FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Chauhan, D Hideshima, T Rosen, S Reed, JC Kharbanda, S Anderson, KC AF Chauhan, D Hideshima, T Rosen, S Reed, JC Kharbanda, S Anderson, KC TI Apaf-1/cytochrome c-independent and Smac-dependent induction of apoptosis in multiple myeloma (MM) cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYTOCHROME-C; ACTIVATION; PROCASPASE-9; CASPASES; PROTEINS; KINASE; IAP; INTERLEUKIN-6; MITOCHONDRIA; SMAC/DIABLO AB Smac, a second mitochondria-derived activator of caspases, promotes caspase activation in the cytochrome c (cyto-c)/Apaf-1/caspase-9 pathway. Here, we show that treatment of multiple myeloma (MM) cells with dexamethasone (Dex) triggers the release of Smac from mitochondria to cytosol and activates caspase-9 without concurrent release of cyto-e and Apaf-1 oligomerization. Smac binds to XIAP tan inhibitor of apoptosis protein) and thereby, at least in part, eliminates its inhibitory effect on caspase-9. Interleukin-6, a growth factor for MM, blocks Dex-induced apoptosis and prevents release of Smac, Taken together, these findings demonstrate that Smac plays a functional role in mediating I)ex-induced caspase-9 activation and apoptosis in MM cells. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Adult Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Northwestern Univ, Sch Med, Robert H Lurie Canc Ctr, Chicago, IL 60611 USA. Burnham Inst, La Jolla, CA 92037 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Adult Oncol, Jerome Lipper Multiple Myeloma Ctr, Mayer 557,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 78373] NR 29 TC 154 Z9 162 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 6 PY 2001 VL 276 IS 27 BP 24453 EP 24456 DI 10.1074/jbc.C100074200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451KF UT WOS:000169800700006 PM 11356822 ER PT J AU Blobe, GC Schiemann, WP Pepin, MC Beauchemin, M Moustakas, A Lodish, HF O'Connor-McCourt, MD AF Blobe, GC Schiemann, WP Pepin, MC Beauchemin, M Moustakas, A Lodish, HF O'Connor-McCourt, MD TI Functional roles for the cytoplasmic domain of the type III transforming growth factor beta receptor in regulating transforming growth factor beta signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENDOTHELIAL-CELLS; GENE-EXPRESSION; LIGAND-BINDING; I RECEPTOR; BETAGLYCAN; ENDOGLIN; COMPLEX; FORM; RESPONSIVENESS; PATHWAY AB Transforming growth factor beta (TGF-beta) signals through three high affinity cell surface receptors, TGF-beta type I, type II, and type III receptors, The type III receptor, also known as betaglycan, binds to the type II receptor and is thought to act solely by "presenting" the TGF-beta ligand to the type II receptor. The short cytoplasmic domain of the type III receptor is thought to have no role in TGF-beta signaling because deletion of this domain has no effect on association with the type II receptor, or with the presentation role of the type III receptor. Here we demonstrate that the cytoplasmic domains of the type III and type II receptors interact specifically in a manner dependent on the kinase activity of the type II receptor and the ability of the type II receptor to autophosphorylate, This interaction results in the phosphorylation of the cytoplasmic domain of the type III receptor by the type II receptor, The type III receptor with the cytoplasmic domain deleted is able to bind TGF-beta, to bind the type II receptor, and to enhance TGF-beta binding to the type II receptor but is unable to enhance TGF-beta signaling, determining that the cytoplasmic domain is essential for some functions of the type III receptor. The type III receptor functions by selectively binding the autophosphorylated type II receptor via its cytoplasmic domain, thus promoting the preferential formation of a complex between the autophosphorylated type II receptor and the type I receptor and then dissociating from this active signaling complex. These studies, for the first time, elucidate important functional roles of the cytoplasmic domain of the type III receptor and demonstrate that these roles are essential for regulating TGF-beta signaling. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Biotechnol Res Inst, Cell Surface Recognot Grp, Montreal, PQ H4P 2R2, Canada. Ludwig Inst Canc Res, SE-75124 Uppsala, Sweden. RP Blobe, GC (reprint author), Duke Univ, Med Ctr, Dept Med, Box 2631, Durham, NC 27710 USA. FU NCI NIH HHS [CA63260, CA73161-01] NR 30 TC 88 Z9 95 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 6 PY 2001 VL 276 IS 27 BP 24627 EP 24637 DI 10.1074/jbc.M100188200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451KF UT WOS:000169800700030 PM 11323414 ER PT J AU Ogretmen, B Schady, D Usta, J Wood, R Kraveka, JM Luberto, C Birbes, H Hannun, YA Obeid, LM AF Ogretmen, B Schady, D Usta, J Wood, R Kraveka, JM Luberto, C Birbes, H Hannun, YA Obeid, LM TI Role of ceramide in mediating the inhibition of telomerase activity in A549 human lung adenocarcinoma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CATALYTIC SUBUNIT GENE; GLUCOSYLCERAMIDE SYNTHASE; REVERSE-TRANSCRIPTASE; ADRIAMYCIN RESISTANCE; CELLULAR SENESCENCE; INDUCED APOPTOSIS; INTERFERON-ALPHA; CANCER-CELLS; TUMOR-CELLS; IN-VITRO AB This study was designed to analyze whether ceramide, a bioeffector of growth suppression, plays a role in the regulation of telomerase activity in A549 cells. Telomerase activity was inhibited significantly by exogenous C-6-ceramide, but not by the biologically inactive analog dihydro-C-6-ceramide, in a time- and dose-dependent manner, with 85% inhibition produced by 20 muM C-6-ceramide at 24 h, Moreover, analysis of phosphatidylserine translocation from the inner to the outer plasma membrane by flow cytometry and of poly(ADP-ribose) polymerase degradation by Western blotting showed that ceramide treatment (20 muM for 24 h) had no apoptotic effects. Trypan blue exclusion, [H-3]thymidine incorporation, and cell cycle analyses, coupled with clonogenic cell survival assay on soft agar, showed that ceramide treatment with a 20 muM concentration at 24 h resulted in the cell cycle arrest of the majority of the cell population at G(0)/G(1) with no detectable cell death, These results suggest that the inhibition of telomerase by ceramide is not a consequence of cell death but is correlated with growth arrest. Next, to determine the role of endogenous ceramide in telomerase modulation, A549 cells were transiently transfected with an expression vector containing the full-length bacterial sphingomyelinase cDNA (b-SMase). The overexpression of b-SMase, but not exogenously applied purified b-SMase enzyme, resulted in significantly decreased telomerase activity compared with controls, showing that the increased endogenous ceramide is sufficient for telomerase inhibition. Moreover, treatment of A549 cells with daunorubicin at 1 muM for 6 h resulted in the inhibition of telomerase, which correlated with the elevation of endogenous ceramide levels and growth arrest. Finally, stable overexpression of human glucosylceramide synthase, which attenuates ceramide levels by converting ceramide to glucosylceramide, prevented the inhibitory effects of C-6-ceramide and daunorubicin on telomerase, Therefore, these results provide novel data showing for the first time that ceramide is a candidate upstream regulator of telomerase. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pediat, Div Hematol Oncol, Charleston, SC 29425 USA. Amer Univ Beirut, Dept Biochem, Beirut, Lebanon. RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, POB 250779, Charleston, SC 29425 USA. OI obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [CA87584]; NIA NIH HHS [AG16583, AG12467]; NIGMS NIH HHS [GM43825] NR 56 TC 83 Z9 87 U1 2 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 6 PY 2001 VL 276 IS 27 BP 24901 EP 24910 DI 10.1074/jbc.M100314200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451KF UT WOS:000169800700063 PM 11335714 ER PT J AU Zhang, XA Bontrager, AL Hemler, ME AF Zhang, XA Bontrager, AL Hemler, ME TI Transmembrane-4 superfamily proteins associate with activated protein kinase C (PKC) and link PHC to specific beta(1) integrins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID T-CELLS; BINDING PROTEINS; TM4SF PROTEINS; CROSS-LINKING; GROWTH-FACTOR; CDNA CLONE; RECEPTOR; ADHESION; COMPLEXES; MOLECULES AB Translocation of conventional protein kinases C (PKCs) to the plasma membrane leads to their specific association with transmembrane-4 superfamily (TM4SF; tetraspanin) proteins (CD9, CD53, CD81, CD82, and CD151), as demonstrated by reciprocal co-immunoprecipitation and covalent cross-linking experiments. Although formation and maintenance of TM4SF-PKC complexes are not dependent on integrins, TM4SF proteins can act as linker molecules, recruiting PKC into proximity with specific integrins. Previous studies showed that the extracellular large loop of TM4SF proteins determines integrin associations. In contrast, specificity for PKC association probably resides within cytoplasmic tails or the first two transmembrane domains of TM4SF proteins, as seen from studies with chimeric CD9 molecules, Consistent with a TM4SF linker function, only those integrins (alpha (3)beta (1), alpha (6)beta (1), and a chimeric "X3TC5" alpha (3) mutant) that associated strongly with tetraspanins were found in association with PKC, We propose that PKC-TM4SF-integrin structures represent a novel type of signaling complex. The simultaneous binding of TM4SF proteins to the extracellular domains of the integrin alpha (3) subunit and to intracellular PKC helps to explain why the integrin alpha (3) extracellular domain is needed for both intracellular PKC recruitment and PKC-dependent phosphorylation of the alpha (3) integrin cytoplasmic tail. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Rm D-1430,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA86712] NR 68 TC 248 Z9 264 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 6 PY 2001 VL 276 IS 27 BP 25005 EP 25013 DI 10.1074/jbc.M102156200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451KF UT WOS:000169800700077 PM 11325968 ER PT J AU Zang, MW Waelde, CA Xiang, XQ Rana, A Wen, R Luo, ZJ AF Zang, MW Waelde, CA Xiang, XQ Rana, A Wen, R Luo, ZJ TI Microtubule integrity regulates pak leading to ras-independent activation of Raf-1 - Insights into mechanisms of Raf-1 activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYSTEINE-RICH DOMAIN; PROTEIN-KINASE; TYROSINE PHOSPHORYLATION; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION; DEPENDENT MECHANISM; BINDING; C-RAF-1; IDENTIFICATION; SERINE-338 AB Growth factors activate Raf-1 by engaging a complex program, which requires Res binding, membrane recruitment, and phosphorylation of Raf-1, The present study employs the microtubule-depolymerizing drug nocodazole as an alternative approach to explore the mechanisms of Raf activation, Incubation of cells with nocodazole leads to activation of Pak1/2, kinases downstream of small GTPases Rac/Cdc42, which. have been previously indicated to phosphorylate Raf-1 Ser(338). No- codazole-induced stimulation of Raf-1 is augmented by co-expression of small GTPases Rac/Cdc42 and Pak1/2. Dominant negative mutants of these proteins block activation of Raf-1 by nocodazole, but not by epidermal growth factor (EGF), Thus, our studies define Rac/ Cdc42/Pak as a module upstream of Raf-1 during its activation by microtubule disruption. Although it is Res-independent, nocodazole-induced activation of Raf-1 appears to involve the amino-terminal regulatory region in which the integrity of the Ras binding domain is required. Surprisingly, the Raf zinc finger mutation (C165S/C168S) causes a robust activation of Raf-1 by nocodazole, whereas it diminishes Res-dependent activation of Raf-1, We also show that mutation of residues Ser(338) to Ala or Tyr(340)-Tyr(341) to Phe-Phe immediately amino-terminal to the catalytic domain abrogates activation of both the wild type and zinc finger mutant Raf by both EGF/4 beta- 12-O-tetradecanoylphorbol- 13-acetate and nocodazole. Finally, an in vitro kinase assay demonstrates that the zinc finger mutant serves as a better substrate of Pak1 than the wild type Raf-l, Collectively, our results indicate that 1) the zinc finger exerts an inhibitory effect on Raf-1 activation, probably by preventing phosphorylation of (SSYY341)-S-338; 2) such inhibition is first overcome by an unknown factor binding in place of Ras-GTP to the amino-terminal regulatory region in response to nocodazole; and 3) EGF and nocodazole utilize different kinases to phosphorylate Ser338, an event crucial for Raf activation. C1 Boston Univ, Sch Med, Evans Dept Med, Diabet & Metab Res Unit,Endocrinol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. Univ Penn, Sch Med, Dept Ophthalmol, Philadelphia, PA 19104 USA. RP Luo, ZJ (reprint author), Boston Univ, Sch Med, Evans Dept Med, Diabet & Metab Res Unit,Endocrinol Sect, 650 Albany St,Rm 820, Boston, MA 02118 USA. FU NIGMS NIH HHS [GM 57959] NR 52 TC 35 Z9 35 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 6 PY 2001 VL 276 IS 27 BP 25157 EP 25165 DI 10.1074/jbc.M100152200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451KF UT WOS:000169800700098 PM 11274179 ER PT J AU Schmidlin, F Dery, O DeFea, KO Slice, L Patierno, S Sternini, C Grady, EF Bunnett, NW AF Schmidlin, F Dery, O DeFea, KO Slice, L Patierno, S Sternini, C Grady, EF Bunnett, NW TI Dynamin and Rab5a-dependent trafficking and signaling of the neurokinin 1 receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SUBSTANCE-P RECEPTOR; ACTIVATED PROTEIN-KINASE; MUSCARINIC ACETYLCHOLINE-RECEPTOR; ARRESTIN-DEPENDENT ENDOCYTOSIS; KAPPA-OPIOID RECEPTOR; BETA-ARRESTIN; RAB GTPASES; BETA(2)-ADRENERGIC RECEPTOR; INDUCED INTERNALIZATION; NEUTRAL ENDOPEPTIDASE AB Understanding the molecular mechanisms of agonist-induced trafficking of G-protein-coupled receptors is important because of the essential role of trafficking in signal transduction. We examined the role of the GT-Pases dynamin 1 and Rab5a in substance P (SP)-induced trafficking and signaling of the neurokinin 1 receptor (NK1R), an important mediator of pain, depression, and inflammation, by studying transfected cells and enteric neurons that naturally express the NK1R, In unstimulated cells, the NK1R colocalized with dynamin at the plasma membrane, and Rab5a was detected in endosomes, SP induced translocation of the receptor into endosomes containing Rab5a