTIA; NERVOUS-SYSTEM; PROTEIN; MUTANTS; MUTATIONS AB Frontotemporal dementia with parkinsonism chromosome 17 type (FTDP-17) is caused by mutations in MAPT, the gene encoding tau. FTDP-17 begins with executive function deficits and other abnormal behaviors, which progress to dementia. Neurodegenerative changes include accumulation of aggregated tau as neuronal and glial fibrillary tangles. Aggregated tau is seen in numerous other neurodegenerative diseases, including Alzheimer's disease (AD). We expressed normal and FTDP-17 mutant human tau (mutations (P)301(L) and (V)337(M)) in Caenorhabditis elegans to model tauopathy disorders. Tau pan-neuronal expression caused progressive uncoordinated locomotion (Unc), characteristic of nervous system defects in worms. Subsequently, insoluble tau accumulates and both soluble and insoluble tau is phosphorylated at many of the sites hyperphosphorylated in FTDP-17, AD, and other tauopathies. Substantial neurodegeneration, seen as bulges and gaps in nerve cords followed by loss of neurons, occurs after insoluble tau begins to accumulate. Axons show vacuoles, membranous infoldings, and whorls with associated amorphous tau accumulations and abnormal tau-positive aggregates. FTDP-17 mutation lines had a more severe Unc phenotype, accumulated more insoluble tau at a younger age, were more resistant to cholinergic inhibitors, and had more severe axonal degeneration when compared with lines expressing normal tau. The Unc phenotype is caused by a presynaptic defect. Postsynaptic transmission is intact. This transgenic model will enable mechanistic dissection of tau-induced neurodegeneration and identification of genes and compounds that inhibit pathological tau formation. C1 Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Mental Illness & Parkinson Dis Res Educ & Clin Ct, Seattle, WA 98108 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. Univ Washington, Div Gerontol & Geriatr Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Div Neurogenet, Dept Neurol, Seattle, WA 98195 USA. Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Schellenberg, GD (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. FU NIA NIH HHS [AG 17583]; NIGMS NIH HHS [GM 48700, R01 GM048700] NR 37 TC 166 Z9 180 U1 2 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 19 PY 2003 VL 100 IS 17 BP 9980 EP 9985 DI 10.1073/pnas.1533448100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 714QY UT WOS:000184926000065 PM 12872001 ER PT J AU Jaiswal, S Traver, D Miyamoto, T Akashi, K Lagasse, E Weissman, IL AF Jaiswal, S Traver, D Miyamoto, T Akashi, K Lagasse, E Weissman, IL TI Expression of BCR/ABL and BCL-2 in myeloid progenitors leads to myeloid leukemias SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOCYTIC-LEUKEMIA; HEMATOPOIETIC STEM-CELLS; BCR-ABL; TRANSGENIC MICE; PHILADELPHIA-CHROMOSOME; GENE-EXPRESSION; CLONAL ORIGIN; V-ABL; APOPTOSIS AB Chronic myelogenous leukemia is a myeloproliferative disorder (MPD) that, over time, progresses to acute leukemia. Both processes are closely associated with the t(9;22) chromosomal translocation that creates the BCR/ABL fusion gene in hematopoietic stem cells (HSCs) and their progeny. Chronic myelogenous leukemia is therefore classified as an HSC disorder in which a clone of multipotent HSCs is likely to be malignantly transformed, although direct evidence for malignant t(9;22)(+) HSCs is lacking. To test whether HSC malignancy is required, we generated hMRP8p210(BCR/ABL) transgenic mice in which expression of BCR/ABL is absent in HSCs and targeted exclusively to myeloid progenitors and their myelomonocytic progeny. Four of 13 BCR/ABL transgenic founders developed a chronic MPD, but only one progressed to blast crisis. To address whether additional oncogenic events are required for progression to acute disease, we crossed hMRP8p210(BCR/ABL) mice to apoptosis-resistant hMRP8BCL-2 mice. Of 18 double-transgenic animals, 9 developed acute myeloid leukemias that were transplantable to wild-type recipients. Taken together, these data indicate that a MPD can arise in mice without expression of BCR/ABL in HSCs and that additional mutations inhibiting programmed cell death may be critical in the transition of this disease to blast-crisis leukemia. C1 Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Stem Cells Inc, Palo Alto, CA 94304 USA. RP Weissman, IL (reprint author), Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. FU NCI NIH HHS [CA 42551]; NIAID NIH HHS [5T32 AI 07290, AI07290] NR 52 TC 115 Z9 128 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 19 PY 2003 VL 100 IS 17 BP 10002 EP 10007 DI 10.1073/pnas.1633833100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 714QY UT WOS:000184926000069 PM 12890867 ER PT J AU Segal-Lieberman, G Bradley, RL Kokkotou, E Carlson, M Trombly, DJ Wang, XM Bates, S Myers, MG Flier, JS Maratos-Flier, E AF Segal-Lieberman, G Bradley, RL Kokkotou, E Carlson, M Trombly, DJ Wang, XM Bates, S Myers, MG Flier, JS Maratos-Flier, E TI Melanin-concentrating hormone is a critical mediator of the leptin-deficient phenotype SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID STEAROYL-COA DESATURASE-1; NEUROPEPTIDE-Y; BODY-WEIGHT; GENE-EXPRESSION; OBESE GENE; MICE; HYPOTHALAMUS; RESISTANCE; ADIPOCYTES; INSULIN AB Energy homeostasis is regulated by a complex network involving peripheral and central signals that determine food intake and energy expenditure. Melanin-concentrating hormone (MCH) plays an essential role in this process. Animals treated with MCH develop hyperphagia and obesity. Ablation of the prepro-MCH gene leads to a lean phenotype, as does ablation of the rodent MCH receptor, MCHR-1. MCH is overexpressed in the leptin-deficient ob/ob mouse, and we hypothesized that ablation of MCH in this animal would lead to attenuation of its obese phenotype. Compared with ob/ob animals, mice lacking both leptin and MCH (double null) had a dramatic reduction in body fat. Surprisingly, the hyperphagia of the ob/ob mouse was unaffected. Instead, leanness was secondary to a marked increase in energy expenditure resulting from both increased resting energy expenditure and locomotor activity. Furthermore, double-null mice showed improvements in other parameters impaired in ob/ob mice. Compared with ob/ob mice, double-null animals had increased basal body temperature, improved response to cold exposure, lower plasma glucocorticoid levels, improved glucose tolerance, and reduced expression of stearoyl-CoA desaturase 1 (SCD-1). These results highlight the importance of MCH in integration of energy homeostasis downstream of leptin and, in particular, the role of MCH in regulation of energy expenditure. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Maratos-Flier, E (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM emf1@joslin.harvard.edu FU NIDDK NIH HHS [P30 DK036836, DK 36836-16, P01 DK 56113, P01 DK056116, R01 DK 53978, R01 DK 56116] NR 27 TC 165 Z9 172 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 19 PY 2003 VL 100 IS 17 BP 10085 EP 10090 DI 10.1073/pnas.1633636100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 714QY UT WOS:000184926000083 PM 12897241 ER PT J AU Cooper, DKC AF Cooper, DKC TI Clinical xenotransplantion - how close are we? SO LANCET LA English DT Review ID DISSEMINATED INTRAVASCULAR COAGULATION; NUCLEAR TRANSFER; ANTIBODIES; PIGS; BABOONS; SERUM; TRANSPLANTATION; SPECIFICITY; REJECTION; PRIMATE AB Context Xenotransplantation with pig organs offers a medium-term solution to the shortage of organs available for clinical transplantation. The immunological barriers to xenotransplantation have been and remain formidable. In the early 1990s the identification of Galalpha1,3Gal (Gal) as the main target for human xenoreactive (anti pig) antibodies and the development of pigs transgenic for a human complement regulatory protein, decay accelerating factor (hDAF), were major advances. The presence of hDAF on the vascular endothelium of pig organs provided some protection against complement mediated hyperacute rejection. This protection, however, was short lived and until recently, the longest median time for organ survival that had been achieved (with combinations of biological and pharmacological immunosuppressants) in a series of pig-to-primate organ transplants was under a month. Starting point. Christopher McGregor and colleagues recently reported to the International Society of Heart and Lung Transplantation (J Heart Lung Transplant 2003: 22: S89) that, by combining the use of organs which express hDAF with the administration of a soluble Gal glycoconjugate and other immunosuppressive agents, the survival of pig hearts in baboons can be extended to a median of 76 days. McGregor is work suggests that immunological barriers to xenotransplantation are not insurmountable. Where next? The recent generation of pigs that do not express Gal epitopes (alpha1,3 galactosyltransferase gene-knockout pigs) might remove the need both for the expression of hDAF and the administration of a soluble Gal glycoconjugate. The absence of a natural antibody response will allow investigation of the cellular immune response and of any molecular incompatibilities between pig and primate that may be detrimental to graft survival. Furthermore, the absence of a humoral response may open the way for the induction of immunological tolerance (or unresponsiveness in the absence of exogenous immunosuppression) to a transplanted pig organ. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Cooper, DKC (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bldg 149-9019,13th St, Boston, MA 02129 USA. FU PHS HHS [1PO1 A145897] NR 23 TC 69 Z9 76 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD AUG 16 PY 2003 VL 362 IS 9383 BP 557 EP 559 DI 10.1016/S0140-6736(03)14118-9 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 712UW UT WOS:000184817600024 PM 12932390 ER PT J AU El-Serag, HB Talley, NJ AF El-Serag, HB Talley, NJ TI Systematic review: health-related quality of life in functional dyspepsia SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Review ID REFLUX DISEASE; DUODENAL-ULCER; IMPACT; DISORDERS; ENDOSCOPY; QUESTIONNAIRE; VALIDATION; INDEX AB Background: We performed a systematic review of the literature to compare the health-related quality of life (HRQOL) of patients with functional dyspepsia with either healthy controls or those with other diseases. Methods: Full-length published manuscripts during 1980-2002 were included if (a) patients had functional dyspepsia, but not uninvestigated dyspepsia; and (b) HRQOL was measured using a validated generic or dyspepsia-specific instruments, but not global assessment alone. Results: Twelve studies were reviewed; six fulfilled the selection criteria. None examined HRQOL among samples of the general population. None used dyspepsia-specific HRQOL instruments. Three studies contained four comparisons of HRQOL between functional dyspepsia patients and controls; two studies examined HRQOL changes in response to therapy. Two studies demonstrated a significant reduction at least in some domains of HRQOL among patients with functional dyspepsia compared to controls, while one study was negative. In general, studies that reported a decline in HRQOL Short Form-36 (SF-36) showed that changes in the physical domain were similar to those on mental domain of the SF-36. Conclusions: There is some evidence for a decrease in HRQOL in patients with moderate to severe functional dyspepsia who seek care for their symptoms; however, more studies are needed. A therapeutic response in functional dyspepsia-related pain or discomfort might result in a corresponding improvement in HRQOL. C1 Houston Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. Mayo Clin, Ctr Enter Neurosci & Translat Epidemiol Res, Rochester, MN USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr, Gastroenterol Sect, 152,2002 Holcombe Blvd, Houston, TX 77030 USA. RI Talley, nicholas/D-5399-2013 OI Talley, nicholas/0000-0003-2537-3092 NR 27 TC 76 Z9 82 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD AUG 15 PY 2003 VL 18 IS 4 BP 387 EP 393 DI 10.1046/j.0269-2813.2003.01706.x PG 7 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 717RF UT WOS:000185103200003 PM 12940923 ER PT J AU Kang, JH Pasquale, LR Willett, W Rosner, B Egan, KM Faberowski, N Hankinson, SE AF Kang, JH Pasquale, LR Willett, W Rosner, B Egan, KM Faberowski, N Hankinson, SE TI Antioxidant intake and primary open-angle glaucoma: A prospective study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Glaucoma-Society CY MAR 01-04, 2001 CL NEWPORT BEACH, CALIFORNIA SP Amer Glaucoma Soc DE antioxidants; glaucoma; open-angle; prospective studies ID CALF TRABECULAR MESHWORK; FOOD FREQUENCY QUESTIONNAIRE; ALPHA-TOCOPHEROL LEVELS; CORONARY HEART-DISEASE; TOTAL-ENERGY-INTAKE; AQUEOUS-HUMOR; DIETARY QUESTIONNAIRE; CAROTENOID DATABASE; OUTFLOW FACILITY; GANGLION-CELLS AB The relation between dietary antioxidant intake and primary open-angle glaucoma risk was examined in participants aged over 40 years in the Nurses' Health Study (n=76,200) and the Health Professionals Follow-up Study (n=40,284). They were followed biennially from 1980 and 1986, respectively, to 1996, during periods when they received an eye examination. Dietary intakes were measured repeatedly from 1980 in the Nurses' Health Study and from 1986 in the Health Professionals Follow-up Study using validated food frequency questionnaires. The authors analyzed 474 self-reported glaucoma cases confirmed by medical chart review to have primary open-angle glaucoma with visual field loss. The authors used Cox proportional hazards models for cohort-specific multivariate analyses, and results were pooled using random effects models. The pooled multivariate rate ratios for primary open-angle glaucoma comparing the highest versus lowest quintile of cumulative updated intake were 1.17 (95% confidence interval (CI): 0.87, 1.58) for alpha-carotene, 1.10 (95% CI: 0.82, 1.48) for beta-carotene, 0.95 (95% CI: 0.70, 1.29) for beta-cryptoxanthin, 0.82 (95% CI: 0.60, 1.12) for lycopene, 0.92 (95% CI: 0.69, 1.24) for lutein/zeaxanthin, 1.05 (95% CI: 0.59, 1.89) for vitamin C, 0.97 (95% CI: 0.62, 1.52) for vitamin E, and 1.11 (95% CI: 0.82, 1.51) for vitamin A. In conclusion, the authors did not observe any strong associations between antioxidant consumption and the risk of primary open-angle glaucoma. C1 Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. RP Kang, JH (reprint author), Harvard Univ, Sch Med, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA 40356, CA 55075, CA 87969]; NEI NIH HHS [EY 09611]; NHLBI NIH HHS [HL 35464] NR 61 TC 51 Z9 52 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 15 PY 2003 VL 158 IS 4 BP 337 EP 346 DI 10.1093/aje/kwg167 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 712EY UT WOS:000184785300007 PM 12915499 ER PT J AU Glatt, SJ Faraone, SV Tsuang, MT AF Glatt, SJ Faraone, SV Tsuang, MT TI CAG-repeat length in exon 1 of KCNN3 does not influence risk for schizophrenia or bipolar disorder: A meta-analysis of association studies SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE schizophrenia; bipolar disorder; KCNN3; CAG-repeat; allelic association; meta-analysis ID POTASSIUM CHANNEL GENE; TRANSMISSION DISEQUILIBRIUM ANALYSIS; TRINUCLEOTIDE REPEAT; NO ASSOCIATION; HKCA3 GENE; SMALL-CONDUCTANCE; CHROMOSOME 1Q21; HSKCA3 GENE; ANTICIPATION; LINKAGE AB Schizophrenia and bipolar disorder both show some evidence for genetic anticipation. In addition, significant expansion of anonymous CAG repeats throughout the genome has been detected in both of these disorders. The gene KCNN3, which codes for a small/intermediate conductance, calcium-regulated potassium channel, contains a highly polymorphic CAG-repeat array in exon 1. Initial evidence for association of both schizophrenia and bipolar disorder with increased CAG-repeat length of KCNN3 has not been consistently replicated. In the present study, we performed several meta-analyses to evaluate the pooled evidence for association with CAG-repeat length of KCNN3 derived from case-control and family-based studies of both disorders. Each group of studies was analyzed under two models, including a test for direct association with repeat length, and a test for association with dichotomized repeat-length groups. No evidence for a linear relationship between disease risk and repeat length was observed, as all pooled odds ratios approximated 1.0. Results of dichotomized allele-group analyses were more variable, especially for schizophrenia, where case-control studies found a significant association with longer repeats but family-based studies implicated shorter alleles. The results of these meta-analyses demonstrate that the risks for both schizophrenia and bipolar disorder are largely, if not entirely, independent of CAG-repeat length in exon 1 of KCNN3. This study cannot exclude the possibility that some aspect of this polymorphism, such as repeat-length disparity in heterozygotes, influences risk for these disorders. Further, it remains unknown if this polymorphism, or one in linkage disequilibrium with it, contributes to some distinct feature of the disorder, such as symptom severity or anticipation. (C) 2003 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Brocton W Roxbury Vet Affairs Med Ctr, Psychiat Serv, Brockton, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. RP Tsuang, MT (reprint author), Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, 74 Fenwood Rd, Boston, MA 02115 USA. OI Glatt, Stephen/0000-0002-0360-7567; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R25 MH60485, R01 MH43518, R01 MH59624, R01 MH60485] NR 38 TC 12 Z9 14 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD AUG 15 PY 2003 VL 121B IS 1 BP 14 EP 20 DI 10.1002/ajmg.b.20048 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 708CF UT WOS:000184548900003 PM 12898569 ER PT J AU McMahon, WM Carter, AS Fredine, N Pauls, DL AF McMahon, WM Carter, AS Fredine, N Pauls, DL TI Children at familial risk for Tourette's disorder: Child and parent diagnoses SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE Gilles de la Tourette syndrome; prospective longitudinal study; bilineal transmission; obsessive-compulsive disorder; attention deficit hyperactivity disorder ID STREPTOCOCCAL INFECTIONS; INHERITANCE; LINKAGE; SCHIZOPHRENIA; RELIABILITY; SEVERITY; SCHEDULE; SCALE AB Tourette's disorder (TD) is a neuropsychiatric disorder that onsets in childhood and appears to result from an interaction of genetic and environmental factors. The goal of the current prospective longitudinal study is to examine the onset of TD in offspring of parents with TD. At-risk children and control children were enrolled between the ages of 3 and 6 years and prospectively studied with yearly structured assessments over intervals of 2-5 years. Of 34 at-risk children free of ties at baseline, 10 (29%) subsequently developed a tic disorder, including 3 with TD. None of the 13 control children developed a tic disorder (P = 0.045). OCD or subclinical OCD emerged in 11 cases but no controls (P = 0.021). Finally, ADHD occurred in 14 at-risk children but no controls (P = 0.005). When at-risk families were dichotomized into bilineal or unilineal categories, rates of TD in children with two affected parents were three times the rate observed for children with one affected parent. These findings support the hypothesis that at least some cases of TD result from a complex genetic etiology. TD, OCD, and ADHD are significantly increased in children with TD parents. Furthermore, the risk is even greater when both parents are affected. Finally, our diagnosis of tic disorders in 21% of subjects initially reported by parents to be unaffected affirms the value of structured clinical assessments. (C) 2003 Wiley-Liss, Inc. C1 Univ Utah, Dept Psychiat, Salt Lake City, UT USA. Univ Utah, Dept Pediat, Salt Lake City, UT USA. Primary Childrens Med Ctr, Salt Lake City, UT USA. Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Psychiat, Psychiat & Neurodev Genet Unit, Charlestown, MA USA. RP McMahon, WM (reprint author), 421 Wakara Way,Suite 143, Salt Lake City, UT 84108 USA. FU NICHD NIH HHS [HD03008]; NIMH NIH HHS [MH58868, MH00980]; NINDS NIH HHS [NS16648] NR 30 TC 27 Z9 27 U1 2 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD AUG 15 PY 2003 VL 121B IS 1 BP 105 EP 111 DI 10.1002/ajmg.b.20065 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 708CF UT WOS:000184548900017 PM 12898584 ER PT J AU Ofman, JJ Maclean, CH Straus, WL Morton, SC Berger, ML Roth, EA Shekelle, PG AF Ofman, JJ Maclean, CH Straus, WL Morton, SC Berger, ML Roth, EA Shekelle, PG TI Meta-analysis of dyspepsia and nonsteroidal antiinflammatory drugs SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Review DE NSAIDs; dyspepsia; meta-analysis; adverse events ID DOUBLE-BLIND MULTICENTER; PLACEBO-CONTROLLED TRIAL; DEGENERATIVE JOINT DISEASE; TIAPROFENIC ACID SURGAM; ANTI-INFLAMMATORY DRUG; RANDOMIZED CONTROLLED TRIAL; COMPARATIVE CLINICAL-TRIAL; PEPTIC-ULCER DISEASE; LOW-BACK-PAIN; RHEUMATOID-ARTHRITIS AB Objective. Nonsteroidal antiinflammatory drug (NSAID) use is a known risk factor for gastrointestinal (GI) perforations, ulcers, and bleeds, but there are limited data on its association with the very common symptom of dyspepsia. Using published and unpublished data sources, we sought to determine estimates of the risks of dyspepsia associated with NSAIDs. Methods. We searched computerized databases (1966-1998) for primary studies of NSAIDs reporting on GI complications. We also obtained Food and Drug Administration (FDA) new drug application reviews for the 5 most common NSAIDs. We included studies reporting defined upper GI outcomes among subjects (> 17 years old) who used oral NSAIDs for more than 4 days. Two reviewers evaluated 4,881 published titles, identifying 55 NSAID versus placebo randomized controlled trials (RCTs), 37 unpublished (FDA data) placebo-controlled RCTs; 86 NSAID versus NSAID RCTs (sample size 2:50); and 103 observational studies. Results. The majority of clinical trials were of good quality. Meta-regression identified an increased risk of dyspepsia for users of specific NSAIDs (adjusted odds ratio [OR] of indomethacin, meclofenamate, piroxicam = 2.8), and for high dosages of other NSAIDs (OR = 3.1), but not for other NSAIDs regardless of dosage (OR = 1.1). Dyspepsia was not reported as an outcome in the case control or cohort studies. Conclusions. Clinical trial data indicate that high dosages of any NSAID along with any dosage of indomethacin, meclofenamate, or piroxicam increase the risk of dyspepsia by about 3-fold. Other NSAIDs at lower dosages were not associated with an increased risk of dyspepsia. C1 Cedars Sinai Hlth Syst, Los Angeles, CA USA. Zynx Hlth Inc, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA USA. Merck & Co Inc, W Point, PA USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. RP Ofman, JJ (reprint author), Cedars Sinai, Zynx Hlth, 9100 Wilshire Blvd,Suite 655E, Beverly Hills, CA 90212 USA. NR 185 TC 52 Z9 52 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 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD AUG 15 PY 2003 VL 49 IS 4 BP 508 EP 518 DI 10.1002/art.11192 PG 11 WC Rheumatology SC Rheumatology GA 709KL UT WOS:000184624300006 PM 12910557 ER PT J AU Xiong, JP Stehle, T Goodman, SL Arnaout, MA AF Xiong, JP Stehle, T Goodman, SL Arnaout, MA TI New insights into the structural basis of integrin activation SO BLOOD LA English DT Article ID INSIDE-OUT ACTIVATION; CYSTEINE-RICH REPEAT; GLY-ASP-BINDING; I-LIKE DOMAIN; A-DOMAIN; CONFORMATIONAL-CHANGE; CRYSTAL-STRUCTURE; LIGAND-BINDING; EXTRACELLULAR SEGMENT; FIBRINOGEN BINDING AB Integrins are cell adhesion receptors that communicate biochemical and mechanical signals in a bidirectional manner across the plasma membrane and thus influence most cellular functions. Intracellular signals switch integrins into a ligand-competent state as a result of elicited conformational changes in the integrin ectodomain. Binding of extracellular ligands induces, in turn, structural changes that convey distinct signals to the cell interior. The structural basis of this bidirectional signaling has been the focus of intensive study for the past 3 decades. In this perspective, we develop a new hypothesis for integrin activation based on recent crystallographic, electron microscopic, and biochemical studies. (C) 2003 by The American Society of Hematology. C1 Massachusetts Gen Hosp East, Renal Unit, Struct Biol Program, Leukocyte Biol & Inflammat Program, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Merck KGaA, Dept Oncol Res, Darmstadt, Germany. RP Arnaout, MA (reprint author), Massachusetts Gen Hosp East, Renal Unit, Struct Biol Program, Leukocyte Biol & Inflammat Program, Charlestown, MA 02129 USA. NR 59 TC 130 Z9 135 U1 2 U2 11 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 2003 VL 102 IS 4 BP 1155 EP 1159 DI 10.1182/blood-2003-01-0334 PG 5 WC Hematology SC Hematology GA 709XJ UT WOS:000184651600010 PM 12714499 ER PT J AU Stier, S Cheng, T Forkert, R Lutz, C Dombrowski, DM Zhang, JL Scadden, DT AF Stier, S Cheng, T Forkert, R Lutz, C Dombrowski, DM Zhang, JL Scadden, DT TI Ex vivo targeting of p21(Cip1/Waf1) permits relative expansion of human hematopoietic stem cells SO BLOOD LA English DT Article ID BLOOD CD34(+) CELLS; MURINE MARROW-CELLS; MAMMALIAN-CELLS; FUNCTIONAL-HETEROGENEITY; REPOPULATING CAPACITY; GENE-EXPRESSION; CYCLE; RNAI; ENGRAFTMENT; INHIBITORS AB Relative quiescence is a defining characteristic of hematopoietic stem cells. Reasoning that inhibitory tone dominates control of stem cell cycling, we previously showed that mice engineered to be deficient in the cyclin-dependent kinase inhibitor, p21(Cip1/Waf1) (p21), have an increased stem cell pool under homeostatic conditions. Since p21 was necessary to maintain stem cell quiescence and its absence sufficient to permit increased murine stem cell cycling, we tested whether reduction of p21 alone in human adult-derived stem cells could affect stem cell proliferation. We demonstrate here that interrupting p21 expression ex vivo resulted in expanded stem cell number and in vivo stem cell function compared with control, manipulated cells. Further, we demonstrate full multilineage reconstitution capability in cells where p21 expression was knocked down. Therefore, lifting the brake on cell proliferation by altering cell cycle checkpoints provides an alternative paradigm for increasing hematopoietic stem cell numbers. This approach may be useful for relative ex vivo human stem cell expansion. (C) 2003 by The American Society of Hematology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. Ctr AIDS Res, Ctr Regenerat Med & Technol, Boston, MA USA. RP Scadden, DT (reprint author), 149 13th St,Rm5212, Boston, MA 02129 USA. FU NHLBI NIH HHS [HL44851, HL65909]; NIAID NIH HHS [AI29530, AI142851]; NIDDK NIH HHS [DK02761] NR 26 TC 49 Z9 55 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 2003 VL 102 IS 4 BP 1260 EP 1266 DI 10.1182/blood-2002-10-3053 PG 7 WC Hematology SC Hematology GA 709XJ UT WOS:000184651600024 PM 12702511 ER PT J AU Lacout, C Haddad, E Sabri, S Svinarchouk, F Garcon, L Capron, C Foudi, A Mzali, R Snapper, SB Louache, F Vainchenker, W Dumenil, D AF Lacout, C Haddad, E Sabri, S Svinarchouk, F Garcon, L Capron, C Foudi, A Mzali, R Snapper, SB Louache, F Vainchenker, W Dumenil, D TI A defect in hematopoietic stem cell migration explains the nonrandorn X-chromosome inactivation in carriers of Wiskott-Aldrich syndrome SO BLOOD LA English DT Article ID CHEMOKINE RECEPTOR CXCR4; SYNDROME PROTEIN; T-CELL; LINKED THROMBOCYTOPENIA; NOD/SCID MICE; WASP-FAMILY; IN-VITRO; ACTIVATION; CDC42; DIFFERENTIATION AB A defect in cell trafficking and chemotaxis plays an important role in the immune deficiency observed in Wiskott-Aldrich syndrome (WAS). In this report, we show that marrow cells from WAS protein (WASP)-deficient mice also have a defect in chemotaxis. Serial transplantation and competitive reconstitution experiments demonstrated that marrow cells, including hematopoietic progenitors and stem cells (HSCs), have decreased homing capacities that were associated with a defect in adhesion to collagen. During development, HSCs migrate from the liver to the marrow and the spleen, prompting us to ask if a defect in HSC homing during development may explain the skewed X-chromosome inactivation in WAS carriers. Preliminary evidence has shown that, in contrast to marrow progenitor cells, fetal liver progenitor cells from heterozygous females had a random X-chromosome inactivation. When fetal liver cells from WASP-carrier females were injected into irradiated recipients, a nonrandom inactivation of the X-chromosome was found at the level of hematopoietic progenitors and HSCs responsible for the short- and long-term hematopoietic reconstitution. Therefore, the mechanism of the skewed X-chromosomal inactivation observed in WAS carriers may be related to a migration defect of WASP-deficient HSCs. (C) 2003 by The American Society of Hematology. C1 Inst Gustave Roussy, INSERM, U362, F-94800 Villejuif, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. Fac Pharm Chatenay Malabry, U461, INSERM, Chatenay Malabry, France. RP Dumenil, D (reprint author), Inst Gustave Roussy, INSERM, U362, Rue Camille Desmoulins, F-94800 Villejuif, France. RI Sabri, Siham/K-1101-2015 NR 38 TC 44 Z9 45 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 2003 VL 102 IS 4 BP 1282 EP 1289 DI 10.1182/blood-2002-07-2099 PG 8 WC Hematology SC Hematology GA 709XJ UT WOS:000184651600027 PM 12730112 ER PT J AU Hayashi, T Hideshima, T Akiyama, M Rajo, N Richardson, P Chauhan, D Anderson, KC AF Hayashi, T Hideshima, T Akiyama, M Rajo, N Richardson, P Chauhan, D Anderson, KC TI Ex vivo induction of multiple myeloma-specific cytotoxic T lymphocytes SO BLOOD LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; BONE-MARROW TRANSPLANTATION; STEM-CELL TRANSPLANTATION; COLONY-STIMULATING FACTOR; DENDRITIC CELLS; APOPTOTIC CELLS; TUMOR-CELLS; PHOSPHATIDYLSERINE RECEPTOR; VITRONECTIN RECEPTOR; IN-VIVO AB Multiple myeloma (MM) is an incurable plasma cell malignancy characterized by immunosuppression. In this study, we identified factors in patients' bone marrow (BM) sera inhibiting autologous anti-MM immunity and developed an ex vivo strategy for inducing MM-specific cytotoxic T lymphocytes (CTLs). We found that sera from BM of MM patients inhibited induction of dendritic cells (DCs), evidenced by both phenotype and only weak stimulation of T-cell proliferation. Anti-vascular endothelial growth factor (anti-VEGF) and/or anti-interleukin 6 (anti-IL-6) antibodies neutralized this inhibitory effect, confirming that VEGF and IL-6, at least in part, mediate immunosuppression in MM patients. To induce MM-specific CTLs ex vivo, immature DCs were generated by culture of adherent mononuclear cells in medium containing granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4 for 5 days and then cocultured with apoptotic MM bodies in the presence of tumor necrosis factor alpha (TNF-alpha) for 3 days to induce their maturation. Autologous BM or peripheral blood mononuclear cells were stimulated weekly with these DCs, and cytotoxicity was examined against the MM cells used to pulse DCs. DCs cultured with apoptotic bodies stimulated significantly greater T-cell proliferation (stimulation index [SI] = 23.2 at a T-DC ratio of 360:1) than T cells stimulated by MM cells only (SI = 5.6), DCs only (SI = 9.3), or MM lysate-pulsed DCs (SI = 13.5). These CTLs from MM patients demonstrated specific cytotoxicity (24.7% at the effector-target [E/T] ratio of 40:1) against autologous primary MM cells. These studies therefore show that CTLs from MM patients can recognize and lyse autologous tumor cells and provide the framework for novel immunotherapy to improve patient outcome in MM. (C) 2003 by The American Society of Hematology. C1 Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Anderson, KC (reprint author), Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. FU PHS HHS [P0-1 78378] NR 45 TC 76 Z9 85 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 2003 VL 102 IS 4 BP 1435 EP 1442 DI 10.1182/blood-2002-09-2828 PG 8 WC Hematology SC Hematology GA 709XJ UT WOS:000184651600047 PM 12714512 ER PT J AU Kornblith, AB Herndon, JE Weiss, RB Zhang, CF Zuckerman, EL Rosenberg, S Mertz, M Payne, D Massie, MJ Holland, JF Wingate, P Norton, L Holland, JC AF Kornblith, AB Herndon, JE Weiss, RB Zhang, CF Zuckerman, EL Rosenberg, S Mertz, M Payne, D Massie, MJ Holland, JF Wingate, P Norton, L Holland, JC TI Long-term adjustment of survivors of early-stage breast carcinoma, 20 years after adjuvant chemotherapy SO CANCER LA English DT Article DE breast carcinoma; survivors; adjustment; quality of life ID QUALITY-OF-LIFE; LEUKEMIA GROUP-B; CONSERVING TREATMENT; PSYCHOSOCIAL ADAPTATION; HODGKINS-DISEASE; CANCER-TREATMENT; CLINICAL-TRIALS; SOCIAL SUPPORT; IMPACT; MASTECTOMY AB BACKGROUND. The long-term impact of breast carcinoma and its treatment was assessed in 153 breast carcinoma survivors previously treated on a Phase III randomized trial ( Cancer and Leukemia Group B [CALGB 7581]) a median of 20 years after entry to CALGB 7581. METHODS. Survivors were interviewed by telephone using the following standardized measures: Brief Symptom Inventory (BSI), PostTraumatic Stress Disorder Checklist with the trauma defined as survivors' response to having had cancer (PCL-C), Conditioned Nausea, Vomiting and Distress, European Organization for Research and Treatment of Cancer QLQ-C30 (quality of life), Life Experience Survey (stressful events), MOS Social Support Survey, comorbid conditions (Older Americans Resources and Services Questionnaire), and items developed to assess long-term breast carcinoma treatment side effects and their interference with functioning. RESULTS. Only 5% of survivors had scores that were suggestive of clinical levels of distress (BSI), 15% reported 2 or more posttraumatic stress disorder (PTSD) symptoms (PCL-C) that were moderately to extremely bothersome, 1-6% reported conditioned nausea, emesis, and distress as a consequence of sights, smells, and tastes triggered by reminders of their treatment, 29% reported sexual problems attributed to having had cancer, 39% reported lymphedema, and 33%, reported numbness. Survivors who reported greater lymphedema and numbness that interfered with functioning had significantly worse PTSD (PCL-C; P = 0.008) compared with survivors who reported less lymphedema and numbness. Survivors with a lower level of education (P = 0.026), less adequate social support (P = 0.0033), more severe negative life events (P = 0.0098), and greater dissatisfaction with their medical care (P = 0.037) had worse PTSD compared with other survivors. CONCLUSIONS. Twenty years after the initial treatment, the impact of breast carcinoma on survivors' adjustment was minimal. However, the higher prevalence of PTSD symptoms in response to having had cancer is indicative of continuing psychologic sequelae long after treatment completion. Findings related to lymphedema and numbness and continued symptoms of PTSD suggest that the long-term psychologic and medical sequelae on adjustment may be underrecognized. To establish in more detail whether survivors' overall psychologic state is any different from that of individuals without cancer, a population of community residents without cancer would need to be studied. C1 Dana Farber Canc Inst, Womens Canc Program, Dept Adult Oncol, Boston, MA 02115 USA. Duke Univ, Med Ctr, Canc & Leukemia Grp Stat Ctr B, Durham, NC USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10021 USA. Univ Pretoria, Dept Med, ZA-0002 Pretoria, South Africa. CUNY Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. Brown Univ, Mem Hosp Rhode Isl, Dept Med, Providence, RI 02912 USA. RP Kornblith, AB (reprint author), Dana Farber Canc Inst, Womens Canc Program, Dept Adult Oncol, Room D1210,44 Binney St, Boston, MA 02115 USA. OI Norton, Larry/0000-0003-3701-9250 FU NCI NIH HHS [CA31946] NR 32 TC 173 Z9 175 U1 1 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 15 PY 2003 VL 98 IS 4 BP 679 EP 689 DI 10.1002/cncr.11531 PG 11 WC Oncology SC Oncology GA 708JA UT WOS:000184562400003 PM 12910510 ER PT J AU Laverdiere, C Kolb, EA Supko, JG Gorlick, R Meyers, PA Maki, RG Wexler, L Demetri, GD Healey, JH Huvos, AG Goorin, AM Bagatell, R Ruiz-Casado, A Guzman, C Jimeno, J Harmon, D AF Laverdiere, C Kolb, EA Supko, JG Gorlick, R Meyers, PA Maki, RG Wexler, L Demetri, GD Healey, JH Huvos, AG Goorin, AM Bagatell, R Ruiz-Casado, A Guzman, C Jimeno, J Harmon, D TI Phase II study of ecteinascidin 743 in heavily pretreated patients with recurrent osteosarcoma SO CANCER LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 18-21, 2002 CL ORLANDO, FLORIDA SP Amer Soc Clin Oncol DE ecteinascidin-743 (ET-743); osteosarcoma; sarcoma; Phase II study ID CONTINUOUS INTRAVENOUS-INFUSION; PEDIATRIC-ONCOLOGY-GROUP; HUMAN TUMOR XENOGRAFTS; CARIBBEAN TUNICATE; MINOR-GROOVE; CHILDHOOD OSTEOSARCOMA; SOLID MALIGNANCIES; ANTITUMOR-ACTIVITY; MARINE COMPOUND; TOPOISOMERASE-I AB BACKGROUND. Recurrent osteosarcoma is a drug-resistant disease with a dismal prognosis. The objective of this Phase II study was to evaluate the activity of ecteinascidin 743 (ET-743) as a salvage therapy in these patients. METHODS. Patients with recurrent osteosarcoma who had received standard chemotherapeutic agents were eligible. ET-743 was administered at a dose of 1500 mug/m(2) as a 24-hour infusion every 3 weeks. Pharmacokinetic studies were performed during the first cycle. RESULTS. Twenty-five patients were enrolled, 23 of whom were assessable for response (median age of 18 years; range, 12-67 years). The median number of previous chemotherapeutic agents was five (range, three to eight previous agents). Sixty-one cycles were administered (median number of cycles per patient was 2; range, 1-9 cycles per patient). Three patients (12%) achieved minor responses (49% 36% and 25%, respectively). Fifteen patients (60%) developed a transient elevation of hepatic transaminases (Grade 3 or 4 [according to the National Cancer Institute Common Toxicity Criteria]), which was not cumulative. Grade 3 or 4 neutropenia and thrombocytopenia were observed in 12 patients (48%) and 6 patients (24%), respectively. The mean area under the curve (AUC) in 4 patients experiencing Grade 4 toxicity (76.4 +/- 29.3 ng X hr/mL) was significantly greater (P = 0.034) than that in those for whom the most severe toxicity was Grade 3 (39.5 +/- 17.2 ng X hr/mL [n = 12]) or Grade 1-2 (52.6 +/- 15.6 ng X hr/mL [n = 5]). There were no other significant correlations found between pharmacokinetic variables and patient characteristics, toxicity, or therapeutic response. CONCLUSIONS. ET-743 was found to be well tolerated in heavily pretreated osteosarcoma patients but had limited antitumor activity as a single agent. The combination of ET-743 with cisplatin or doxorubicin should be considered. C1 Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. Harvard Med Sch, Div Hematol Oncol, Dana Farber Harvard Canc Ctr, Boston, MA USA. Mem Sloan Kettering Canc Ctr, Dept Med, Div Med Oncol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Surg, Div Orthoped Surg, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Univ Arizona, Hlth Sci Ctr, Dept Pediat, Tucson, AZ 85721 USA. PharmaMar SA, Tres Cantos, Spain. RP Gorlick, R (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pediat, Howard Bldg 11th Floor,Room 1110,1275 York Ave, New York, NY 10021 USA. OI Meyers, Paul/0000-0001-6146-6101 FU NCI NIH HHS [P01-CA47179] NR 60 TC 56 Z9 59 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 15 PY 2003 VL 98 IS 4 BP 832 EP 840 DI 10.1002/cncr.11563 PG 9 WC Oncology SC Oncology GA 708JA UT WOS:000184562400022 PM 12910529 ER PT J AU Lieberfarb, ME Lin, M Lechpammer, M Li, C Tanenbaum, DM Febbo, PG Wright, RL Shim, J Kantoff, PW Loda, M Meyerson, M Sellers, WR AF Lieberfarb, ME Lin, M Lechpammer, M Li, C Tanenbaum, DM Febbo, PG Wright, RL Shim, J Kantoff, PW Loda, M Meyerson, M Sellers, WR TI Genome-wide loss of heterozygosity analysis from laser capture microdissected prostate cancer using single nucleotide polymorphic allele (SNP) arrays and a novel bioinformatics platform dChipSNP SO CANCER RESEARCH LA English DT Article ID IN-SITU HYBRIDIZATION; BLADDER-CANCER; CHROMOSOME 8P; EXPRESSION; CARCINOMAS; 16Q; RETINOBLASTOMA; ADENOCARCINOMA; DELETION; BEHAVIOR AB Oligonucleotide arrays that detect single nucleotide polymorphisms were used to generate genome-wide loss of heterozygosity (LOH) maps from laser capture microdissected paraffin-embedded samples using as little as 5 ng of DNA. The allele detection rate from such samples was comparable with that obtained with standard amounts of DNA prepared from frozen tissues. A novel informatics platform, dChipSNP, was used to automate the definition of statistically valid regions of LOH, assign LOH genotypes to prostate cancer samples, and organize by hierarchical clustering prostate cancers based on the pattern of LOH. This organizational strategy revealed apparently distinct genetic subsets of prostate cancer. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02115 USA. RP Sellers, WR (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RI Meyerson, Matthew/E-7123-2012 FU NCI NIH HHS [P50CA09038, U01CA84995] NR 28 TC 94 Z9 99 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2003 VL 63 IS 16 BP 4781 EP 4785 PG 5 WC Oncology SC Oncology GA 715AM UT WOS:000184948400006 PM 12941794 ER PT J AU Farazi, PA Glickman, J Jiang, S Yu, A Rudolph, KL DePinho, RA AF Farazi, PA Glickman, J Jiang, S Yu, A Rudolph, KL DePinho, RA TI Differential impact of telomere dysfunction on initiation and progression of hepatocellular carcinoma SO CANCER RESEARCH LA English DT Article ID CHRONIC LIVER-DISEASE; REVERSE-TRANSCRIPTASE; DEFICIENT MICE; CANCER; MOUSE; RNA; HEPATOCARCINOGENESIS; DIETHYLNITROSAMINE; CARCINOGENESIS; TUMORIGENESIS AB Telomere maintenance and telomerase reactivation are near universal features of human hepatocellular carcinoma (HCC), yet the shorter telomeres and highly abnormal cytogenetic profiles of HCC suggest that telomere erosion and dysfunction may be operative during the formative stages of tumorigenesis. Previous studies have established that the cancer-enhancing or suppressing impact of telomere dysfunction is highly dependent on several parameters including cell type, tumor stage, and p53 status. Here, to understand better the pathogenetic role of telomere dysfunction in the initiation and progression in human HCC, we have used three mechanistically distinct liver cancer-prone model systems (urokinase plasminogen activator transgenic mice, carbon tetrachloride exposure, and diethylnistrosamine treatment) in the context of successive generations of telomerase-deficient mice null for the telomerase RN component, mTERC. Across all of the HCC model systems, telomere dysfunction suppressed both the incidence and growth of HCC lesions, a trend that mirrored the level of intratumoral proliferative arrest and apoptosis. On the histological level, telomere dysfunction was associated with a significant increase in the number of early stage neoplastic lesions and a reciprocal decline in the occurrence of high-grade malignancies. These genetic data in the mouse indicate that telomere dysfunction exerts an opposing role in the initiation versus progression of HCC and provide a framework for understanding the intimate link among chronic liver disease, chromosomal instability, and increased HCC in humans. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,M413, Boston, MA 02115 USA. FU NCI NIH HHS [5R01CA84628-11] NR 39 TC 93 Z9 100 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2003 VL 63 IS 16 BP 5021 EP 5027 PG 7 WC Oncology SC Oncology GA 715AM UT WOS:000184948400041 PM 12941829 ER PT J AU Zhang, L Sharma, S Zhu, LX Kogai, T Hershman, JM Brent, GA Dubinett, SM Huang, M AF Zhang, L Sharma, S Zhu, LX Kogai, T Hershman, JM Brent, GA Dubinett, SM Huang, M TI Nonradioactive iodide effectively induces apoptosis in genetically modified lung cancer cells SO CANCER RESEARCH LA English DT Article ID SODIUM/IODIDE SYMPORTER GENE; THYROID PEROXIDASE; OXIDATIVE STRESS; BREAST-CANCER; RADIOIODIDE UPTAKE; DNA-DAMAGE; EXPRESSION; THERAPY; P21; INHIBITOR AB We assessed a nonradioactive approach to induce apoptosis in non-small cell lung cancer by a novel iodide uptake and retention mechanism. To enhance tumor apoptosis, we transduced non-small cell lung cancer cells with retroviral vectors containing the sodium iodide symporter (NIS) and thyroperoxidase (TPO) genes. Expression of NIS and TPO facilitated concentration of iodide in tumors. As a consequence of the marked increase in intracellular levels of iodide, apoptosis was seen in >95% of NIS/TPO-modified lung cancer cells. Intraperitoneal injection of potassium iodide resulted in significant tumor volume reduction in NIS/TPO-modified tumor xenografts without apparent adverse effects in SCID mice. Iodide induced an increase in the level of reactive oxygen species. Iodide-induced apoptosis is sensitive to N-acetylcysteine inhibition, suggesting an important role by reactive oxygen species in this apoptotic process. In addition, iodide-induced apoptosis is associated with overexpression of CDKN1A (p21/Waf1) and down-regulation of survivin at both mRNA and protein levels. This is the first report demonstrating that a therapeutic dose of nonradioactive iodide has potent efficacy and high selectivity against lung cancer when used in combination with genetic modification of cancer cells to express the NIS/TPO genes. C1 Univ Calif Los Angeles, W Los Angeles VA, Div Pulm & Crit Care Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Div Endocrinol & Metab, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Lung Canc Res Program, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90073 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, W Los Angeles VA, Div Pulm & Crit Care Med, Bldg 114,Room 103, Los Angeles, CA 90073 USA. FU NCI NIH HHS [R01 CA085686, P50 CA90388] NR 62 TC 28 Z9 29 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2003 VL 63 IS 16 BP 5065 EP 5072 PG 8 WC Oncology SC Oncology GA 715AM UT WOS:000184948400048 PM 12941836 ER PT J AU Steere, AC Sikand, VK Schoen, RT Nowakowski, J AF Steere, AC Sikand, VK Schoen, RT Nowakowski, J TI Asymptomatic infection with Borrelia burgdorferi SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; LYME-DISEASE; POPULATION; PEPTIDE; SERODIAGNOSIS; PREVALENCE; REGION; RISK; VLSE AB The natural history of asymptomatic seroconversion to Borrelia burgdorferi has been unclear. We report here, on the basis of a post hoc assessment, the frequency and outcome of asymptomatic seroconversion to B. burgdorferi in participants of a large Lyme disease vaccine trial. We show that infection with B. burgdorferi may be asymptomatic but that asymptomatic infection is unusual in the United States. C1 Tufts Univ, New England Med Ctr, Div Rheumatol Immunol, Sch Med, Boston, MA 02111 USA. Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. New York Med Coll, Div Infect Dis, Valhalla, NY 10595 USA. RP Steere, AC (reprint author), Massachusetts Gen Hosp, Div Rheumatol, 149 13th St,Rm 8301, Boston, MA 02129 USA. FU ODCDC CDC HHS [CCU110291] NR 15 TC 40 Z9 43 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG 15 PY 2003 VL 37 IS 4 BP 528 EP 532 DI 10.1086/376914 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 709HC UT WOS:000184618900009 PM 12905137 ER PT J AU D'Andrea, AD AF D'Andrea, AD TI The Fanconi road to cancer SO GENES & DEVELOPMENT LA English DT Editorial Material ID HOMOLOGY-DIRECTED REPAIR; ANEMIA-BRCA PATHWAY; TARGETED DISRUPTION; NUCLEAR-COMPLEX; DNA-DAMAGE; GROUP-A; MICE; GENE; PROTEINS; DELETION C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 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. NR 34 TC 68 Z9 70 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD AUG 15 PY 2003 VL 17 IS 16 BP 1933 EP 1936 DI 10.1101/gad.1128303 PG 4 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 712UZ UT WOS:000184817900001 PM 12893780 ER PT J AU Lin, JD Tarr, PT Yang, RJ Rhee, J Puigserver, P Newgard, CB Spiegelman, BM AF Lin, JD Tarr, PT Yang, RJ Rhee, J Puigserver, P Newgard, CB Spiegelman, BM TI PGC-1 beta in the regulation of hepatic glucose and energy metabolism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COACTIVATOR PGC-1; RECEPTOR-ALPHA; MITOCHONDRIAL BIOGENESIS; GAMMA COACTIVATOR-1; GLUCONEOGENESIS; LIVER; TRANSCRIPTION; PGC-1-ALPHA; ADENOVIRUS; CELLS AB Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) is a transcriptional coactivator that regulates multiple aspects of cellular energy metabolism, including mitochondrial biogenesis, hepatic gluconeogenesis, and beta-oxidation of fatty acids. PGC-1alpha mRNA levels are increased in both type-1 and type-2 diabetes and may contribute to elevated hepatic glucose production in diabetic states. We have recently described PGC-1beta, a novel transcriptional coactivator that is a homolog of PGC-1alpha. Although PGC-1beta shares significant sequence similarity and tissue distribution with PGC-1alpha, the biological activities of PGC-1beta in the regulation of cellular metabolism is unknown. In this study, we used an adenoviral-mediated expression system to study the function of PGC-1beta both in cultured hepatocytes and in the liver of rats. PGC-1beta, like PGC-1alpha, potently induces the expression of an array of mitochondrial genes involved in oxidative metabolism. However, in contrast to PGC-1alpha, PGC-1beta poorly activates the expression of gluconeogenic genes in hepatocytes or liver in vivo, illustrating that these two coactivators play distinct roles in hepatic glucose metabolism. The reduced ability of PGC-1beta to induce gluconeogenic genes is due, at least in part, to its inability to physically associate with and coactivate hepatic nuclear receptor 4alpha (HNF4alpha) and forkhead transcription factor O1 (FOXO1), two critical transcription factors that mediate the activation of gluconeogenic gene expression by PGC-1alpha. These data illustrate that PGC-1beta and PGC-1alpha have distinct arrays of activities in hepatic energy metabolism. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. RP Spiegelman, BM (reprint author), Dana Farber Canc Inst, Smith Bldg,Rm 958,1 Jimmy Fund Way, Boston, MA 02115 USA. FU NIDDK NIH HHS [P01DK58398, R01DK61562] NR 27 TC 153 Z9 166 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 15 PY 2003 VL 278 IS 33 BP 30843 EP 30848 DI 10.1074/jbc.M303643200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 710AN UT WOS:000184658800054 PM 12807885 ER PT J AU Potolicchio, I Santambrogio, L Strominger, JL AF Potolicchio, I Santambrogio, L Strominger, JL TI Molecular interaction and enzymatic activity of macrophage migration inhibitory factor with immunorelevant peptides SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CLASS-II MOLECULES; HEAT-SHOCK PROTEINS; IMMATURE DENDRITIC CELLS; LYSOSOMAL THIOL REDUCTASE; MIF TAUTOMERASE ACTIVITY; RHEUMATOID-ARTHRITIS; CRYSTAL-STRUCTURE; MATRIX METALLOPROTEINASES; ANTIGEN PRESENTATION; DISULFIDE BONDS AB Disulfide reduction is an important step in antigen processing for HLA class II restricted T cell responses. Migration inhibitory factor (MIF) is a member of the thioredoxin family and has been classically defined as a cytokine. Using enzyme-linked immunosorbent assay and CD analysis, here we describe the binding to MIF of two peptides, hepatitis B surface antigen (HBsAg) and insulin B (InsB) with high affinity for HLA class II allotypes, HLA-DP2 and HLA-DQ8, respectively. At neutral pH, cysteinylated InsB was a substrate for MIF thiol reductase activity, as assessed by mass spectroscopy/electrospray analysis. Finally, a biologically active form of MIF co-immunopurified with mature forms of HLA DP2/15, and a peptide derived from the HLA-DP beta1 helix could be used for affinity purification of MIF. The possibility that MIF participates in class II antigen presentation and/or as a chaperone is discussed. C1 Harvard Univ, Dept Mol Cell Biol, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Strominger, JL (reprint author), Harvard Univ, Dept Mol Cell Biol, Cambridge, MA 02138 USA. FU NCI NIH HHS [CA-47554]; NIAID NIH HHS [AI-49524, AI-48832] NR 62 TC 22 Z9 24 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 15 PY 2003 VL 278 IS 33 BP 30889 EP 30895 DI 10.1074/jbc.M302854200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 710AN UT WOS:000184658800061 PM 12740374 ER PT J AU Mao, CG Xu, RJ Szulc, ZM Bielawski, J Becker, KP Bielawska, A Galadari, SH Hu, W Obeid, LM AF Mao, CG Xu, RJ Szulc, ZM Bielawski, J Becker, KP Bielawska, A Galadari, SH Hu, W Obeid, LM TI Cloning and characterization of a mouse endoplasmic reticulum alkaline ceramidase - An enzyme that preferentially regulates metabolism of very long chain ceramides SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN ACID CERAMIDASE; MOLECULAR-CLONING; NEUTRAL CERAMIDASE; SACCHAROMYCES-CEREVISIAE; PSEUDOMONAS-AERUGINOSA; PURIFICATION; SYNTHASE; DISEASE; SPHINGOMYELINASE; NEUTRAL/ALKALINE AB Ceramidases deacylate ceramides, important intermediates in the metabolic pathway of sphingolipids. In this study, we report the cloning and characterization of a novel mouse alkaline ceramidase (maCER1) with a highly restricted substrate specificity. maCER1 consists of 287 amino acids, and it has a 28 and 32% identity to the Saccharomyces alkaline ceramidases (YPC1p and YDC1p) and the human alkaline phytoceramidase, respectively. Reverse transcriptase-PCR analysis demonstrated that maCER1 was predominantly expressed in skin. maCER1 was localized to the endoplasmic reticulum as revealed by immunocytochemistry. In vitro biochemical characterization determined that maCER1 hydrolyzed D-erythro-ceramide exclusively but not D-erythro-dihydroceramide or D-ribo-phytoceramide. Similar to other alkaline ceramidases, maCER1 had an alkaline pH optimum of 8.0, and it was activated by Ca2+ but inhibited by Zn2+, Cu2+, and Mn2+. maCER1 was also inhibited by sphingosine, one of its products. Metabolic labeling studies showed that overexpression of maCER1 caused a decrease in the incorporation of radiolabeled dihydrosphingosine into ceramide and complex sphingolipids but led to a concomitant increase in sphingosine-1-P (S1P) in HeLa cells. Mass measurement showed that overexpression of maCER1 selectively lowered the cellular levels of D-erythro-C-24:1-ceramide, but not other ceramide species and caused an increase in the levels of S1P. Taken together, these data suggest that maCER1 is a novel alkaline ceramidase with a stringent substrate specificity and that maCER1 is selectively expressed in skin and may have a role in regulating the levels of bioactive lipids ceramide and S1P, as well as complex sphingolipids. C1 Med Univ S Carolina, Dept Med, Div Gen Internal Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson Vet Adm Hosp, Charleston, SC 29425 USA. United Arab Emirates Univ, Dept Biochem, Fac Med & Hlth Sci, Al Ain, U Arab Emirates. RP Mao, CG (reprint author), Med Univ S Carolina, Dept Med, Div Gen Internal Med, 114 Doughty St,Rm 605 STB,POB 250779, Charleston, SC 29425 USA. OI obeid, lina/0000-0002-0734-0847 FU NCRR NIH HHS [1P20RR017677-01]; NIGMS NIH HHS [GM62887-01] NR 30 TC 59 Z9 61 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 15 PY 2003 VL 278 IS 33 BP 31184 EP 31191 DI 10.1074/jbc.M303875200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 710AN UT WOS:000184658800096 PM 12783875 ER PT J AU Kinoshita, A Fukumoto, H Shah, T Whelan, CM Irizarry, MC Hyman, BT AF Kinoshita, A Fukumoto, H Shah, T Whelan, CM Irizarry, MC Hyman, BT TI Demonstration by FRET of BACE interaction with the amyloid precursor protein at the cell surface and in early endosomes SO JOURNAL OF CELL SCIENCE LA English DT Article DE Alzheimer's disease; amyloid-beta peptide; amyloid precursor protein; BACE; co-localization; fluorescence resonance energy transfer; endocytosis ID BETA-SECRETASE CLEAVAGE; RESONANCE ENERGY-TRANSFER; RECEPTOR-RELATED PROTEIN; ALZHEIMERS-DISEASE; ENDOCYTIC PATHWAYS; NT2N CELLS; BRAIN; COMPARTMENT; ASSOCIATION; EXPRESSION AB Amyloid-beta peptide, which accumulates in senile plaques in Alzheimer's disease, is derived from the amyloid precursor protein (APP) by proteolytic processing. beta-secretase (Asp2), which cleaves APP at the N-terminus of amyloid-beta, has recently been identified to be the protease BACE. In the present study, we examined the subcellular localization of interactions between APP and BACE by using both double immunofluorescence and a fluorescence resonance energy transfer (FRET) approach. Cell surface APP and BACE, studied by using antibodies directed against their ectodomains in living H4 neuroglioma cells co-transfected with APP and BACE, showed exquisite co-localization and demonstrated a very close interaction by FRET analysis. The majority of cell surface APP and BACE were internalized after 15 minutes, but they remained strongly co-localized together in the early endosomal compartment, where FRET analysis demonstrated a continued close interaction. By contrast, at later timepoints, almost no co-localization or FRET was observed in lysosomal compartments. To determine whether the APP-BACE interaction on cell surface and endosomes contributed to amyloid-beta synthesis, we labeled cell surface APP and demonstrated detectable levels of labeled amyloid-beta within 30 minutes. APP-Swedish mutant protein enhanced amyloid-beta synthesis from cell surface APP, consistent with the observation that it is a better BACE substrate than wild-type APP. Taken together, these data confirm a close APP-BACE interaction in early endosomes, and highlight the cell surface as an additional potential site of APP-BACE interaction. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Alzheimer Dis Res Lab, Boston, MA 02129 USA. RP Hyman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Alzheimer Dis Res Lab, Boston, MA 02129 USA. FU NIA NIH HHS [AG12406, AG15379, P01 AG05134] NR 32 TC 149 Z9 155 U1 2 U2 16 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD AUG 15 PY 2003 VL 116 IS 16 BP 3339 EP 3346 DI 10.1242/jcs.00643 PG 8 WC Cell Biology SC Cell Biology GA 755GH UT WOS:000187394800010 PM 12829747 ER PT J AU Fossella, F Pereira, JR von Pawel, J Pluzanska, A Gorbounova, V Kaukel, E Mattson, KV Ramlau, R Szczesna, A Fidias, P Millward, M Belani, CP AF Fossella, F Pereira, JR von Pawel, J Pluzanska, A Gorbounova, V Kaukel, E Mattson, KV Ramlau, R Szczesna, A Fidias, P Millward, M Belani, CP TI Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: The TAX 326 study group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 27th European-Society-for-Medical-Oncology Congress CY OCT 18-22, 2002 CL NICE, FRANCE SP European Soc Med Oncol ID SOUTHWEST-ONCOLOGY-GROUP; TRIAL COMPARING CISPLATIN; QUALITY-OF-LIFE; CHEMOTHERAPY REGIMENS; CLINICAL-TRIALS; SUPPORTIVE CARE; STAGE-IIIB; CARBOPLATIN; MULTICENTER; PACLITAXEL AB Purpose: To investigate whether docetaxel plus platinum regimens improve survival and affect quality of life (QoL) in advanced non-small-cell lung cancer (NSCLC) compared with vinorelbine plus cisplatin as first-line chemotherapy. Patients and Methods: Patients (n = 1,218) with stage IIIB to IV NSCLC were randomly assigned to receive docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) every 3 weeks (DC); docetaxel 75 mg/m(2) and carboplatin area under the curve of 6 mg/mL . min every 3 weeks (DCb); or vinorelbine 25 mg/ m(2)/wk and cisplatin 100 mg/m(2) every 4 weeks (VC). Results: Patients treated with DC had a median survival of 11.3 v 10.1 months for VC-treated patients (P =.044; hazard ratio, 1.183 [97.2% confidence interval, 0.989 to 1.416]). The 2-year survival rate was 21% for DC-treated patients and 14% for VC-treated patients. Overall response rate was 31.6% for DC-treated patients v 24.5% for VC-treated patients (P =.029). Median survival (9.4 v 9.9 months [for VC]; P =.657; hazard ratio, 1.048 [97.2 confidence interval, 0.877 to 1.253]) and response (23.9%) with DCb were similar to those results for VC. Neutropenia,. thrombocytopenia, infection, and febrile neutropenia were similar with all three regimens. Grade 3 to 4 anemia, nausea, and vomiting were more common (P <.01) with VC than with DC or DCb. Patients treated with either docetaxel regimen had consistently improved Gal. compared with VC-treated patients, who experienced deterioration in QoL. Conclusion: DC resulted in a more favorable overall response and survival rate than VC. Both DC and DCb were better tolerated and provided patients with consistently improved QoL compared with VC. These findings demonstrate that a docetaxel plus platinum combination is an effective treatment option with a favorable therapeutic index for firstline treatment of advanced or metastatic NSCLC. C1 Univ Pittsburgh, Med Ctr, Inst Canc, Div Med Oncol, Pittsburgh, PA 15232 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Inst Canc Arnaldo Vieira de Carvalho, Sao Paulo, Brazil. Asklepios Fachklin Munchen Gauting, Gauting, Germany. M Kopernik Mem Hosp, Lodz, Poland. RAMS, Canc Res Ctr, Moscow, Russia. AK Hamburg Harbug, Hamburg, Germany. Univ Helsinki, Cent Hosp, Helsinki, Finland. Reg Lung Dis Ctr, Poznan, Poland. Reg Lung Dis Hosp, Otwock, Poland. Massachusetts Gen Hosp, Boston, MA 02114 USA. Sydney Canc Ctr, Camperdown, NSW, Australia. RP Belani, CP (reprint author), Univ Pittsburgh, Med Ctr, Inst Canc, Div Med Oncol, Canc Pavil,5150 Ctr Ave,Suite 570, Pittsburgh, PA 15232 USA. RI Millward, Michael/H-5456-2014; OI Belani, Chandra/0000-0001-5049-5329 NR 38 TC 604 Z9 645 U1 1 U2 18 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 15 PY 2003 VL 21 IS 16 BP 3016 EP 3024 DI 10.1200/JCO.2003.12.046 PG 9 WC Oncology SC Oncology GA 712CZ UT WOS:000184780300005 PM 12837811 ER PT J AU Clark, JI Atkins, MB Urba, WJ Creech, S Figlin, RA Dutcher, JP Flaherty, L Sosman, JA Logan, TF White, R Weiss, GR Redman, BG Tretter, CPG McDermott, D Smith, JW Gordon, MS Margolin, KA AF Clark, JI Atkins, MB Urba, WJ Creech, S Figlin, RA Dutcher, JP Flaherty, L Sosman, JA Logan, TF White, R Weiss, GR Redman, BG Tretter, CPG McDermott, D Smith, JW Gordon, MS Margolin, KA TI Adjuvant high-dose bolus interleukin-2 for patients with high-risk renal cell carcinoma: A cytokine working group randomized trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 01, 2003 CL CHICAGO, ILLINOIS SP Amer Soc Clin Oncol ID PHASE-II TRIAL; GROUP EXPERIENCE 1986-2001; RECOMBINANT INTERLEUKIN-2; RADICAL NEPHRECTOMY; INTERFERON-ALPHA; CLINICAL-TRIALS; KIDNEY CANCER; STAGE-II; IMMUNOTHERAPY; MANAGEMENT AB Purpose : This prospective, randomized, controlled phase III trial assessed high-dose bolus interleukin-2 (IL-2) postoperatively in patients with high-risk renal cell carcinoma (RCC). Patients and Methods: Eligibility requirements were resected locally advanced (LA, T3b-4 or N1-3) or metastatic (M1) RCC, no prior systemic therapy, and excellent organ function. Randomized assignment was to one course of IL-2 (600,000 U/kg every 8 hours on days 1 to 5 and days 15 to 19 [maximum 28 doses]) or observation. The study was designed and powered to show an improvement in predicted 2-year disease-free survival (DFS) from 400% for the observation group to 70% for the treatment group. The accrual goal was 68 patients with LA disease, with 34 patients per treatment arm. Metastasectomy patients were to be analyzed separately because of their unpredictable natural history. Results : Sixty-nine patients were enrolled onto the study (44 LA and 25 M1 patients). Toxic effects of IL-2 were as anticipated; no unexpected serious adverse events or treatment-related deaths occurred. Early closure occurred when an interim analysis determined that the 30% improvement in 2-year DFS could not be achieved despite full accrual. Sixteen of 21 LA patients receiving IL-2 experienced relapse, compared with 15 of 23 patients in the observation arm (P =.73); in the LA group, three deaths occurred in the IL-2 arm, and five deaths occurred in the observation arm (P =.38). Analysis including metastasectomy patients made no difference in DFS or overall survival. Conclusion: One course of high-dose bolus IL-2, though feasible, did not produce the ambitious clinically meaningful benefit anticipated when administered postoperatively to patients with resected high-risk RCC. C1 Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Providence Portland Med Ctr, Earle A Chiles Res Inst, Portland, OR USA. Univ Calif Los Angeles, Los Angeles, CA USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Our Lady Mercy Comprehens Canc Ctr, New York, NY USA. Wayne State Univ, Detroit, MI USA. Univ Michigan, Ann Arbor, MI 48109 USA. Vanderbilt Univ, Nashville, TN USA. Indiana Univ, Indianapolis, IN 46204 USA. Carolinas Med Ctr, Charlotte, NC 28203 USA. Univ Texas, S Texas Vet Hlth Care Syst, San Antonio, TX 78285 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Arizona Hlth Sci Ctr, Phoenix, AZ USA. RP Clark, JI (reprint author), Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, 2160 S 1st Ave, Maywood, IL 60153 USA. NR 30 TC 143 Z9 153 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 15 PY 2003 VL 21 IS 16 BP 3133 EP 3140 DI 10.1200/JCO.2003.02.014 PG 8 WC Oncology SC Oncology GA 712CZ UT WOS:000184780300021 PM 12810695 ER PT J AU Tzachanis, D Appleman, LJ van Puijenbroek, AAFL Berezovskaya, A Nadler, LM Boussiotis, VA AF Tzachanis, D Appleman, LJ van Puijenbroek, AAFL Berezovskaya, A Nadler, LM Boussiotis, VA TI Differential localization and function of ADP-ribosylation factor-6 in anergic human T cells: A potential marker for their identification SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LONG-TERM ACCEPTANCE; MEDIATED ENDOCYTOSIS; CARDIAC ALLOGRAFTS; SIGNALING PATHWAY; ACTIVATION; ARF6; VAV; STIMULATION; PROTEIN; CD28 AB Anergy is a state of immunologic tolerance in which T cells are viable but incapable of responding to antigenic stimulation. Recent data indicate that anergic cells have a distinct gene expression program that determines their unique function. In this study we show that anergic human T cells selectively express the small GTPase ADP-ribosylation factor-6 (ARF6), which is involved in membrane traffic and regulation of the cortical actin cytoskeleton. ARF6 was expressed in the GTP-bound form that localizes at the plasma membrane, resulting in a distinct morphologic appearance of anergic cells. Forced expression of ARF6-GTP in Jurkat T cells prevented TCR-mediated reorganization of cortical actin, extracellular signal-regulated kinase1/2 activation, and IL-2 transcription. Forced expression of ARF6-GTP in primary human T cells inhibited extracellular signal-regulated kinase1/2 activation and proliferative responses. Importantly, T cells with the distribution pattern of ARF6-GTP were detected in peripheral blood, suggesting that anergic T cells may constitutively exist in vivo. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Boussiotis, VA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Mayer 547,44 Binney St, Boston, MA 02115 USA. OI Appleman, Leonard/0000-0003-4951-7388 FU NIAID NIH HHS [AI46584, AI41584, AI43552] NR 40 TC 4 Z9 5 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 AUG 15 PY 2003 VL 171 IS 4 BP 1691 EP 1696 PG 6 WC Immunology SC Immunology GA 710EG UT WOS:000184667400013 PM 12902467 ER PT J AU Cariappa, A Chen, LJ Haider, K Tang, M Nebelitskiy, E Moran, ST Pillai, S AF Cariappa, A Chen, LJ Haider, K Tang, M Nebelitskiy, E Moran, ST Pillai, S TI A catalytically inactive form of protein kinase C-associated kinase/receptor interacting protein 4, a protein kinase C beta-associated kinase that mediates NF-kappa B activation, interferes with early B cell development SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BRUTONS TYROSINE KINASE; PHOSPHOLIPASE C-GAMMA-2; BONE-MARROW; RECEPTOR; RIP; LYMPHOCYTES; APOPTOSIS; DEATH; PHOSPHORYLATION; DIFFERENTIATION AB Protein kinase C-associated kinase (PKK)/receptor interacting protein 4 (RIP4) is a protein kinase C (PKC) beta-associated kinase that links PKC to NF-kappaB activation. The kinase domain of PKK is similar to that of RIP, RIP2, and RIP3. We show in this study that PKK is expressed early during lymphocyte development and can be detected in common lymphoid progenitor cells. Targeting of a catalytically inactive version of PKK to lymphoid cells resulted in a marked impairment in pro-B cell generation in the bone marrow. Although peripheral B cell numbers were markedly reduced, differentiation into follicular and marginal zone B cells was not defective in these mice. B-1a and B-1b B cells could not be detected in these mice, but this might be a reflection of the overall defect in B cell production observed in these animals. In keeping with a possible link to PKCbeta, peripheral B cells in these mice exhibit a defect in anti-IgM-mediated proliferation. These studies suggest that PKK may be required early in B cell development and for BCR-mediated B cell proliferation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. RP Pillai, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NIAID NIH HHS [AI33507]; NIDDK NIH HHS [DK43351] NR 39 TC 16 Z9 16 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 AUG 15 PY 2003 VL 171 IS 4 BP 1875 EP 1880 PG 6 WC Immunology SC Immunology GA 710EG UT WOS:000184667400035 PM 12902489 ER PT J AU Reche, PA Reinherz, EL AF Reche, PA Reinherz, EL TI Sequence variability analysis of human class I and class II MHC molecules: Functional and structural correlates of amino acid polymorphisms SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE HLA polymorphism; T-cell receptor; sequence variability; alloreactivity; major histocompatibility complex ID MAJOR HISTOCOMPATIBILITY COMPLEX; T-CELL-RECEPTOR; CRYSTAL-STRUCTURE; NUCLEOTIDE SUBSTITUTION; 3-DIMENSIONAL STRUCTURE; OVERDOMINANT SELECTION; ANTIGEN RECOGNITION; NEGATIVE SELECTION; NONCLASSICAL MHC; PEPTIDE BINDING AB Major histocompatibility complex class I (MHCI) and class II (MHCII) molecules display peptides on antigen-presenting cell surfaces for subsequent T-cell recognition. Within the human population, allelic variation among the classical MHCI and II gene products is the basis for differential peptide binding, thymic repertoie bias and allograft rejection. While available 3D structural analysis suggests that polymorphisms are found primarily within the peptide-binding site, a broader informatic approach pinpointing functional polymorphisms relevant for immune recognition is currently lacking. To this end, we have now analyzed known human class I (774) and class II (485) alleles at each amino acid position using a variability metric (V). Polymorphisms (V > 1) have been identified in residues that contact the peptide and/or T-cell receptor (TCR). Using sequence logos to investigate TCR contact sites on HLA molecules, we have identified conserved MHCl residues distinct from those of conserved MHCII residues. In addition, specific class II (HLA-DP, -DQ, -DR) and class I (HLA-A, -13, -C) contacts for TCR binding are revealed. We discuss these findings in the context of TCR restriction and alloreactivity. (C) 2003 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. RP Reinherz, EL (reprint author), Harvard Univ, Sch Med, Dept Med, 44 Binney St, Boston, MA 02115 USA. RI Reche, Pedro/B-1881-2013 OI Reche, Pedro/0000-0003-3966-5838 FU NIAID NIH HHS [AI50900] NR 69 TC 190 Z9 200 U1 2 U2 19 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD AUG 15 PY 2003 VL 331 IS 3 BP 623 EP 641 DI 10.1016/S0022-2836(03)00750-2 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 709XH UT WOS:000184651500008 PM 12899833 ER PT J AU Schulten, AJM Zimmermann, CE Glowacki, J AF Schulten, AJM Zimmermann, CE Glowacki, J TI Osteoclastic bone resorption around intraosseous screws in rat and pig mandibles SO MICROSCOPY RESEARCH AND TECHNIQUE LA English DT Article DE implant loosening; nicotine; cartilage; fixation; distraction osteogenesis ID DISTRACTION; COMPLICATIONS; ARTHROPLASTY; OBSTACLES; FIXATION AB This report describes osteoclastic bone resorption around intraosseous fixation screws in rat and pig mandibles. These screws supported distraction devices and provided for neutral fixation following the distraction period. Progressive clinical instability of bicortical screws and radiographic and histologic evidence of osseous resorption were frequent findings. In rats, clinical evaluation revealed screw loss and/or loosening in 50% of the rats between 11 and 30 days of neutral fixation. Radiographic signs of resorption were apparent around 60% of the screws that were in place at the end of the observation period. The total rate of resorption or loss was 64 of 80 screws (80%). Histologic examination showed partial or extensive osteolysis around the screw holes in 87% of screws that were clinically fixed in the bone at sacrifice. In histologic sections of porcine specimens, osseous resorption around identifiable screw holes was present in 75% of the cases, and showed progressive increase in resorption with time. Osteoclastic resorption was common around bicortical screws that were evaluated after they had served for osseous stability. (C) 2003 Wiley-Liss, Inc. C1 Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. RP Glowacki, J (reprint author), Brigham & Womens Hosp, Dept Orthoped Surg, 75 Francis St, Boston, MA 02115 USA. NR 26 TC 6 Z9 6 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-910X J9 MICROSC RES TECHNIQ JI Microsc. Res. Tech. PD AUG 15 PY 2003 VL 61 IS 6 BP 533 EP 539 DI 10.1002/jemt.10376 PG 7 WC Anatomy & Morphology; Biology; Microscopy SC Anatomy & Morphology; Life Sciences & Biomedicine - Other Topics; Microscopy GA 703ML UT WOS:000184283300007 PM 12879420 ER PT J AU Atlas, SJ Deyo, RA van den Ancker, M Singer, DE Keller, RB Patrick, DL AF Atlas, SJ Deyo, RA van den Ancker, M Singer, DE Keller, RB Patrick, DL TI The Maine-Seattle back questionnaire: A 12-item disability questionnaire for evaluating patients with lumbar sciatica or stenosis - Results of a derivation and validation cohort analysis SO SPINE LA English DT Article DE health-related quality of life; outcome measures; sciatica; lumbar intervertebral disc herniation; lumbar spinal stenosis; prospective cohort study ID QUALITY-OF-LIFE; HEALTH-STATUS; NONSURGICAL MANAGEMENT; 1-YEAR OUTCOMES; PAIN; SPINE; INSTRUMENTS AB Study Design. Analysis of health-related quality of life data obtained from a prospective cohort study of patients with sciatica due to an intervertebral disc herniation or lumbar spinal stenosis. Objective. To derive and validate a shortened version of a previously validated 23-item modification of the Roland-Morris Disability Questionnaire. Summary of Background Data. For patients with low back pain, improving health-related quality of life is often the main goal of therapy. The Roland-Morris Disability Questionnaire is one of the best validated and most frequently used back-specific functional status measures. A shortened version may permit more widespread use in clinical and research settings. Methods. Data from 507 patients with sciatica enrolled in the Maine Lumbar Spine Study were used to derive a shortened version of a 23-item modification of the original Roland-Morris Disability Questionnaire using qualitative and cluster analysis techniques. The internal consistency, construct validity, reproducibility, and responsiveness in detecting change over a 3-month period for a new 12-item scale was compared to the original 23-item scale. The 12-item scale was then validated in an independent cohort of 148 patients with lumbar spinal stenosis. Results. Internal consistency was very good but modestly lower for the 12-item instrument compared to the 23-item original scale. Reproducibility over a 3-month interval was good and did not differ between the 12-item and original scale. Findings from the validation cohort were similar or better than the derivation cohort. A high degree of construct validity with patient-reported symptoms was demonstrated for the 12-item and original scales. The responsiveness and interpretability of the 12-item scale over 3 months was excellent and comparable to the original scale. Responsiveness assessed in patients with lumbar spinal stenosis in the independent validation cohort showed consistent findings compared to patients with a disc herniation in the derivation cohort. Conclusions. This short, simple, self-administered 12-item back-specific functional status questionnaire performed extremely well in comparison with the original 23-item scale. If validated in additional study populations, this new questionnaire may be useful in the clinical setting as a way for providers to prospectively compare their outcomes of care to other patient populations, and to study treatment effectiveness. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv,Clin Epidemiol Unit, Boston, MA USA. Univ Washington, Ctr Cost & Outcomes Res, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Maine Med Assessment Fdn, Augusta, ME USA. RP Atlas, SJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, 50 Staniford St, Boston, MA 02114 USA. FU AHRQ HHS [HS-06344, HS-08194, HS-09804] NR 19 TC 30 Z9 31 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD AUG 15 PY 2003 VL 28 IS 16 BP 1869 EP 1876 DI 10.1097/01.BRS.0000083205.82614.01 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 715JV UT WOS:000184969100019 PM 12923478 ER PT J AU Yamada, K Vagefi, PA Utsugi, R Kitamura, H Barth, RN LaMattina, JC Sachs, DH AF Yamada, K Vagefi, PA Utsugi, R Kitamura, H Barth, RN LaMattina, JC Sachs, DH TI Thymic transplantation in miniature swine. III. Induction of tolerance by transplantation of composite thymokidneys across fully major histocompatibility complex-mismatched barriers SO TRANSPLANTATION LA English DT Article ID DISPARATE RENAL-ALLOGRAFTS; ACTIVATED T-CELLS; CLASS-I; ADULT THYMUS; IMMUNOTOXIN; CYCLOSPORINE; RESPONSES; PCD3-CRM9; ANTIGENS; ANTIBODY AB Background. This study determines whether composite thymokidney (TK) grafts, created by implantation of autologous thymic tissue beneath the donor's renal capsule before transplantation, could induce allogeneic transplantation tolerance across two-haplotype fully major histocompatibility complex (MHC)mismatched barriers in juvenile AGH-miniature swine. Methods. TK grafts were prepared by implanting autologous thymic tissue under the renal capsule of donor animals 2 to 3 months before transplantation. Four recipients were treated with a T-cell-depleting immunotoxin and received fully AMC-mismatched TK grafts plus a 12-day course of cyclosporine A (CsA). Control animals were treated with CsA alone or both CsA and immunotoxin, but with a normal kidney or a kidney implanted with autologous lymph node rather than thymus. Renal graft function was assessed by plasma creatinine levels and histologic analyses. Immunologic status was monitored by cell-mediated lympholysis assays. Results. All four recipients of fully AMC-mismatched TK transplants treated with immunotoxin and a 12-day course of CsA accepted their composite renal allografts long-term. All control recipients receiving a TK and CsA alone, a normal kidney or a composite kidney containing lymph node tissue acutely rejected their grafts. Conclusions. To our knowledge, this is the first demonstration that functional vascularized thymic grafts can induce transplantation tolerance across fully MHC-mismatched barriers in a large animal model. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02129 USA. RP Sachs, DH (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH-E,Bldg 149-9019,13th St, Boston, MA 02129 USA. RI Barth, Rolf/B-2542-2014; LaMattina, John/B-2976-2014 OI LaMattina, John/0000-0001-7016-0382 FU NIAID NIH HHS [1P01 AI45897, 2R01 AI31046] NR 29 TC 30 Z9 31 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 AUG 15 PY 2003 VL 76 IS 3 BP 530 EP 536 DI 10.1097/01.TP.0000080608.42480.E8 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 712DJ UT WOS:000184781500014 PM 12923439 ER PT J AU Yang, XZ Mahony, E Holm, GH Kassa, A Sodroski, J AF Yang, XZ Mahony, E Holm, GH Kassa, A Sodroski, J TI Role of the gp120 inner domain beta-sandwich in the interaction between the human immunodeficiency virus envelope glycoprotein subunits SO VIROLOGY LA English DT Article DE human immunodeficiency virus; envelope glycoproteins; gp120; gp41 ID IN-VIVO; CHEMOKINE RECEPTORS; RHESUS-MONKEYS; HIV-1 ENTRY; TRANSMEMBRANE GLYCOPROTEIN; AIDS PATIENTS; HTLV-III; TYPE-1; PROTEIN; GP41 AB The inner domain of the human immunodeficiency virus (HIV-1) gp120 glycoprotein has been proposed to mediate the noncovalent interaction with the gp41 transmembrane envelope glycoprotein. We used mutagenesis to investigate the functional importance of a conserved b-sandwich located within the gp120 inner domain. Changes in aliphatic residues lining a hydrophobic groove on the surface of the b-sandwich decreased the association of the gp120 and gp41 glycoproteins. Other changes in the base of the hydrophobic groove resulted in envelope glycoproteins that were structurally intact and able to bind receptors, but were inefficient in mediating either syncytium formation or virus entry. These results support a model in which the b-sandwich in the gp120 inner domain contributes to gp120-gp41 contacts, thereby maintaining the integrity of the envelope glycoprotein complex and allowing adjustments in the gp120-gp41 interaction required for membrane fusion. 2003 Elsevier Science (USA). All rights reserved. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div AIDS, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. RI Holm, Geoffrey/C-3188-2009 FU NIAID NIH HHS [AI40895, AI24755, AI28691, AI39420, AI41851] NR 41 TC 39 Z9 39 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD AUG 15 PY 2003 VL 313 IS 1 BP 117 EP 125 DI 10.1016/S0042-6822(03)00273-3 PG 9 WC Virology SC Virology GA 719NJ UT WOS:000185209200012 PM 12951026 ER PT J AU Modlin, JF Grant, PE Makar, RS Roberts, DJ Krishnamoorthy, KS Walsh, S Harris, NL Catlin, EA Casavant, DW AF Modlin, JF Grant, PE Makar, RS Roberts, DJ Krishnamoorthy, KS Walsh, S Harris, NL Catlin, EA Casavant, DW TI A newborn boy with petechiae and thrombocytopenia - Congenital cytomegalovirus infection. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PRENATAL-DIAGNOSIS; TRANSMISSION; CARE; MANIFESTATIONS; PREGNANCY; CHILDREN; PLACENTA; ANTIBODY; DISEASE C1 Dartmouth Hitchcock Med Ctr, Dept Pediat, Lebanon, NH 03766 USA. Dartmouth Hitchcock Med Ctr, Dept Med, Lebanon, NH 03766 USA. Dartmouth Coll Sch Med, Lebanon, NH USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Modlin, JF (reprint author), Dartmouth Hitchcock Med Ctr, Dept Pediat, Lebanon, NH 03766 USA. NR 35 TC 8 Z9 8 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 AUG 14 PY 2003 VL 349 IS 7 BP 691 EP 700 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 711FL UT WOS:000184728900012 PM 12917307 ER PT J AU Sheridan, RL AF Sheridan, RL TI Burn care - Results of technical and organizational progress SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID TOXIC EPIDERMAL NECROLYSIS; ACUTE HAND BURNS; HYPERBARIC-OXYGEN; 10-YEAR EXPERIENCE; CHILDREN; MANAGEMENT; INJURIES; TRIAL C1 Shriners Hosp Children, Burn Surg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Div Burns & Trauma, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Sheridan, RL (reprint author), Shriners Hosp Children, Burn Surg Serv, 51 Blossom St, Boston, MA 02114 USA. NR 29 TC 38 Z9 40 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 13 PY 2003 VL 290 IS 6 BP 719 EP 722 DI 10.1001/jama.290.6.719 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 709VU UT WOS:000184647700002 PM 12915409 ER PT J AU Fize, D Vanduffel, W Nelissen, K Denys, K d'Hotel, CC Faugeras, O Orban, GA AF Fize, D Vanduffel, W Nelissen, K Denys, K d'Hotel, CC Faugeras, O Orban, GA TI The retinotopic organization of primate dorsal V4 and surrounding areas: A functional magnetic resonance imaging study in awake monkeys SO JOURNAL OF NEUROSCIENCE LA English DT Article DE functional imaging; macaque; retinotopy; extrastriate cortex; cortical magnification; homology ID SUPERIOR TEMPORAL SULCUS; HUMAN VISUAL-CORTEX; LATERAL INTRAPARIETAL AREA; MACAQUE MONKEY; RHESUS-MONKEY; CORTICAL CONNECTIONS; PRELUNATE GYRUS; TOPOGRAPHIC ORGANIZATION; VISUOTOPIC ORGANIZATION; EXTRASTRIATE CORTEX AB Using functional magnetic resonance imaging (fMRI), we mapped the retinotopic organization throughout the visual cortex of fixating monkeys. The retinotopy observed in areas V1, V2, and V3 was completely consistent with the classical view. V1 and V3 were bordered rostrally by a vertical meridian representation, and V2 was bordered by a horizontal meridian. More anterior in occipital cortex, both areas V3A and MT-V5 had lower and upper visual field representations split by a horizontal meridian. The rostral border of dorsal V4 was characterized by the gradual transition of a representation of the vertical meridian (dorsally) to a representation of the horizontal meridian (more ventrally). Central and ventral V4, on the other hand, were rostrally bordered by a representation of the horizontal meridian. The eccentricity lines ran perpendicular to the ventral V3-V4 border but were parallel to the dorsal V3-V4 border. These results indicate different retinotopic organizations within dorsal and ventral V4, suggesting that the latter regions may not be merely the lower and upper visual field representations of a single area. Moreover, because the present fMRI data are in agreement with previously published electrophysiological results, reported distinctions in the retinotopic organization of human and monkey dorsal V4 reflect genuine species differences that cannot be attributed to technical confounds. Finally, aside from dorsal V4, the retinotopic organization of macaque early visual cortex (V1, V2, V3, V3A, and ventral V4) is remarkably similar to that observed in human fMRI studies. This finding indicates that early visual cortex is mostly conserved throughout hominid evolution. C1 Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, MIT,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Katholieke Univ Leuven, Neuro & Psychofysiol Lab, B-3000 Louvain, Belgium. INRIA Sophia Antipolis, Inst Natl Rech Informat & Automat, F-06902 Sophia Antipolis, France. RP Vanduffel, W (reprint author), Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, MIT,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RI Fize, Denis/F-4525-2011 NR 67 TC 106 Z9 110 U1 1 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 13 PY 2003 VL 23 IS 19 BP 7395 EP 7406 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 712UX UT WOS:000184817700020 PM 12917375 ER PT J AU Cook, SA Novikov, MS Ahn, Y Matsui, T Rosenzweig, A AF Cook, SA Novikov, MS Ahn, Y Matsui, T Rosenzweig, A TI A20 is dynamically regulated in the heart and inhibits the hypertrophic response SO CIRCULATION LA English DT Article DE hypertrophy; apoptosis; inflammation ID FACTOR-KAPPA-B; INDUCED CARDIOMYOCYTE HYPERTROPHY; APOPTOSIS; GENE; PROTEIN; ACTIVATION; MYOCYTES; MICE AB Background-Nuclear factor (NF)-kappaB signaling has been implicated in cardiomyocyte hypertrophy. Here, we determine the cardiac regulation and biological activity of A20, an inhibitor of NF-kappaB signaling. Methods and Results-Mice were subjected to aortic banding, and A20 expression was examined. A20 mRNA upregulation (4.3 +/- 1.5- fold; P < 0.05) was detected 3 hours after banding, coinciding with peak NF-κB activation. A20 was also upregulated in cultured neonatal cardiomyocytes stimulated with phenylephrine or endothelin-1 (2.8 &PLUSMN; 0.6- and 4 &PLUSMN; 1.1-fold, respectively; P < 0.05), again paralleling NF-kappaB activation. Infection of cardiomyocytes with an adenoviral vector ( Ad) encoding A20 inhibited tumor necrosis factor-alpha-stimulated NF-kappaB signaling with an efficacy comparable to dominant negative inhibitor of kappa-B kinase beta (dnIKKbeta). Ad.dnIKKbeta-infected cardiomyocytes exhibited increased apoptosis when they were serum starved or subjected to hypoxia-reoxygenation, whereas Ad. A20-infected cardiomyocytes did not. Expression of Ad. A20 inhibited the hypertrophic response in cardiomyocytes stimulated with phenylephrine or endothelin-1. Conclusions-A20 is dynamically regulated during acute biomechanical stress in the heart and functions to attenuate cardiac hypertrophy through the inhibition of NF-kappaB signaling without sensitizing cardiomyocytes to apoptotic cell death. C1 Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Sch Med, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Program Cardiovasc Gene Therapy, Sch Med,Cardiovasc Res Ctr, Boston, MA 02129 USA. RP Rosenzweig, A (reprint author), Massachusetts Gen Hosp, 114 16th St,Rm 2600, Charlestown, MA 02129 USA. RI Cook, Stuart/G-9567-2011; OI Cook, Stuart/0000-0001-6628-194X FU NHLBI NIH HHS [HL-04250, HL-59521, HL-61557] NR 17 TC 52 Z9 56 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 12 PY 2003 VL 108 IS 6 BP 664 EP 667 DI 10.1161/01.CIR.0000086978.95976.41 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 710ZM UT WOS:000184712700008 PM 12900338 ER PT J AU Kubo, SJ Saeki, Y Chiocca, EA Mitani, K AF Kubo, SJ Saeki, Y Chiocca, EA Mitani, K TI An HSV amplicon-based helper system for helper-dependent adenoviral vectors SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE gene therapy; HSV amplicon; helper-dependent adenoviral vector; helper virus-free stock ID BACTERIAL ARTIFICIAL CHROMOSOME; ESCHERICHIA-COLI; IN-VIVO; VIRUS; DNA; CAPACITY; REPLICATION; EXPRESSION; RESCUE; TYPE-5 AB To produce a helper virus-free stock of helper-dependent adenoviral vectors (HDAdVs), we have developed a new helper system in which adenoviral genes for propagation of HDAdVs are delivered into producer cells by a herpes simplex virus-1 (HSV) amplicon-adenovirus hybrid. The hybrid amplicon was constructed to carry the E1 gene (HA-E1) or the entire adenoviral genome except E1 (HA-Ad). El expression from the HSV amplicon successfully complemented propagation of an El-deleted adenoviral vector in a human glioma cell line. HDAdVs were propagated in 293 cells infected with HA-Ad. In addition, HDAdVs were rescued and propagated in a glioma cell line superinfected with both HA-E1 and HA-Ad amplicons, although relatively low titers of HSV amplicon resulted in low propagation efficiency of HDAdVs. Since the HSV amplicon can be easily and completely inactivated by chloroform extraction and/or heat treatment from the HDAdV stock, this helper system might be an alternative method to produce helper virus-free HDAdVs. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90024 USA. Massachusetts Gen Hosp, Mol Neurooncol Labs, Charlestown, MA USA. Harvard Med Sch, Charlestown, MA USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Med, Los Angeles, CA 90024 USA. RP Mitani, K (reprint author), Univ Calif Los Angeles, Sch Med, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90024 USA. NR 20 TC 6 Z9 6 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 8 PY 2003 VL 307 IS 4 BP 826 EP 830 DI 10.1016/SO006-291X(03)01256-7 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 707KP UT WOS:000184510100012 PM 12878185 ER PT J AU Huang, RY Boulton, SJ Vidal, M Almo, SC Bresnick, AR Chance, MR AF Huang, RY Boulton, SJ Vidal, M Almo, SC Bresnick, AR Chance, MR TI High-throughput expression, purification, and characterization of recombinant Caenorhabditis elegans proteins SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID X-RAY RADIOLYSIS; MASS-SPECTROMETRY; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; STRUCTURAL GENOMICS; STEP PURIFICATION; BINDING PROTEIN; COMPLEXES; PIPELINE; LYSOZYME AB Modern proteomics approaches include techniques to examine the expression, localization, modifications, and complex formation of proteins in cells. In order to address issues of protein function in vitro using classical biochemical and biophysical approaches, high-throughput methods of cloning the appropriate reading frames, and expressing and purifying proteins efficiently are an important goal of modern proteomics approaches. This process becomes more difficult as functional protcomics efforts focus on the proteins from higher organisms, since issues of correctly identifying intron-exon boundaries and efficiently expressing and solubilizing the (often) multi-domain proteins from higher eukaryotes are challenging. Recently, 12,000 open-reading-frame (ORF) sequences from Caenorhabditis elegans have become available for functional proteomics studies [Nat. Gen. 34 (2003) 35]. We have implemented a high-throughput screening procedure to express, purify, and analyze by mass spectrometry hexa-histidine-tagged C elegans ORFs in Escherichia coli using metal affinity ZipTips. We find that over 65% of the expressed proteins are of the correct mass as analyzed by matrix-assisted laser desorption MS. Many of the remaining proteins indicated to be "incorrect" can be explained by high-throughput cloning or genome database annotation errors. This provides a general understanding of the expected error rates in such high-throughput cloning projects. The ZipTip purified proteins can be further analyzed under both native and denaturing conditions for functional proteomics efforts. (C) 2003 Elsevier Inc. All rights reserved. C1 Albert Einstein Coll Med, Ctr Synchrotron Biosci, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Physiol & Biophys, Bronx, NY 10461 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA. RP Chance, MR (reprint author), Albert Einstein Coll Med, Ctr Synchrotron Biosci, Bronx, NY 10461 USA. OI Huang, Raymond/0000-0001-7661-797X FU NCI NIH HHS [CA13330, R33-CA-83179]; NIBIB NIH HHS [P41-EB-01979]; NIDDK NIH HHS [DK20541]; NIGMS NIH HHS [P50-GM-62529] NR 29 TC 11 Z9 15 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 8 PY 2003 VL 307 IS 4 BP 928 EP 934 DI 10.1016/S0006-291X(03)01265-8 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 707KP UT WOS:000184510100027 PM 12878200 ER PT J AU Lee-Huang, S Zhang, L Huang, PL Chang, YT Huang, PL AF Lee-Huang, S Zhang, L Huang, PL Chang, YT Huang, PL TI Anti-HIV activity of olive leaf extract (OLE) and modulation of host cell gene expression by HIV-1 infection and OLE treatment SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE anti-HIV agent; olive leaf extract; antiviral; cDNA microarray; gene expression profile; LC-MS ID LOW-DENSITY-LIPOPROTEIN; PHENOLIC-COMPOUNDS; ANTIMICROBIAL ACTIVITY; OIL; OLEUROPEIN; ANTIOXIDANT; INHIBITION; OXIDATION; HYDROXYTYROSOL; METABOLISM AB We investigated the antiviral activity of olive leaf extract (OLE) preparations standardized by liquid chromatography-coupled mass spectrometry (LC-MS) against HIV-1 infection and replication. We find that OLE inhibits acute infection and cell-to-cell transmission of HIV-1 as assayed by syncytia formation using uninfected MT2 cells co-cultured with HIV-1-infected H9 T lymphocytes. OLE also inhibits HIV-1 replication as assayed by p24 expression in infected H9 cells. These anti-HIV effects of OLE are dose dependent, with EC(50)s of around 0.2 mug/ml. In the effective dose range, no cytotoxicity on uninfected target cells was detected. The therapeutic index of OLE is above 5000. To identify viral and host targets for OLE, we characterized gene expression profiles associated with HIV-1 infection and OLE treatment using cDNA microarrays. HIV-1 infection modulates the expression patterns of cellular genes involved in apoptosis, stress, cytokine, protein kinase C, and hedgehog signaling. HIV-1 infection up-regulates the expression of the heat-shock proteins hsp27 and hsp90, the DNA damage inducible transcript 1 gadd45, the p53-binding protein mdm2, and the hedgehog signal protein patched 1, while it down-regulates the expression of the anti-apoptotic BCL2-associated X protein Bax. Treatment with OLE reverses many of these HIV-1 infection-associated changes. Treatment of HIV-1-infected cells with OLE also up-regulates the expression of the apoptosis inhibitor proteins IAP1 and 2, as well as the calcium and protein kinase C pathway signaling molecules IL-2, IL-2Ralpha, and ornithine decarboxylase ODC1. (C) 2003 Elsevier Inc. All rights reserved. C1 NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. Amer Biosci Inc, New York, NY 10021 USA. NYU, Dept Chem, New York, NY 10003 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lee-Huang, S (reprint author), NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. RI Chang, Young-Tae/B-2780-2010 OI Chang, Young-Tae/0000-0002-1927-3688 NR 39 TC 86 Z9 91 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 8 PY 2003 VL 307 IS 4 BP 1029 EP 1037 DI 10.1016/S0006-291X(03)01292-0 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 707KP UT WOS:000184510100042 PM 12878215 ER PT J AU Wang, YJ Wang, J Sun, HQ Martinez, M Sun, YX Macia, E Kirchhausen, T Albanesi, JP Roth, MG Yin, HL AF Wang, YJ Wang, J Sun, HQ Martinez, M Sun, YX Macia, E Kirchhausen, T Albanesi, JP Roth, MG Yin, HL TI Phosphatidylinositol 4 phosphate regulates targeting of clathrin adaptor AP-1 complexes to the golgi SO CELL LA English DT Article ID ADP-RIBOSYLATION FACTOR-1; 4-KINASE TYPE-II; PLASMA-MEMBRANE; SORTING SIGNALS; MAMMALIAN-CELLS; COATED PITS; 4,5-BISPHOSPHATE; PROTEIN; DOMAIN; YEAST AB Phosphatidylinositol 4 phosphate [PI(4)P] is essential for secretion in yeast, but its role in mammalian cells is unclear. Current paradigms propose that PI(4)P acts primarily as a precursor to phosphatidylinositol 4,5 bisphosphate (PIP2), an important plasma membrane regulator. We found that PI(4)P is enriched in the mammalian Golgi, and used RNA interference (RNAi) of PI4KIIalpha, a Golgi resident phosphatidylinositol 4 kinase, to determine whether PI(4)P directly regulates the Golgi. PI4KIIalpha RNAi decreases Golgi PI(4)P, blocks the recruitment of clathrin adaptor AP-1 complexes to the Golgi, and inhibits AP-1-dependent functions. This AP-1 binding defect is rescued by adding back PI(4)P. In addition, purified AP-1 binds PI(4)P, and anti-PI(4)P inhibits the in vitro recruitment of cytosolic AP-1 to normal cellular membranes. We propose that PI4KIIalpha establishes the Golgi's unique lipid-defined organelle identity by generating PI(4)P-rich domains that specify the docking of the AP-1 coat machinery. C1 Univ Texas, SW Med Ctr, Dept Physiol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75390 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Yin, HL (reprint author), Univ Texas, SW Med Ctr, Dept Physiol, Dallas, TX 75390 USA. OI Roth, Michael/0000-0002-9056-332X FU NIGMS NIH HHS [GM36548, GM21681, GM37547, R01 GM51112, R01 GM55562] NR 51 TC 304 Z9 308 U1 2 U2 20 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD AUG 8 PY 2003 VL 114 IS 3 BP 299 EP 310 DI 10.1016/S0092-8674(03)00603-2 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 710KK UT WOS:000184679200007 PM 12914695 ER PT J AU Lamb, J Ramaswamy, S Ford, HL Contreras, B Martinez, RV Kittrell, FS Zahnow, CA Patterson, N Golub, TR Ewen, ME AF Lamb, J Ramaswamy, S Ford, HL Contreras, B Martinez, RV Kittrell, FS Zahnow, CA Patterson, N Golub, TR Ewen, ME TI A mechanism of cyclin D1 action encoded in the patterns of gene expression in human cancer SO CELL LA English DT Article ID BINDING-PROTEIN-BETA; MESSENGER-RNA; TRANSCRIPTION FACTOR; ESTROGEN-RECEPTOR; BREAST-CANCER; MOLECULAR CLASSIFICATION; RETINOBLASTOMA PROTEIN; INHIBITORY PROTEIN; CDK INHIBITORS; IN-SITU AB Here we describe how patterns of gene expression in human tumors have been deconvoluted to reveal a mechanism of action for the cyclin D1 oncogene. Computational analysis of the expression patterns of thousands of genes across hundreds of tumor specimens suggested that a transcription factor, C/EBPbeta/Nf-II6, participates in the consequences of cyclin Di overexpression. Functional analyses confirmed the involvement of C/EBPbeta in the regulation of genes affected by cyclin D1 and established this protein as an indispensable effector of a potentially important facet of cyclin D1 biology. This work demonstrates that tumor gene expression databases can be used to study the function of a human oncogene in situ. C1 Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biochem, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD 21231 USA. RP Ewen, ME (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA88843, F32-CA79197, P01-CA80111, R01-CA61253, R01-CA65842] NR 48 TC 303 Z9 315 U1 2 U2 13 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD AUG 8 PY 2003 VL 114 IS 3 BP 323 EP 334 DI 10.1016/S0092-8674(03)00570-1 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 710KK UT WOS:000184679200009 PM 12914697 ER PT J AU Bassing, CH Suh, H Ferguson, DO Chua, KF Manis, J Eckersdorff, M Gleason, M Bronson, R Lee, C Alt, FW AF Bassing, CH Suh, H Ferguson, DO Chua, KF Manis, J Eckersdorff, M Gleason, M Bronson, R Lee, C Alt, FW TI Histone H2AX: A dosage-dependent suppressor of oncogenic translocations and tumors SO CELL LA English DT Article ID DOUBLE-STRAND BREAKS; DNA-DAMAGE CHECKPOINT; GENOMIC INSTABILITY; V(D)J RECOMBINATION; GENE AMPLIFICATION; THYMIC LYMPHOMA; PATHOGENIC ROLE; MICE; 53BP1; ATM AB We employed gene targeting to study H2AX, a histone variant phosphorylated in chromatin surrounding DNA double-strand breaks. Mice deficient for both H2AX and p53 ((HP-/-)-P-Delta/Delta) rapidly developed immature T and B lymphomas and solid tumors. Moreover, H2AX haploinsufficiency caused genomic instability in normal cells and, on a p53-deficient background, early onset of various tumors including more mature B lymphomas. Most H2AX(Delta/Delta)p53(-/-) or H2AX(+/Delta) p53(-/-) B lineage lymphomas harbored chromosome 12 (IgH)/15 (c-myc) translocations with hallmarks of either aberrant V(D)J or class switch recombination. In contrast, H2AX(Delta/Delta)p53(-/-) thymic lymphomas had clonal translocations that did not involve antigen receptor loci and which likely occurred during cellular expansion. Thus, H2AX helps prevent aberrant repair of both programmed and general DNA breakage and, thereby, functions as a dosage-dependent suppressor of genomic instability and tumors in mice. Notably, H2AX maps to a cytogenetic region frequently altered in human cancers, possibily implicating similar functions in man. C1 Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst,Dept Genet, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Tufts Univ, Sch Vet Med, North Grafton, MA 01536 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cytogenet, Boston, MA 02155 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02155 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst,Dept Genet, Boston, MA 02115 USA. FU NCI NIH HHS [CA92625]; NHLBI NIH HHS [K08 HL67580-03]; NIAID NIH HHS [AI35714] NR 53 TC 351 Z9 360 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD AUG 8 PY 2003 VL 114 IS 3 BP 359 EP 370 DI 10.1016/S0092-8674(03)00566-X PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 710KK UT WOS:000184679200012 PM 12914700 ER PT J AU Lindsey, ML Yoshioka, J MacGillivray, C Muangman, S Gannon, J Verghese, A Aikawa, M Libby, P Krane, SM Lee, RT AF Lindsey, ML Yoshioka, J MacGillivray, C Muangman, S Gannon, J Verghese, A Aikawa, M Libby, P Krane, SM Lee, RT TI Effect of a cleavage-resistant collagen mutation on left ventricular remodeling SO CIRCULATION RESEARCH LA English DT Article DE matrix metalloproteinases; collagen; left ventricular remodeling; myocardial infarction ID MATRIX-METALLOPROTEINASE INHIBITION; EXPERIMENTAL MYOCARDIAL-INFARCTION; HEART-FAILURE; EXTRACELLULAR-MATRIX; I COLLAGEN; INTERSTITIAL COLLAGENASE; BONE-RESORPTION; MURINE MODEL; RAT-HEART; MICE AB Matrix metalloproteinase - mediated degradation of type I collagen may play a role in cardiac remodeling after strain or injury. To explore this hypothesis, we used mice homozygous (r/r) for a targeted mutation in Col1a1; these mice synthesize collagen I that resists collagenase cleavage at Gly975-Leu976. A total of 64 r/r and 84 littermate wild-type mice (WT) underwent experimental pressure overload by transverse aortic constriction (TAC) or myocardial infarction (MI). Echocardiographic, hemodynamic, and histological parameters were evaluated up to 12 weeks after TAC or 21 days after MI. At 4 weeks after TAC, collagen levels, wall thickness, and echocardiographic parameters were similar in the 2 groups. At 12 weeks after TAC, r/r mice had smaller LV dimensions ( ESD: 2.7 +/- 0.2 mm WT versus 1.7 +/- 0.2 mm r/r, P <0.013; EDD: 3.8 +/- 0.2 mm WT versus 3.1 +/- 0.1 mm r/r, P < 0.013); better fractional shortening ( 30 +/- 2% WT versus 46 +/- 4% r/r; P < 0.013); and lower LV/body weight ratios (7.3 +/- 0.6 WT and 5.1 +/- 0.5 r/r; P < 0.013). Surprisingly, these differences were not accompanied by differences in collagen accumulation, myocyte cross-sectional areas, wall thickness, or microvessel densities. Furthermore, no differences in LV remodeling assessed by echocardiography, fibrosis, or hemodynamic parameters were found between r/r and WT mice after MI. Thus, a mutation that encodes a collagenase cleavage-resistant collagen I does not affect early LV remodeling after TAC or MI, suggesting that collagen cleavage at this site is not the mechanism by which metalloproteinases mediate LV remodeling. Collagen cleavage could, however, have a role in preservation of cardiac function in late remodeling by mechanisms independent of collagen accumulation. We were not able to detect collagen cleavage fragments, and could not, therefore, rule out the possibility of collagen cleavage at additional sites. C1 Brigham & Womens Hosp, Div Cardiovasc, Leducq Ctr Cardiovasc Res, Dept Med, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Lee, RT (reprint author), Brigham & Womens Hosp, Div Cardiovasc, Leducq Ctr Cardiovasc Res, Dept Med, Partners Res Facil,Room 279,65 Landsdowne St, Cambridge, MA 02139 USA. EM rlee@rics.bwh.harvard.edu RI Lindsey, Merry/B-2650-2012 FU NHLBI NIH HHS [HL-65273, HL-10337]; NIAMS NIH HHS [AR-44815] NR 48 TC 26 Z9 26 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 EI 1524-4571 J9 CIRC RES JI Circ.Res. PD AUG 8 PY 2003 VL 93 IS 3 BP 238 EP 245 DI 10.1161/01.RES.0000085580.45279.60 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 709GX UT WOS:000184618400011 PM 12855673 ER PT J AU Neumeyer, JL Kula, NS Bergman, J Baldessarini, RJ AF Neumeyer, JL Kula, NS Bergman, J Baldessarini, RJ TI Receptor affinities of dopamine D1 receptor-selective novel phenylbenzazepines SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE dopamine; dopamine D1 receptor; partial-agonist; phenylbenzazepine ID RAT STRIATAL TISSUE; AGONISTS; ANTAGONISTS; BEHAVIOR; BINDING; LIGAND; SITES AB We prepared a series of 18 novel substituted phenylbenzazepine congeners of the dopamine D1/D5 receptor partial-agonist SKF-83959 (R,S-3-methyl-6-chloro-7,8-dihydroxy-1-[3'-methylphenyl]-2,3,4,5-tetrahydro-1H-benzazepine) and characterized their potency and selectivity in assays of dopamine, 5-HT and adrenoceptors in rat brain tissue or membranes of genetically transfected cells. The R-enantiomer of SKF-83959 (MCL-202) and three other novel racemic 1-phenyl-7,8-dihydroxybenzazepines (MCL-204, -203, and -207) showed very high dopamine D5 receptor affinity; MCL-209 displayed the greatest dopamine D5 receptor affinity. These five potent novel ligands also had >100fold selectivity for dopamine D1 over dopamine D2, D3, scrotonin 5-HT-2A receptors and alpha2-adrenoceptors. They require further functional testing to characterize their intrinsic activity, and for potential stimulant-antagonist actions, as observed with SKF-83959 and MCL-202. (C) 2003 Elsevier B.V. All rights reserved. C1 Brain Res Labs Inc, Belmont, MA 02478 USA. Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02478 USA. Massachusetts Gen Hosp, McLean Div, Addict Res Ctr, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Neumeyer, JL (reprint author), McLean Hosp, Alcohol & Drug Addict Res Ctr, 115 Mill St, Belmont, MA 02478 USA. FU NIDA NIH HHS [DA-1311] NR 17 TC 54 Z9 56 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD AUG 8 PY 2003 VL 474 IS 2-3 BP 137 EP 140 DI 10.1016/S0014-2999(03)02008-9 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 714DA UT WOS:000184896000001 PM 12921854 ER PT J AU Cao, C Leng, YM Kufe, D AF Cao, C Leng, YM Kufe, D TI Catalase activity is regulated by c-Abl and Arg in the oxidative stress response SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE KINASE; INDUCED APOPTOSIS; CU,ZN-SUPEROXIDE DISMUTASE; TRANSCRIPTION FACTOR; CELL-DEATH; LIFE-SPAN; ACTIVATION; DNA; MITOCHONDRIA; GENERATION AB The Abl family of mammalian non-receptor tyrosine kinases includes c-Abl and Arg. Recent studies have demonstrated that c-Abl and Arg are activated in the response of cells to oxidative stress. This work demonstrates that catalase, a major effector of the cellular defense against H2O2, interacts with c-Abl and Arg. The results show that H2O2 induced binding of c-Abl and Arg to catalase. The SH3 domains of c-Abl and Arg bound directly to catalase at a (PFNP)-F-293 site. c-Abl and Arg phosphorylated catalase at Tyr(231) and Tyr(386) in vitro and in the response of cells to H2O2. The functional significance of the interaction is supported by the demonstration that cells deficient in both c-Abl and Arg exhibit substantial increases in H2O2 levels. In addition, c-abl(-/-) arg(-/-) cells exhibited a marked increase in H2O2-induced apoptosis compared with that found in the absence of either kinase. These findings indicate that c-Abl and Arg regulate catalase and that this signaling pathway is of importance to apoptosis in the oxidative stress response. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Beijing Inst Biotechnol, Beijing 100850, Peoples R China. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA42802, CA49639] NR 44 TC 103 Z9 105 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 8 PY 2003 VL 278 IS 32 BP 29667 EP 29675 DI 10.1074/jbc.M301292200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 707JF UT WOS:000184507000037 PM 12777400 ER PT J AU Yu, MX Nagren, K Chen, YI Livni, E Elmaleh, D Kozikowski, A Wang, XK Jokivarsi, K Brownell, AL AF Yu, MX Nagren, K Chen, YI Livni, E Elmaleh, D Kozikowski, A Wang, XK Jokivarsi, K Brownell, AL TI Radiolabeling and biodistribution of methyl 2-(methoxycarbonyl)-2-(methylamino) bicyclo [2.1.1]-hexane-5-carboxylate, a potential neuroprotective drug SO LIFE SCIENCES LA English DT Article DE metabotropic glutamate receptors; neuroprotection; positron emission tomography; carbon-11 ID METABOTROPIC GLUTAMATE RECEPTORS; PARKINSONS-DISEASE; ESTER HYDROLASE; RAT-BRAIN; DEMETHYLATION; PLASTICITY; TRIFLATE AB Methyl 2-(methoxycarbonyl) -2-(methylamino) bicyclo[2.1.1]-hexane-5-carboxylate (MMMHC) is developed as a potential neuroprotective drug. It was labeled with C-11 from the desmethyl precursor methyl 2(methoxycarbonyl)-2-amino bicyclo[2.1.1]-hexane-5-carboxylate with [C-11]methyl triflate in acetone solution at 60 degreesC with labeling yield of 69% and with radiochemical purity of >99%. Positron Emission Tomography (PET) studies in a normal rat showed that Methyl 2-(methoxycarbonyl)-2-([C-11]methylamino)bicyclo[2.1.1]-hexane-5-carboxylate ([C-11] MMMHC) accumulated mainly in the cortical brain areas after iv administration. Frontal cortex/ cerebellum ratios in a rat brain were 8.0/6.0, 6.8/4.2, 6.3/4.3, 5.5/4.2 and 5.2/4.5 percent of the injected dose in 100 ml at 2 min, 5 min, 10 min, 20 min and 40 min respectively after i.v. injection. During 20-40 min, 2.9 +/- 0.4% of the total activity stayed in the brain. These results showed that MMMHC could be labeled with C-11 with high yield, and it passed the brain-blood barrier and accumulated in several brain regions. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Turku PET Ctr, Turku, Finland. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. RP Yu, MX (reprint author), Massachusetts Gen Hosp, Dept Radiol, Barlett Hall 511R, Boston, MA 02114 USA. EM ymeixiang@partners.org NR 30 TC 2 Z9 2 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD AUG 8 PY 2003 VL 73 IS 12 BP 1577 EP 1585 DI 10.1016/S0024-3205(03)00482-X PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 703ZY UT WOS:000184314300010 PM 12865097 ER PT J AU Sharpless, NE Kannan, K Xu, J Bosenberg, MW Chin, LD AF Sharpless, NE Kannan, K Xu, J Bosenberg, MW Chin, LD TI Both products of the mouse Ink4a/Arf locus suppress melanoma formation in vivo SO ONCOGENE LA English DT Article DE melanoma; RAS ID HUMAN-DIPLOID FIBROBLASTS; SPORADIC MELANOMA; INDUCED SENESCENCE; GERMLINE MUTATION; TUMOR SUPPRESSION; CELL-LINES; RAS; P16(INK4A); P19(ARF); P53 AB Deletion of the INK4a/ARF locus at 9p21 is detected with high frequency in human melanoma. Within a short genomic distance, this locus encodes several proteins with established tumor-suppressor roles in a broad spectrum of cancer types. Several lines of evidence support the view that p10(INKa4) and p19(ARF) exert the tumor-suppressor activities of this locus, although their relative importance in specific cancer types such as melanoma has been less rigorously documented on the genetic level. Here, we exploit a well-defined mouse model of RAS-induced melanomas to examine the impact of germline p16(INK4a) or p19(ARF) nullizygosity on melanoma formation. We demonstrate that loss of either Ink4a/Arf product can cooperate with RAS activation to produce clinically indistinguishable melanomas. In line with the common phenotypic end point, we further show that RAS+ p16(INK4a)-/- melanomas sustain somatic inactivation of p19(ARF)-p53 and, correspondingly, that RAS+ p19(ARF)-/- melanomas experience high-frequency loss of p16(INK4a). These genetic studies provide definitive proof that p16(INK4a), and p19(ARF) cooperate to suppress the development of melanoma in vivo. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA. Harvard Univ, Dept Dermatol, Sch Med, Boston, MA 02115 USA. RP Chin, LD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,M413, Boston, MA 02115 USA. NR 29 TC 60 Z9 62 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 7 PY 2003 VL 22 IS 32 BP 5055 EP 5059 DI 10.1038/sj.onc.1206809 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 708QF UT WOS:000184578900013 PM 12902988 ER PT J AU Boas, DA Strangman, G Culver, JP Hoge, RD Jasdzewski, G Poldrack, RA Rosen, BR Mandeville, JB AF Boas, DA Strangman, G Culver, JP Hoge, RD Jasdzewski, G Poldrack, RA Rosen, BR Mandeville, JB TI Can the cerebral metabolic rate of oxygen be estimated with near-infrared spectroscopy? SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; RODENT BARREL CORTEX; EVENT-RELATED FMRI; BLOOD-FLOW; OXIDATIVE-METABOLISM; FUNCTIONAL MRI; OPTICAL SPECTROSCOPY; FOREPAW STIMULATION; RELATIVE CMRO2; FOCAL CHANGES AB We have measured the changes in oxy-haemoglobin and deoxy-haemoglobin in the adult human brain during a brief finger tapping exercise using near-infrared spectroscopy (NIRS). The cerebral metabolic rate of oxygen (CMRO2) can be estimated from these NIRS data provided certain model assumptions. The change in CMRO2 is related to changes in the total haemoglobin concentration, deoxy-haemoglobin concentration and blood flow. As NIRS does not provide a measure of dynamic changes in blood flow during brain activation, we relied on a Windkessel model that relates dynamic blood volume and flow changes, which has been used previously for estimating CMRO2 from functional magnetic resonance imaging (fMRI) data. Because of the partial volume effect we are unable to quantify the absolute changes in the local brain haemoglobin concentrations with NIRS and thus are unable to obtain an estimate of the absolute CMRO2 change. An absolute estimate is also confounded by uncertainty in the flow-volume relationship. However, the ratio of the flow change to the CMRO2 change is relatively insensitive to these uncertainties. For the finger tapping task, we estimate a most probable flow-consumption ratio ranging from 1.5 to 3 in agreement with previous findings presented in the literature, although we cannot exclude the possibility that there is no CMRO2 change. The large range in the ratio arises from the large number of model parameters that must be estimated from the data. A more precise estimate of the flow-consumption ratio will require better estimates of the model parameters or flow information, as call be provided by combining NIRS with fMRI. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neural Syst Grp, Charlestown, MA 02129 USA. Univ Calif Los Angeles, Dept Cognit Psychol, Los Angeles, CA 90095 USA. RP Boas, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. FU NCRR NIH HHS [P41-RR14075, R01-RR14543]; NIBIB NIH HHS [R01-EB00790]; NINDS NIH HHS [K25-NS44339, R29-NS38842] NR 48 TC 103 Z9 103 U1 1 U2 9 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD AUG 7 PY 2003 VL 48 IS 15 BP 2405 EP 2418 AR PII S0031-9155(03)58338-5 DI 10.1088/0031-9155/48/15/311 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 717NZ UT WOS:000185097400011 PM 12953906 ER PT J AU Eyding, D Macklis, JD Neubacher, U Funke, K Worgotter, F AF Eyding, D Macklis, JD Neubacher, U Funke, K Worgotter, F TI Selective elimination of corticogeniculate feedback abolishes the electroencephalogram dependence of primary visual cortical receptive fields and reduces their spatial specificity SO JOURNAL OF NEUROSCIENCE LA English DT Article DE visual cortex; corticogeniculate loop; photoactivation of chlorin e(6); neuronal apoptosis; state dependence; receptive-field characteristics ID LATERAL GENICULATE-NUCLEUS; CAT STRIATE CORTEX; UNDERLYING CONTRAST ADAPTATION; RELAY CELLS; NEOCORTICAL NEURONS; TEMPORAL STRUCTURE; CORTICOFUGAL INFLUENCE; SYNAPTIC CONNECTIONS; PROJECTION NEURONS; QUANTAL AMPLITUDE AB The role of corticogeniculate feedback in the organization, function, and state dependence of visual responses and receptive fields (RFs) is not well understood. We investigated the contribution of the corticogeniculate loop to state-dependent changes of characteristics of the primary visual cortex response by using a novel approach of eliminating corticogeniculate projection neurons with targeted neuronal apoptosis. Experiments were performed in anesthetized cats (N2O plus halothane) with parallel recordings of single units from experimental (right) and control (left) hemispheres similar to2 weeks after induction of apoptosis. Within the experimental hemispheres, neurons of area 17 and of the dorsal lateral geniculate nucleus (dLGN) showed an unusually enhanced and prolonged tonic visual response during episodes of synchronized ( syn) EEG activity, whereas response levels during less synchronized states were almost normal. In addition, dLGN cells showed a reduced tendency for burst firing and a less regular spike interval distribution compared with those of controls. These changes are likely attributable to a tonic depolarization of dLGN relay neurons or, more likely, to a decreased responsiveness of thalamic inhibitory processes to cortical feedback. Cortical neurons also displayed an activity-dependent increase in RF size, in contrast to an almost activity-invariant RF size of controls, a phenomenon likely related to the elimination of collateral, intracortical projections of layer 6 neurons. Together, these results demonstrate that selective chronic elimination of corticogeniculate feedback results in the loss of EEG-correlated differences of visual processing in the remaining thalamocortical network, accompanied by a significant increase in excitability during syn EEG, at the expense of noticeably reduced spatial receptive-field specificity in the remaining cortical neurons. C1 Ruhr Univ Bochum, Fac Med, Dept Neurophysiol, D-44780 Bochum, Germany. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Childrens Hosp, Div Neurosci, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Nervous Syst Repair, Boston, MA 02115 USA. Univ Stirling, Dept Psychol, Stirling FK9 4LA, Scotland. RP Funke, K (reprint author), Ruhr Univ Bochum, Fac Med, Dept Neurophysiol, D-44780 Bochum, Germany. NR 64 TC 12 Z9 13 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 AUG 6 PY 2003 VL 23 IS 18 BP 7021 EP 7033 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 708UD UT WOS:000184587100007 PM 12904463 ER PT J AU Schubert, M Brazil, DP Burks, DJ Kushner, JA Ye, J Flint, CL Farhang-Fallah, J Dikkes, P Warot, XM Rio, C Corfas, G White, MF AF Schubert, M Brazil, DP Burks, DJ Kushner, JA Ye, J Flint, CL Farhang-Fallah, J Dikkes, P Warot, XM Rio, C Corfas, G White, MF TI Insulin receptor substrate-2 deficiency impairs brain growth and promotes tau phosphorylation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE diabetes; insulin receptor substrates; Irs2; growth factors; tau phosphorylation; brain size; neuron survival; Alzheimer's disease ID AMYLOID PRECURSOR PROTEIN; CENTRAL-NERVOUS-SYSTEM; I IGF-I; ALZHEIMERS-DISEASE; NEURITE FORMATION; TRANSGENIC MICE; PHOSPHATASE 2A; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION; POSTNATAL-GROWTH AB Insulin resistance and diabetes might promote neurodegenerative disease, but a molecular link between these disorders is unknown. Many factors are responsible for brain growth, patterning, and survival, including the insulin-insulin-like growth factor (IGF)-signaling cascades that are mediated by tyrosine phosphorylation of insulin receptor substrate (IRS) proteins. Irs2 signaling mediates peripheral insulin action and pancreatic beta-cell function, and its failure causes diabetes in mice. In this study, we reveal two important roles for Irs2 signaling in the mouse brain. First, disruption of the Irs2 gene reduced neuronal proliferation during development by 50%, which dissociated brain growth from Irs1-dependent body growth. Second, neurofibrillary tangles containing phosphorylated tau accumulated in the hippocampus of old Irs2 knock-out mice, suggesting that Irs2 signaling is neuroprotective. Thus, dysregulation of the Irs2 branch of the insulin-Igf-signaling cascade reveals a molecular link between diabetes and neurodegenerative disease. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Neurol, Div Neurosci, Boston, MA 02115 USA. RP White, MF (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, 1 Joslin Pl, Boston, MA 02215 USA. RI Schubert, Markus/F-5150-2010 FU NIDDK NIH HHS [DK43808, DK38712] NR 86 TC 251 Z9 271 U1 1 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 6 PY 2003 VL 23 IS 18 BP 7084 EP 7092 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 708UD UT WOS:000184587100013 PM 12904469 ER PT J AU Chaput, JC Szostak, JW AF Chaput, JC Szostak, JW TI TNA synthesis by DNA polymerases SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NUCLEIC-ACID STRUCTURE; IN-VITRO SELECTION; CRYSTAL-STRUCTURE; REPLICATION FIDELITY; CHEMICAL ETIOLOGY; LARGE FRAGMENT; MOLECULES; TEMPLATE; COMPLEX; DUPLEX C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. NR 23 TC 86 Z9 87 U1 3 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD AUG 6 PY 2003 VL 125 IS 31 BP 9274 EP 9275 DI 10.1021/ja035917n PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 707MW UT WOS:000184515300018 PM 12889939 ER PT J AU Badgaiyan, RD Fischman, AJ Alpert, NM AF Badgaiyan, RD Fischman, AJ Alpert, NM TI Striatal dopamine release during unrewarded motor task in human volunteers SO NEUROREPORT LA English DT Article DE alternative neuroimaging; basal ganglia; caudate; dopamine; neuroimaging; neurotransmitter release; putamen; raclopride; striatum; unrewarded motor task ID POSITRON-EMISSION-TOMOGRAPHY; BASAL GANGLIA; PARKINSONS-DISEASE; MOVEMENT; PET; SCHIZOPHRENIA; ACTIVATION; IMAGERY; MONKEY; REWARD AB Striatal dopamine is associated with the processing of rewarded motor tasks. Its involvement in mediating unrewarded tasks is, however, unclear. We used a recently developed PET technique to dynamically measure the rate of displacement of a dopamine receptor ligand raclopride in healthy volunteers performing a finger opposition task. Rapid displacement of the ligand from the posterior putamen and the caudate immediately after the task initiation suggested striatal dopamine release during task performance. Since dopamine release was observed in the striatal areas that are implicated in unrewarded tasks by neuroimaging studies, the results demonstrate that the PET method can be used to extend the findings of conventional neuroimaging techniques, that do not provide information about signal transduction. C1 Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RP Badgaiyan, RD (reprint author), Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. FU NCI NIH HHS [T32 CA 09362] NR 25 TC 26 Z9 26 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD AUG 6 PY 2003 VL 14 IS 11 BP 1421 EP 1424 DI 10.1097/01.wnr.0000080021.91618.ee PG 4 WC Neurosciences SC Neurosciences & Neurology GA 718TA UT WOS:000185161500003 PM 12960756 ER PT J AU Gibson, CM AF Gibson, CM TI Has my patient achieved adequate myocardial reperfusion? SO CIRCULATION LA English DT Review ID ST-SEGMENT RECOVERY; CORONARY BLOOD-FLOW; PERFUSION GRADE; FRAME COUNT; NO-REFLOW; INFARCTION; PREDICTOR; THROMBOLYSIS; RESOLUTION; TIME C1 Harvard Univ, Sch Med, TIMI Study Grp, Boston, MA USA. RP Gibson, CM (reprint author), TIMI, Data Coordinating Ctr, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. NR 21 TC 24 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 5 PY 2003 VL 108 IS 5 BP 504 EP 507 DI 10.1161/01.CIR.0000082932.69023.74 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 708CH UT WOS:000184549200001 PM 12900495 ER PT J AU Wang, TJ Nam, BH D'Agostino, RB Wolf, PA Lloyd-Jones, DM MacRae, CA Wilson, PW Polak, JF O'Donnell, CJ AF Wang, TJ Nam, BH D'Agostino, RB Wolf, PA Lloyd-Jones, DM MacRae, CA Wilson, PW Polak, JF O'Donnell, CJ TI Carotid intima-media thickness is associated with premature parental coronary heart disease - The Framingham Heart Study SO CIRCULATION LA English DT Article DE atherosclerosis; carotid arteries; genetics; epidemiology; risk factors ID CARDIOVASCULAR RISK-FACTORS; FAMILY-HISTORY; MYOCARDIAL-INFARCTION; ARTERY-DISEASE; DIABETES-MELLITUS; WALL THICKNESS; ATHEROSCLEROSIS; ADULTS; CLASSIFICATION; ABNORMALITIES AB Background-A family history of coronary heart disease (CHD) is an independent risk factor for cardiovascular events. However, the mechanisms underlying this susceptibility have not been fully elucidated. We hypothesized that an important mediator of the familial predisposition to CHD is subclinical atherosclerosis, which is detectable by noninvasive imaging. Methods and Results-We studied 1662 subjects (mean age 57, 51% women) in the Framingham Offspring Study who underwent carotid ultrasonography and had both biological parents in the original (parental) cohort. Parental CHD events were validated prospectively by a physician endpoint committee. The associations of carotid intima-media thickness (IMT) with premature parental CHD (occurring before age 60) and any parental CHD (no age restriction) were examined in age- and multivariable-adjusted analyses. Age-adjusted mean internal carotid IMT was higher in subjects who had at least one parent with premature CHD than in those without a validated parental history of premature CHD (men 1.13 versus 1.04 mm, P<0.01; women 0.92 versus 0.85 mm, P=0.03). In both sexes, these differences remained significant after adjustment for cardiovascular risk factors. In analyses without a restriction on parental age of CHD onset, the association between carotid IMT and parental CHD was not statistically significant. There was also no significant association of common carotid IMT with premature or any parental CHD. Conclusions-These findings suggest that subclinical atherosclerosis, assessed in the carotid arteries, is more prevalent in individuals with a family history of CHD. Early-onset parental CHD, in particular, identifies offspring with a strong familial predisposition to atherosclerosis. C1 Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. NHLBI, Bethesda, MD 20892 USA. RP O'Donnell, CJ (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte,Suite No 2, Framingham, MA 01702 USA. RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [N01-HC-25195] NR 37 TC 64 Z9 68 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 5 PY 2003 VL 108 IS 5 BP 572 EP 576 DI 10.1161/01.CIR.0000081764.35431.DE PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 708CH UT WOS:000184549200014 PM 12874190 ER PT J AU Flesch, M Hoper, A Dell'Italia, L Evans, K Bond, R Peshock, R Diwan, A Brinsa, TA Wei, CC Sivasubramanian, N Spinale, FG Mann, DL AF Flesch, M Hoper, A Dell'Italia, L Evans, K Bond, R Peshock, R Diwan, A Brinsa, TA Wei, CC Sivasubramanian, N Spinale, FG Mann, DL TI Activation and functional significance of the renin- angiotensin system in mice with cardiac restricted overexpression of tumor necrosis factor SO CIRCULATION LA English DT Article DE hypertrophy; genes; heart failure; remodeling; apoptosis ID FACTOR-ALPHA; TRANSGENIC MICE; GENE-EXPRESSION; CONVERTING ENZYME; DOWN-REGULATION; MOUSE; HEART; RATS; CARDIOMYOPATHY; DYSFUNCTION AB Background-The functional significance of cross-regulation between the renin-angiotensin system (RAS) and tumor necrosis factor (TNF) has been established in nonmyocyte cell types; however, the degree and functional significance of the interaction between RAS and TNF has not been characterized in the heart. Methods and Results-We examined the expression of components of the RAS in a line of transgenic mice (MHCsTNF) with cardiac restricted overexpression of TNF. When examined at 4, 8, and 12 weeks of age, the MHCsTNF mice had increased activation of myocardial RAS, as shown by an increase in ACE mRNA level and ACE activity and increased angiotensin II peptide levels. Furthermore, myocardial angiotensin receptor mRNA and protein levels were reduced in the MHCsTNF mice, consistent with homologous desensitization of the receptors. However, expression of renin and angiotensinogen was not increased in MHCsTNF mice compared with littermate controls. To determine the functional significance of RAS activation in the MHCsTNF mice, we treated the mice with an angiotensin type I receptor antagonist, losartan (30 mg/kg), or diluent from 4 to 8 weeks of age. Analysis of cardiac structure with MRI showed that treatment with losartan normalized left ventricular mass and wall thickness. Furthermore, treatment with losartan reduced myocardial collagen content and reduced the incidence of myocyte apoptosis. Conclusions-Taken together, these results show that there are functionally significant interactions between RAS and TNF in the heart and that these interactions play an important role in the development and progression of left ventricular remodeling. C1 Houston VAMC, Winters Ctr Heart Failure Res, Cardiol Sect, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Houston, Coll Pharm, Dept Pharmacol & Pharmaceut Sci, Houston, TX 77030 USA. Texas SW Univ, Dept Radiol, Dallas, TX USA. Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. RP Mann, DL (reprint author), Houston VAMC, Winters Ctr Heart Failure Res, Cardiol Sect, Dept Med, 6565 Fannin,MS 524, Houston, TX 77030 USA. OI Mann, Douglas /0000-0002-2516-0145 FU NHLBI NIH HHS [HL-42250-10/10, P50-HL-O6H, R01-HL-58081-01, R01-HL-61543-01] NR 24 TC 44 Z9 54 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 5 PY 2003 VL 108 IS 5 BP 598 EP 604 DI 10.1161/01.CIR.0000081768.13378.BF PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 708CH UT WOS:000184549200018 PM 12874189 ER PT J AU Montero, JA Kilian, B Chan, J Bayliss, PE Heisenberg, CP AF Montero, JA Kilian, B Chan, J Bayliss, PE Heisenberg, CP TI Phosphoinositide 3-kinase is required for process outgrowth and cell polarization of gastrulating mesendodermal cells SO CURRENT BIOLOGY LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE; ZEBRAFISH GASTRULATION; GROWTH-FACTOR; EMBRYONIC-DEVELOPMENT; CONVERGENT EXTENSION; EARLY ENDOSOMES; XENOPUS-LAEVIS; KINASE; CHEMOTAXIS; MOVEMENTS AB Background: During vertebrate gastrulation, cell polarization and migration are core components in the cellular rearrangements that lead to the formation of the three germ layers, ectoderm, mesoderm, and endoderm. Previous studies have implicated the Wnt/planar cell polarity (PCP) signaling pathway in controlling cell morphology and movement during gastrulation. However, cell polarization and directed cell migration are reduced but not completely abolished in the absence of Wnt/PCP signals; this observation indicates that other signaling pathways must be involved. Results: We show that Phosphoinositide 3-Kinases (PI3Ks) are required at the onset of zebrafish gastrulation in mesendodermal cells for process formation and cell polarization. Platelet Derived Growth Factor (PDGF) functions upstream of PI3K, while Protein Kinase B (PKB), a downstream effector of PI3K activity, localizes to the leading edge of migrating mesendodermal cells. In the absence of PI3K activity, PKB localization and cell polarization are strongly reduced in mesendodermal cells and are followed by slower but still highly coordinated and directed movements of these cells. Conclusions: We have identified a novel role of a signaling pathway comprised of PDGF, PI3K, and PKB in the control of morphogenetic cell movements during gastrulation. Furthermore, our findings provide insight into the relationship between cell polarization and directed cell migration at the onset of zebrafish gastrulation. C1 Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Heisenberg, CP (reprint author), Max Planck Inst Mol Cell Biol & Genet, Pfotenhauerstr 108, D-01307 Dresden, Germany. RI Montero, Juan/K-4395-2014 OI Montero, Juan/0000-0001-9099-5344 NR 39 TC 82 Z9 83 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD AUG 5 PY 2003 VL 13 IS 15 BP 1279 EP 1289 DI 10.1016/S0960-9822(03)00505-0 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 709PJ UT WOS:000184633300023 PM 12906787 ER PT J AU Van Etten, RA AF Van Etten, RA TI c-Abl regulation: A tail of two lipids SO CURRENT BIOLOGY LA English DT Editorial Material ID TYROSINE KINASE-ACTIVITY; FAMILY KINASES; SRC; DOMAIN; MUTATION; PROTEIN; PHOSPHORYLATION; AUTOINHIBITION; ACTIVATION; INHIBITOR AB c-Abl is a non-receptor tyrosine kinase whose activity is tightly controlled in vivo through unknown mechanisms. Recent studies suggest that c-Abl may be regulated in different cellular contexts by distinct lipids. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Van Etten, RA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. NR 20 TC 27 Z9 28 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD AUG 5 PY 2003 VL 13 IS 15 BP R608 EP R610 DI 10.1016/S0960-9822(03)00528-1 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 709PJ UT WOS:000184633300018 PM 12906815 ER PT J AU Gladysheva, IP Turner, RB Sazonova, IY Liu, L Reed, GL AF Gladysheva, IP Turner, RB Sazonova, IY Liu, L Reed, GL TI Coevolutionary patterns in plasminogen activation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID STREPTOKINASE BETA-DOMAIN; STREPTOCOCCUS-UBERIS; SUBSTRATE-SPECIFICITY; INTERACTION PARTNERS; CRYSTAL-STRUCTURE; BINDING REGION; ACTIVE-SITE; COMPLEX; KINETICS; SYSTEM AB The generation of plasmin by plasminogen (Pg) activators (PAs) is a physiologic process in animals that dissolves blood clots and promotes wound healing, blood vessel growth, and the migration of normal and cancerous cells. Pathogenic bacteria have evolved PAs [e.g., streptokinase (SK) and staphylokinase] that exploit the Pg system to infect animals. Animal PAs have a conserved ability to cleave a wide spectrum of animal Pgs, but the ability of bacterial PAs to cleave different animal Pgs is surprisingly restricted. We show that the spectrum of activity of an archetypal bacterial PA (SK) with animal Pgs can be profoundly altered by mutations that affect intermolecular complementarity at sites that participate in complex formation or substrate binding. Comparative sequence analysis of animal plasmins vs. close structural homologues (trypsin and chymotrypsin) that are not molecular targets for invading bacteria indicates that the sites in plasmin that interact with SK are preferentially targeted for mutation. Conversely, intermolecular contact sites in SKs that activate human Pg are more highly conserved than other loci in the molecule or than the same sites in other SKs that activate non-human Pgs. We propose that active modulation of intermolecular complementarity at sites of contact. between SK and Pg may represent a competitive evolutionary strategy in a survival battle, whereby animals seek to evade bacterial invasion, and bacteria endeavor to invade their animal hosts. C1 Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Reed, GL (reprint author), Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, 665 Huntington Ave, Boston, MA 02114 USA. OI Gladysheva, Inna/0000-0002-2501-9029 FU NHLBI NIH HHS [HL58496, R01 HL058496] NR 37 TC 44 Z9 45 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 5 PY 2003 VL 100 IS 16 BP 9168 EP 9172 DI 10.1073/pnas.1631716100 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 709HP UT WOS:000184620000015 PM 12878727 ER PT J AU Ranger, AM Zha, JP Harada, H Datta, SR Danial, NN Gilmore, AP Kutok, JL Le Beau, MM Greenberg, ME Korsmeyer, SJ AF Ranger, AM Zha, JP Harada, H Datta, SR Danial, NN Gilmore, AP Kutok, JL Le Beau, MM Greenberg, ME Korsmeyer, SJ TI Bad-deficient mice develop diffuse large B cell lymphoma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DEATH AGONIST; SURVIVAL; APOPTOSIS; PHOSPHORYLATION; BCL-2; PROTEIN; TRANSCRIPTION; MECHANISMS; TRANSGENE; INDUCTION AB The proapoptotic activity of the "BH3-only" molecule BAD can be differentially regulated by survival factor signaling. Bad-deficient mice lacking both BAD long and BAD short proteins proved viable, and most cell types appeared to develop normally. BAD did not exclusively account for cell death after withdrawal of survival factors, but it was an intermediate for epidermal growth factor- or insulin-like growth factor I-countered apoptosis, consistent with a "sensitizing" BH3-only molecule. Lymphocytes developed normally with no premalignant hyperplasia, but they displayed subtle abnormalities in proliferation and IgG production. Despite the minimal phenotype, Bad-deficient mice progressed, with aging, to diffuse large B cell lymphoma of germinal center origin. Exposure of Bad-null mice to sublethal gamma-irradiation resulted in an increased incidence of pre-T cell and pro-/pre-B cell lymphoblastic leukemia/lymphoma. Thus, proapoptotic BAD suppresses tumorigenesis in the lymphocyte lineage. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Div Neurosci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Univ Manchester, Sch Biol Sci, Manchester M13 9PT, Lancs, England. Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Korsmeyer, SJ (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. FU NCI NIH HHS [P01 CA92625, P01 CA092625, U01 CA084221, U01 CA84221] NR 37 TC 192 Z9 198 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 5 PY 2003 VL 100 IS 16 BP 9324 EP 9329 DI 10.1073/pnas.1533446100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 709HP UT WOS:000184620000042 PM 12876200 ER PT J AU Bedecarrats, GY O'Neill, FH Norwitz, ER Kaiser, UB Teixeira, J AF Bedecarrats, GY O'Neill, FH Norwitz, ER Kaiser, UB Teixeira, J TI Regulation of gonadotropin gene expression by Mullerian inhibiting substance SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE luteinizing hormone; follicle-stimulating hormone; pituitary ID FOLLICLE-STIMULATING-HORMONE; MESSENGER-RIBONUCLEIC-ACID; LUTEINIZING-HORMONE; TRANSGENIC MICE; RECEPTOR GENE; II RECEPTOR; SEXUAL DEVELOPMENT; MOUSE OVARY; CELL-LINE; IN-VIVO AB In addition to its role in causing Mullerian duct regression, Mullerian inhibiting substance (MIS) is implicated in the regulation of steroidogenesis, breast and prostate growth, and ovarian follicle recruitment, all of which are processes controlled or influenced by the hypothalamic-pituitary-gonadal axis. Whereas the direct effect of MIS on gonadal, prostate, and breast cells is under investigation, the ability of MIS to modulate pituitary function, thereby affecting those tissues indirectly, has not yet been studied. Using LbetaT2 cells, a murine gonadotrope-derived cell line, we have evaluated the effects of MIS on the expression of the gonadotropin genes. We show that both LbetaT2 cells and adult rat pituitaries express MIS type 11 receptor (MISIRII) mRNA. Within 2 h, follicle-stimulating hormone beta subunit (FSHbeta) mRNA levels are significantly induced by addition of MIS to LbetaT2 cells and remain elevated through 8 h of treatment. Transcriptional activation of both the FSHbeta and luteinizing hormone beta subunit (LHbeta) gene promoters was observed by MIS, which enhances the effect of gonadotropin-releasing hormone (GnRH) agonist on the FSHbeta gene promoter and synergizes with the GnRH agonist to stimulate LHbeta gene promoter activity. Addition of MIS to LbetaT2 cells stimulates the activity of the rat LHbeta gene promoter with as little as 1 mug/ml and in a dose-dependent manner. These studies report both MISRII expression in rat pituitary cells and a gonadotrope-derived cell line and MIS-mediated activation of LHbeta and FSHbeta gene expression, and suggest that MIS may modulate the hypothalamic-pituitary-gonadal axis at more than one level. C1 Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Dept Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. RP Teixeira, J (reprint author), Pediat Surg Res Labs, 32 Fruit St, Boston, MA 02114 USA. OI Teixeira, Jose/0000-0002-6438-5064 FU NCI NIH HHS [R29 CA079459-04, R29-CA79459, R29 CA079459]; NICHD NIH HHS [K12 HD001255, K12-HD00840, K12-HD01255, R01 HD033001, R01-HD33001, U54 HD028138, U54 HD28138] NR 47 TC 32 Z9 36 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 5 PY 2003 VL 100 IS 16 BP 9348 EP 9353 DI 10.1073/pnas.1633592100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 709HP UT WOS:000184620000046 PM 12878721 ER PT J AU Mori-Akiyama, Y Akiyama, H Rowitch, DH de Crombrugghe, B AF Mori-Akiyama, Y Akiyama, H Rowitch, DH de Crombrugghe, B TI Sox9 is required for determination of the chondrogenic cell lineage in the cranial neural crest SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSCRIPTION FACTOR AP-2; AUTOSOMAL SEX REVERSAL; VITAL DYE ANALYSIS; SRY-RELATED GENE; OSTEOBLAST DIFFERENTIATION; CAMPOMELIC DYSPLASIA; CARTILAGE FORMATION; BONE-FORMATION; STEM-CELLS; GLIAL FATE AB Sox9 has essential roles in endochondral bone formation during axial and appendicular skeletogenesis. Sox9 is also expressed in neural crest cells, but its function in neural crest remains largely unknown. Because many craniofacial skeletal elements are derived from cranial neural crest (CNC) cells, we asked whether deletion of Sox9 in CNC cells by using the Cre recombinase/loxP recombination system would affect craniofacial development. Inactivation of Sox9 in neural crest resulted in a complete absence of cartilages and endochondral bones derived from the CNC. In contrast, all of the mesodermal skeletal elements and intramembranous bones were essentially conserved. The migration and the localization of Sox9-null mutant CNC cells were normal. Indeed, the size of branchial arches and the frontonasal mass of mutant embryos was comparable to that of WT embryos, and the pattern of expression of Ap2, a marker of migrating CNC cells, was normal. Moreover, in mouse embryo chimeras Sox9-null mutant cells migrated to their correct location in endochondral skeletal elements; however, Sox9-null CINC cells were unable to contribute chondrogenic mesenchymal condensations. In mutant embryos, ectopic expression of osteoblast marker genes, such as Runx2, Osterix, and Col1a1, was found in the locations where the nasal cartilages exist in WT embryos. These results indicate that inactivation of Sox9 causes CNC cells to lose their chondrogenic potential. We hypothesize that these cells change their cell fate and acquire the ability to differentiate into osteoblasts. We conclude that Sox9 is required for the determination of the chondrogenic lineage in CNC cells. C1 Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP de Crombrugghe, B (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, 1515 Holcolme Blvd, Houston, TX 77030 USA. FU NCI NIH HHS [CA16672, P30 CA016672]; NIAMS NIH HHS [P01 AR042919, P01 AR42919] NR 45 TC 206 Z9 213 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 5 PY 2003 VL 100 IS 16 BP 9360 EP 9365 DI 10.1073/pnas.1631288100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 709HP UT WOS:000184620000048 PM 12878728 ER PT J AU Hong, YK Mikami, A Schaffhausen, B Jun, T Roberts, TM AF Hong, YK Mikami, A Schaffhausen, B Jun, T Roberts, TM TI A new class of mutations reveals a novel function for the original phosphatidylinositol 3-kinase binding site SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MIDDLE-T-ANTIGEN; POLYOMA-VIRUS; TUMOR-ANTIGEN; KINASE-ACTIVITY; TYROSINE PHOSPHORYLATION; PROTEIN PHOSPHATASE-2A; TRANSFORMING PROTEIN; DIRECTED MUTAGENESIS; C-SRC; ASSOCIATION AB Previous studies have demonstrated that the specificity of Src homology 2 (SH2) and phosphotyrosine-binding domain interactions are mediated by phosphorylated tyrosines and their neighboring amino acids. Two of the first phosphotyrosine-based binding sites were found on middle T antigen of polyoma virus. Tyr-250 acts as a binding site for ShcA, whereas Tyr-315 forms a binding site for the SH2 domain of the p85 subunit of phosphatidylinositol 3-kinase. However, genetic analysis of a given phosphotyrosine's role in signaling can be complicated when it serves as a binding site for multiple proteins. The situation is particularly difficult when the phosphotyrosine serves as a secondary binding site for a protein with primary binding determinates elsewhere. Mutation of a tyrosine residue to phenylalanine blocks association of all bound proteins. Here we show that the mutation of the amino acids following the phosphorylated tyrosine to alanine can reveal phosphotyrosine function as a secondary binding site, while abrogating the phosphotyrosine motif's role as a primary binding site for SH2 domains. We tested this methodology by using middle T antigen. Our results suggest that Tyr-250 is a secondary binding site for phosphatidylinositol 3-kinase, whereas Tyr-315 is a secondary binding site for a yet-to-be-identified protein, which is critical for transformation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. RP Roberts, TM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 1 Jimmy Fund Way, Boston, MA 02115 USA. FU NCI NIH HHS [CA50661, CA34722, P01 CA050661, P01 CA089021, P01 CA89021-02, R01 CA030002, R01 CA034722, R01 CA3002-21] NR 44 TC 7 Z9 7 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 5 PY 2003 VL 100 IS 16 BP 9434 EP 9439 DI 10.1073/pnas.1432964100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 709HP UT WOS:000184620000061 PM 12881485 ER PT J AU Sze, JY Ruvkun, G AF Sze, JY Ruvkun, G TI Activity of the Caenorhabditis elegans UNC-86POU transcription factor modulates olfactory sensitivity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID C-ELEGANS; HOMEODOMAIN PROTEIN; CELL LINEAGE; GENE-EXPRESSION; HOMEOBOX GENE; HOMEOPROTEINS UNC-86; NERVOUS-SYSTEM; MOTOR-NEURONS; RECEPTOR; ADAPTATION AB The activity of transcription factors modulates several neural pathways that mediate complex behaviors. We describe here the role of the POU transcription factor UNC-86 in the olfactory behavior of Caenorhabditis elegans. unc-86-null mutants are defective in response to odor attractants but avoid odor repellents normally. Continuous UNC-86 activity is necessary for maintenance of odortaxis behavior; hyperactivation of UNC-86 by fusion to a VP16 activation domain dramatically enhances sensitivity to odor attractants and promotes odor-attractant adaptation. UNC-86 is not expressed in olfactory sensory neurons but is expressed throughout the life of the animal in the AIZ interneurons of the odorsensory pathway. We suggest that UNC-86 transcriptional activity regulates the expression of genes that mediate synaptic properties of AIZ and that hyperactive UNC-86::VP16 may enhance the expression of synaptic components to affect the capacity to analyze and process sensory information. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Univ Calif Irvine, Dept Neurobiol & Anat, Irvine, CA 92697 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RI Marion-Poll, Frederic/D-8882-2011 OI Marion-Poll, Frederic/0000-0001-6824-0180 NR 53 TC 14 Z9 19 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 5 PY 2003 VL 100 IS 16 BP 9560 EP 9565 DI 10.1073/pnas.1530752100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 709HP UT WOS:000184620000082 PM 12883006 ER PT J AU Ishida, S Usui, T Yamashiro, K Kaji, Y Amano, S Ogura, Y Hida, T Oguchi, Y Ambati, J Miller, JW Gragoudas, ES Ng, YS D'Amore, PA Shima, DT Adamis, AP AF Ishida, S Usui, T Yamashiro, K Kaji, Y Amano, S Ogura, Y Hida, T Oguchi, Y Ambati, J Miller, JW Gragoudas, ES Ng, YS D'Amore, PA Shima, DT Adamis, AP TI VEGF(164)-mediated inflammation is required for pathological, but not physiological, ischemia-induced retinal neovascularization SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE retina; angiogenesis; VEGF; leukocyte; immunity ID ENDOTHELIAL GROWTH-FACTOR; ADHESION MOLECULE-1 ICAM-1; CELL-ADHESION; FACTOR VEGF; ANGIOGENESIS; RETINOPATHY; EXPRESSION; POTENCY; FLT-1 AB Hypoxia-induced VEGF governs both physiological retinal vascular development and pathological retinal neovascularization. In the current paper, the mechanisms of physiological and pathological neovascularization are compared and contrasted. During pathological neovascularization, both the absolute and relative expression levels for VEGF(164) increased to a greater degree than during physiological neovascularization. Furthermore, extensive leukocyte adhesion was observed at the leading edge of pathological, but not physiological, neovascularization. When a VEGF(164)-specific neutralizing aptamer was administered, it potently suppressed the leukocyte adhesion and pathological neovascularization, whereas it had little or no effect on physiological neovascularization. In parallel experiments, genetically altered VEGF(164)-deficient (VEGF(120/188)) mice exhibited no difference in physiological neovascularization when compared with wild-type (VEGF(+/+)) controls. In contrast, administration of a VEGFk-1/Fc fusion protein, which blocks all VEGF isoforms, led to significant suppression of both pathological and physiological neovascularization. In addition, the targeted inactivation of monocyte lineage cells with clodronate-liposomes led to the suppression of pathological neovascularization. Conversely, the blockade of T lymphocyte-mediated immune responses with an anti-CD2 antibody exacerbated pathological neovascularization. These data highlight important molecular and cellular differences between physiological and pathological retinal neovascularization. During pathological neovascularization, VEGF(164) selectively induces inflammation and cellular immunity. These processes provide positive and negative angiogenic regulation, respectively. Together, new therapeutic approaches for selectively targeting pathological, but not physiological, retinal neovascularization are outlined. C1 Eyetech Res Ctr, Woburn, MA 01801 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Angiogenesis Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol & Ophthalmol, Schepens Eye Res Inst, Boston, MA 02114 USA. Keio Univ, Sch Med, Dept Ophthalmol, Tokyo 1608582, Japan. Univ Tokyo, Fac Med, Dept Ophthalmol, Tokyo 1138655, Japan. Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Kyoto 6068507, Japan. Nagoya City Univ, Sch Med, Dept Ophthalmol, Nagoya, Aichi 4678601, Japan. Kyorin Eye Ctr, Mitaka, Tokyo 1818611, Japan. Univ Kentucky, Dept Ophthalmol, Lexington, KY 40517 USA. RP Adamis, AP (reprint author), Eyetech Res Ctr, 42 Cummings Pk, Woburn, MA 01801 USA. RI ISHIDA, SUSUMU/D-7067-2012 NR 15 TC 264 Z9 293 U1 0 U2 11 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 4 PY 2003 VL 198 IS 3 BP 483 EP 489 DI 10.1084/jem.20022027 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 712TQ UT WOS:000184813700012 PM 12900522 ER PT J AU Campbell, EG Weissman, JS Clarridge, B Yucel, R Causino, N Blumenthal, D AF Campbell, EG Weissman, JS Clarridge, B Yucel, R Causino, N Blumenthal, D TI Characteristics of medical school faculty members serving on institutional review boards: Results of a national survey SO ACADEMIC MEDICINE LA English DT Article ID ACADEMIC MEDICINE; LIFE-SCIENCE; PARTICIPATION; ACCESS; SALE AB Purpose. To understand the characteristics of medical school faculty members who serve on institutional review boards (IRBs) in U.S. academic health centers. Method. Between October 2001 and March 2002, a questionnaire was mailed to a stratified random sample of 4,694 faculty members in 121 four-year medical schools in the United States (excluding Puerto Rico). The sample was drawn from the Association of American Medical College's faculty roster database for 1999. The primary independent variable was service on an IRB. Data were analyzed using standard statistical procedures. Results. A total of 2,989 faculty members responded (66.5%). Eleven percent of respondents reported they had served on an IRB in the three years before the study. Of these, 73% were male, 81% were white (non-Hispanic). Virtually all faculty IRB members (94%) conducted some research in the three years before the study, and, among these, 71% reported conducting clinical research, and 47% served as industrial consultants to industry. Underrepresented minority faculty members were 3.2 times more likely than white faculty members to serve on the IRB. Clinical researchers were 1.64 times more likely to be on an IRB than were faculty members who conducted nonclinical research. No significant difference was found in the average number of articles published in the three years before the study comparing IRB faculty to non-IRB faculty. Conclusions. The faculty members who serve on IRBs tend to have research experience and knowledge that may be used to inform their IRB-retated activities. However, the fact that almost half of all faculty IRB members serve as consultants to industry raises potential conflicts of interest. C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp Partners HealthCare Syst, Inst Hlth Policy, Boston, MA USA. Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. RP Campbell, EG (reprint author), Inst Hlth Policy, 50 Stanford St 9th Floor, Boston, MA 02114 USA. EM ecampbell@partners.org NR 17 TC 23 Z9 23 U1 0 U2 3 PU ASSOC AMER MEDICAL COLLEGES PI WASHINGTON PA 2450 N ST N W, WASHINGTON, DC 20037-1126 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD AUG PY 2003 VL 78 IS 8 BP 831 EP 836 DI 10.1097/00001888-200308000-00019 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 801BD UT WOS:000220070500015 PM 12915379 ER PT J AU Wilhelm, S Buhlmann, U McNally, RJ AF Wilhelm, S Buhlmann, U McNally, RJ TI Negative priming for threatening vs. non-threatening information in body dysmorphic disorder SO ACTA NEUROPSYCHIATRICA LA English DT Article DE body dysmorphic disorder; cognitive inhibition; negative priming AB Background: Individuals with body dysmorphic disorder (BDD) suffer from unpleasant, repetitive thoughts about imagined defects in appearance which are difficult to control. Objective: The purpose of this study was to test for deficits in cognitive inhibition in BDD. Methods: To test for deficits in cognitive inhibition in BDD, we applied a negative priming paradigm. Specifically, we explored whether BDD patients exhibit greater deficits in cognitive inhibition when lexical targets are threatening than when they are non-threatening. Results: Surprisingly, BDD patients exhibited deficits in cognitive inhibition only for non-threatening but not for threatening information. Conclusions: Although BDD patients often describe their negative thoughts about their appearance as distressing, they may experience them as valid and thus may not try to control them. C1 Massachusetts Gen Hosp, Obsess Compuls Disorder Clin, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wilhelm, S (reprint author), Massachusetts Gen Hosp, Obsess Compuls Disorder Clin, Dept Psychiat, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 14 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0924-2708 J9 ACTA NEUROPSYCHIATR JI Acta Neuropsychiatr. PD AUG PY 2003 VL 15 IS 4 BP 180 EP 183 DI 10.1034/j.1601-5215.2003.00037.x PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 711WE UT WOS:000184763400004 PM 26983565 ER PT J AU Santavirta, S Bohler, M Harris, WH Konttinen, YT Lappalainen, R Muratoglu, O Rieker, C Salzer, M AF Santavirta, S Bohler, M Harris, WH Konttinen, YT Lappalainen, R Muratoglu, O Rieker, C Salzer, M TI Alternative materials to improve total hip replacement tribology SO ACTA ORTHOPAEDICA SCANDINAVICA LA English DT Article ID MOLECULAR-WEIGHT POLYETHYLENE; JOINT PROSTHESES; WEAR DEBRIS; IMPLANTS AB An improvement in tribology of bearing surfaces is an effective means of increasing the longevity of total hip replacement (THR). Currently, 3 approaches are available to achieve this aim: first, use of highly cross-linked UHMWPE; second, aluminum oxide ceramic bearings, and third, metal-on-metal bearings. Cross-linking reduces the wear resistance of UHMWPE markedly without impairment of other significant properties of the material. Simulator studies and some clinical long-term (10-22 years) follow-up surveys suggest an almost immeasurable wear of the highly cross-linked UHMWPE-based acetabular components during an expected clinical life span. Bioinert alumina ceramic (aluminum oxide) was introduced 3 decades ago for THR-bearing surfaces to improve performance and longevity. Alumina ceramic is entirely biostable and bioinert and has good mechanical properties. For correctly positioned alumina-on-alumina bearings, the annual linear wear rate has been reported to be 3.9 mum. Alumina heads have been successfully used in combination with polyethylene sockets, but as regards wear, the best results have been obtained with alumina-on-alumina bearings. In ceramic THR bearings, precise manufacture and contact surface geometry, including optimal clearance, are most important. For the currently available products, the component fracture risk is almost nonexistent (less than 1 per 1000). Metal-on-metal bearings were used in the early stage of THR surgery, although not all old designs were successful. More recent analyses of the early series have shown the advantages of metal-on-metal to be better and have led to a renaissance of this articulation. Initially, stainless steel was used because it was easy to manufacture and polish. Current metal-on-metal bearings are based on cobalt-chromium-molybdenum alloys with varying carbon contents. Such bearings are self-polishing. Linear wear rates remain at the level of a few gm a year. An improvement in technology has increased the life span of the above three THR-bearing systems. Although the technical solutions differ considerably, they all seem to improve clearly the tribology and longevity of the THR. Each of these bearing concepts will probably permit the use of larger head sizes, to reduce the risk of impingement and luxations. C1 Univ Helsinki, Cent Hosp, Dept Orthopaed & Traumatol, Helsinki, Finland. Univ Vienna, Inst Histol & Embryol, A-1090 Vienna, Austria. Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Univ Helsinki, Cent Hosp, Dept Med, Helsinki, Finland. Univ Kuopio, Dept Appl Phys, Inst Biomed Technol, FIN-70211 Kuopio, Finland. Sulzer Medica Ltd, Dept Tribol Res, Winterthur, Switzerland. Herz Jesu Hosp, Dept Orthopaed, Vienna, Austria. RP Santavirta, S (reprint author), Univ Helsinki, Cent Hosp, Dept Orthopaed & Traumatol, Helsinki, Finland. NR 31 TC 60 Z9 63 U1 1 U2 17 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0001-6470 J9 ACTA ORTHOP SCAND JI Acta Orthop. Scand. PD AUG PY 2003 VL 74 IS 4 BP 380 EP 388 PG 9 WC Orthopedics SC Orthopedics GA 719JU UT WOS:000185200600002 PM 14521286 ER PT J AU Ferlito, A Arnold, W Rinaldo, A Niedermeyer, HP Grayeli, AB Devaney, KO McKenna, MJ Anniko, M Pulec, JL McCabe, BF van den Broek, P Shea, JJ AF Ferlito, A Arnold, W Rinaldo, A Niedermeyer, HP Grayeli, AB Devaney, KO McKenna, MJ Anniko, M Pulec, JL McCabe, BF van den Broek, P Shea, JJ TI Viruses and otosclerosis: Chance association or true causal link? SO ACTA OTO-LARYNGOLOGICA LA English DT Editorial Material ID MEASLES-VIRUS; INFLAMMATORY DISEASE; ACTIVE OTOSCLEROSIS; INNER-EAR; LESIONS; ANTIGENS; SECTIONS; BONE; RNA C1 Univ Udine, Policlin Univ, Dept Otolaryngol Head & Neck Surg, IT-33100 Udine, Italy. Tech Univ Munich, Klinikum Rechts Isar, Dept Otorhinolaryngol Head & Neck Surg, D-8000 Munich, Germany. Hop Beaujon, INSERM, Clichy, France. Hop Beaujon, AP HP, Dept Otolaryngol, Clichy, France. Foote Hosp, Jackson, MI USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Univ Hosp, Dept Otolaryngol Head & Neck Surg, Uppsala, Sweden. Ear Int & Pulec Ear Clin, Los Angeles, CA USA. Univ Iowa Hosp & Clin, Dept Otolaryngol, Iowa City, IA 52242 USA. St Radboud Hosp, Dept Otolaryngol Head & Neck Surg, Nijmegen, Netherlands. Shea Clin, Memphis, TN USA. RP Ferlito, A (reprint author), Univ Udine, Policlin Univ, Dept Otolaryngol Head & Neck Surg, Piazzale S Maria Misericordia, IT-33100 Udine, Italy. NR 45 TC 5 Z9 5 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0001-6489 J9 ACTA OTO-LARYNGOL JI Acta Oto-Laryngol. PD AUG PY 2003 VL 123 IS 6 BP 741 EP 746 DI 10.1080/00016480310000502 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 706ME UT WOS:000184456800014 PM 12953776 ER PT J AU Musi, N Goodyear, LJ AF Musi, N Goodyear, LJ TI AMP-activated protein kinase and muscle glucose uptake SO ACTA PHYSIOLOGICA SCANDINAVICA LA English DT Article; Proceedings Paper CT International Symposium on Signalling in Muscle Metabolism held in conjunction with the Baltic Summer School 2002 CY AUG 25-27, 2002 CL COPENHAGEN, DENMARK SP Scandinavian Physiol Soc DE AICAR; AMPK; contraction; glucose uptake; metformin; skeletal muscle; type 2 diabetes ID RAT SKELETAL-MUSCLE; ACETYL-COA CARBOXYLASE; OBESE ZUCKER RAT; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; RECEPTOR SUBSTRATE-1 PHOSPHORYLATION; NITRIC-OXIDE SYNTHASE; INSULIN ACTION; GLUT4 TRANSLOCATION; CONTRACTILE ACTIVITY; EXERCISE INTENSITY AB The AMP-activated protein kinase (AMPK) is an enzyme that is activated in situations where there are changes in the cellular energy status such as muscle contraction and hypoxia. AMPK can also be pharmacologically activated by the compound 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and the antidiabetic agent metformin. Several studies support the hypothesis that AMPK plays an important role in the stimulation of muscle glucose uptake by these physiological and pharmacological stimuli. In isolated rat muscles, activation of AMPK is associated with increases in glucose uptake through an insulin-independent mechanism. Studies done in rodents have shown that the activation of AMPK by AICAR is accompanied by decreases in blood glucose concentrations, in part due to enhanced muscle glucose uptake. Similar to exercise, AICAR not only directly stimulates glucose uptake into the skeletal muscle, but also enhances insulin sensitivity. The activation of AMPK and associated increases in muscle glucose uptake are affected by factors such as glycogen content, exercise training and fibre type. The effects of AMPK on muscle glucose uptake makes this protein a promising pharmacological target for the treatment of type 2 diabetes. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIAMS NIH HHS [AR45670] NR 77 TC 79 Z9 85 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0001-6772 J9 ACTA PHYSIOL SCAND JI Acta Physiol. Scand. PD AUG PY 2003 VL 178 IS 4 BP 337 EP 345 DI 10.1046/j.1365-201X.2003.01168.x PG 9 WC Physiology SC Physiology GA 710PZ UT WOS:000184689800007 PM 12864738 ER PT J AU Keebler, ME McGuire, DK AF Keebler, ME McGuire, DK TI Subclinical diabetes mellitus: Is it really "sub-clinical"? SO AMERICAN HEART JOURNAL LA English DT Editorial Material ID DIAGNOSIS; RISK C1 Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. Univ Texas, SW Med Ctr, Donald W Reynolds Cardiovasc Res Ctr, Dept Med, Dallas, TX USA. RP Keebler, ME (reprint author), Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. NR 11 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 0002-8703 J9 AM HEART J JI Am. Heart J. PD AUG PY 2003 VL 146 IS 2 BP 210 EP 212 DI 10.1016/S0002-8703(03)00236-9 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 710XP UT WOS:000184708400008 PM 12891185 ER PT J AU Whang, W Bigger, JT AF Whang, W Bigger, JT TI Comparison of the prognostic value of RR-interval variability after acute myocardial infarction in patients with versus those without diabetes mellitus SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ARRHYTHMIA SUPPRESSION TRIAL; FREQUENCY-DOMAIN MEASURES; HEART PERIOD VARIABILITY; AUTONOMIC NEUROPATHY; INCREASED MORTALITY; SHORT-TERM; PREDICTORS; PLACEBO; DISEASE; HISTORY AB Diabetic patients have substantially greater long-term mortality after acute myocardial infarction (AMI) than nondiabetic patients. Traditionally, cardiac autonomic neuropathy is believed to contribute significantly to the increased mortality rate in patients with diabetes mellitus. In contrast, a recent study suggested that RR-interval variability (RRV) did not predict mortality after AMI in diabetic patients. We compared, in diabetic and nondiabetic patients, the relation between low RRV and long-term mortality in the Multicenter Post Infarction Program (MPIP), a longitudinal observational study of 715 survivors of AMI, including 117 diabetic patients. We studied the association between mortality and 6 frequency-domain measurements and 1 time-domain measurement of RRV. We tested 2 hypotheses: (1) RRV is lower in diabetic patients; and (2) low RRV is less predictive of mortality in diabetic patients. Reduced RRV was significantly more frequent in diabetic patients than nondiabetic patients for all measurements, except high-frequency (HF) power. In diabetic patients, the association between reduced RRV and long-term mortality was at least as strong as it was in nondiabetic patients for all measurements except HF power; this pattern was found for all-cause, cardiac, and arrhythmic death. In multivariable models, reduced RRV was significantly associated with all-cause mortality in diabetic patients even when adjusted for left ventricular ejection fraction, heart failure class, and ventricular arrhythmias. In our post-AMI sample, RRV provided valuable prognostic information among diabetic patients. Our findings suggest that cardiac autonomic neuropathy plays a role in the high mortality rate seen in diabetic patients after AMI. (C)2003 by Excerpta Medica, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Columbia Univ, Dept Med, New York, NY USA. RP Whang, W (reprint author), Harvard Univ, Massachusetts Gen Hosp, Cardiac Unit, Bulfinch 001,55 Fruit St, Boston, MA 02114 USA. NR 24 TC 20 Z9 21 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 1 PY 2003 VL 92 IS 3 BP 247 EP 251 DI 10.1016/S0002-9149(03)00618-0 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 707GX UT WOS:000184503800001 PM 12888125 ER PT J AU Leitzmann, MF Tsai, CJ Stampfer, MJ Rimm, EB Colditz, GA Willett, WC Giovannucci, EL AF Leitzmann, MF Tsai, CJ Stampfer, MJ Rimm, EB Colditz, GA Willett, WC Giovannucci, EL TI Alcohol consumption in relation to risk of cholecystectomy in women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE alcohol; cholelithiasis; cholecystectomy; cohort; women ID HIGH-DENSITY-LIPOPROTEIN; CLINICAL GALLBLADDER-DISEASE; BILE CHOLESTEROL SATURATION; GALLSTONE-DISEASE; UNITED-STATES; SYMPTOMATIC GALLSTONES; DANISH POPULATION; PHYSICAL-ACTIVITY; NUCLEATION TIME; PREVALENCE AB Background: Alcohol consumption has been linked to a lower risk of gallstone disease. However, the magnitude of the association is uncertain, and little is known about the relation of alcohol consumption patterns and individual types of alcoholic beverages to gallstone disease risk. Objective: We prospectively examined the association between alcohol intake and cholecystectomy, a surrogate for symptomatic gallstone disease, in a large cohort of women. Design: Women from the Nurses' Health Study who had no history of gallstone disease in 1980 (n = 80 898) were followed for 20 y. Alcohol consumption, which was measured every 2-4 y by food-frequency questionnaires, was used to predict subsequent cholecystectomy through multivariate analysis. Results: We ascertained 7831 cases of cholecystectomy. Relative to subjects who had no alcohol intake, subjects who had alcohol intakes of 0.1-4.9, 5.0-14.9, 15.0-29.9, 30.0-49.9, and greater than or equal to 50.0 g/d had multivariate relative risks of cholecystectomy of 0.95, 0.86, 0.80, 0.67, and 0.62 (95% CI: 0.49, 0.79), respectively. Relative to subjects who never consumed alcohol, subjects who consumed alcohol 1-2, 3-4, 5-6, and 7 d/wk had multivariate relative risks of cholecystectomy of 0.94, 0.88, 0.87, and 0.73 (0.63, 0.84), respectively. All alcoholic beverage types were inversely associated with cholecystectomy risk, independent of consumption patterns (for quantity of alcohol consumed, P = 0.04, 0.001, and 0.003 for wine, beer, and liquor, respectively; for frequency of alcohol consumption, P = 0.01, 0.07, and <0.0001 for wine, beer, and liquor, respectively). Conclusions: The intake of all alcoholic beverage types is inversely associated with the risk of cholecystectomy. Recommendations regarding the benefit of consuming moderate quantities of alcohol should be weighed against the potential health hazards. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Ctr Canc Prevent, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Program Epidemiol, Boston, MA USA. RP Leitzmann, MF (reprint author), NCI, 6120 Execut Blvd,EPS 3028, Rockville, MD 20852 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA 87969, 5T32 CA09001-26]; NIAAA NIH HHS [AA11181]; NIDDK NIH HHS [DK 46200] NR 53 TC 27 Z9 27 U1 0 U2 1 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 2003 VL 78 IS 2 BP 339 EP 347 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 704XE UT WOS:000184366300024 PM 12885719 ER PT J AU Stockwell, DH Woo, P Jacobson, BC Remily, R Syngal, S Wolf, J Farraye, FA AF Stockwell, DH Woo, P Jacobson, BC Remily, R Syngal, S Wolf, J Farraye, FA TI Determinants of colorectal cancer screening in women undergoing mammography SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Digestive Disease Week/102nd Annual Meeting of the American-Gastroenterological-Association CY MAY 20-23, 2001 CL ATLANTA, GEORGIA SP Amer Gastroenterol Assoc ID FLEXIBLE SIGMOIDOSCOPY; PATIENT PREFERENCES; RECOMMENDATIONS; PARTICIPATION; RISK; GUIDELINES; PHYSICIANS; PROSTATE; GENDER; SEX AB OBJECTIVES: Women who participate in screening for breast cancer are more likely to participate in screening for colorectal cancer. We studied such a motivated group of women to identify predictors of, and barriers to, participation in colorectal cancer screening by endoscopy. METHODS: We distributed surveys to 551 women greater than or equal to 50 yr of age while they were awaiting mammography at four sites in and around Boston, MA from June to September, 2000. The 40-question survey assessed knowledge, attitudes, and beliefs about, and behaviors toward, breast and colorectal cancer screening. Regression models were used to determine factors associated with having had sigmoidoscopy or colonoscopy. RESULTS: Seventy-nine percent of the women completed all or part of the survey. Half (221/438) reported ever having had sigmoidoscopy or colonoscopy. Of these, 93% did so at the recommendation of their primary care provider. Factors associated with participation in endoscopic screening included compliance with annual fecal occult blood testing, a family history of colorectal cancer, and indifference toward the gender of the doctor performing the endoscopy. CONCLUSIONS: Women undergoing mammography overwhelmingly cite the recommendation of their primary care provider as the reason for participating in colorectal cancer screening by endoscopy. Women who preferred a female endoscopist were less likely to have been screened. Whenever possible, primary care providers should offer women the choice of a female endoscopist for colorectal cancer screening. (Am J Gastroenterol 2003;98:1875-1880. (C) 2003 by Am. Coll. of Gastroenterology) C1 Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Internal Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA. Boston Univ, Med Ctr, Gastroenterol Sect, Boston, MA USA. RP Stockwell, DH (reprint author), Brigham & Womens Hosp, Div Gastroenterol, 75 Francis St, Boston, MA 02115 USA. NR 33 TC 37 Z9 37 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD AUG PY 2003 VL 98 IS 8 BP 1875 EP 1880 DI 10.1016/S0002-9270(03)00426-X PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 708TF UT WOS:000184584900031 PM 12907347 ER PT J AU Pastore, Y Jedlickova, K Guan, YL Liu, EL Fahner, J Hasle, H Prchal, JF Prchal, JT AF Pastore, Y Jedlickova, K Guan, YL Liu, EL Fahner, J Hasle, H Prchal, JF Prchal, JT TI Mutations of von Hippel-Lindau tumor-suppressor gene and congenital polycythemia SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID REGULATE HIF; VHL GENE; DISEASE; PROTEIN; HYDROXYLATION; COMPLEX; CANCER; DEFINE; ALPHA AB The von Hippel-Lindau (pVHL) protein plays an important role in hypoxia sensing. It binds to the hydroxylated hypoxia-inducible factor 1alpha (HIF-1alpha) and serves as a recognition component of an E3-ubiquitin ligase complex. In hypoxia or secondary to a mutated VHL gene, the nondegraded HIF-1alpha forms a heterodimer with HIF-beta and leads to increased transcription of hypoxia-inducible genes, including erythropoietin (EPO). The autosomal dominant cancer-predisposition von Hippel-Lindau (VHL) syndrome is due to inheritance of a single mutated allele of VHL. In contrast, we recently showed that homozygous germline 598C-->T VHL mutation leads to Chuvash polycythemia (CP). We subsequently found VHL mutations in three unrelated individuals unaffected with CP, one of whom was compound heterozygous for the 598C-->T mutation and another VHL mutation. We now report seven additional polycythemic patients with VHL mutations in both alleles. Two Danish siblings and another American boy were homozygous for the VHL 598C-->T mutation. Three unrelated white Americans were compound heterozygotes for 598C-->T and another VHL mutation, 562C-->G in two and 574C-->T in the third. Additionally, a Croatian boy was homozygous for a 571C-->G VHL mutation, the first example of homozygous VHL germline mutation causing polycythemia, other than the VHL 598C-->T mutation. We have not observed VHL syndrome - associated tumors in polycythemic subjects or their heterozygous relatives; however, this will need to be evaluated by longitudinal studies. Over all, we found that up to half of the consecutive patients with apparent congenital polycythemia and increased serum Epo we have examined have mutations of both VHL alleles. Those findings, along with reports of CP, underscore that VHL mutations are the most frequent cause of congenital polycythemia and define a new class of polycythemic disorder, polycythemias due to augmented hypoxia sensing. C1 Baylor Coll Med, Houston, TX 77030 USA. Texas Childrens Canc Ctr & Hematol Serv, Houston, TX USA. Vet Adm Hosp, Houston, TX USA. DeVos Childrens Hosp, Grand Rapids, MI USA. Viborg Hosp, Dept Pediat, Viborg, Denmark. McGill Univ, Dept Hematol Oncol, Montreal, PQ, Canada. RP Prchal, JT (reprint author), Baylor Coll Med, 1 Baylor Plaza,Suite 802E, Houston, TX 77030 USA. FU NHLBI NIH HHS [R01 HL066333, R01HL5007-08, R01HL66333-01] NR 28 TC 76 Z9 79 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD AUG PY 2003 VL 73 IS 2 BP 412 EP 419 DI 10.1086/377108 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 702KW UT WOS:000184223900018 PM 12844285 ER PT J AU Taylor, JGC Zwillich, CW Kaehny, WD Levi, M Popovtzer, MM AF Taylor, JGC Zwillich, CW Kaehny, WD Levi, M Popovtzer, MM TI Hyperkalemia with concomitant watery diarrhea: An unusual association SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE herkalemia; diarrhea; angiotensin-converting enzyme (ACE) inhibitor ID HYPOKALEMIA; ABSORPTION; SECRETION AB Four patients presented to the emergency room with life-threatening hyperkalemia and concomitant watery diarrhea. Hypovolemia, acidosis, and renal insufficiency were present in all 4 cases. In 2 patients, hyperkalemia followed initiation of angiotensin-converting enzyme (ACE) inhibitor therapy, whereas 1 patient experienced hyperkalemia after a dose increase of an ACE inhibitor, and the fourth patient was on continuous ACE-inhibitor therapy at the time of the hyperkalemia episode. Two of the 3 patients with functioning kidneys required hemodialysis to correct the hyperkalemia, whereas the other patient was on long-term hemodialysis therapy. In the 2 patients in whom transtubular potassium (K+) gradients were available, their values ranged far below normal, indicating tubular failure to secrete K+. This abnormality was attributed to decreased distal delivery of sodium and water and to renin/angiotensin II/aldosterone blockade. It has been proposed that aldosterone blockade impairs the capacity of the colonic epithelial cells to secrete K+. In all 4 patients the watery diarrhea ceased in parallel with the correction of serum K+ to normal values. It is suggested that hyperkalemia, most likely by stimulating intestinal motility, induced the watery diarrhea in all 4 patients. The watery diarrhea, however, failed to compensate for the renal tubular failure to secrete K+. C1 Denver VA Med Ctr, Renal Sect 111C, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Div Renal Dis & Hypertens, Denver, CO 80262 USA. RP Popovtzer, MM (reprint author), Denver VA Med Ctr, Renal Sect 111C, 1055 Clermont St, Denver, CO 80220 USA. NR 15 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD AUG PY 2003 VL 42 IS 2 AR E5 DI 10.1016/S0272-6386(03)00667-X PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 708FV UT WOS:000184557300036 ER PT J AU Hoh, BL Rabinov, JD Pryor, JC Carter, BS Barker, FG AF Hoh, BL Rabinov, JD Pryor, JC Carter, BS Barker, FG TI In-hospital morbidity and mortality after endovascular treatment of unruptured intracranial aneurysms in the United States, 1996-2000: Effect of hospital and physician volume SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID GUGLIELMI DETACHABLE COILS; NEW-YORK-STATE; CORONARY ANGIOPLASTY; CEREBRAL ANEURYSMS; SUBARACHNOID HEMORRHAGE; ADMINISTRATIVE DATA; CAROTID-ENDARTERECTOMY; CONSECUTIVE SERIES; SURGICAL-TREATMENT; PUBLICATION BIAS AB Background and Purpose: Endovascular therapy is increasingly being used for the treatment of unruptured intracranial aneurysms. Our purpose was to determine the risk of adverse outcomes after contemporary endovascular treatment of unruptured intracranial aneurysms in the United States. Patient, treating physician, and hospital characteristics were tested as potential outcome predictors, with particular attention paid to volume of care. Methods: We conducted a retrospective cohort study by using the Nationwide Inpatient Sample, 1996-2000. Multivariate logistic and ordinal regressions were used with end points of mortality, discharge other than to home, length of stay, and total hospital charges. Results: Four hundred twenty-one patients underwent endovascular treatment at 81 hospitals. The in-hospital mortality rate was 1.7%, and 7.6% were discharged to institutions other than home. Analysis was adjusted for age, sex, race, primary payer, year of treatment, and four variables measuring acuity of treatment and medical comorbidity. Median annual number of unruptured aneurysms treated was nine per hospital and three per treating physician. Higher volume hospitals had fewer adverse outcomes; discharge other than to home occurred after 5.2% of operations at high volume hospitals (>23 admissions per year) compared with 17.6% at low volume hospitals (fewer than four admissions per year) (P<.001). Higher physician volume had a similar effect (0% versus 16.4%, P=.03). The mortality rate was lower at high volume hospitals (1.0% versus 3.7%) but not significantly so. At high volume hospitals, length of stay was shorter (P<.001) and total hospital charges were lower (P<.001). Conclusion: For patients with unruptured aneurysms treated in the United States from 1996 to 2000, endovascular treatment at high volume institutions or by high volume physicians was associated with significantly lower morbidity rates and modestly lower mortality rates. Length of stay was shorter and total hospital charges lower at high volume centers. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Neurosurg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, Neurosurg Serv, Cox 3,Fruit St, Boston, MA 02114 USA. NR 80 TC 103 Z9 105 U1 1 U2 1 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD AUG PY 2003 VL 24 IS 7 BP 1409 EP 1420 PG 12 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 713MB UT WOS:000184860800030 PM 12917139 ER PT J AU Rabinov, JD Hellinger, FR Morris, PP Ogilvy, CS Putman, CM AF Rabinov, JD Hellinger, FR Morris, PP Ogilvy, CS Putman, CM TI Endovascular management of vertebrobasilar dissecting aneurysms SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Neuroradiology CY MAY 23-28, 1999 CL SAN DIEGO, CALIFORNIA SP Amer Soc Neuroradiol ID INTRACRANIAL VERTEBRAL ARTERY; SUBARACHNOID HEMORRHAGE; BASILAR ARTERY; OCCLUSION; AORTA AB Background and Purpose: Several approaches to the treatment of dissecting aneurysms of the vertebrobasilar system have been used. We evaluated our endovascular experience, which includes trapping and proximal occlusion. Methods: Thirty-five patients with intradural vertebrobasilar dissecting aneurysms presented to our institution between 1992 and 2002. Twenty-six were treated by endovascular means and two with surgery. In the endovascular group, 14 were in a supra-posterior inferior cerebellar artery (PICA) location, and three of these extended to the vertebrobasilar junction on the initial angiogram. Ten were located in an infra-PICA location, or no antegrade flow was seen in the PICA or anterior spinal artery. Two were located at the PICA with antegrade flow preserved in the branch. Twelve lesions were treated with trapping; another 14 were initially treated with proximal occlusion techniques, two of which eventually required trapping procedures. Follow-up images were obtained within 1 year of initial treatment in 24 patients. Mean follow-up for these patients was 3.5 years. Results: Initial treatments were technically successful and without complication in all 26 patients. Follow-up examinations showed complete cure in 19 of 24 patients. One patient died of global ischemia after presenting as Hunt and Hess grade 5 with subarachanoid hemorrhage. Two recurrent hemorrhages occurred in patients in the proximal occlusion group; one died, and the other underwent a trapping procedure. One patient developed contralateral vertebral dissection 24 hours after occlusion of a dissecting aneurysm of the dominant vertebral artery and died of a brain stem infarct. Another died of probable vasospasm, and the last died of an unknown cause 1 month after treatment. Two patients had recanalization despite an initial trapping procedure, both underwent further treatment. Mortality rate was 20% in the treated group (including the two patients treated surgically), with four of five deaths occurring during the initial hospital course. Mortality rate was 50% in the six patients in the untreated group who were available for follow-up. Conclusion: Dissecting aneurysms of the vertebrobasilar system remain high-risk lesions because of their natural history. They can be managed by endovascular methods according to aneurysm location, configuration, collateral circulation, and time of presentation. Trapping results in better prevention of rehemorrhage. Proximal occlusion can achieve occlusion without manipulation of the affected segment when more direct endovascular occlusion or stent placement cannot be performed. C1 Massachusetts Gen Hosp, Dept Intervent Neuroradiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Florida Hosp Med Ctr, Orlando, FL 32803 USA. Wake Forest Med Ctr, Dept Radiol, Winston Salem, NC USA. Fairfax Hosp, Dept Radiol, Fairfax, VA USA. RP Rabinov, JD (reprint author), Massachusetts Gen Hosp, Dept Intervent Neuroradiol, Gray 289,55 Fruit St, Boston, MA 02114 USA. NR 33 TC 122 Z9 132 U1 3 U2 6 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD AUG PY 2003 VL 24 IS 7 BP 1421 EP 1428 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 713MB UT WOS:000184860800031 PM 12917140 ER PT J AU Grodstein, F Fretts, R Lifford, K Resnick, N Curhan, G AF Grodstein, F Fretts, R Lifford, K Resnick, N Curhan, G TI Association of age, race, and obstetric history with urinary symptoms among women in the Nurses' Health Study SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE incontinence; urinary ID RISK-FACTORS; INCONTINENCE PREVALENCE; AFRICAN-AMERICAN; LATER LIFE; POPULATION; CORRELATE; COMMUNITY; DELIVERY; PARITY; FEMALE AB OBJECTIVE: The purpose of this study was to better understand associations among age, race, obstetric history, and urinary incontinence in women. STUDY DESIGN: Race and obstetric history were assessed through the use of biennial mailed questionnaires from 1976 to 1996 among participants of the Nurses' Health Study. In 1996, 83,168 women aged 50 to 75 years reported their frequency of leaking urine and quantity leaked. We used logistic regression to calculate multivariate-adjusted odds ratios and 95% Cls for the relation of risk factors to leaking urine. RESULTS: Overall, 34.1% of the women reported leaking urine at least once per month during the previous 12 months; this prevalence was lowest in the black women (21.2%). After potential confounders were controlled, there were strong trends of increasing prevalence of occasional and frequent leaking with increasing age (P trend <.0001). There was also increasing prevalence of leaking urine with increasing parity; for example, compared with nulliparous women, the odds ratio for frequent leaking was 1.72 (95% Cl, 1.55-1.90) among those with 5 births. Odds ratios that were associated with parity were higher in women aged <60 years than in women aged 60 years. Age at first birth of >35 years was associated with a slight elevation in frequent leaking compared with women with age at first birth from 21 to 25 years but was stronger for women with age at first birth of <21 years (OR, 1.27; 95% Cl, 1.13-1.42). CONCLUSION: In these women, leaking urine is common; this condition is most prevalent in white women, in older women, in parous women, and in women with a younger age at first birth. C1 Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nephrol,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Univ Pittsburgh, Med Ctr, Dept Med, Div Geriatr Med, Pittsburgh, PA 15260 USA. RP Grodstein, F (reprint author), Harvard Univ, Sch Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA40356]; NIDDK NIH HHS [DK26438] NR 23 TC 100 Z9 101 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 2003 VL 189 IS 2 BP 428 EP 434 DI 10.1067/S0002-9378(03)00361-2 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 719RV UT WOS:000185219100034 PM 14520212 ER PT J AU Schaumberg, DA Sullivan, DA Buring, JE Dana, MR AF Schaumberg, DA Sullivan, DA Buring, JE Dana, MR TI Prevalence of dry eye syndrome among US women SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID LACRIMAL GLAND; EPIDEMIOLOGY; SICCA; TESTS AB PURPOSE: Dry eye syndrome (DES) is believed to be one of the most common ocular problems in the United States (US), particularly among older women. However, there are few studies describing the magnitude of the problem in women and how this may vary with demographic characteristics. DESIGN: Cross-sectional prevalence survey. METHODS: Study population: we surveyed 39,876 US women participating in the Women's Health Study about a history of diagnosed DES and dry eye symptoms. Main outcome measure: we defined DES as the presence of clinically diagnosed DES or severe symptoms (both dryness and irritation constantly or often). We calculated the age-specific prevalence of DES and adjusted the overall prevalence to the age distribution of women in the US population. We used logistic regression to examine associations between DES and other demographic factors. RESULTS: The prevalence of DES increased with age, from 5.7% among women < 50 years old to 9.8% among women aged : 75 years old. The age-adjusted prevalence of DES was 7.8%, or 3.23 million women aged : 50 in the US. Compared with Whites, Hispanic (odds ratio [OR] = 1.81, confidence interval [CI] = 1.18-2.80) and Asian (OR = 1.7 7, CI = 1.17-2.69) women were more likely to report severe symptoms, but not clinically diagnosed DES. There were no significant differences by income (P-[trend] =.78), but more educated women were less likely to have DES (P-[trend] =.03). Women from the South had the highest prevalence of DES, though the magnitude of geographic differences was modest. CONCLUSIONS: Dry eye syndrome leading to a clinical diagnosis or severe symptoms is prevalent, affecting over 3.2 million American women middle,aged and older. Although the condition is more prevalent among older women, it also affects many women in their 40s and 50s. Further research is needed to better understand DES and its impact on public health and quality of life. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. RP Schaumberg, DA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. FU NCI NIH HHS [CA47988]; NEI NIH HHS [EY00365, K23 EY000365, K23 EY000365-04, K23 EY000365-05]; NHLBI NIH HHS [HL43851] NR 21 TC 475 Z9 491 U1 9 U2 24 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD AUG PY 2003 VL 136 IS 2 BP 318 EP 326 DI 10.1016/S0002-9394(03)00218-6 PG 9 WC Ophthalmology SC Ophthalmology GA 702YT UT WOS:000184253200015 PM 12888056 ER PT J AU Pepose, JS Margolis, TP LaRussa, P Pavan-Langston, D AF Pepose, JS Margolis, TP LaRussa, P Pavan-Langston, D TI Ocular complications of smallpox vaccination SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; VACCINIAL KERATITIS; THERAPY; ARABINOSIDE; INTERFERON AB PURPOSE: To describe the ocular complications of smallpox vaccination and to discuss potential therapeutic options. DESIGN: Review of pertinent medical literature and recent treatment recommendations of the Centers for Disease Control and Prevention. RESULTS: After immunization against smallpox, vaccinia infection of the eyelid, conjunctiva, or ocular surface can result from accidental autoinoculation from a vaccination site before scab formation or from contact with a recently vaccinated individual. While uncommon, corneal involvement can lead to stromal opacification and scarring. Clinical findings of ocular and periocular vaccinia must be differentiated from those produced by other pathogens such as molluscum contagiosum, herpes simplex, varicella zoster, and acanthamoeba infections. Clinical diagnosis can be confirmed by electron microscopy to identify the presence of orthopoxvirus, as well as by virologic culture, polymerase chain reaction, and/or restriction endonuclease analysis of viral isolates. CONCLUSIONS: While the majority of ocular complications of smallpox vaccination in immunocompetent patients are self-limiting, selective cases may require treatment with trifluridine drops, topical corticosteroids and vaccinia immune globulin (VIG). Vaccinia virus does not appear to be sensitive to acyclovir. Specific treatment recommendations are outlined for the spectrum of ocular manifestations. C1 Pepose Vis Inst, Chesterfield, MO 63017 USA. Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA. Univ Calif San Francisco, Francis I Proctor Fdn, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA. Columbia Univ, Dept Pediat, New York, NY 10027 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Pepose, JS (reprint author), Pepose Vis Inst, 16216 Baxter Rd,Suite 205, Chesterfield, MO 63017 USA. NR 39 TC 17 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD AUG PY 2003 VL 136 IS 2 BP 343 EP 352 DI 10.1016/S0002-9394(03)00293-9 PG 10 WC Ophthalmology SC Ophthalmology GA 702YT UT WOS:000184253200019 PM 12888060 ER PT J AU Stein, J Shafqat, S Doherty, D Frates, EP Furie, KL AF Stein, J Shafqat, S Doherty, D Frates, EP Furie, KL TI Patient knowledge and expectations for functional recovery after stroke SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE stroke; rehabilitation; health education ID RISK-FACTORS; INFORMATION; PREVENTION; ADVICE; CARERS; SIGNS AB Objective: Understanding the causes and outcomes of stroke is important for stroke survivors and may affect their success in rehabilitation and their risk of recurrent stroke; therefore, this study was performed to assess the knowledge and expectation of functional recovery in stroke patients undergoing acute inpatient rehabilitation. Design: Survey study of 50 consecutive stroke patients undergoing inpatient rehabilitation at a single urban rehabilitation hospital. Results: Forty-six percent of participants were able to correctly identify whether they had sustained a cerebral infarct or hemorrhage. Rehabilitation length of stay was, on average, 1 wk longer than anticipated by patients. Patients overestimated their functional abilities on initial assessment and at discharge compared with staff assessments, with some improvement in accuracy for discharge predictions. Ninety-four percent of participants expected to be discharged home, and most achieved this goal. Although no participant anticipated discharge to a nursing home, 10% of patients were discharged to this location. Conclusions: Knowledge of stroke and its treatment was limited, and expectations for recovery tended to exceed actual accomplishments. There are significant areas of opportunity for enhanced educational efforts for stroke patients undergoing inpatient rehabilitation. C1 Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. RP Stein, J (reprint author), Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, 125 Nashua St, Boston, MA 02114 USA. NR 12 TC 12 Z9 12 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD AUG PY 2003 VL 82 IS 8 BP 591 EP 596 DI 10.1097/01.phm.0000078197.34363.02 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 702RW UT WOS:000184238100004 PM 12872015 ER PT J AU Koutkia, P Canavan, B Johnson, ML DePaoli, A Grinspoon, S AF Koutkia, P Canavan, B Johnson, ML DePaoli, A Grinspoon, S TI Characterization of leptin pulse dynamics and relationship to fat mass, growth hormone, cortisol, and insulin SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE subcutaneous fat; abdominal fat; synchronicity; pulsatility; cross-approximate entropy ID NORMAL FEMALE MICE; CIRCULATING LEPTIN; SERUM LEPTIN; LUTEINIZING-HORMONE; PLASMA LEPTIN; BODY; SECRETION; RECEPTOR; WOMEN; HYPERINSULINEMIA AB To investigate the regulation of leptin secretion and pulsatility by fat mass, we performed overnight leptin sampling every 20 min for 12 h and compared leptin dynamics with total body and regional fat measurements in 20 healthy male subjects. Simultaneous growth hormone (GH), cortisol, and insulin levels were assessed to determine relatedness and synchronicity during overnight fasting. Deconvolution analyses were performed to determine simultaneous hormonal dynamics, synchronicity, and interrelatedness using cross-correlation and cross-approximate entropy (X-ApEn) analyses. Subjects demonstrated 4.7 +/- 0.4 leptin pulses/ 12 h. Leptin secretion correlated highly with total body fat ( r = 0.78, P < 0.001) and regional fat depots. In contrast, leptin pulsatility did not correlate with total fat ( r = 0.07, P = 0.785) or other measures of fat. There was synchronicity between GH and leptin (lag - 39 minutes), cortisol and leptin ( lag - 211 min), and leptin and insulin, with leptin following insulin by 275 min. The mean random X-ApEn was significant between leptin and GH ( 0.854 +/- 0.030), cortisol ( 0.891 +/- 0.023), and insulin ( 0.868 +/- 0.034), demonstrating a high degree of regularity and pattern frequency. These data demonstrate differential regulation of leptin secretion and pulsatility in adipocytes and suggest that the leptin pulse generator is extrinsic to fat, whereas fat mass acts as an amplifier to modulate secretion and amplitude for a given pulsatility. We demonstrate synchronicity between leptin and GH, cortisol, and insulin. The directionality of the cross correlation suggests a temporal construct in which changes in leptin follow those of insulin but precede those of GH and cortisol during overnight fasting. C1 Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Virginia, Hlth Sci Ctr, Dept Pharmacol, Charlottesville, VA 22908 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, Lon 207,55 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [M01 RR-01066] NR 39 TC 28 Z9 29 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD AUG PY 2003 VL 285 IS 2 BP E372 EP E379 DI 10.1152/ajpendo.00097.2003 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 702BU UT WOS:000184205400016 PM 12721156 ER PT J AU Reeve, JR Green, GM Chew, P Eysselein, VE Keire, DA AF Reeve, JR Green, GM Chew, P Eysselein, VE Keire, DA TI CCK-58 is the only detectable endocrine form of cholecystokinin in rat SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE pancreas; radioimmunoassay; blood processing; plasma; molecular forms ID PLASMA; INTESTINE; BLOOD; DEGRADATION; BRAIN AB CCK-58 differs from CCK-8 in patterns of expression of pancreatic secretion of fluid and amylase and gallbladder contraction. These differences have physiological relevance only if CCK-58 release is stimulated by nutrients entering the intestine and if CCK-58 circulates in sizeable amounts. In this study, we report that when radiolabeled CCK-58 is added to rat blood and plasma is formed, there is extensive loss and degradation of the radioactive peptide. Therefore, a new method was developed to minimize loss and degradation of this label. This method recovered >85% of the label with no detectable degradation. Furthermore, the optimized method recovered all unlabeled exogenous cholecystokinin molecular forms in >80% yields. Blood from fasted rats and rats in which cholecystokinin release was stimulated by the trypsin inhibitor camostat contained only CCK-58 (3.5 +/- 0.5 and 17 +/- 1.5 fmol/ml, respectively). Because CCK-58 predominates in the blood, this molecular form should be used in studieson the physiology and pathophysiology of cholecystokinin. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv 151, Digest Dis Res Ctr, Ctr Ulcer Res & Educ, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Div Digest Dis, Los Angeles, CA 90024 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. Harbor Univ Los Angeles Med Ctr, Div Gastroenterol, Torrance, CA 90509 USA. RP Reeve, JR (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv 151, Digest Dis Res Ctr, Ctr Ulcer Res & Educ, Bldg 115,Rm 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-33850, DK-37482, DK-41301] NR 27 TC 62 Z9 63 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD AUG PY 2003 VL 285 IS 2 BP G255 EP G265 DI 10.1152/ajpgi.00523.2002 PG 11 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 698TY UT WOS:000184015900002 PM 12686511 ER PT J AU Ihlemann, N Rask-Madsen, C Perner, A Dominguez, H Hermann, T Kober, L Torp-Pedersen, C AF Ihlemann, N Rask-Madsen, C Perner, A Dominguez, H Hermann, T Kober, L Torp-Pedersen, C TI Tetrahydrobiopterin restores endothelial dysfunction induced by an oral glucose challenge in healthy subjects SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE nitric oxide; postprandial; hyperglycemia ID NITRIC-OXIDE SYNTHASE; DEPENDENT VASODILATION; ACUTE HYPERGLYCEMIA; DIABETES-MELLITUS; SUPEROXIDE GENERATION; INSULIN; FOREARM; HYPERTRIGLYCERIDEMIA; HYPERCHOLESTEROLEMIA; RESISTANCE AB An oral glucose challenge causes transient impairment of endothelial function, probably because of increased oxidative stress. During oxidative stress, endothelial nitric oxide (NO) synthase (eNOS) becomes uncoupled because of decreased bioavailability of tetrahydrobiopterin (BH4), an essential cofactor of eNOS. Therefore, we examined whether an acute supplement of BH4 could restore endothelial dysfunction induced by an oral glucose challenge. Healthy subjects were examined in 53 experiments. Forearm blood flow was measured by venous occlusion plethysmography. Dose-response studies were obtained during intra-arterial infusion of serotonin to elicit endothelium-dependent, NO-specific vasodilation and during sodium nitroprusside ( SNP) infusion to elicit endothelium-independent vasodilation. Subjects were examined before (fasting) and 1 and 2 h after an oral glucose challenge (75 g) with serotonin (n = 10) and SNP (n = 8). On different days (6R)-5,6,7,8-tetrahydro-L-biopterin dihydrochloride (6R-BH4; n = 10), the active cofactor of eNOS or its stereoisomer (6S)-5,6,7,8-tetrahydro-L-biopterin sulfate (6S-BH4; n = 10), which is inactive as a cofactor, was added 10 min (500 mug/min) before and during the 1-h postchallenge serotonin dose-response study. In vitro studies showed that 6R-BH4 and 6S-BH4 were equipotent antioxidants. Serotonin response was reduced by 24 +/- 7% (at the highest dose) at 1 h postchallenge compared with fasting (P = 0.001) and was restored 2 h postchallenge. The reduction was reversed by the administration of 6R-BH4 but not by 6S-BH4. SNP responses were slightly increased 1 and 2 h postchallenge (increased by 15 +/- 13% at third dose 2 h postchallenge, P = 0.0001). An oral glucose challenge causes transient, NO-specific, endothelial dysfunction, which may be reversed by BH4. Transient postprandial endothelial dysfunction may be partly explained by reduced bioavailability of BH4 and NO. C1 Bispebjerg Univ Hosp, Dept Cardiol, DK-2400 Copenhagen, Denmark. Joslin Diabet Ctr, Boston, MA 02215 USA. Rigshosp, Dept Cardiol, DK-2100 Copenhagen, Denmark. Herlev Hosp, Dept Med Gastroenterol, DK-2730 Herlev, Denmark. RP Ihlemann, N (reprint author), Bispebjerg Univ Hosp, Dept Cardiol, Bldg 40,Bispebjerg Bakke 23, DK-2400 Copenhagen, Denmark. RI Torp-Pedersen, Christian/E-5931-2013; OI DOMINGUEZ, HELENA/0000-0002-7089-2636 NR 42 TC 68 Z9 70 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD AUG PY 2003 VL 285 IS 2 BP H875 EP H882 DI 10.1152/ajpheart.00008.2003 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 701DN UT WOS:000184153100050 PM 12730050 ER PT J AU Wei, CC Lucchesi, PA Tallaj, J Bradley, WE Powell, PC Dell'Italia, LJ AF Wei, CC Lucchesi, PA Tallaj, J Bradley, WE Powell, PC Dell'Italia, LJ TI Cardiac interstitial bradykinin and mast cells modulate pattern of LV remodeling in volume overload in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE hypertrophy; chymase; angiotensin-converting enzyme ID ANGIOTENSIN-CONVERTING ENZYME; CONGESTIVE-HEART-FAILURE; IN-VIVO; MYOCARDIAL-INFARCTION; RECEPTOR ANTAGONISTS; II FORMATION; DOG HEART; CHYMASE; KININS; INHIBITORS AB In the current study, interstitial fluid (ISF), bradykinin (BK), and angiotensin II (ANG II) levels were measured using cardiac microdialysis in conscious, nonsedated rats at baseline and at 48 h and 5 days after each of the following: sham surgery ( sham, n = 6), sham + administration of ANG-converting enzyme inhibitor ramipril (R, n = 6), creation of aortocaval fistula (ACF, n = 6), ACF + R (n = 6), and ACF + R + BK2 receptor antagonist (HOE-140) administration (n = 6). At 5 days, both ISF ANG II and BK increased in ACF rats (P < 0.05); however, in ACF + R rats, ISF ANG II did not differ from basal levels and ISF BK increased greater than threefold above baseline at 2 and 5 days (P < 0.05). Five days after ACF, the left ventricular (LV) weight-to-body weight ratio increased 30% (P < 0.05) in ACF but did not differ from sham in ACF + R and ACF + R + HOE-140 rats despite similar systemic arterial pressures across all ACF groups. However, ACF + R + HOE-140 rats had greater postmortem wall thickness-to-diameter ratio and smaller cross-sectional diameter compared with ACF + R rats. There was a significant increase in mast cell density in ACF and ACF + R rats that decreased below sham in ACF + R + HOE-140 rats. These results suggest a potentially important interaction of mast cells and BK in the cardiac interstitium that modulates the pattern of LV remodeling in the acute phase of volume overload. C1 Birmingham Vet Affairs Med Ctr, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35233 USA. RP Dell'Italia, LJ (reprint author), Univ Alabama, Dept Med, Div Cardiovasc Dis, 834 MCLM,1918 Univ Blvd, Birmingham, AL 35294 USA. RI Lucchesi, Pamela/E-3558-2011 FU NHLBI NIH HHS [HL 60707, R01 HL 54816] NR 43 TC 27 Z9 27 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD AUG PY 2003 VL 285 IS 2 BP H784 EP H792 DI 10.1152/ajpheart.00793.2001 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 701DN UT WOS:000184153100040 PM 12663259 ER PT J AU Li, LF Ouyang, B Choukroun, G Matyal, R Mascarenhas, M Jafari, B Bonventre, JV Force, T Quinn, DA AF Li, LF Ouyang, B Choukroun, G Matyal, R Mascarenhas, M Jafari, B Bonventre, JV Force, T Quinn, DA TI Stretch-induced IL-8 depends on c-Jun NH2-terminal and nuclear factor-kappa B-inducing kinases SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE A549 cells; mitogen-activated protein kinase; ventilation ID INTERLEUKIN-8 GENE-EXPRESSION; RESPIRATORY-DISTRESS SYNDROME; N-TERMINAL KINASE; INDUCED LUNG INJURY; CELL-LINE; TRANSCRIPTION FACTOR; COOPERATIVE INTERACTION; MECHANICAL VENTILATION; IN-VITRO; ACTIVATION AB Positive pressure ventilation with large tidal volumes has been shown to cause release of cytokines, including interleukin (IL)-8. The mechanisms regulating lung stretch-induced cytokine production are unclear. We hypothesized that stretch-induced IL-8 production is dependent on the activation of the mitogen-activated protein kinases, c-Jun NH2-terminal kinases (JNK), p38, and/or extracellular signal-regulated kinase (ERK) 1/2. We exposed A549 cells, a type II-like alveolar epithelial cell line, to cyclic stretch at 20 cycles/min for 5 min-2 h. Cyclic stretch induced IL-8 protein production, IL-8 mRNA expression, and JNK activation, but only transient activation of p38 and ERK1/2. Inhibition of stretch-induced JNK activation by adenovirus-mediated gene transfer of stress-activated protein kinase (SEK-1), a dominant-negative mutant of SEK-1, the immediate upstream activator of the JNKs, and pharmacological JNK inhibitor II SP-600125 blocked IL-8 mRNA expression and attenuated IL-8 production. Inhibition of p38 and ERK1/2 did not affect stretch-induced IL-8 production. Stretch-induced activation NF-kappaB and activator protein (AP)-1 was blocked by NF-kappaB inhibitor and JNK inhibitor, respectively. An NF-IL-6 site was not essential for cyclic stretch-induced IL-8 promoter activity. Stretch also induced NF-kappaB-inducing kinase (NIK) activation, and inhibition of NF-kappaB attenuated IL-8 mRNA expression and IL-8 production. We conclude that stretch-induced transcriptional regulation of IL-8 mRNA and IL-8 production was via activation of AP-1 and NF-kappaB and was dependent on JNK and NIK activation, respectively. C1 Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Tufts Univ, Sch Med, Tufts New England Med Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. Chang Gung Univ, Tao Yuan 333, Taiwan. Amiens Hosp, Internal Med & Nephrol Dept, F-80054 Amiens, France. RP Quinn, DA (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-61688, HL-039020, HL-67371] NR 45 TC 81 Z9 88 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD AUG PY 2003 VL 285 IS 2 BP L464 EP L475 DI 10.1152/ajplung.00031.2003 PG 12 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 698HE UT WOS:000183992300024 PM 12716652 ER PT J AU Gorin, Y Ricono, JM Kim, NH Bhandari, B Choudhury, GG Abboud, HE AF Gorin, Y Ricono, JM Kim, NH Bhandari, B Choudhury, GG Abboud, HE TI Nox4 mediates angiotensin II-induced activation of Akt/protein kinase B in mesangial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE reactive oxygen species; Rac1; arachidonic acid; protein synthesis ID SMOOTH-MUSCLE-CELLS; NAD(P)H OXIDASE ACTIVITY; JUN NH2-TERMINAL KINASE; PROTEIN-KINASE; NADPH OXIDASE; ARACHIDONIC-ACID; INDUCED HYPERTROPHY; DEPENDENT PATHWAY; RAC1; GROWTH AB ANG II induces protein synthesis through the serine-threonine kinase Akt/protein kinase B (PKB) in mesangial cells (MCs). The mechanism(s) of activation of Akt/PKB particularly by G protein-coupled receptors, however, is not well characterized. We explored the role of the small GTPase Rac1, a component of the phagocyte NADPH oxidase, and the gp91(phox) homologue Nox4/Renox in this signaling pathway. ANG II causes rapid activation of Rac1, an effect abrogated by phospholipase A(2) inhibition and mimicked by arachidonic acid (AA). Northern blot analysis revealed high levels of Nox4 transcript in MCs and transfection with antisense (AS) oligonucleotides for Nox4 markedly decreased NADPH-dependent reactive oxygen species (ROS)-producing activity. Dominant negative Rac1 (N17Rac1) as well as AS Nox4 inhibited ROS generation in response to ANG II and AA, whereas constitutively active Rac1 stimulated ROS formation. Moreover, N17Rac1 blocked stimulation of NADPH oxidase activity by AA. N17Rac1 or AS Nox4 abolished ANG II- or AA-induced activation of the hypertrophic kinase Akt/PKB. In addition, AS Nox4 inhibited ANG II- induced protein synthesis. These data provide the first evidence that activation by AA of a Rac1-regulated, Nox4-based NAD(P) H oxidase and subsequent generation of ROS mediate the effect of ANG II on Akt/PKB activation and protein synthesis in MCs. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Mem Hosp Div, Geriatr Res & Educ Ctr, San Antonio, TX 78229 USA. RP Abboud, HE (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, MC 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM abboud@uthscsa.edu FU NIDDK NIH HHS [DK-43988, DK-33665, DK-55815] NR 46 TC 200 Z9 203 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD AUG PY 2003 VL 285 IS 2 BP F219 EP F229 DI 10.1152/ajprenal.00414.2002 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 697KM UT WOS:000183941900006 PM 12842860 ER PT J AU Marder, SR Glynn, SM Wirshing, WC Wirshing, DA Ross, D Widmark, C Mintz, J Liberman, RP Blair, KE AF Marder, SR Glynn, SM Wirshing, WC Wirshing, DA Ross, D Widmark, C Mintz, J Liberman, RP Blair, KE TI Maintenance treatment of schizophrenia with risperidone or haloperidol: 2-year outcomes SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DOUBLE-BLIND; RATING-SCALE; OLANZAPINE; CLOZAPINE; PLACEBO; ANTIPSYCHOTICS; MULTICENTER; PREVENTION; EFFICACY; SYMPTOMS AB Objective: Most controlled studies comparing second-generation and conventional antipsychotics have focused on the acute treatment of schizophrenia. The authors compared symptom outcomes, side effects, and social adjustment in stable schizophrenia outpatients who received 2 years of maintenance treatment with risperidone or haloperidol. Method: This was a 2-year, randomized, double-blind comparison of 6 mg of risperidone versus haloperidol in 63 patients with stabilized DSM-IV schizophrenia. Study patients also received 15 months of standard behavioral skills training or enhanced training with a case manager who promoted patients' use of their skills in the community. Results: The risk of psychotic exacerbations and the risk of leaving the study were similar for both drug treatment groups. However, patients who received both risperidone and the enhanced community-based skills training were more likely to re-main in the study than those in the other treatment groups. Patients demonstrated significant improvement in score on the Brief Psychiatric Rating Scale over time with both medications. There were no between-group differences in cluster scores for thought disturbance, hostile-suspiciousness, and withdrawal-retardation. A significant between-group difference favoring risperidone was found for the anxious-depression cluster. Risperidone resulted in significantly greater reductions in tremor and akathisia and greater improvements in most items on the SCL-90-R. Conclusions: When compared with patients given a low dose of haloperidol, risperidone-treated patients experienced similar improvements in positive and negative symptoms and similar risks of psychotic exacerbations. However, risperidone-treated patients appeared to feel subjectively better, as indicated by less anxiety and depression and fewer extrapyramidal side effects. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Long Beach Vet Affairs Med Ctr, Long Beach, CA USA. RP Marder, SR (reprint author), W Los Angeles VA Hlth Care Ctr, MIRECC-210A,11301 Wiltshire Blvd, Los Angeles, CA 90073 USA. FU NIMH NIH HHS [MH-49573] NR 31 TC 62 Z9 65 U1 3 U2 4 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 2003 VL 160 IS 8 BP 1405 EP 1412 DI 10.1176/appi.ajp.160.8.1405 PG 8 WC Psychiatry SC Psychiatry GA 708AK UT WOS:000184543700008 PM 12900301 ER PT J AU Cohen, LS Soares, CN Poitras, JR Prouty, J Alexander, AB Shifren, JL AF Cohen, LS Soares, CN Poitras, JR Prouty, J Alexander, AB Shifren, JL TI Short-term use of estradiol for depression in perimenopausal and postmenopausal women: A preliminary report SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ESTROGEN-REPLACEMENT; AFFECTIVE-DISORDERS; MENOPAUSE; SYMPTOMS; MOOD; PREVALENCE; THERAPY; HORMONE; SCALE AB Objective: The authors examined the effect of a 4-week course of estrogen therapy on depression in perimenopausal and postmenopausal women. Method: Twenty-two depressed women who were either perimenopausal (N=10) or postmenopausal (N=12) received open-label treatment with transdermal 17beta-estradiol (100 mug/day) for 4 weeks. The Montgomery-Asberg Depression Rating Scale and the Beck Depression Inventory were used to assess depressive symptoms, the Greene Climacteric Scale was used to assess menopause-related symptoms, and the Clinical Global Impression (CGI) was used to,assess global clinical improvement in these women at baseline and after treatment. Remission of depression was defined as a score less than or equal to10 on the Montgomery-Asberg Depression Rating Scale and a score less than or equal to2 on the CGI at week 4. Results: Remission of depression was noted in eight of the 20 women who completed the study; two of these women were postmenopausal, and six were perimenopausal. Antidepressant response was not associated with severity or subtypes of depression at study entry or with concomitant improvement in menopause-related symptoms. Conclusions: Some perimenopausal women with depression may benefit from short-term use of estrogen therapy, and its role for postmenopausal depressed women warrants further investigation. Antidepressant benefit associated with estrogen therapy may be independent of improvement in physical symptoms. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. RP Cohen, LS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, 15 Parkman St,WACC 815, Boston, MA 02114 USA. NR 20 TC 89 Z9 93 U1 0 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 2003 VL 160 IS 8 BP 1519 EP 1522 DI 10.1176/appi.ajp.160.8.1519 PG 4 WC Psychiatry SC Psychiatry GA 708AK UT WOS:000184543700025 PM 12900318 ER PT J AU Kalra, MK Maher, MM Boland, GW Saini, S Fischman, AJ AF Kalra, MK Maher, MM Boland, GW Saini, S Fischman, AJ TI Correlation of positron emission tomography and CT in evaluating pancreatic tumors: Technical and clinical implications SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review ID FDG-PET; F-18 FLUORODEOXYGLUCOSE; DIFFERENTIAL-DIAGNOSIS; CANCER; CARCINOMA; MANAGEMENT; LESIONS; ADENOCARCINOMA; INVOLVEMENT; ANGIOGRAPHY C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Fischman, AJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 56 TC 15 Z9 17 U1 1 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2003 VL 181 IS 2 BP 387 EP 393 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 704CV UT WOS:000184320900015 PM 12876016 ER PT J AU Abbara, S Kalan, MMH Lewicki, AM AF Abbara, S Kalan, MMH Lewicki, AM TI Intrathoracic stomach revisited SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 Georgetown Univ, Med Ctr, Dept Radiol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Surg, Washington, DC 20007 USA. RP Abbara, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, CIMIT, Ste 400,100 Charles River Plaza, Boston, MA 02114 USA. NR 10 TC 14 Z9 16 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2003 VL 181 IS 2 BP 403 EP 414 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 704CV UT WOS:000184320900017 PM 12876018 ER PT J AU Shankar, S vanSonnenberg, E Silverman, SG Tuncali, K Morrison, PR AF Shankar, S vanSonnenberg, E Silverman, SG Tuncali, K Morrison, PR TI Diagnosis and treatment of intrahepatic biloma complicating radiofrequency ablation of hepatic metastases SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID MANAGEMENT; THERAPY C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. RP vanSonnenberg, E (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. NR 7 TC 10 Z9 12 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2003 VL 181 IS 2 BP 475 EP 477 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 704CV UT WOS:000184320900028 PM 12876029 ER PT J AU Tambouret, R Clement, PB Young, RH AF Tambouret, R Clement, PB Young, RH TI Endometrial endometrioid adenocarcinoma with a deceptive pattern of spread to the uterine cervix - A manifestation of stage IIB endometrial carcinoma liable to be misinterpreted as an independent carcinoma or a benign lesion SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE endometrioid adenocarcinoma; spread of endometrial cancer; uterine cervix; uterine corpus ID ADENOID BASAL CARCINOMA; ENDOCERVICAL ADENOCARCINOMAS; PROGNOSTIC-SIGNIFICANCE; DIFFERENTIAL-DIAGNOSIS; INVOLVEMENT; HYPERPLASIA; MYOINVASION; DISTINCTION; VARIANTS; CANCER AB The prognosis of endometrial endometrioid adenocarcinoma is determined in part by stage; endocervical stromal involvement (stage IIB) imparts a worsened prognosis. We describe a deceptive pattern of stage IIB disease that mimics a primary endocervical glandular proliferation and may lead to understaging of endometrial endometrioid adenocarcinoma. Fifteen cases of endometrial endometrioid adenocarcinoma with a peculiar pattern of cervical involvement were identified from our consultation files. All cases were referred in consultation because of doubt about the nature of the cervical process and its relation to the corpus tumor; in a few instances, the cervical proliferation was considered possibly benign and in one case was misinterpreted as mesonephric hyperplasia. The patients ranged from 49 to 84 years in age (mean age 64.9 years). There was usually a grossly evident endometrial tumor. The cervix was unremarkable grossly in at least 11 patients. The cervical tumors were composed of variably shaped, often tubular glands with little or no stromal response and mainly invaded as widely spaced glands that often appeared deceptively benign. In 14 cases luminal secretions, mainly eosinophilic, were identified, often leading to consideration of a mesonephric lesion. Ten of the endometrial tumors were grade 1, four grade 2, and one grade 3. One was noninvasive, nine superficially invasive, and five deeply invasive. In four cases myoinvasion had, at least in part, a diffusely infiltrative pattern. The tumors in the cervix showed no in situ component and no definite surface involvement. Continuity with the corpus tumor could be demonstrated in 12 cases. Ten of the cervical tumors invaded more deeply than the endometrial tumor, four invaded to a similar depth, and only one was more superficial than its endometrial counterpart. The cervical and corpus tumors had a similar immunoprofile in nine cases: all were vimentin positive, eight estrogen positive and one negative, four carcinoembryonic antigen negative, and five with focal apical or rare cytoplasmic staining. This immunoprofile in conjunction with routine morphologic similarity between the two tumors and the usual documented continuity between them indicate that the cervical process represents spread from the endometrial endometrioid adenocarcinoma. It is important for both therapeutic and prognostic reasons that the cervical abnormality is not misinterpreted as a benign or malignant primary endocervical glandular process. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA 02114 USA. Univ British Columbia, Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. RP Tambouret, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,James Homer Wright Pathol Labs, 55 Fruit St, Boston, MA 02114 USA. NR 31 TC 21 Z9 22 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD AUG PY 2003 VL 27 IS 8 BP 1080 EP 1088 DI 10.1097/00000478-200308000-00005 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 705XA UT WOS:000184420700005 PM 12883240 ER PT J AU Misdraji, J Yantiss, RK Graeme-Cook, FM Balis, UJ Young, RH AF Misdraji, J Yantiss, RK Graeme-Cook, FM Balis, UJ Young, RH TI Appendiceal mucinous neoplasms - A clinicopathologic analysis of 107 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 91st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 23-MAR 01, 2002 CL CHICAGO, ILLINOIS SP US & Canadian Acad Pathol DE appendix; mucinous tumor; mucinous tumor of low malignant potential; mucinous adenocarcinoma; pseudomyxoma peritonei ID DISSEMINATED PERITONEAL ADENOMUCINOSIS; PSEUDOMYXOMA-PERITONEI; VERMIFORM APPENDIX; OVARIAN-TUMORS; EPITHELIAL NEOPLASMS; ORIGIN; ADENOCARCINOMA; CYSTADENOMA; PROGNOSIS; MUCOCELE AB The classification of appendiceal mucinous tumors is controversial and terminology used for them inconsistent, particularly when they lack overtly malignant features but are associated with extra-appendiceal spread. We reviewed 107 appendiceal mucinous neoplasms and classified them as low-grade appendiceal mucinous neoplasm (LAMN) (n = 88), mucinous adenocarcinomas (MACAs) (n = 16), or discordant (n = 3) based on architectural and cytologic features. LAMNs were characterized by a villous or flat proliferation of mucinous epithelium with low-grade atypia. Thirty-nine tumors were confined to the appendix, but 49 had extra-appendiceal turner spread, including 39 with peritoneal tumor characterized by mucin pools harboring low-grade mucinous epithelium, usually dissecting in a hyalinized stroma. Eight of the 16 MACAs lacked destructive invasion of the appendiceal wall and eight showed an infiltrative pattern of invasion. Extra-appendiceal tumor spread was present in 12 MACAs (four peritoneum, seven peritoneum and ovaries; one ovaries only). In MACAs with an infiltrative pattern, peritoneal turner consisted of glands and single cells in a desmoplastic stroma. The peritoneal tumor in the remaining cases consisted of mucin pools that contained mucinous epithelium with high-grade atypia and, in some cases, increased cellularity compared with that seen in peritoneal spread in cases of LAMN. Three cases were classified as discordant because the appendiceal tumors were LAMNs but the peritoneal tumors were high-grade. Follow-up was available for 49 LAMNs, 15 MACAs, and 2 discordant cases. None of the patients with LAMNs confined to the appendix experienced recurrence (median follow-up 6 years). LAMNs with extra-appendiceal spread were associated with 3-, 5-, and 10-year survival rates of 100%, 86%, and 45%, respectively. Patients with MACA had 3- and 5-year survival rates of 90% and 44%, respectively (p = 0.04). The bulk of peritoneal disease correlated with prognosis among patients with MACA (p = 0.04) and, to a lesser degree, among patients with LAMNs (p = 0.07). We conclude that: 1) appendiceal mucinous neoplasms can be classified as either low-grade mucinous neoplasms or mucinous adenocarcinoma based on architectural and cytologic features; 2) tumors that can be confidently placed in the low-grade group (which requires rigorous pathologic evaluation of the appendix) and are confined to the appendix are clinically benign in our experience to date; 3) low-grade tumors confined to the appendix are morphologically identical to those with extra-appendiceal spread (except for the usual identification of breach of the wall in the latter cases) and the same designation is appropriate for the appendiceal neoplasia in each situation; 4) the long-term outlook for patients with low-grade tumors and peritoneal spread is guarded with just over half dying of disease after 10 years; 5) appendiceal mucinous tumors with destructive invasion of the appendiceal wall, complex epithelial proliferations, or high-grade nuclear atypia generally pursue an aggressive clinical course and should be classified as mucinous adenocarcinomas; 6) peritoneal tumor can be classified as involvement by LAMN or MACA, and this distinction is of prognostic significance; 7) bulky peritoneal tumor worsens prognosis; and 8) LAMNs associated with high-grade peritoneal tumor behave as adenocarcinoma. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA 02114 USA. Univ Massachusetts, Worcester, MA 01605 USA. RP Misdraji, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, 55 Fruit St, Boston, MA 02114 USA. NR 40 TC 199 Z9 213 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD AUG PY 2003 VL 27 IS 8 BP 1089 EP 1103 DI 10.1097/00000478-200308000-00006 PG 15 WC Pathology; Surgery SC Pathology; Surgery GA 705XA UT WOS:000184420700006 PM 12883241 ER PT J AU Fishman, JA AF Fishman, JA TI SARS, xenotransplantation and bioterrorism: Preventing the next epidemic SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material DE bioterrorism; coronavirus; infection; SARS; surveillance; transplantation; xenotransplantation ID LEGIONNAIRES-DISEASE C1 Massachusetts Gen Hosp, Transplantat & Immunocompromised Host Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Transplantat & Immunocompromised Host Program, Boston, MA 02114 USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD AUG PY 2003 VL 3 IS 8 BP 909 EP 912 DI 10.1034/j.1600-6143.2003.00213.x PG 4 WC Surgery; Transplantation SC Surgery; Transplantation GA 705MQ UT WOS:000184399200001 PM 12859521 ER PT J AU Bishop, MJ O'Donnell, JT Salemi, JR AF Bishop, MJ O'Donnell, JT Salemi, JR TI Mivacurium and bronchospasm SO ANESTHESIA AND ANALGESIA LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Anesthesiologists CY OCT 12-16, 2002 CL ORLANDO, FLORIDA SP Amer Soc Anesthesiologists ID LUNG-MECHANICS; RELAXANTS; HISTAMINE C1 Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Dept Anesthesiol, Seattle, WA 98108 USA. Rush Med Coll, Dept Pharmacol, Chicago, IL 60612 USA. Pharmaconsultant Inc, Palatine, IL USA. RP Bishop, MJ (reprint author), Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Dept Anesthesiol, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 11 TC 4 Z9 5 U1 0 U2 1 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 AUG PY 2003 VL 97 IS 2 BP 484 EP 485 DI 10.1213/01.ANE.0000067433.05538.3D PG 2 WC Anesthesiology SC Anesthesiology GA 704RW UT WOS:000184354600032 PM 12873940 ER PT J AU Asplin, BR Magid, DJ Rhodes, KV Solberg, LI Lurie, N Camargo, CA AF Asplin, BR Magid, DJ Rhodes, KV Solberg, LI Lurie, N Camargo, CA TI A conceptual model of emergency department crowding SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID PUBLIC HOSPITAL EMERGENCY; ADVANCED ACCESS; CARE; CONSEQUENCES; CALIFORNIA; PHYSICIAN; LENGTH; DELAYS; LEAVE; STAY AB Emergency department (ED) crowding has become a major barrier to receiving timely emergency care in the United States. Despite widespread recognition of the problem, the research and policy agendas needed to understand and address ED crowding are just beginning to unfold. We present a conceptual model of ED crowding to help researchers, administrators, and policymakers understand its causes and develop potential solutions. The conceptual model partitions ED crowding into 3 interdependent components: input, throughput, and output. These components exist within an acute care system that is characterized by the delivery of unscheduled care. The goal of the conceptual model is to provide a practical framework on which an organized research, policy, and operations management agenda can be based to alleviate ED crowding. C1 Reg Hosp, Dept Emergency Med, St Paul, MN 55101 USA. HealthPartners Res Fdn, St Paul, MN 55101 USA. Univ Minnesota, Sch Med, Dept Emergency Med, Minneapolis, MN 55455 USA. Univ Colorado, Hlth Sci Ctr, Div Emergency Med, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Clin Res Unit, Colorado Permanente Med Grp, Denver, CO 80262 USA. Univ Chicago Hosp, Sect Emergency Med, Chicago, IL 60637 USA. HealthPartners Res Fdn, Minneapolis, MN USA. RAND Corp, Arlington, VA USA. Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Asplin, BR (reprint author), Reg Hosp, Dept Emergency Med, 640 Jackson St, St Paul, MN 55101 USA. FU AHRQ HHS [K08-HS13007]; PHS HHS [290-00-0015] NR 33 TC 295 Z9 305 U1 0 U2 30 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD AUG PY 2003 VL 42 IS 2 BP 173 EP 180 DI 10.1067/mem.2003.302 PG 8 WC Emergency Medicine SC Emergency Medicine GA 705XW UT WOS:000184423400002 PM 12883504 ER PT J AU Hernan, MA Chen, HL Schwarzschild, MA Ascherio, A AF Hernan, MA Chen, HL Schwarzschild, MA Ascherio, A TI Alcohol consumption and the incidence of Parkinson's disease SO ANNALS OF NEUROLOGY LA English DT Article ID FOOD-FREQUENCY QUESTIONNAIRE; ENVIRONMENTAL RISK-FACTORS; CIGARETTE-SMOKING; COFFEE CONSUMPTION; NEUROPROTECTION; DRINKING; CAFFEINE; REPRODUCIBILITY; NEUROTOXICITY; ACETALDEHYDE AB Cigarette smoking and caffeine consumption are associated with a decreased incidence of Parkinson's disease (PD). This inverse association may result from neuroprotective effects of cigarette smoke and caffeine, or from a disinclination of future PD patients to engage in habituating behaviors. We investigated the association between consumption of alcoholic beverages, another potentially habituating behavior, and risk of PD in two large prospective cohorts Nurses' Health Study, and Health Professionals' Follow-up Study. We detected 415 new cases of PD during follow-up. Compared with nondrinkers at baseline, the relative rate (95% confidence interval) was 1.0 (0.8-1.3) for drinkers of less than 5gm/day, 1.0 (0.8-1.4) for 5 to less than 15gm/day, 1.1 (0.8-1.6) for 15 to less than 30gm/day, and 0.7 (0-5-1.2) for 30gm/day or more (p for trend = 0.45). Consumption of wine or liquor was not associated with the incidence of PD. Compared with those who consumed beer less than once per month, the relative rate (95% confidence interval) was 0.7 (0.5-0.9) for one to three drinks of beer per month, and 0.7 (0.5, 0.9),for one or more drinks of beer per week. The risk of PD was similar in individuals who usually consume moderate amounts of alcohol and in abstainers. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Hernan, MA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. OI Chen, Honglei/0000-0003-3446-7779 FU NCI NIH HHS [CA87969]; NINDS NIH HHS [NS35624] NR 43 TC 42 Z9 45 U1 0 U2 7 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 AUG PY 2003 VL 54 IS 2 BP 170 EP 175 DI 10.1002/ana.10611 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 704RA UT WOS:000184352700007 PM 12891669 ER PT J AU Lee, SJ Zelen, M AF Lee, SJ Zelen, M TI Modelling the early detection of breast cancer SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT Global Summit Meeting on Mammography Screening CY JUN 03-05, 2002 CL MILAN, ITALY SP European Inst Oncol DE breast cancer; clinical trials; mammography; mathematical models ID SCREENING TRIAL; RANDOMIZED-TRIAL; DEATH RATES; FOLLOW-UP; MAMMOGRAPHY; MORTALITY; STOCKHOLM AB A mathematical model was developed to predict the outcome of early detection clinical trials or programs targeted at evaluating mortality benefit from earlier diagnosis of breast cancer. The model was applied to eight randomized breast cancer trials, which were carried out to evaluate the benefits of mammography, physical examination or their combination. The model assumes that breast cancer is a progressive disease and any mortality benefit from earlier diagnosis is generated from a favorable shift in the stage at diagnosis relative to usual care. The model predicted the reduction in mortality for seven of the eight trials within the reported confidence intervals. Input data required by the models are: stage shift distribution, examination schedules, population age distribution, follow up time, and survival conditional on stage at diagnosis. Survival distributions were obtained from the 1973-82 SEER database whereas the remaining data was obtained for each of the trials. Information on sensitivity and stage was ordinarily available during the early phase of the trials. The theoretical model has the promise of being able to predict the long-term outcome of early detection trials or programs during the initial examination phase. The theoretical model is general and may be applied to other chronic diseases, which satisfy the basic assumptions. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Lee, SJ (reprint author), Dana Farber Canc Inst, 677 Huntington Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA-78607, CA88270] NR 16 TC 15 Z9 15 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD AUG PY 2003 VL 14 IS 8 BP 1199 EP 1202 DI 10.1093/annonc/mdg323 PG 4 WC Oncology SC Oncology GA 709ZH UT WOS:000184656100012 PM 12881377 ER PT J AU Goldhirsch, A Colleoni, M Domenighetti, G Gelber, RD AF Goldhirsch, A Colleoni, M Domenighetti, G Gelber, RD TI Systemic treatments for women with breast cancer: outcome with relation to screening for the disease SO ANNALS OF ONCOLOGY LA English DT Article DE adjuvant treatments; breast cancer; screening ID RANDOMIZED TRIALS; COMBINATION AB Early detection and proper care of breast cancer are currently the best available approaches to the treatment of patients with the disease. In countries with a breast cancer screening programme, there has been a demonstrated reduction in breast cancer-related mortality. Such reduction has also been observed in Switzerland, a country in which no national programme of screening is available. Although there is no doubt that early diagnosis might have had a major role in reducing breast cancer mortality the magnitude of this effect is unknown. Research with tailored approaches on alternative imaging for early detection of breast cancer in high-risk women and on treatments offered according to proper criteria of responsiveness to therapies is warranted. C1 European Inst Oncol, Dept Med, Int Breast Canc Study Grp, I-20141 Milan, Italy. Osped Reg Lugano Civ, Oncol Inst So Switzerland, Lugano, Switzerland. Cantonal Hlth Off Canton Ticino, Bellinzona, Switzerland. Univ Lausanne, Inst Hlth Econ & Management, CH-1015 Lausanne, Switzerland. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Goldhirsch, A (reprint author), European Inst Oncol, Dept Med, Int Breast Canc Study Grp, Via Ripamonti 435, I-20141 Milan, Italy. NR 18 TC 18 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD AUG PY 2003 VL 14 IS 8 BP 1212 EP 1214 DI 10.1093/annonc/mdg327 PG 3 WC Oncology SC Oncology GA 709ZH UT WOS:000184656100016 PM 12881381 ER PT J AU Netscher, DT Eladoumikdachi, F McHugh, PM Thornby, J Soltero, E AF Netscher, DT Eladoumikdachi, F McHugh, PM Thornby, J Soltero, E TI Sternal wound debridement and muscle flap reconstruction: Functional implications SO ANNALS OF PLASTIC SURGERY LA English DT Article ID MCGILL PAIN QUESTIONNAIRE; LATISSIMUS-DORSI MUSCLE; POSTSTERNOTOMY MEDIASTINITIS; CHEST-WALL; STERNOTOMY WOUNDS; PECTORALIS FLAPS; TRANSPOSITION; MANAGEMENT; INFECTIONS; DEFECTS AB The mortality rate for poststernotomy infection, which occurs in as many as 5% of median sternotomy incisions after cardiovascular surgery, was 37.5% until sternal debridement with muscle or omental flap reconstruction became the standard treatment for this postoperative complication and lowered the mortality rate to just more than 5%. There are few reports in the literature of physical functional deficits and long-term outcome resulting from such reconstruction. The authors evaluated two groups of patients who had undergone coronary bypass surgery at least 6 months earlier. One group had no postoperative complications; the other group had developed marked sternal wound infections that required debridement and pectoralis major or rectus abdominis muscle reconstruction. Both groups underwent pectoralis and rectus muscle strength testing, evaluation of pain and ability to perform those activities of daily living that are dependent on pectoral and rectus muscle function, and completed self-assessment questionnaires. Differences between the two groups were significant (p < 0.05) with regard to pain and patient satisfaction with appearance and general functional capacity. Pectoral muscle function and strength were significantly different in patients in whom that muscle was transposed. Rectus muscle strength was not affected by the transposition of a single rectus muscle. Physical morbidity and loss of strength seemed to be related directly to loss of sternal stability stemming from marked infection and debridement rather than from loss of the muscles used in reconstruction. C1 Baylor Coll Med, Div Plast Surg, Houston, TX 77030 USA. Baylor Coll Med, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Houston, TX USA. RP Netscher, DT (reprint author), 6560 Fannin,Suite 800, Houston, TX 77030 USA. NR 30 TC 15 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD AUG PY 2003 VL 51 IS 2 BP 115 EP 122 DI 10.1097/01.SAP.0000058497.92264.E2 PG 8 WC Surgery SC Surgery GA 714LN UT WOS:000184915900001 PM 12897511 ER PT J AU Etzioni, DA Liu, JH Maggard, MA Ko, CY AF Etzioni, DA Liu, JH Maggard, MA Ko, CY TI The aging population and its impact on the surgery workforce SO ANNALS OF SURGERY LA English DT Article ID GENERAL-SURGERY; RELATIVE VALUES; WORK LOADS; SHORTAGE; SPECIALTIES; PHYSICIANS; MEDICINE; THERES; TRENDS; CARE AB Objective: To predict the impact of the aging population on the demand for surgical procedures. Summary Background Data: The population is expanding and aging. According to the US Census Bureau, the domestic population will increase 7.9% by 2010, and 17.0% by 2020. The fastest growing segment of this population consists of individuals over the age of 65; their numbers are expected to increase 13.3% by 20 10 and 53.2% by 2020. Methods: Data on the age-specific rates of surgical procedures were obtained from the 1996 National Hospital Discharge Survey and the National Survey of Ambulatory Surgery. These procedure rates were combined with corresponding relative value units from the Centers for Medicare and Medicaid Services. The result quantifies the amount of surgical work used by an average individual within specific age groups (<15 years old, 15-44 years old, 45-64 years old, 65+ years old). This estimate of work per capita was combined with population forecasts to predict future use of surgical services. Results: Based on the assumption that age-specific per capita use of surgical services will remain constant, we predict significant increases (14-47%) in the amount of work in all surgical fields. These increases vary widely by specialty. Conclusions: The aging of the US population will result in significant growth in the demand for surgical services. Surgeons need to develop strategies to manage an increased. workload without sacrificing quality of care. C1 VA Greater Los Angeles Hlth Care Syst, Dept Surg, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA USA. RP Etzioni, DA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 1015 9th St Apt 106, Santa Monica, CA 90403 USA. FU NCI NIH HHS [K08 CA090403] NR 30 TC 246 Z9 253 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD AUG PY 2003 VL 238 IS 2 BP 170 EP 177 DI 10.1097/01.SLA.0000081085.98792.3d PG 8 WC Surgery SC Surgery GA 730MR UT WOS:000185835000003 PM 12894008 ER PT J AU Dolan, SE Huang, JS Killilea, KM Sullivan, MP Aliabadi, N Grinspoon, S AF Dolan, SE Huang, JS Killilea, KM Sullivan, MP Aliabadi, N Grinspoon, S TI Reduced bone density in HIV-infected women SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 5th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV CY JUL 08-11, 2003 CL Paris, FRANCE C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PD AUG PY 2003 VL 8 IS 4 MA 23 BP L19 EP L20 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 955YQ UT WOS:000231266500046 ER PT J AU Driscoll, SD Meininger, G Lareau, M Dolan, SE Killilea, KM Hadigan, C Lloyd-Jones, D Klibanski, A Frontera, WR Grinspoon, S AF Driscoll, SD Meininger, G Lareau, M Dolan, SE Killilea, KM Hadigan, C Lloyd-Jones, D Klibanski, A Frontera, WR Grinspoon, S TI Effects of exercise training and metformin on body composition and cardiovascular indices in HIV-infected patients SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 5th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV CY JUL 08-11, 2003 CL Paris, FRANCE C1 Massachusetts Gen Hosp, Program Human Metab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Phys Therapy Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. RI Lloyd-Jones, Donald/C-5899-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PD AUG PY 2003 VL 8 IS 4 MA 4 BP L7 EP L7 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 955YQ UT WOS:000231266500027 ER EF