immediately beneath the plasma membrane and then in a perinuclear location. Expression of the dominant negative mutants dynamin 1 K44E and Rab5aS34N inhibited endocytosis of SP by 45 and 32%, respectively. Dynamin K44E caused membrane retention of the NK1R, whereas Rab5aS34N also impeded the translocation of the receptor from superficially located to perinuclear endosomes, Both dynamin K44E and Rab5aS34N strongly inhibited resensitization of SP-induced Ca2+ mobilization by 60 and 85%, respectively, but had no effect on NK1R desensitization. Dynamin K44E but not Rab5aS34N markedly reduced SP-induced phosphorylation of extracellular signal regulated kinases 1 and 2. Thus, dynamin mediates the formation of endosomes containing the NK1R, and Rab5a mediates both endosomal formation and their translocation from a superficial to a perinuclear location. Dynamin and Rab5a-dependent trafficking is essential for NK1R resensitization but is not necessary for desensitization of signaling. Dynamin-dependent but not Rab5a-dependent trafficking is required for coupling of the NK1R to the mitogen-activated protein kinase cascade. These processes may regulate the nociceptive, depressive, and proinflammatory effects of SP. C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. W Los Angeles Vet Affairs Med Ctr, Digest Dis Res Ctr, CURE, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Neurobiol, Los Angeles, CA 90073 USA. RP Bunnett, NW (reprint author), Univ Calif San Francisco, Dept Surg, 521 Parnassus Ave, San Francisco, CA 94143 USA. FU NIDDK NIH HHS [DK35740, DK39957, DK43207, DK52388, DK54155] NR 65 TC 51 Z9 51 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 6 PY 2001 VL 276 IS 27 BP 25427 EP 25437 DI 10.1074/jbc.M101688200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451KF UT WOS:000169800700133 PM 11306580 ER PT J AU Shen, ZJ Warren, CD Newburg, DS AF Shen, ZJ Warren, CD Newburg, DS TI Resolution of structural isomers of sialylated oligosaccharides by capillary electrophoresis SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE milk; structural isomer separation; oligosaccharides; sialylated oligosaccharides ID ANION-EXCHANGE CHROMATOGRAPHY; PERFORMANCE LIQUID-CHROMATOGRAPHY; PULSED AMPEROMETRIC DETECTION; HUMAN-MILK; SEPARATION; HYDRAZINOLYSIS AB The resolution of structural isomers in mixtures of oligosaccharides is often challenging. Capillary electrophoresis was employed to separate three sets of structural isomers of sialylated oligosaccharides found in human milk and bovine colostrum. Different running buffers were necessary to achieve optimal baseline resolution. To resolve 3'- and 6'-sialyllactoses, 0.2 M aqueous sodium phosphate containing 40% methanol as an organic modifier was used as a running buffer. To resolve 3'- and 6'-sialyllactosamines, 0.4 M aqueous sodium phosphate without organic modifier was used. Baseline resolution of sialyllacto-N-tetraose-a and -b and sialyllacto-N-neotetraose-c was achieved with a 0.4 M Tris-HCl buffer containing 250 mM sodium dodecyl sulfate and 10% methanol as the organic modifier. Thus, each of these sets of structural isomers of sialylated oligosaccharides required a unique running buffer with respect to buffer type, concentration, pH, presence of organic modifiers, and surfactants. Similar electrophoresis conditions may be useful for resolving and analyzing other structural isomers of acidic oligosaccharides by capillary electrophoresis. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Shriver Ctr Mental Retardat, Program Glycobiol, Waltham, MA 02452 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Newburg, DS (reprint author), Shriver Ctr Mental Retardat, Program Glycobiol, 200 Trapelo Rd, Waltham, MA 02452 USA. FU NICHD NIH HHS [HD13021] NR 14 TC 10 Z9 10 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUL 6 PY 2001 VL 921 IS 2 BP 315 EP 321 DI 10.1016/S0021-9673(01)00872-X PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 448VT UT WOS:000169651200021 PM 11471815 ER PT J AU Jain, RK AF Jain, RK TI Delivery of molecular medicine to solid tumors: lessons from in vivo imaging of gene expression and function SO JOURNAL OF CONTROLLED RELEASE LA English DT Article; Proceedings Paper CT International Symposium on Tumor Targeted Delivery Systems CY SEP 25-27, 2000 CL BETHESDA, MD SP NCI, Controlled Release Soc DE drug delivery; gene expression and function; intravital microscopy; molecular imaging ID INTERSTITIAL FLUID PRESSURE; ENDOTHELIAL GROWTH-FACTOR; NATURAL-KILLER-CELLS; VASCULAR-PERMEABILITY FACTOR; COLON ADENOCARCINOMA XENOGRAFT; ENZYME-CONJUGATED ANTIBODIES; POSITRON EMISSION TOMOGRAPHY; INDUCED LEUKOCYTE ADHESION; HUMAN-MELANOMA XENOGRAFTS; NECROSIS-FACTOR-ALPHA AB Extraordinary advances in molecular medicine and biotechnology have led to the development of a vast number of anti-cancer therapeutic agents. To reach cancer cells in a tumor, a blood-borne therapeutic molecule, particle or cell must make its way into the blood vessels of the tumor and across the vessel wall into the interstitium and finally migrate through the interstitium. Unfortunately, tumors often develop in ways that hinder each of these steps. Our research goals are to analyze each of these steps, experimentally and theoretically and then integrate the resulting information in a unified theoretical framework. This paradigm of analysis and synthesis has allowed us to obtain a better understanding of microcirculatory barriers in solid tumors and to develop novel strategies to exploit and/or to overcome these barriers for improved cancer detection and treatment. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu NR 204 TC 195 Z9 208 U1 3 U2 21 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 EI 1873-4995 J9 J CONTROL RELEASE JI J. Control. Release PD JUL 6 PY 2001 VL 74 IS 1-3 BP 7 EP 25 DI 10.1016/S0168-3659(01)00306-6 PG 19 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 465RK UT WOS:000170603600003 PM 11489479 ER PT J AU Eifel, P Axelson, JA Costa, J Crowley, J Curran, WJ Deshler, A Fulton, S Hendricks, CB Kemeny, M Kornblith, AB Louis, TA Markman, M Mayer, R Roter, D AF Eifel, P Axelson, JA Costa, J Crowley, J Curran, WJ Deshler, A Fulton, S Hendricks, CB Kemeny, M Kornblith, AB Louis, TA Markman, M Mayer, R Roter, D CA Natl Inst Hlth Consensus Dev Panel TI National Institutes of Health Consensus Development Conference statement: Adjuvant therapy for breast cancer, November 1-3, 2000 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HIGH-DOSE CHEMOTHERAPY; COOPERATIVE-ONCOLOGY-GROUP; RANDOMIZED TRIAL; PREMENOPAUSAL WOMEN; PROGNOSTIC FACTORS; STAGE-II; DOXORUBICIN-CYCLOPHOSPHAMIDE; PREOPERATIVE CHEMOTHERAPY; TAMOXIFEN THERAPY; CELL SUPPORT AB Our goal was to provide health-care providers, patients, and the general public with an assessment of currently available data regarding the use of adjuvant therapy for breast cancer. Participants: The participants included a non-Federal, non-advocate, 14-member panel representing the fields of oncology, radiology, surgery, pathology, statistics, public health, and health policy as well as patient representatives. In addition, 30 experts in medical oncology, radiation oncology, biostatistics, epidemiology, surgical oncology, and clinical trials presented data to the panel and to a conference audience of 1000. Evidence: The literature was searched with the use of MEDLINE(R) for January 1995 through July 2000, and an extensive bibliography of 2230 references was provided to the panel. Experts prepared abstracts for their conference presentations with relevant citations from the literature. Evidence from randomized clinical trials and evidence from prospective studies were given precedence over clinical anecdotal experience. Consensus Process: The panel, answering predefined questions, developed its conclusions based on the evidence presented in open forum and the scientific literature. The panel composed a draft statement, which was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. The draft statement was made available on the World Wide Web immediately after its release at the conference and was updated with the panel's final revisions. The statement is available at http://consensus.nih.gov. Conclusions. The panel concludes that decisions regarding adjuvant hormonal therapy should be based on the presence of hormone receptor protein in tumor tissues. Adjuvant hormonal therapy should be offered only to women whose tumors express hormone receptor protein. Because adjuvant polychemotherapy improves survival, it should be recommended to the majority of women with localized breast cancer regardless of lymph node, menopausal, or hormone receptor status. The inclusion of anthracyclines in adjuvant chemotherapy regimens produces a small but statistically significant improvement in survival over non-anthracycline-containing regimens. Available data are currently inconclusive regarding the use of taxanes in adjuvant treatment of lymph node-positive breast cancer. The use of adjuvant dose-intensive chemotherapy regimens in high-risk breast cancer and of taxanes in lymph node-negative breast cancer should be restricted to randomized trials. Ongoing studies evaluating these treatment strategies should be supported to determine if such strategies have a role in adjuvant treatment. Studies to date have included few patients older than 70 years. There is a critical need for trials to evaluate the role of adjuvant chemotherapy in these women. There is evidence that women with a high risk of locoregional tumor recurrence after mastectomy benefit from postoperative radiotherapy. This high-risk group includes women with four or more positive lymph nodes or an advanced primary cancer. Currently, the role of postmastectomy radiotherapy for patients with one to three positive lymph nodes remains uncertain and should be tested in a randomized controlled trial. Individual patients differ in the importance they place on the risks and benefits of adjuvant treatments. Quality of life needs to be evaluated in selected randomized clinical trials to examine the impact of the major acute and long-term side effects of adjuvant treatments, particularly premature menopause, weight gain, mild memory loss, and fatigue. Methods to support shared decision-making between patients and their physicians have been successful in trials; they need to be tailored for diverse populations and should be tested for broader dissemination. C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Hematol & Oncol Associates, Jackson, MI USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Thomas Jefferson Univ Hosp, Dept Radiat Oncol, Philadelphia, PA 19107 USA. Inst Res & Educ Hlth Syst Minnesota, Metro Minnesota Community Clin Oncol Program, St Louis Pk, MN USA. Superior Court Judge Off, Charlotte, NC USA. Suburban Specialty Care Phys PC, Bethesda, MD USA. SUNY Stony Brook, Univ Hosp & Med Ctr, Div Surg Oncol, Stony Brook, NY 11794 USA. Beth Israel Med Ctr, Dept Pain Med & Palliat Care, New York, NY 10003 USA. Beth Israel Med Ctr, Ctr Canc, New York, NY 10003 USA. RAND Corp, Arlington, VA USA. Cleveland Clin Fdn, Dept Hematol & Med Oncol, Lee & Jerome Burkons Res Chair Oncol, Cleveland, OH 44195 USA. Cleveland Clin, Taussig Canc Ctr, Cleveland, OH 44106 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. RP Eifel, P (reprint author), Care of Bowersox JA, NIH, Off Med Applicat Res, Bldg 31,Rm 1B03, Bethesda, MD 20892 USA. RI Roter, Debra/N-8830-2014 NR 88 TC 504 Z9 515 U1 5 U2 25 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 4 PY 2001 VL 93 IS 13 BP 979 EP 989 PG 11 WC Oncology SC Oncology GA 447TK UT WOS:000169588400008 PM 11438563 ER PT J AU Casarett, DJ Inouye, SK AF Casarett, DJ Inouye, SK CA Amer Coll Physicians Amer Soc In TI Diagnosis and management of delirium near the end of life SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID HOSPITALIZED OLDER PATIENTS; ACUTE CONFUSIONAL STATES; ILL CANCER-PATIENTS; TERMINAL CANCER; OPIOID ROTATION; DOUBLE-BLIND; BEHAVIORAL SYMPTOMS; RENAL-FAILURE; MENTAL STATUS; RATING-SCALE AB Delirium is a common and distressing symptom that constitutes a significant challenge for end-of-life care. However, reliable techniques are available for the diagnosis of delirium, and effective therapies exist as well. This consensus paper uses a case-based format that begins with an overview of the definition and presentation of delirium. Next, strategies for diagnosis are suggested, with attention to the unique challenges that clinicians face in pursuing a diagnostic work-up for patients near the end of life. The paper concludes with a review of therapeutic options. C1 Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Philadelphia, PA 19104 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. RP Casarett, DJ (reprint author), Care of Snyder L, Amer Coll Phys, Amer Soc Internal Med, 190 N Independence Mall W, Philadelphia, PA 19106 USA. FU NIA NIH HHS [AG00949] NR 49 TC 80 Z9 84 U1 0 U2 4 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 3 PY 2001 VL 135 IS 1 BP 32 EP 40 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 449JC UT WOS:000169680500005 PM 11434730 ER PT J AU Chen, J Fuji, K Zhang, LX Roberts, T Fu, H AF Chen, J Fuji, K Zhang, LX Roberts, T Fu, H TI Raf-1 promotes cell survival by antagonizing apoptosis signal-regulating kinase 1 through a MEK-ERK independent mechanism SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN-KINASE; ACTIVATION; PATHWAY; PHOSPHORYLATION; INHIBITOR; DEATH; DIFFERENTIATION; MITOCHONDRIA; TRANSDUCTION; DROSOPHILA AB The Ser/Thr kinase Raf-1 is a protooncogene product that is a central component in many signaling pathways involved in normal cell growth and oncogenic transformation, Upon activation, Raf-l phosphorylates mitogen-activated protein kinase kinase (MEK), which in turn activates mitogen-activated protein kinase/extracellular signal-regulated kinases (MAPK/ERKs), leading to the propagation of signals. Depending on specific stimuli and cellular environment, the Raf-1-MEK-ERK cascade regulates diverse cellular processes such as proliferation, differentiation, and apoptosis, Here, we describe a MEK-ERK-independent prosurvival function of Raf-1. We found that Raf-1 interacts with the proapoptotic, stress-activated protein kinase ASK1 (apoptosis signal-regulating kinase 1) in vitro and in vivo. Deletion analysis localized the Raf-1 binding site to the N-terminal regulatory fragment of ASK1. This interaction allows Raf-1 to act independently of the MEK-ERK pathway to inhibit apoptosis, Furthermore, catalytically inactive forms of Raf-1 can mimic the wild-type effect, raising the possibility of a kinase-independent function of Raf-1, Thus, Raf-1 may promote cell survival through its protein-protein interactions in addition to its established MEK kinase function. C1 Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Grad Program Biochem Cell & Dev Biol, Atlanta, GA 30322 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fu, H (reprint author), Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. FU NIGMS NIH HHS [GM53165, GM60033, R01 GM053165, R01 GM060033, R29 GM053165] NR 33 TC 202 Z9 211 U1 0 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 JUL 3 PY 2001 VL 98 IS 14 BP 7783 EP 7788 DI 10.1073/pnas.141224398 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 450LK UT WOS:000169744200027 PM 11427728 ER PT J AU Rangarajan, A Talora, C Okuyama, R Nicolas, M Mammucari, C Oh, H Aster, JC Krishna, S Metzgers, D Chambon, P Miele, L Aguet, M Radtke, F Dotto, GP AF Rangarajan, A Talora, C Okuyama, R Nicolas, M Mammucari, C Oh, H Aster, JC Krishna, S Metzgers, D Chambon, P Miele, L Aguet, M Radtke, F Dotto, GP TI Notch signaling is a direct determinant of keratinocyte growth arrest and entry into differentiation SO EMBO JOURNAL LA English DT Article DE cell cycle; integrins; keratins; p21(WAF1/Cip1); RBP-J kappa-CBF-1 ID PROTEIN-KINASE-C; TRANSDUCTION PATHWAY; MAMMALIAN NOTCH; MOUSE NOTCH1; KAPPA-B; RBP-J; CELL; EXPRESSION; EPIDERMIS; GENE AB The role of Notch signaling in growth/differentiation control of mammalian epithelial cells is still poorly defined. We show that keratinocyte-specific deletion of the Notch1 gene results in marked epidermal hyperplasia and deregulated expression of multiple differentiation markers. In differentiating primary keratinocytes in vitro endogenous Notch1 is required for induction of p21(WAF1/Cip1) expression, and activated Notch1 causes growth suppression by inducing p21(WAF1/Cip1) expression. Activated Notch1 also induces expression of 'early' differentiation markers, while suppressing the late markers. Induction of p21(WAF1/Cip1) expression and early differentiation markers occur through two different mechanisms, The RBP-JK protein binds directly to the endogenous p21 promoter and p21 expression is induced specifically by activated Notch1 through RBP-J kappa -dependent transcription. Expression of early differentiation markers is RBP-J kappa -independent and can be induced by both activated Notch1 and Notch2, as well as the highly conserved ankyrin repeat domain of the Notch1 cytoplasmic region. Thus, Notch signaling triggers two distinct pathways leading to keratinocyte growth arrest and differentiation. C1 Ludwig Inst Canc Res, CH-1066 Epalinges, Switzerland. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Harvard Univ, Sch Med, Brigham Womens Hosp, Dept Pathol, Boston, MA USA. Loyola Univ, Cardinal Bernardin Canc Ctr, Chicago, IL 60611 USA. TIFR, Natl Ctr Biol Sci, Bangalore, Karnataka, India. Swiss Inst Expt Canc Res, CH-1066 Epalinges, Switzerland. CNRS, Inst Genet Biol Mol & Cellulaire, Strasbourg, France. RP Dotto, GP (reprint author), Ludwig Inst Canc Res, Lausanne Branch, Ch Boveresses 155, CH-1066 Epalinges, Switzerland. FU NCI NIH HHS [P01 CA016038, CA16038, CA73796, R01 CA073796]; NIAMS NIH HHS [AR39190, R01 AR039190] NR 34 TC 528 Z9 548 U1 4 U2 30 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 2 PY 2001 VL 20 IS 13 BP 3427 EP 3436 DI 10.1093/emboj/20.13.3427 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 451LN UT WOS:000169803700015 PM 11432830 ER PT J AU Kosofsky, BE Hyman, SE AF Kosofsky, BE Hyman, SE TI No time for complacency: The fetal brain on drugs SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Editorial Material ID CHRONIC COCAINE EXPOSURE; VISUAL-CORTEX; RHESUS-MONKEY; NEURONS; MICE; INNERVATION; DEFICIENT; SEROTONIN; LACKING C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Lab Mol & Dev Neurosci, Charlestown, MA 02129 USA. NIMH, NIH, Bethesda, MD 20892 USA. RP Kosofsky, BE (reprint author), Harvard Univ, Sch Med, Lab Mol & Dev Neurosci, MGH E,149 13th St, Charlestown, MA 02129 USA. NR 29 TC 13 Z9 13 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUL 2 PY 2001 VL 435 IS 3 BP 259 EP 262 DI 10.1002/cne.1027 PG 4 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 438EY UT WOS:000169041700001 PM 11406809 ER PT J AU Coggeshall, RE Lekan, HA White, FA Woolf, CJ AF Coggeshall, RE Lekan, HA White, FA Woolf, CJ TI A-fiber sensory input induces neuronal cell death in the dorsal horn of the adult rat spinal cord SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE primary afferents; sprouting; A-fibers; postsynaptic neuron death ID PERIPHERAL-NERVE INJURY; DEAFFERENTATION-INDUCED ALTERATIONS; PERFORANT PATH STIMULATION; TRANSSYNAPTIC DEGENERATION; LAMINA-II; GABA-IMMUNOREACTIVITY; ORGANIZATION; TRANSECTION; STRYCHNINE; AFFERENTS AB Excitoxicity due to excessive synaptic glutamate release is featured in many neurological conditions in which neuronal death occurs. Whether activation of primary sensory pathways can ever produce sufficient over-activity in secondary sensory neurons in the dorsal horn of the spinal cord to induce cell death, however, has not been determined. In this study, we asked whether activity in myelinated afferents (A fibers), which use glutamate as a transmitter, can induce cell death in the dorsal horn. Using stereological estimates of neuron numbers from electron microscopic sections, we found that stimulation of A-fibers in an intact sciatic nerve at 10 Hz, 20 Hz, and 50 Hz in 10-minute intervals at a stimulus strength that activates both A beta and A delta fibers resulted in the loss of 25% of neurons in lamina III, the major site of termination of large A beta fibers, but not in lamina I, where A delta fibers terminate. Furthermore, sciatic nerve lesions did not result in detectable neuron loss, but activation of A fibers in a previously sectioned sciatic nerve did cause substantial cell death not only in lamina III but also in laminae I and II. The expansion of the territory of A-fiber afferent-evoked cell death is likely to reflect the sprouting of the fibers into these laminae after peripheral nerve injury. The data show, therefore, that primary afferent A-fiber activity can cause neuronal cell death in the dorsal horn with an anatomical distribution that depends on whether intact or injured fibers are activated. Stimulation-induced cell death potentially may contribute to the development of persistent pain. (C) 2001 Wiley-Liss, Inc. C1 Univ Texas, Med Branch, Dept Anat & Neurosci, Galveston, TX 77555 USA. Univ Texas, Med Branch, Inst Marine Biomed, Galveston, TX 77555 USA. Yale Univ, Dept Neurol, West Haven, CT 06516 USA. Massachusetts Gen Hosp, Anesthesia Neural Plastic Res Grp, Charlestown, MA 02129 USA. RP Coggeshall, RE (reprint author), Univ Texas, Med Branch, Dept Anat & Neurosci, 301 Univ Blvd, Galveston, TX 77555 USA. EM recogges@utmb.edu RI White, Fletcher/F-2895-2012; White, Fletcher/F-3203-2015 OI White, Fletcher/0000-0002-8408-9262 FU NINDS NIH HHS [NS11255, NS10161, NS38253-01] NR 43 TC 36 Z9 38 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUL 2 PY 2001 VL 435 IS 3 BP 276 EP 282 DI 10.1002/cne.1029 PG 7 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 438EY UT WOS:000169041700003 PM 11406811 ER PT J AU Maher, MM Tonra, BM Malone, DE Gibney, RG AF Maher, MM Tonra, BM Malone, DE Gibney, RG TI Portal venous gas: detection by gray-scale and Doppler sonography in the absence of correlative findings on computed tomography SO ABDOMINAL IMAGING LA English DT Article DE portal venous gas; ultrasound; computer tomography; Pneumatosis coli; ischemic bowel ID CT; ISCHEMIA; DIAGNOSIS; VEIN AB Two cases are described in which portal venous gas (PVG) was detectable by ultrasound, but the liver appeared normal on computed tomography (CT). The finding of PVG was associated with ischemic bowel in one case but was a benign finding in the other case. The gray-scale and Doppler ultrasound findings associated with PVG are described. This case report illustrates two key points. First, ultrasound may detect gas within the portal venous system when CT is negative. Second, when PVG is detected on ultrasound, urgent clinical assessment followed by contrast-enhanced CT is indicated to assess for associated intestinal ischemia. C1 St Vincents Univ Hosp, Dept Radiol, Dublin 4, Ireland. RP Maher, MM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ellison 234, Boston, MA 02114 USA. NR 10 TC 20 Z9 20 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD JUL-AUG PY 2001 VL 26 IS 4 BP 390 EP 394 DI 10.1007/s002610000192 PG 5 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 443JN UT WOS:000169338200006 PM 11441551 ER PT J AU Oinonen, MJ Crowley, WF Moskowitz, J Vlasses, PH AF Oinonen, MJ Crowley, WF Moskowitz, J Vlasses, PH TI How do academic health centers value and encourage clinical research? SO ACADEMIC MEDICINE LA English DT Article ID INSTITUTES-OF-HEALTH; MEDICAL-SCHOOLS; RESEARCH AWARDS; CARE AB To investigate whether there is a misalignment of the perceived values of and incentives fur clinical research within U.S. academic health centers (AHCs), in 1999 the authors surveyed medical school deans, academic administrators, department chairs, and faculty members at 80 AHCs that are the members of the University HealthSystem Consortium, a not-fur-profit consortium of AHCs. A total of 358 faculty from 58% of the institutions surveyed responded, with a mean of 3.76 resyonses/institution. There was general agreement that clinical research offers AHCs a considerable spectrum of benefits, including prestige, recruitment and retention of faculty, criteria for promotion of faculty, and financial support. Investigator-initiated research and government-funded research ranked highest in terms of their desirability compared with industry-sponsored and contract research. This preference was agreed upon across all categories of respondents and types of research (translational, clinical tests, and outcomes). Significant differences existed between the perceptions of deans/AHC administrators, who stated that they were increasing their emphasis on clinical investigation in the areas of research space (56% of responders), administrative support (81%), and patient recruitment (61%) and the perceptions of their departmental chairs/faculties in the same areas (34%, 52%, and 40%, respectively; p <.05). Faculty opinions documented few new investments in the actual infrastructure dedicated to clinical research. The authors conclude that their findings, which they consider reasonably representative, strongly suggest that the value of clinical research to AHCs is well understood. Their findings also identify important opportunities for AHCs to provide a wider range of incentives for the conduct of clinical research. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Univ HealthSyst Consortium, Oak Brook, IL 60523 USA. NR 10 TC 14 Z9 14 U1 0 U2 3 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUL PY 2001 VL 76 IS 7 BP 700 EP 706 DI 10.1097/00001888-200107000-00010 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 451NV UT WOS:000169808900010 PM 11448823 ER PT J AU Lester, JS Bosch, JL Kaufman, JA Halpern, EF Gazelle, GS AF Lester, JS Bosch, JL Kaufman, JA Halpern, EF Gazelle, GS TI Inpatient costs of routine endovascular repair of abdominal aortic aneurysm SO ACADEMIC RADIOLOGY LA English DT Article DE aortic aneurysm, abdominal; hospital costs; stents ID OPEN SURGICAL REPAIR; ELECTIVE SURGERY; HOSPITAL COST; UNITED-STATES; CARE; EXPERIENCE; MANAGEMENT AB Rationale and Objectives. The purpose of this study was to determine the inpatient cost of routine (ie, without emergent conversion to open repair during the hospital stay) endovascular stent-graft placement in a consecutive series of patients undergoing elective endovascular repair of abdominal aortic aneurysm (AAA) at a single institution. Materials and Methods. Inpatient hospital costs of 91 patients who underwent initial elective endovascular repair of AAA were analyzed retrospectively. All patients had participated in clinical trials at the authors' institution during the previous 6 years. Financial data were derived from the hospital's cost-accounting system; additional procedural data were collected from a departmental database and with chart review. Stent-graft and professional costs were excluded. Results. The mean total cost for endovascular repair was $11,842 (standard deviation [SD], $5,127), mean procedure time was 149 minutes (SD, 79 minutes), and mean length of stay was 3.5 days (SD, 2.3 days). Total cost depended on stent-graft type (means, $12,428 [bifurcated] vs $9,622 [tube]; P = .0002) and strongly correlated with procedure time and length of hospital stay (r = 0.78 and 0.66, respectively; P < .0001). Ninety-six percent of total costs for all patients were attributable to the following departments: operating theater (31%), radiology (31%), nursing (22%), and anesthesia (12%). Conclusion. Overall costs are greater with bifurcated than with tube stent-grafts. Total procedure-related costs are divided relatively equally between the operating theater, the radiology department, and the combination of the nursing and anesthesia departments. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, DATA Grp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Erasmus Univ, Med Ctr, Dept Epidemiol & Biostat, Rotterdam, Netherlands. RP Gazelle, GS (reprint author), Harvard Univ, Sch Med, Zero Emerson Pl,Ste 2H, Boston, MA 02114 USA. NR 31 TC 4 Z9 4 U1 2 U2 4 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JUL PY 2001 VL 8 IS 7 BP 639 EP 646 DI 10.1016/S1076-6332(03)80689-X PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 447FP UT WOS:000169561100010 PM 11450965 ER PT J AU Vakil, NB Shaker, R Johnson, DA Kovacs, T Baerg, RD Hwang, C D'Amico, D Hamelin, B AF Vakil, NB Shaker, R Johnson, DA Kovacs, T Baerg, RD Hwang, C D'Amico, D Hamelin, B TI The new proton pump inhibitor esomeprazole is effective as a maintenance therapy in GERD patients with healed erosive oesophagitis: a 6-month, randomized, double-blind, placebo-controlled study of efficacy and safety SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID GASTROESOPHAGEAL REFLUX DISEASE; LONG-TERM THERAPY; ENDOSCOPIC ASSESSMENT; NATURAL-HISTORY; ESOPHAGITIS; OMEPRAZOLE; CLASSIFICATION; RELAPSE AB Background: Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor to be developed as an optical isomer, In patients with erosive oesophagitis, esomeprazole has produced significantly greater healing rates and improved symptom resolution vs. omeprazole. Aim: This study assesses the efficacy of esomeprazole for preventing relapse in patients with healed oesophagitis. Methods: In this 6-month US multicentre randomized double-blind placebo-controlled trial, 375 Helicobacter pylori-negative patients with endoscopically healed oesophagitis received esomeprazole 40 mg, 20 mg, 10 mg, or placebo once daily. The primary efficacy end-point was maintenance of healing at 6 months. Secondary end-points assessed changes in symptoms, and long-term safety and tolerability. Results: Significantly (P < 0.001) more patients remained healed with esomeprazole 40 mg (87.9%), 20 mg (78.7%), or 10 mg (54.2%), than with placebo (29.1%). Relapse, when it occurred, was later with esomeprazole. Sustained resolution of heartburn was observed in the 40 mg and 20 mg groups; there was a high correlation between absence of heartburn and maintenance of healing. Adverse effects were mild, infrequent and not significantly different between groups. Conclusions: Esomeprazole is effective and well-tolerated in the maintenance of healing of erosive oesophagitis, Esomeprazole 40 mg and 20 mg offer significant clinical benefit to patients. C1 Univ Wisconsin, Sch Med, Sinai Samaritan Med Ctr, Milwaukee, WI 53233 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. W Los Angeles VAMC, CURE Clin, Los Angeles, CA USA. Tacoma Digest Dis Ctr, Tacoma, WA USA. AstraZeneca LP, Wayne, PA USA. RP Vakil, NB (reprint author), Univ Wisconsin, Sch Med, Sinai Samaritan Med Ctr, 945 N 12th St,Room 4040, Milwaukee, WI 53233 USA. NR 19 TC 79 Z9 82 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD JUL PY 2001 VL 15 IS 7 BP 927 EP 935 DI 10.1046/j.1365-2036.2001.01024.x PG 9 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 447HK UT WOS:000169565700004 PM 11421866 ER PT J AU Ferris, TGG Kuhlthau, K AF Ferris, TGG Kuhlthau, K TI Why should pediatricians be concerned about risk adjustment? SO AMBULATORY PEDIATRICS LA English DT Editorial Material ID MEDICAID C1 MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA USA. RP Ferris, TGG (reprint author), MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMBULATORY PEDIATRIC ASSOC PI MCLEAN PA 6728 OLD MCLEAN VILLAGE DR, MCLEAN, VA 22101-3906 USA SN 1530-1567 J9 AMBUL PEDIATR JI Ambul. Pediatr. PD JUL-AUG PY 2001 VL 1 IS 4 BP 225 EP 226 DI 10.1367/1539-4409(2001)001<0225:WSPBCA>2.0.CO;2 PG 2 WC Pediatrics SC Pediatrics GA 473YL UT WOS:000171076900009 PM 11888405 ER PT J AU Sanchez, PL Rubenstein, MH Harrell, LC Colon-Hernandez, PJ Choo, JK Palacios, IF AF Sanchez, PL Rubenstein, MH Harrell, LC Colon-Hernandez, PJ Choo, JK Palacios, IF TI Frequency of gross hematuria shortly after percutaneous coronary intervention SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ANTICOAGULANT-THERAPY; CLINICAL-SIGNIFICANCE; COMPLICATIONS; TRIAL C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit,Dept Med, Boston, MA 02114 USA. RP Sanchez, PL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit,Dept Med, Bulfinch 105,55 Fruit St, Boston, MA 02114 USA. OI Sanchez, Pedro L/0000-0002-4288-345X NR 17 TC 1 Z9 1 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUL 1 PY 2001 VL 88 IS 1 BP 71 EP 73 DI 10.1016/S0002-9149(01)01590-9 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 446UL UT WOS:000169532500015 ER PT J AU Kerr, AJ Chia, KKM Buck, T Fry, SJ Myron, PMB Rudski, LG Chow, CM Mucci, RA Picard, MH Levine, RA AF Kerr, AJ Chia, KKM Buck, T Fry, SJ Myron, PMB Rudski, LG Chow, CM Mucci, RA Picard, MH Levine, RA TI Bed tilt as an effort-independent maneuver to improve patent foramen ovale assessment by transthoracic contrast echocardiography SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID TRANSCRANIAL DOPPLER ULTRASOUND; YOUNG STROKE PATIENTS; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; ISCHEMIC STROKE; FLOW; QUANTIFICATION; SONOGRAPHY; RISK C1 Massachusetts Gen Hosp, Cardiac Ultrsound Lab, Div Cardiol, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kerr, AJ (reprint author), Massachusetts Gen Hosp, Cardiac Ultrsound Lab, Div Cardiol, Dept Med, VBK508,55 Fruit St, Boston, MA 02114 USA. OI Picard, Michael/0000-0002-9264-3243 NR 18 TC 6 Z9 6 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUL 1 PY 2001 VL 88 IS 1 BP 94 EP 98 DI 10.1016/S0002-9149(01)01599-5 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 446UL UT WOS:000169532500023 ER PT J AU Ross, JS Sheehan, CE Williams, SS Malfetano, JH Szyfelbein, WM Kallakury, BVS AF Ross, JS Sheehan, CE Williams, SS Malfetano, JH Szyfelbein, WM Kallakury, BVS TI Decreased CD44 standard form expression correlates with prognostic variables in ovarian carcinomas SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE CD44s; immunohistochemistry; ovarian tumors; prognosis ID LYMPHOCYTE HOMING RECEPTOR; METASTASIS-ASSOCIATED VARIANT; CELL-ADHESION MOLECULE; BREAST-CANCER; DIFFERENTIAL EXPRESSION; COLORECTAL-CANCER; TUMOR-DEVELOPMENT; SPLICE VARIANTS; MESSENGER-RNA; IN-VIVO AB Expression of CD44 standard form (CD44s) was evaluated by automated immunohistochemical analysis using the anti-CD44 A3D8 clone in 101 ovarian epithelial neoplasms including 82 primary tumors (64 carcinomas and 18 tumors of low malignant potential [LMP]), 9 lymph node metastases, 8 malignant ascites, and 2 peritoneal implants. Immunostaining was scored semiquantitatively. Tumors were graded according to the FIGO (International Federation of Gynecology and Obstetrics) classification system, Tumor stage and patient survival were determined from the patient records. While 9 of 18 LMP tumors expressed CD44s, only 15 of 64 carcinomas expressed it. In the carcinomas, univariate analysis revealed that decreased CD44s expression correlated with high tumor grade, advanced stage and shortened survival. Loss of CD44s expression also was noted in the tumor cells in 8 of 9 lymph node metastases, 7 of 8 malignant ascites, and 1 of 2 implants, Multivariate analysis revealed that only tumor stage independently correlated with patient survival. Loss of CD44s expression determined by immunohistochemical analysis is more common in ovarian carcinomas than in LMP tumors; correlates with prognostic variables including tumor grade, stage, and survival; and may have an important role in the dissemination of ovarian cancer. C1 Albany Med Coll, Dept Pathol & Lab Med, Albany, NY 12208 USA. Albany Med Coll, Dept Obstet & Gynecol, Albany, NY 12208 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Albany Med Coll, Dept Obstet & Gynecol, Albany, NY 12208 USA. RP Ross, JS (reprint author), Albany Med Coll, Dept Pathol & Lab Med, A-81,47 New Scotland Ave, Albany, NY 12208 USA. NR 58 TC 23 Z9 24 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JUL PY 2001 VL 116 IS 1 BP 122 EP 128 PG 7 WC Pathology SC Pathology GA 446UE UT WOS:000169531900017 PM 11447742 ER PT J AU Radeos, MS Leak, LV Lugo, BP Hanrahan, JP Clark, S Camargo, CA AF Radeos, MS Leak, LV Lugo, BP Hanrahan, JP Clark, S Camargo, CA CA MARC Investigators TI Risk factors for lack of asthma self-management knowledge among ED patients not on inhaled steroids SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE asthma; controlled trials; patient education; questionnaires; self-care ID QUALITY-OF-LIFE; EDUCATION-PROGRAM; ADULTS; QUESTIONNAIRE; GUIDELINES; PLANS; CARE; REDUCTION; MORBIDITY; PATTERNS AB The study objective was to estimate the level of asthma knowledge and self-management skills among asthmatic patients who are not on inhaled corticosteroids and who present with acute asthma to the emergency department (ED), The design was to interview of patients by telephone at 90 to 100 days after enrollment in the Fourth Multicenter Airways Research Collaboration (MARC-4), a randomized trial comparing inhaled fluticasone versus placebo in addition to standard post-ED therapy. The setting was a multicenter trial involving 41 US urban EDs, Persons aged 12 to 54, not on inhaled steroids, who presented to the ED with acute asthma were studied. Of the 617 patients enrolled on MARC-4 405 (66%) were contacted, Mean (+/-SD) age was 30(+/-11); 54% were women; acute asthma severity was 44% moderate and 56% severe; and 9% had prior intubation, Twenty percent (95% CI 16%-24%) responded that asthma could not be monitored and 40% (95% CI 35%-44%) scored low on a hypothetical acute asthma attack scenario. Predictors for lack of asthma knowledge and self management skills were: less than a high school education; current smoking; lower median household income; and no history of steroid use, These data suggest that many ED patients with asthma have poor knowledge of asthma monitoring and poor self management skills and that a "high risk" group is also identifiable. Efforts to design and implement an ED-based educational program should be tailored to better meet the needs of this high risk group. (Am J Emerg Med 2001;19:253 259. Copyright (C) 2001 by W,B, Saunders Company). C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Channing Lab, Dept Med,Sch Med, Boston, MA 02115 USA. SUNY Brooklyn, Dept Emergency Med, Brookdale Univ Hosp Med Ctr, Coll Med, Brooklyn, NY USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Clin Bldg 397,55 Fruit St, Boston, MA 02114 USA. EM marc@partners.org FU NHLBI NIH HHS [HL-03533, HL-63253, HL-07427] NR 49 TC 22 Z9 22 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD JUL PY 2001 VL 19 IS 4 BP 253 EP 259 DI 10.1053/ajem.2001.21712 PG 7 WC Emergency Medicine SC Emergency Medicine GA 452CH UT WOS:000169839200001 PM 11447507 ER PT J AU El-Serag, HB Hepworth, EJ Lee, P Sonnenberg, A AF El-Serag, HB Hepworth, EJ Lee, P Sonnenberg, A TI Gastroesophageal reflux disease is a risk factor for laryngeal and pharyngeal cancer SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID UNITED-STATES; CARCINOMA; EPIDEMIOLOGY; ESOPHAGITIS; ALCOHOLISM AB OBJECTIVE: Gastroesophageal reflux disease (GERD) is a proposed risk factor for developing laryngeal and pharyngeal cancers. No controlled study has examined this association. METHODS: A case-control study was performed using the computerized hospitalization and outpatient databases of the US Department of Veterans Affairs. All patients, who were veterans, had been identified as being hospitalized with laryngeal or pharyngeal during 1991 to 1997. In addition, all persons diagnosed with laryngeal or pharyngeal cancer in 1999 in the outpatient files were identified. From the same patient populations, four nonmatched control subjects were randomly assigned for each case. The medical history for cases and controls was retrospectively searched for GERD diagnoses, tobacco use, and alcohol dependence. Multivariable logistic regression analyses were performed to assess the risk factors for laryngeal and pharyngeal cancers. RESULTS: A total of 8,228 hospitalized patients with laryngeal cancers and 1,912 with pharyngeal cancers were compared to 32,912 and 7,648 hospitalized controls, while 9,292 outpatients with laryngeal cancer and 2,769 outpatients with pharyngeal cancer were compared with 37,168 and 11,076 outpatient controls without cancer. Among hospitalized persons, the prevalence of GERD was higher among patients with laryngeal cancer (8.9 vs 4.0%, p < 0.0001) and pharyngeal cancer (6.2 vs 3.8%, p < 0.0001). In a multivariable logistic regression analysis that was controlled for age, gender, ethnicity, smoking, and alcohol, GERD was associated with an adjusted odds ratio (OR) of 2.40 for laryngeal cancer among hospitalized patients (95% CI 2.15-2.69, p < 0.0001) and an adjusted OR of 2.38 (95% CI 1.87-3.02, p < 0.0001) for pharyngeal cancer. For outpatients, GERD was associated with an adjusted OR = 2.31 (95% CI 2.10-2.53) for laryngeal cancer and adjusted OR = 1.92 (95% CI 1.72-2.15). CONCLUSIONS: Among US veterans, the risk for laryngeal or pharyngeal cancers is modestly increased in the presence of GERD. This effect seems to be independent of age, gender, smoking, and alcohol intake. 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, Houston, TX 77030 USA. Univ New Mexico, Albuquerque, NM 87131 USA. Albuquerque Vet Affairs Med Ctr, Albuquerque, NM USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr, Gastroenterol Sect, 39 A,2002 Holcombe Blvd, Houston, TX 77030 USA. NR 27 TC 67 Z9 73 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUL PY 2001 VL 96 IS 7 BP 2013 EP 2018 DI 10.1016/S0002-9270(01)02497-2 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 452CM UT WOS:000169839600013 PM 11467626 ER PT J AU Lee, OY Mayer, EA Schmulson, M Chang, L Naliboff, B AF Lee, OY Mayer, EA Schmulson, M Chang, L Naliboff, B TI Gender-related differences in IBS symptoms SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID IRRITABLE-BOWEL-SYNDROME; CHRONIC PAIN; GENERAL-POPULATION; MENSTRUAL-CYCLE; INTESTINAL GAS; EPIDEMIOLOGY; CONSTIPATION; PREVALENCE; DIAGNOSIS; FEMALES AB OBJECTIVE: Women are more likely than men to report irritable bowel syndrome (IBS) symptoms as well as chronic visceral and musculoskeletal pain. The study tests the general hypothesis that female IBS patients differ from their male counterparts in symptoms related to the viscera and musculoskeletal system, and that these differences are related to the menstrual cycle. METHODS: Seven hundred fourteen Rome positive IBS patients were evaluated for GI and extracolonic symptoms, psychological symptoms (SCL-90R), and quality of Life (QOL) (SF-36). In addition, 54 postmenopausal women were compared with 61 premenopausal women and 54 age-matched mates, all with IBS. RESULTS: Male and female subjects reported similar GI levels of symptom;severity and psychological problems. Abdominal distension associated with a sensation of bloating was more commonly reported by female patients, as were symptoms of constipation. Female patients more often reported nausea, alterations of taste and smell, and unpleasant sensations on the tongue, muscle stiffness in the morning, greater food sensitivity, and side effects from medications. Forty percent of female patients reported menstrual cycle-related worsening of symptoms, but few symptom differences were found between pre- and postmenopausal women, making it unlikely that most of the gender differences observed are directly tied to the menstrual cycle. CONCLUSIONS: Female patients report higher levels of a variety of intestinal and nonintestinal sensory symptoms despite similar levels of IBS severity, abdominal pain, psychological symptoms, and illness impact. The apparent differences in sensitivity to nonpainful visceral sensations, medications, and food may represent altered sensory processes, autonomic responses, and/or cognitive hypervigilance. (C) 2001 by Am. Coll. of Gastroenterology. C1 Univ Calif Los Angeles, Sch Med, CURE Digest Dis Res Ctr, Neuroenter Dis Program,Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, CURE Digest Dis Res Ctr, Neuroenter Dis Program,Dept Physiol, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Dept Psychol, Los Angeles, CA USA. Hanyang Univ, Dept Med, Coll Med, Seoul, South Korea. Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Gastroenterol, Mexico City, DF, Mexico. RP Naliboff, B (reprint author), Univ Calif Los Angeles, CURE Neuroenter Dis program, WLA VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 115,Room 223, Los Angeles, CA 90073 USA. NR 50 TC 122 Z9 125 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUL PY 2001 VL 96 IS 7 BP 2184 EP 2193 DI 10.1016/S0002-9270(01)02524-2 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 452CM UT WOS:000169839600038 PM 11467651 ER PT J AU Hampel, H Bynum, GD Zamora, E El-Serag, HB AF Hampel, H Bynum, GD Zamora, E El-Serag, HB TI Risk factors for the development of renal dysfunction in hospitalized patients with cirrhosis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID SPONTANEOUS BACTERIAL PERITONITIS; AMINOGLYCOSIDE NEPHROTOXICITY; LIVER-DISEASE; FAILURE; IMPAIRMENT AB OBJECTIVE: Hospitalized patients with liver cirrhosis are predisposed to acute renal failure. We sought to identify the role of liver disease severity, infectious complications, and in-hospital treatment with aminoglycosides as risk factors for acute renal failure among patients with cirrhosis. METHODS: In a retrospective, case-control study at the Albuquerque VA Medical Center, electronic and manual chart review was employed to identify all hospitalized patients with a diagnosis of cirrhosis and normal renal function (serum creatinine less than or equal to 1.3 mg/dl) at the time of hospitalization. Cases were defined as patients who developed renal dysfunction (increase in creatinine of greater than or equal to 1.0 mg/dl) within 15 days of hospitalization, and the remaining patients were controls. RESULTS: Of 93 patients, there were 23 cases and 70 controls. There were no significant differences in age; etiology of cirrhosis, serum levels of albumin, or bilirubin, prothrombin time, encephalopathy, bacteremia, urinary tract infection, or occurrence of esophageal variceal bleeding. Patients who developed renal dysfunction were more likely to have ascites (87% vs 41%, p < 0.01), spontaneous bacterial peritonitis (44% vs 1%, p < 0.01), and treatment with i.v. aminoglycosides (48% vs 19%, p < 0.01). In a multivariate logistic regression analysis, aminoglycosides treatment was a strong risk factor for renal dysfunction (adjusted odds ratio = 4.0, 95% CI = 1.4-11), independent of the severity of liver disease or peritonitis. CONCLUSION: Avoidance: of aminoglycoside antibiotics may reduce the occurrence of renal dysfunction in-hospitalized patients with cirrhosis. In addition, close monitoring of renal function should be employed among patients with ascites and/or spontaneous bacterial peritonitis. (C) 2001 by Am. Cell. of Gastroenterology. C1 Baylor Coll Med, Houston Dept Vet Affairs Med Ctr, Sect Internal Med & Gastroenterol, Houston, TX 77030 USA. Baylor Coll Med, Houston Dept Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA. Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA. RP El-Serag, HB (reprint author), Houston VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 15 TC 79 Z9 85 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUL PY 2001 VL 96 IS 7 BP 2206 EP 2210 DI 10.1016/S0002-9270(01)02521-7 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 452CM UT WOS:000169839600041 PM 11467654 ER PT J AU Fagan, P Eisenberg, M Stoddard, AM Frazier, L Sorensen, G AF Fagan, P Eisenberg, M Stoddard, AM Frazier, L Sorensen, G TI Social influences, social norms, social support, and smoking behavior among adolescent workers SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE working youth; adolescent smoking; social influences; social norms ID CIGARETTE-SMOKING; SUBSTANCE USE; PREVENTION PROGRAMS; CESSATION; HEALTH; INITIATION; CONSEQUENCES; METAANALYSIS; INTERVENTION; REPLICATION AB Purpose. To examine the relationships between worksite interpersonal influences and smoking and quitting behavior among adolescent workers. Design. The cross-sectional survey assessed factors influencing tobacco use behavior. Setting. During the fall of 1998, data were collected from 10 grocery stores in Massachusetts that were owned and managed by the same company. Subjects. Eligible participants included 474 working adolescents ages 15 to I8. Eighty-three percent of workers (n = 379) completed the survey. Measures. The self-report questionnaire assessed social influences, social norms, social support, friendship networks, stage of smoking and quitting behavior, employment patterns, and demographic factors. Results. Thirty-five percent of respondents were never smokers, 21% experimental, 5% occasional, 18% regular and 23% former smokers. Using analysis of variance (ANOVA), results indicate that regular smokers were 30% more likely than experimental or occasional smokers to report coworker encouragement to quit (p =.0002). Compared with regular smokers, never. smokers were 15% move likely to report greater nonacceptability of smoking(p =.01). chi (2) tests of association revealed no differences in friendship, networks by stage of smoking: Conclusions. These data provide evidence for the need to further explore social factors inside and outside the work environment that influence smoking and quitting behavior among working teens. Interpretations of the data are limited because of cross-sectional and self-report data collection methods used in one segment of the retail sector. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Channing Lab, Boston, MA USA. RP Sorensen, G (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St, Boston, MA 02115 USA. FU NINR NIH HHS [5 R01 NR04748, 3 R01 NR04748] NR 48 TC 25 Z9 25 U1 3 U2 8 PU AMER J HEALTH PROMOTION INC PI KEEGO HARBOR PA 1660 CASS LAKE RD, STE 104, KEEGO HARBOR, MI 48320 USA SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD JUL-AUG PY 2001 VL 15 IS 6 BP 414 EP 421 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 452YA UT WOS:000169886200003 PM 11523498 ER PT J AU Astuti, D Latif, F Dallol, A Dahia, PLM Douglas, F George, E Skoldberg, F Husebye, ES Eng, C Maher, ER AF Astuti, D Latif, F Dallol, A Dahia, PLM Douglas, F George, E Skoldberg, F Husebye, ES Eng, C Maher, ER TI Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; HIPPEL-LINDAU-DISEASE; COMPLEX-II; VHL; RET; MITOCHONDRIA; INVOLVEMENT; APOPTOSIS; BINDING AB The pheochromocytomas are an important cause of secondary hypertension. Although pheochromocytoma susceptibility may be associated with germline mutations in the tumor-suppressor genes VHL and NF1 and in the proto-oncogene RET, the genetic basis for most cases of nonsyndromic familial pheochromocytoma is unknown. Recently, pheochromocytoma susceptibility has been associated with germline SDHD mutations. Germline SDHD mutations were originally described in hereditary paraganglioma, a dominantly inherited disorder characterized by vascular tumors in the head and the neck, most frequently at the carotid bifurcation. The gene products of two components of succinate dehydrogenase, SDHC and SDHD, anchor the gene products of two other components, SDHA and SDHB, which form the catalytic core, to the inner-mitochondrial membrane. Although mutations in SDHC and in SDHD may cause hereditary paraganglioma, germline SDHA mutations are associated with juvenile encephalopathy, and the phenotypic consequences of SDHB mutations have not been defined. To investigate the genetic causes of pheochromocytoma, we analyzed SDHB and SDHC, in familial and in sporadic cases. Inactivating SDHB mutations were detected in two of the five kindreds with familial pheochromocytoma, two of the three kindreds with pheochromocytoma and paraganglioma susceptibility, and 1 of the 24 cases of sporadic pheochromocytoma. These findings extend the link between mitochondrial dysfunction and tumorigenesis and suggest that germline SDHB mutations are an important cause of pheochromocytoma susceptibility. C1 Univ Birmingham, Sch Med, Dept Paediat & Child Hlth, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Royal Victoria Infirm, No Reg Genet Serv, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. Kings Lynn Hosp, Dept Med, Norfolk, England. Uppsala Univ, Dept Med Sci, Uppsala, Sweden. Ohio State Univ, Ctr Comprehens Canc, Clin Canc Genet Programs, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA. Ohio State Univ, Dept Internal Med, Div Human Genet, Columbus, OH 43210 USA. Univ Cambridge, CRC, Human Canc Genet Res Grp, Cambridge, England. RP Maher, ER (reprint author), Univ Birmingham, Sch Med, Dept Paediat & Child Hlth, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England. RI MAHER, EAMONN/A-9507-2008; Dallol, Ashraf/H-8661-2012; OI MAHER, EAMONN/0000-0002-6226-6918; Dallol, Ashraf/0000-0002-8803-228X; Eng, Charis/0000-0002-3693-5145 FU NCI NIH HHS [P30 CA016058, P30 CA16058] NR 26 TC 614 Z9 639 U1 1 U2 17 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 JUL PY 2001 VL 69 IS 1 BP 49 EP 54 DI 10.1086/321282 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 456XM UT WOS:000170108100005 PM 11404820 ER PT J AU Hirschhorn, JN Lindgren, CM Daly, MJ Kirby, A Schaffner, SF Burtt, NP Altshuler, D Parker, A Rioux, JD Platko, J Gaudet, D Hudson, TJ Groop, LC Lander, ES AF Hirschhorn, JN Lindgren, CM Daly, MJ Kirby, A Schaffner, SF Burtt, NP Altshuler, D Parker, A Rioux, JD Platko, J Gaudet, D Hudson, TJ Groop, LC Lander, ES TI Genomewide linkage analysis of stature in multiple populations reveals several regions with evidence of linkage to adult height SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID RECEPTOR GENE; QUANTITATIVE TRAITS; VARIANCE-COMPONENTS; HIP FRACTURE; BODY HEIGHT; POLYMORPHISM; CHILDREN; WOMEN; RISK; PEDIGREES AB Genomewide linkage analysis has been extremely successful at identification of the genetic variation underlying single-gene disorders. However, linkage analysis has been less successful for common human diseases and other complex traits in which multiple genetic and environmental factors interact to influence disease risk. We hypothesized that a highly heritable complex trait, in which the contribution of environmental factors was relatively limited, might be more amenable to linkage analysis. We therefore chose to study stature (adult height), for which heritability is 75%-90% (Phillips and Matheny 1990; Carmichael and McGue 1995; Preece 1996; Silventoinen et al. 2000). We reanalyzed genomewide scans from four populations for which genotype and height data were available, using a variance-components method implemented in GENEHUNTER 2.0 (Pratt et al. 2000). The populations consisted of 408 individuals in 58 families from the Botnia region of Finland, 753 individuals in 183 families from other parts of Finland, 746 individuals in 179 families from Southern Sweden, and 420 individuals in 63 families from the Saguenay-Lac-St.-Jean region of Quebec. Four regions showed evidence of linkage to stature: 6q24-25, multipoint LOD score 3.85 at marker D6S1007 in Botnia (genomewide P<.06), 7q31.3-36 (LOD 3.40 at marker D7S2195 in Sweden, P<.02), 12p11.2-q14 (LOD 3.35 at markers D12S10990-D12S398 in Finland,P<.05) and 13q32-33 (LOD 3.56 at markers D13S779-D13S797 in Finland, P<.05). In a companion article (Perola et al. 2001 [in this issue]), strong supporting evidence is obtained for linkage to the region on chromosome 7. These studies suggest that highly heritable complex traits such as stature may be genetically tractable and provide insight into the genetic architecture of complex traits. C1 MIT, Whitehead Ctr Genome Res, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Millennium Pharmaceut Inc, Dept Genet, Cambridge, England. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Genet, Boston, MA 02114 USA. Univ Lund, Dept Endocrinol, Malmo, Sweden. Ctr Hosp Univ Montreal, Chicoutimi Hosp, Prevent Genet & Community Genet Ctr, Montreal, PQ, Canada. McGill Univ, Ctr Hlth, Montreal Genome Ctr, Montreal, PQ, Canada. RP Hirschhorn, JN (reprint author), MIT, Whitehead Ctr Genome Res, 1 Kendall Sq, Cambridge, MA 02139 USA. RI Altshuler, David/A-4476-2009; Schaffner, Stephen/D-1189-2011; Rioux, John/A-9599-2015 OI Altshuler, David/0000-0002-7250-4107; Rioux, John/0000-0001-7560-8326 FU Wellcome Trust [090532] NR 37 TC 133 Z9 135 U1 0 U2 6 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 JUL PY 2001 VL 69 IS 1 BP 106 EP 116 DI 10.1086/321287 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 456XM UT WOS:000170108100011 PM 11410839 ER PT J AU White, RF Proctor, SP Heeren, T Wolfe, J Krengel, M Vasterling, J Lindem, K Heaton, KJ Sutker, P Ozonoff, DM AF White, RF Proctor, SP Heeren, T Wolfe, J Krengel, M Vasterling, J Lindem, K Heaton, KJ Sutker, P Ozonoff, DM TI Neuropsychological function in Gulf War Veterans: Relationships to self-reported toxicant exposures SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE neuropsychology; Gulf War veterans; cognitive function; environmental exposures ID OCCUPATIONAL LEAD NEUROTOXICITY; POSTTRAUMATIC-STRESS-DISORDER; CHRONIC NEUROLOGICAL SEQUELAE; TEST BATTERIES; HEALTH; SARIN; SYMPTOMS; SOLVENTS AB Background The present study was aimed at (1) exploring evidence of central nervous system (CNS) dysfunction among Gulf War (GW) veterans on neuropsychological tests and (2) examining whether performance on neuropsychological tests was related to specific neurotoxicant exposures experienced in the Gulf Methods The GW-deployed groups were selected using stratified random sampling methods from two distinct cohorts of GW veterans. A comparison group that had been called up for GW service but deployed to Germany rather than the Gulf also was examined. Neuropsychological function was assessed using a pre-determined battery chosen to include tests known to be highly sensitive to the behavioral effects of the neurotoxicants thought to have been present in the Gulf. Results Self-reported exposures were related to neuropsychological test performance controlling for post-traumatic stress disorder major depression, and other known covariates of neuropsychological test performance. Results showed that GW-deployed veterans performed more poorly than the Germany-deployed veterans on several specific neuropsychological tests, but after adjustment for multiple comparisons, only the differences in mood complaints remained significant. Within the GW-deployed group, self-reported exposure to chemical warfare agents was associated with poorer performance on cognitive tests involving specific functional domains. Conclusions Results provide evidence that there are subtle differences in CNS function among GW-deployed veterans who report chemical warfare agent exposure while in the GW theater. (C) 2001 Wiley-Liss, Inc. C1 VA Boston Healthcare Syst, Boston Environm Hazards Ctr, Boston, MA 02130 USA. VA Boston Healthcare Syst, Dept Psychol, Boston, MA 02130 USA. Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. New Orleans DVAMC, New Orleans, LA USA. Tulane Univ, Sch Med Psychiat & Neurol, New Orleans, LA 70118 USA. VA Boston Healthcare Syst, Med Serv, Boston, MA 02130 USA. RP White, RF (reprint author), VA Boston Healthcare Syst, Boston Environm Hazards Ctr, 150 S Huntington Ave,116B-4, Boston, MA 02130 USA. RI Heaton, Kristin/E-3660-2013 NR 60 TC 48 Z9 48 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUL PY 2001 VL 40 IS 1 BP 42 EP 54 DI 10.1002/ajim.1070 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 448YL UT WOS:000169657500006 PM 11439396 ER PT J AU Oliver, LC Miracle-McMahill, H Littman, AB Oakes, JM Gaita, RR AF Oliver, LC Miracle-McMahill, H Littman, AB Oakes, JM Gaita, RR TI Respiratory symptoms and lung function in workers in heavy and highway construction: A cross-sectional study SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE heavy and highway construction; tunnel workers; laborers; operating engineers; asthma; healthy worker effect ID DIESEL EXHAUST; MUCUS HYPERSECRETION; PULMONARY-FUNCTION; DUST EXPOSURE; ASTHMA; MORTALITY; AIRWAYS; RISK AB Background Occupational exposures for workers in heavy and highway (HH) construction include cement-containing dusts and diesel exhaust (DE). To investigate possible health effects, respiratory symptoms and lung function were examined in laborers, tunnel workers (TW), and operating engineers (OE) in HH and tunnel construction. The principal outcome of interest was airways disease. Methods Subjects were recruited through their unions. Medical and occupational histories and flow-volume loops were obtained. Based on self-report, asthma and chronic bronchitis were categorized as (1) physician-diagnosed or (2) for asthma, undiagnosed likely, and (3) for chronic bronchitis, symptomatic. Trade and time in the union were used as surrogates of exposure. Prevalence of asthma and chronic bronchitis, lung function outcome, and relationships with exposure variables were examined. Results Data were obtained on 389 workers: 186 laborers, 45 TWs, and 158 OEs. Prevalence of asthma was 13 and 11.4% for laborers (including TW) and OEs, respectively, and of symptomatic chronic bronchitis, 6.5 and 1.9%, respectively. Odds ratios (OR)for undiagnosed asthma likely were significantly elevated in TWs compared to OEs, and marginally elevated for chronic bronchitis. Inverse relationships were observed between time in the union, and risk for asthma and chronic bronchitis. Asthma (physician-diagnosed or undiagnosed likely) predicted lower FEV1. Current cigarette use was associated with chronic bronchitis but not asthma. Conclusions TWs, laborers, and OEs in HH construction are at increased risk for asthma. TWs also appear to be at increased risk for chronic bronchitis. Our data suggest that symptomatic workers are self-selecting out of their trade. Asthma was associated with lower lung function in those affected. (C) 2001 Wiley-Liss, Inc. C1 Inst Occupat Hlth, Brookline, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Occupat Hlth Inst,Dept Med, Boston, MA 02115 USA. New England Res Inst, Watertown, MA 02172 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Inst Occupat Hlth, Bldg & Construct Trades Council Metropolitan Dist, Boston, MA USA. RP Oliver, LC (reprint author), Inst Occupat Hlth, 1101 Beacon St,4W, Brookline, MA USA. RI Miracle, Maria /G-3482-2016 FU PHS HHS [U02/CCU312014] NR 36 TC 17 Z9 17 U1 3 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUL PY 2001 VL 40 IS 1 BP 73 EP 86 DI 10.1002/ajim.1073 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 448YL UT WOS:000169657500009 PM 11439399 ER PT J AU Thorp, ML Morris, CD Bagby, SP AF Thorp, ML Morris, CD Bagby, SP TI A crossover study of gabapentin in treatment of restless legs syndrome among hemodialysis patients SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE hemodialysis (HD); restless legs syndrome (RLS); gabapentin ID MOVEMENTS AB Restless legs syndrome (RLS) is a common entity affecting hemodialysis patients. Although the cause of RLS remains unclear, a number of therapies have been used successfully to treat the disorder, Gabapentin is an anticonvulsant shown to alleviate symptoms of RLS in two small studies of nonhemodialysis patients, Because it is excreted renally, gabapentin has a long half-life among hemodialysis patients and may be advantageous if proven effective. We conducted a randomized, double-blind, placebo-crossover study of gabapentin in the treatment of RLS among a population of hemodialysis patients. Sixteen patients identified with RLS were randomized to either gabapentin or placebo. After 6 weeks of treatment with 200 to 300 mg of gabapentin after each hemodialysis session, patients' RLS was reassessed. After a I-week washout period, patients were switched from gabapentin to placebo or placebo to gabapentin, After another 6 weeks, patients' RLS was assessed again. Patient data were analyzed using both parametric and nonparametric means. Thirteen of the Is original patients completed the study, Two patients dropped out because of lethargy (believed to be secondary to gabapentin), and 1 patient died secondary to myocardial infarction, Eleven patients responded to gabapentin, but not placebo (P < 0,01), One patient responded to both, and 1 patient responded to placebo, but not gabapentin, Gabapentin is an effective treatment for RLS in hemodialysis patients. (C) 2001 by the National Kidney Foundation, Inc. C1 Oregon Hlth Sci Univ, Div Nephrol Hypertens & Clin Pharmacol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Thorp, ML (reprint author), 6902 SE Lake Rd, Milwaukee, WI USA. NR 13 TC 70 Z9 73 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 JUL PY 2001 VL 38 IS 1 BP 104 EP 108 DI 10.1053/ajkd.2001.25202 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 450EY UT WOS:000169729600016 PM 11431189 ER PT J AU Picard, MH Dennis, CA AF Picard, MH Dennis, CA TI Assessing cardiac risk - How low (risk) should you go? SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID CORONARY-ARTERY DISEASE; EXERCISE ECHOCARDIOGRAPHY; MYOCARDIAL-INFARCTION; CARDIOLOGY C1 Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Deborah Heart & Lung Ctr, Dept Cardiol, Brown Hills, NJ USA. Harvard Univ, Sch Med, Boston, MA USA. RP Picard, MH (reprint author), Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, 55 Fruit St, Boston, MA 02114 USA. OI Picard, Michael/0000-0002-9264-3243 NR 10 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUL PY 2001 VL 111 IS 1 BP 73 EP 74 DI 10.1016/S0002-9343(01)00772-0 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 490LH UT WOS:000172053000012 PM 11448666 ER PT J AU Denton, MD Mauiyyedi, S Bazari, H AF Denton, MD Mauiyyedi, S Bazari, H TI Heparin-induced skin necrosis in a patient with end-stage renal failure and functional protein S deficiency SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE calciphylaxis; heparin; skin; protein S; renal failure, chronic ID INDUCED THROMBOCYTOPENIA; HEMODIALYSIS; CALCIPHYLAXIS; LESIONS AB Skin ulceration is a well-characterized thrombotic complication of the heparin-induced thrombocytopenia (HIT) syndrome. We present the case of a 73-year-old diabetic woman nearing end-stage renal failure who developed extensive upper thigh, abdominal and buttock ulceration following initiation of subcutaneous heparin for prophylaxis against deep vein thrombosis. A preliminary diagnosis of calciphylaxis was made based on the classical distribution and macroscopic appearance of the ulceration in a patient with end-stage renal failure and secondary hyperparathyroidism. However skin biopsy showed complete absence of calcium deposits in the dermal microvasculature. The presence of extensive microthrombi within dermal vessels prompted serologic testing to detect a prothrombotic state. We identified the combined presence of heparin-dependent platelet activating (HIT) antibodies and functional protein S deficiency. To our knowledge this is the first reported case of a dialysis patient presenting with skin ulceration induced by heparin and protein S deficiency. This case highlights the importance of a skin biopsy and testing for a hyper-coaguable state in patients with end-stage renal disease and skin ulceration. We suggest that HIT antibodies should be requested in all dialysis patients presenting with skin ulceration. Copyright (C) 2001 S. Karger AG, Basel. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Div,Dept Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Denton, MD (reprint author), Brigham & Womens Hosp, Div Renal, 75 Francis St, Boston, MA 02116 USA. NR 20 TC 9 Z9 9 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PD JUL-AUG PY 2001 VL 21 IS 4 BP 289 EP 293 DI 10.1159/000046263 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 466LJ UT WOS:000170646800005 PM 11509800 ER PT J AU Gutierrez, MA Roper, JM Hahn, P AF Gutierrez, MA Roper, JM Hahn, P TI Paradoxical reactions to benzodiazepines - When to expect the unexpected SO AMERICAN JOURNAL OF NURSING LA English DT Article ID ENDOSCOPIC PROCEDURES; FLUMAZENIL; MIDAZOLAM; TRIAZOLAM; DRUGS C1 Univ So Calif, Sch Pharm, Los Angeles, CA 90089 USA. Vet Affairs Greater Los Angeles Med Ctr, Dual Diagnosis Treatment Program, Los Angeles, CA USA. RP Gutierrez, MA (reprint author), Univ So Calif, Sch Pharm, 1985 Zonal Ave, Los Angeles, CA 90089 USA. NR 26 TC 8 Z9 8 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD JUL PY 2001 VL 101 IS 7 BP 34 EP 39 PG 6 WC Nursing SC Nursing GA 528ZV UT WOS:000174276300019 PM 11469127 ER PT J AU Robinson, EM AF Robinson, EM TI Caring for incompetent patients and their surrogates - A case study of end-of-life care. SO AMERICAN JOURNAL OF NURSING LA English DT Editorial Material ID CARDIOPULMONARY-RESUSCITATION C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. CUNY Herbert H Lehman Coll, Div Nursing, New York, NY USA. RP Robinson, EM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 10 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD JUL PY 2001 VL 101 IS 7 BP 75 EP 76 PG 2 WC Nursing SC Nursing GA 528ZV UT WOS:000174276300028 PM 11469136 ER PT J AU Signoretti, S Loda, M AF Signoretti, S Loda, M TI Estrogen receptor beta in prostate cancer - Brake pedal or accelerator? SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Editorial Material ID ALPHA ER-ALPHA; MICE LACKING; REPRODUCTIVE PHENOTYPES; EXPRESSION; P27(KIP1); GROWTH; BCL-2; MOUSE; ONCOPROTEIN; HYPERPLASIA C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Loda, M (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, D-740,44 Binney St, Boston, MA 02115 USA. NR 36 TC 55 Z9 56 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 2001 VL 159 IS 1 BP 13 EP 16 DI 10.1016/S0002-9440(10)61666-5 PG 4 WC Pathology SC Pathology GA 448XM UT WOS:000169655300003 PM 11438447 ER PT J AU Giri, D Ittmann, M AF Giri, D Ittmann, M TI Interleukin-8 is a paracrine inducer of fibroblast growth factor 2, a stromal and epithelial growth factor in benign prostatic hyperplasia SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID RECEPTOR MESSENGER-RNA; HUMAN FIBROBLAST-GROWTH-FACTOR-2; ENDOTHELIAL-CELLS; CARDIAC MYOCYTES; CANCER CELLS; EXPRESSION; TUMORIGENICITY; PROLIFERATION; PROMOTER; FGF-2 AB Benign prostatic hyperplasia (BPH) is an extremely common disease of older men in which there is benign overgrowth of the prostatic transition zone, leading to obstruction of urine outflow. Fibroblast growth factor (FGF) 2, a potent growth factor for prostatic stromal and epithelial cells, is increased twofold in BPH and its concentration is correlated with stromal proliferation in this condition, immunohistochemistry of normal and hyperplastic prostate revealed that FGF2-expressing stromal cells were present in higher numbers near the epithelial acini, implying that epithelial cells may express a factor that induces FGF2 expression by stromal cells. Conditioned medium from primary cultures of prostatic epithelial cells was capable of inducing increased expression of FGF2 by primary stromal cultures. Blocking experiments with neutralizing anti-interleukin (IL)-8 antibodies and pretreatment with lipopolysaccharide, which down-regulates the IL-8 receptor, show that this inducing activity is because of the presence of IL-8 in the epithelial-conditioned medium. Analysis of normal prostatic peripheral zone and BPH tissue by enzyme-linked immunosorbent assay reveals that IL-8 is present at increased levels in hyperplastic prostate. Therefore IL-8 produced by prostatic epithelial cells can induce FGF2, a potent stromal and epithelial growth factor, and In this manner promote the abnormal proliferation of the prostatic transition zone that is critical in the pathogenesis of BPH. C1 Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Houston Dept Vet Affairs Med Ctr, Houston, TX USA. RP Ittmann, M (reprint author), Houston VAMC, Res Serv 151, 2002 Holcombe Blvd, Houston, TX 77030 USA. FU NIDDK NIH HHS [R01 DK054170, R01 DK54170] NR 27 TC 73 Z9 79 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 2001 VL 159 IS 1 BP 139 EP 147 DI 10.1016/S0002-9440(10)61681-1 PG 9 WC Pathology SC Pathology GA 448XM UT WOS:000169655300018 PM 11438462 ER PT J AU Sasaki, H Zlatescu, MC Betensky, RA Ino, Y Cairncross, JG Louis, DN AF Sasaki, H Zlatescu, MC Betensky, RA Ino, Y Cairncross, JG Louis, DN TI PTEN is a target of chromosome 10q loss in anaplastic oligodendrogliomas and PTEN alterations are associated with poor prognosis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; GLIOBLASTOMA-MULTIFORME; COCKAYNE-SYNDROME; MALIGNANT ASTROCYTOMAS; MOLECULAR ANALYSIS; PROSTATE-CANCER; HUMAN GLIOMAS; HUMAN BRAIN; MUTATIONS; DELETION AB Allelic loss of 10q is a common genetic event in malignant gliomas, with three 10q tumor suppressor genes, ERCC6, PTEN, and DMBT1, putatively implicated in the most common type of malignant glioma, glioblastoma. Anaplastic oligodendroglioma, another type of malignant glioma, provides a unique opportunity to study the relevance of particular genetic alterations to chemosensitivity and survival. We therefore analyzed these three genes in 72 anaplastic oligodendrogliomas, Deletion mapping demonstrated 10q loss in 14 of 67 Informative cases, with the PTEN and DMBT1 regions involved in all deletions but with the ERCC6 locus spared in two cases. Seven tumors had PTEN gene alterations; two had homozygous DMBT1 deletions, but at least one reflected unmasking of a germline DMBT1 deletion. No mutations were found in ERCC6 exon 2. Chemotherapeutic response occurred in two of the seven tumors with PTEN alterations, but with unexpected short survival times. PTEN gene alterations were not associated with poor therapeutic response in multivariate analysis, but were independently predictive of poor prognosis even after multivariate adjustment for both 10q and 1p loss. In anaplastic oligodendroglioma, therefore, PTEN is a target of 10q loss, and PTEN alterations are associated with poor prognosis, even in chemosensitive cases. C1 Massachusetts Gen Hosp, Mol Neurooncol Lab, Dept Pathol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neurosurg Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Western Ontario, Dept Clin Neurol Sci, London, ON, Canada. Univ Western Ontario, Dept Oncol, London, ON, Canada. London Reg Canc Ctr, London, ON N6A 4L6, Canada. RP Louis, DN (reprint author), Massachusetts Gen Hosp, Mol Neurooncol Lab, Dept Pathol, 149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA57683, R01 CA057683] NR 54 TC 105 Z9 112 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 2001 VL 159 IS 1 BP 359 EP 367 DI 10.1016/S0002-9440(10)61702-6 PG 9 WC Pathology SC Pathology GA 448XM UT WOS:000169655300039 PM 11438483 ER PT J AU Feletou, M Lonchampt, M Coge, F Galizzi, JP Bassoullet, C Merial, C Robineau, P Boutin, JA Huang, PL Vanhoutte, PM Canet, E AF Feletou, M Lonchampt, M Coge, F Galizzi, JP Bassoullet, C Merial, C Robineau, P Boutin, JA Huang, PL Vanhoutte, PM Canet, E TI Regulation of murine airway responsiveness by endothelial nitric oxide synthase SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE epithelium; immunohistochemistry; methacholine; endothelial nitric oxide synthase knockout mice; N-nitro-L-arginine methyl ester; airway reactivity; reverse transcription-polymerase chain reaction; Western blot ID IN-VIVO; GENE-EXPRESSION; NO SYNTHASE; EXHALED AIR; GUINEA-PIGS; HUMAN LUNG; RAT LUNG; EPITHELIUM; LOCALIZATION; MODULATION AB Nitric oxide (NO) is a potent vasodilator, but it can also modulate contractile responses of the airway smooth muscle. Whether or not endothelial (e) NO synthase (NOS) contributes to the regulation of bronchial tone is unknown at present. Experiments were designed to investigate the isoforms of NOS that are expressed in murine airways and to determine whether or not the endogenous release of NO modulates bronchial tone in wild-type mice and in mice with targeted deletion of eNOS [eNOS(-/-)]. The presence of neuronal NOS (nNOS), inducible NOS (iNOS), and eNOS in murine trachea and lung parenchyma was assessed by RT-PCR, immunoblotting, and immunohistochemistry. Airway resistance was measured in conscious unrestrained mice by means of a whole body plethysmography chamber. The three isoforms of NOS were constitutively present in lungs of wild-type mice, whereas only iNOS and nNOS were present in eNOS(-/-) mice. Labeling of nNOS was localized in submucosal airway nerves but was not consistently detected, and iNOS immunoreactivity was observed in tracheal and bronchiolar epithelial cells, whereas eNOS was expressed in endothelial cells. In wild-type mice, treatment with N-nitro-L-arginine methyl ester, but not with aminoguanidine, potentiated the increase in airway resistance produced by inhalation of methacholine. eNOS(-/-) mice were hyperresponsive to inhaled methacholine and markedly less sensitive to N-nitro-L-arginine methyl ester. These results demonstrate that the three NOS isoforms are expressed constitutively in murine lung and that NO derived from eNOS plays a physiological role in controlling bronchial airway reactivity. C1 Inst Rech Servier, F-92150 Suresnes, France. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Canet, E (reprint author), Inst Rech Servier, 11 Rue Moulineaux, F-92150 Suresnes, France. NR 43 TC 33 Z9 33 U1 0 U2 1 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 JUL PY 2001 VL 281 IS 1 BP L258 EP L267 PG 10 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 447AR UT WOS:000169546800032 PM 11404269 ER PT J AU Aschenbach, WG Brower, GL Talmadge, RJ Dobson, JL Gladden, LB AF Aschenbach, WG Brower, GL Talmadge, RJ Dobson, JL Gladden, LB TI Effect of a myocardial volume overload on lactate transport in skeletal muscle sarcolemmal vesicles SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE congestive heart failure; monocarboxylate transporter proteins; monocarboxylate; membrane diffusion ID MYOSIN HEAVY-CHAIN; CHRONIC HEART-FAILURE; SARCOPLASMIC-RETICULUM; GIANT VESICLES; FIBER-TYPE; RAT; EXERCISE; METABOLISM; INCREASES; BINDING AB This study sought to determine the effect of a myocardial volume overload (MVO) on sarcolemmal (SL) lactate (La-) transport and the aerobic profile of skeletal muscle. SL vesicles were obtained from female rats 10 wk after either a MVO was induced by creation of an infrarenal fistula (n = 10), or sham surgeries were performed (n = 11). Influx of C-14-labeled L(+)-La- was measured at various unlabeled La- concentrations under zero-trans conditions. La- transport kinetics were determined using a Michaelis-Menten equation with an added linear component to discriminate between carrier-mediated and diffusional transport. Although heart and lung weights were significantly increased (P < 0.0001) in the MVO group, left ventricular function was only modestly altered (P < 0.05). A significant reduction in type I myosin heavy chain (MHC) in the soleus and a strong trend (P = 0.06) for a reduced type IIx MHC in the plantaris were observed in MVO rats, but no differences in citrate synthase activity or monocarboxylate transporter proteins (MCT)-1 expression were noted in any muscle. Carrier-mediated La- influx into SL vesicles was similar between sham and MVO (K-m =12 +/- 1 and 18 +/- 3 mM; apparent V-max = 772 +/- 99 and 827 +/- 80 nmol.mg(-1).min(-1), respectively). Total influx at 100 mM was lower in MVO, and this was due to a 30% reduction in membrane diffusion. In conclusion, a 10-wk MVO did not alter MCT-mediated La- transport or protein expression but was associated with modest changes in myofibrillar proteins and impaired SL diffusive properties. C1 Auburn Univ, Dept Hlth & Human Performance, Auburn, AL 36849 USA. Auburn Univ, Coll Vet Med, Dept Anat Physiol & Pharmacol, Auburn, AL 36849 USA. Virginia Tech, Dept Human Nutr Foods & Exercise Sci, Blacksburg, VA 24061 USA. RP Aschenbach, WG (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIAMS NIH HHS [1RO1AR-40342] NR 44 TC 5 Z9 5 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD JUL PY 2001 VL 281 IS 1 BP R176 EP R186 PG 11 WC Physiology SC Physiology GA 444DP UT WOS:000169384000021 PM 11404292 ER PT J AU Faraone, SV Doyle, AE Mick, E Biederman, J AF Faraone, SV Doyle, AE Mick, E Biederman, J TI Meta-analysis of the association between the 7-repeat allele of the dopamine D-4 receptor gene and attention deficit hyperactivity disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID HAPLOTYPE-RELATIVE-RISK; III REPEAT POLYMORPHISM; D4 RECEPTOR; DEFICIT/HYPERACTIVITY DISORDER; DRD4 GENE; ADHD; LINKAGE; METAANALYSIS; VARIANTS AB Objective: Family, twin, and adoption studies show attention deficit hyperactivity disorder (ADHD) to have a substantial genetic component. Although several studies have shown an association between ADHD and the 7-repeat allele of the dopamine Dq receptor gene (DRD4), several studies have not. Thus, the status of the ADHD-DRD4 association is uncertain. Method: Meta-analysis was applied to case-control and family-based studies of the association between ADHD and DRD4 to assess the joint evidence for the association, the influence of individual studies, and evidence for publication bias. Results: For both the case-control and family-based studies, the authors found 1) support for the association between ADHD and DRD4, 2) no evidence that this association was accounted for by any one study, and 3) no evidence for publication bias. Conclusions: Although the association between ADHD and DRD4 is small, these results suggest that it is real. Further studies are needed to clarify what variant of DRD4 (or some nearby gene) accounts for this association. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC 725, Child Psychiat Serv, Boston, MA 02114 USA. Massachusetts Mental Hlth Ctr, Harvard Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. RP Faraone, SV (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC 725, Child Psychiat Serv, 15 Parkman St, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [HD-37694]; NIMH NIH HHS [MH-41314, MH-57934, MH-59126] NR 36 TC 476 Z9 491 U1 6 U2 33 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUL PY 2001 VL 158 IS 7 BP 1052 EP 1057 DI 10.1176/appi.ajp.158.7.1052 PG 6 WC Psychiatry SC Psychiatry GA 450YT UT WOS:000169773000010 PM 11431226 ER PT J AU Perry, EK Lee, MLW Martin-Ruiz, CM Court, JA Volsen, SG Merrit, J Folly, E Iversen, PE Bauman, ML Perry, RH Wenk, GL AF Perry, EK Lee, MLW Martin-Ruiz, CM Court, JA Volsen, SG Merrit, J Folly, E Iversen, PE Bauman, ML Perry, RH Wenk, GL TI Cholinergic activity in autism: Abnormalities in the cerebral cortex and basal forebrain SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTORS; MESSENGER-RNA LEVELS; NERVE GROWTH-FACTOR; NEUROTROPHIC FACTOR; HUMAN BRAIN; NEUROCHEMICAL MARKERS; ENZYME-IMMUNOASSAY; BINDING; RATS; SCHIZOPHRENIA AB Objective: Measures of cholinergic transmitter activity were investigated in patients with autism because of reported neuropathological abnormalities in cholinergic nuclei in the basal forebrain. Method: Levels of cholinergic enzyme and receptor activity were measured in the frontal and parietal cerebral cortex of deceased autistic adults, similarly aged normal adults without mental retardation, and nonautistic mentally retarded adults. The immunoreactivity levels of brain-derived neurotrophic factor and nerve growth factor were,measured in the basal forebrain. Results: There were no differences between the autistic and comparison groups in choline acetyltransferase or acetylcholinesterase activity in the cerebral cortex and basal forebrain or in muscarinic Mt receptor or a-bungarotoxin binding within the cortex. Cortical M-1 receptor binding was up to 30% lower than normal in the autistic subjects, and the difference reached significance in the parietal cortex. In both the parietal and frontal cortices, differences in nicotinic receptors assessed by [H-3]epibatidine binding were significant and extensive (65%-73% lower in the autistic group than in the normal subjects); there were no differences in nicotine binding in the basal forebrain. Immunochemical analysis indicated lower levels of both the alpha (4) and beta (2) nicotinic receptor subunits in the parietal cortex. The M1 receptor-abnormality was not evident in the nonautistic group with mental retardation, although the lower [H-3]epibatidine binding was apparent. In the basal forebrain, the level of brain-derived neurotrophic factor in the autistic group was three times as high as the level of the normal group. Conclusions: These neurochemical abnormalities implicate the cholinergic system in developmental disorders such as autism and suggest the potential for intervention based on cholinergic receptor modulation. C1 Newcastle Gen Hosp, Ctr Dev Clin Brain Ageing, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. Univ Arizona, Div Neural Syst Memory & Aging, Tucson, AZ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Childrens Neurol Serv, Boston, MA USA. Cure Autism Now Fdn, Los Angeles, CA USA. Lily Res Ctr, Windlesham, Surrey, England. RP Perry, EK (reprint author), Newcastle Gen Hosp, Ctr Dev Clin Brain Ageing, MRC Bldg, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. NR 53 TC 185 Z9 190 U1 2 U2 12 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUL PY 2001 VL 158 IS 7 BP 1058 EP 1066 DI 10.1176/appi.ajp.158.7.1058 PG 9 WC Psychiatry SC Psychiatry GA 450YT UT WOS:000169773000011 PM 11431227 ER PT J AU Philbin, EF McCullough, PA DiSalvo, TG Dec, GW Jenkins, PL Weaver, WD AF Philbin, EF McCullough, PA DiSalvo, TG Dec, GW Jenkins, PL Weaver, WD TI Underuse of invasive procedures among Medicaid patients with acute myocardial infarction SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CORONARY ANGIOGRAPHY; CARDIAC PROCEDURES; RESOURCE UTILIZATION; UNITED-STATES; REVASCULARIZATION PROCEDURES; CARDIOVASCULAR PROCEDURES; ELDERLY PATIENTS; MANAGED CARE; HEALTH-CARE; OUTCOMES AB Objectives. The purpose of this study was to determine whether underuse of cardiac procedures among Medicaid patients with acute myocardial infarction is explained by or is independent of fundamental differences in age, race, or sex distribution; income, coexistent illness; or location of care. Methods. Administrative data from 226 hospitals in New York were examined for 11579 individuals hospitalized with a primary diagnosis of acute myocardial infarction. Use of various cardiac procedures was compared among Medicaid patients and patients with other forms of insurance. Results. Medicaid patients were older, were more frequently African American and female, and had lower median household incomes. They also had a higher prevalence of hypertension, diabetes, lung disease, renal disease, and peripheral vascular disease. After adjustment for these and other factors, Medicaid patients were less likely to undergo cardiac catheterization, percutaneous transluminal coronary angioplasty, and any revascularization procedure. Conclusions Factors other than age, race, sex, income, coexistent illness, and location of care account for lower use of invasive procedures among Medicaid patients. The influence of Medicaid insurance on medical practice and process of care deserves investigation. C1 Albany Med Coll, Div Cardiol, Albany, NY 12208 USA. Univ Missouri, Sch Med, Truman Med Ctr, Cardiol Sect, Kansas City, MO 64108 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Mary Imogene Bassett Res Inst, Cooperstown, NY USA. Henry Ford Heart & Vasc Inst, Div Cardiovasc Med, Detroit, MI USA. RP Philbin, EF (reprint author), Albany Med Coll, Div Cardiol, Mail Code 44,47 New Scotland Ave, Albany, NY 12208 USA. NR 41 TC 20 Z9 20 U1 1 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 2001 VL 91 IS 7 BP 1082 EP 1088 DI 10.2105/AJPH.91.7.1082 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 461BR UT WOS:000170345500017 PM 11441735 ER PT J AU Mullins, ME Chao, S Ochoa, ER Slanetz, PJ AF Mullins, ME Chao, S Ochoa, ER Slanetz, PJ TI Radiologic-Pathologic Conferences of the Massachusetts General Hospital - Ovarian carcinoma SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Mullins, ME (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Founders House, Boston, MA 02114 USA. NR 3 TC 1 Z9 1 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 JUL PY 2001 VL 177 IS 1 BP 130 EP 130 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 445LA UT WOS:000169457900025 PM 11418412 ER PT J AU Varghese, JC O'Neill, MJ Gervais, DA Boland, GW Mueller, PR AF Varghese, JC O'Neill, MJ Gervais, DA Boland, GW Mueller, PR TI Interventional Radio Case Conference - Massachusetts General Hospital - Transvaginal catheter drainage of tuboovarian abscess using the trocar method: Technique and literature review SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID SONOGRAPHICALLY GUIDED ASPIRATION; PELVIC ABSCESSES; FLUID COLLECTIONS; PERCUTANEOUS DRAINAGE; ULTRASOUND; GUIDANCE; NEEDLE C1 Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Mueller, PR (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 21 TC 14 Z9 17 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 JUL PY 2001 VL 177 IS 1 BP 139 EP 144 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 445LA UT WOS:000169457900028 PM 11418415 ER PT J AU Moy, L Slanetz, PJ Yeh, ED Moore, R Rafferty, E McCarthy, KA Hall, D Kopans, DB AF Moy, L Slanetz, PJ Yeh, ED Moore, R Rafferty, E McCarthy, KA Hall, D Kopans, DB TI The pendent view: An additional projection to confirm the diagnosis of milk of calcium SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Roentgen-Ray-Society CY MAY 08, 2000 CL WASHINGTON, D.C. SP Amer Roentgen Ray Soc ID BENIGN BREAST CYSTS C1 Massachusetts Gen Hosp, Dept Breast Imaging, Boston, MA 02114 USA. RP Moy, L (reprint author), Massachusetts Gen Hosp, Dept Breast Imaging, ACC-219,55 Fruit St, Boston, MA 02114 USA. OI Slanetz, Priscilla/0000-0003-1248-5116 NR 6 TC 4 Z9 4 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2001 VL 177 IS 1 BP 173 EP 175 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 445LA UT WOS:000169457900033 PM 11418421 ER PT J AU Chung, RT Feng, S Delmonico, FL AF Chung, RT Feng, S Delmonico, FL TI Approach to the management of allograft recipients following the detection of hepatitis B virus in the prospective organ donor SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE donor; HBV; heart; kidney; liver; transplantation ID LIVER-TRANSPLANT RECIPIENTS; ANTIBODY-POSITIVE DONORS; CORE ANTIGEN; IMMUNE GLOBULIN; COMBINATION LAMIVUDINE; INFECTION; TRANSMISSION; DISEASE; RISK; REINFECTION AB Hepatitis B virus (HBV) is a highly infectious blood-borne pathogen that can be transmitted by a solid organ allograft and result in substantial morbidity and mortality. Recent advances in the management of HBV infection prompt a reappraisal of the approach to the management of allograft recipients from cadaver donors previously exposed to HBV, because of the ongoing shortage of organ donors. This report reviews current knowledge regarding the risk of HBV transmission by an organ from cadaver donors testing positive for markers of HBV infection and makes recommendations for the evaluation, treatment, and surveillance of the allograft recipients. C1 Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Transplant Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. New England Organ Bank Inc, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. NR 33 TC 52 Z9 54 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 JUL PY 2001 VL 1 IS 2 BP 185 EP 191 DI 10.1034/j.1600-6143.2001.10214.x PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA 514XP UT WOS:000173466600013 PM 12099368 ER PT J AU Greenberg, SM Cohen, AS AF Greenberg, SM Cohen, AS TI Cerebral amyloid angiopathy - Papers presented at the First International Conference on Cerebral Amyloid Angiopathy, Boston, MA, October 5-6, 2000 - Introduction SO AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Med, Amyloid Program, Boston, MA 02118 USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Wang ACC 836, Boston, MA 02114 USA. NR 0 TC 18 Z9 18 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP PI CARNFORTH LANCASHIRE PA CASTERTON HALL, CARNFORTH LANCASHIRE LA6 2LA, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-J. Protein Fold. Disord. PD JUL PY 2001 VL 8 SU 1 BP 1 EP 1 PG 1 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 480VN UT WOS:000171483600001 ER PT J AU Rebeck, GW Cho, HS Grabowski, TJ Greenberg, SM AF Rebeck, GW Cho, HS Grabowski, TJ Greenberg, SM TI The effects of A beta PP mutations and APOE polymorphisms on cerebral amyloid angiopathy SO AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS LA English DT Article; Proceedings Paper CT 1st International Conference on Cerebral Amyloid Angiopathy (CAA) CY OCT 05-06, 2000 CL BOSTON, MASSACHUSETTS SP Neurochem Inc, Massachusetts Gen Hosp DE genetics; Alzheimer's disease; immunohistochemistry; lipoprotein ID APOLIPOPROTEIN-E EPSILON-2; ALZHEIMERS-DISEASE; PROTEIN-PRECURSOR; TYPE-4 ALLELE; DEPOSITION; HEMORRHAGE; RECEPTOR; PEPTIDE; CELLS; ACCUMULATION AB Analysis of causative mutations and genetic risk factors aid in the understanding of important processes of cerebral amyloid angiopathy, (CAA) in humans. We identified a initiation at a novel site of the beta -amyloid precursor protein (A beta PP) gene associated with familial CAA; this initiation causes an aspartate to asparagine substitution at position 23 of the A beta peptide. Neuropathological analysis of a 68-year-old man with this mutation showed dramatic A beta deposition in blood vessels, diffuse parenchymal A beta deposits, dystrophic neurites and neurofibrillary, tangles. The A beta deposition showed complete co-localization of A beta 40 and A beta 42, compared to the predominant A beta 42 deposition seen in AD. We hypothesize that the loss of an acidic residue at position 23 of A beta might be important in the process of A beta aggregation on smooth muscle cells on the cerebrovasculature. We also analyzed how the apolipoprotein E (APOE) gene might influence aggregation of A beta by examining the physical association of apoE domains with A beta via immunohistochemistry We found that the lipid-binding domain of apoE was more strongly, associated with A beta than the receptor binding domain, and that 40% of all A beta deposits had no apoE bound to them, We suggest that the initial deposition of A beta occurs in the absence of apoE, and that the process of A beta deposit growth or stabilization is apoE-dependent. C1 Massachusetts Gen Hosp, Alzheimer Res Unit, Charlestown, MA 02129 USA. Univ Iowa, Coll Med, Dept Neurol, Iowa City, IA USA. Univ Iowa, Coll Med, Dept Radiol, Iowa City, IA USA. RP Rebeck, GW (reprint author), Massachusetts Gen Hosp, Alzheimer Res Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG05134, AG12406, AG00725] NR 29 TC 2 Z9 2 U1 0 U2 1 PU PARTHENON PUBLISHING GROUP PI CARNFORTH LANCASHIRE PA CASTERTON HALL, CARNFORTH LANCASHIRE LA6 2LA, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-J. Protein Fold. Disord. PD JUL PY 2001 VL 8 SU 1 BP 43 EP 47 PG 5 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 480VN UT WOS:000171483600007 PM 11676289 ER PT J AU Christie, R Kimchi, E Kajdasz, S Bacskai, B Hyman, BT AF Christie, R Kimchi, E Kajdasz, S Bacskai, B Hyman, BT TI Multiphoton microscopy and amyloid angiopathy SO AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS LA English DT Article; Proceedings Paper CT 1st International Conference on Cerebral Amyloid Angiopathy (CAA) CY OCT 05-06, 2000 CL BOSTON, MASSACHUSETTS SP Neurochem Inc, Massachusetts Gen Hosp DE multiproton microscopy; amyloid angiopathy ID TRANSGENIC MICE AB The underlying pathophysiological processes of amyloid angiopathy, have been difficult to study because the vessel size affected is too small for imaging in the human condition, and animal models have not yet been adequately developed or characterized. Herein we present characterization of animal models of overexpression of the human A beta PP gene, initially developed as models of Alzheimer disease, but which fortuitously also develop marked cerebral amyloid angiopathy We also present a novel form of microscopy that allows in vivo imaging of vessels affected by amyloid in the anesthetized, but intact, animal. C1 Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Unit, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG08487] NR 6 TC 5 Z9 5 U1 0 U2 1 PU PARTHENON PUBLISHING GROUP PI CARNFORTH LANCASHIRE PA CASTERTON HALL, CARNFORTH LANCASHIRE LA6 2LA, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-J. Protein Fold. Disord. PD JUL PY 2001 VL 8 SU 1 BP 48 EP 50 PG 3 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 480VN UT WOS:000171483600008 PM 11676290 ER PT J AU Greenberg, SM Rosand, J AF Greenberg, SM Rosand, J TI Outcome markers for clinical trials in cerebral amyloid angiopathy SO AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS LA English DT Article; Proceedings Paper CT 1st International Conference on Cerebral Amyloid Angiopathy (CAA) CY OCT 05-06, 2000 CL BOSTON, MASSACHUSETTS SP Neurochem Inc, Massachusetts Gen Hosp DE beta-amyloid; intracerebral hemorrhage; MRI; surrogate markers ID INTRACEREBRAL HEMORRHAGE; LOBAR HEMORRHAGE; MRI AB Determining the effectiveness of candidate treatments for preventing hemorrhagic strokes caused by cerebral amyloid angiopathy will require clinical drug trials. This article explores two potential outcome markers for such trials: (1) clinical recurrence of hemorrhagic stroke, and (2) the appearance of small, clinically silent hemorrhagic lesions on gradient-echo MRI. Using pilot data from our cohort of survivors of lobar hemorrhage, we estimated the sample sizes required to demonstrate efficacy with each of these outcome markers as the study endpoint. A study with recurrent hemorrhagic stroke as the endpoint was estimated to require 145 patients per treatment arm to demonstrate a 50% reduction in the recurrence rate over a 24-month follow-tip period, while a study using new hemorrhagic lesions on MRI was estimated to require 70 patients per arm for a 17-month follow-up interval. The required sample sizes could be further reduced (to 105 and 52 patients, respectively) by limiting the analysis to those at highest risk of recurrence, defined according to apolipoprotein E genotype or the presence of more than one hemorrhagic lesion at study entry. This analysis suggests that radiographic detection of small hemorrhages may be an efficient surrogate endpoint for pilot trials of promising therapeutic approaches to cerebral amyloid angiopathy. C1 Massachusetts Gen Hosp, Dept Neurol, Clin Trials Unit, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA 02114 USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Clin Trials Unit, Wang ACC 836, Boston, MA 02114 USA. FU NIA NIH HHS [AG00725] NR 16 TC 6 Z9 6 U1 0 U2 2 PU PARTHENON PUBLISHING GROUP PI CARNFORTH LANCASHIRE PA CASTERTON HALL, CARNFORTH LANCASHIRE LA6 2LA, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-J. Protein Fold. Disord. PD JUL PY 2001 VL 8 SU 1 BP 56 EP 60 PG 5 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 480VN UT WOS:000171483600010 PM 11676292 ER PT J AU Thomas, PS Kasahara, H Edmonson, AM Izumo, S Yacoub, MH Barton, PJR Gourdie, RG AF Thomas, PS Kasahara, H Edmonson, AM Izumo, S Yacoub, MH Barton, PJR Gourdie, RG TI Elevated expression of Nkx-2.5 in developing myocardial conduction cells SO ANATOMICAL RECORD LA English DT Article DE Nkx-2.5; Csx; conduction system; Purkinje fiber; myocardium; chicken embryo; human; fetus; differentiation; gene expression ID PURKINJE-FIBER DIFFERENTIATION; HOMEOBOX GENE CSX/NKX2.5; HEART; SYSTEM; ENDOTHELIN; CHICK; INDUCTION; TINMAN; HYPERTROPHY; MUTATIONS AB A number of different phenotypes emerge from the mesoderm-derived cardiomyogenic cells of the embryonic tubular heart, including those comprising the cardiac conduction system. The transcriptional regulation of this phenotypic divergence within the cardiomyogenic lineage remains poorly characterized. A relationship between expression of the transcription factor Nkx-2.5 and patterning to form cardiogenic mesoderm subsequent to gastrulation is well established. Nkx-2.5 mRNA continues to be expressed in myocardium beyond the looped, tubular heart stage. To investigate the role of Nkx-2.5 in later development, we have determined the expression pattern of Nkx-2.5 mRNA by in situ hybridization in embryonic chick, fetal mouse, and human hearts, and of Nkx-2.5 protein by immunolocalization in the embryonic chick heart. As development progresses, significant nonuniformities emerge in Nkx-2.5 expression levels. Relative to surrounding force-generating ("working") myocardium, elevated Nkx-2.5 mRNA signal becomes apparent in the specialized cells of the conduction system. Similar differences are found in developing chick, human, and mouse fetal hearts, and nuclear-localized Nkx-2.5 protein is prominently expressed in differentiating chick conduction cells relative to adjacent working myocytes. This tissue-restricted expression of Nkx-2.5 is transient and correlates with the timing of spatio-temporal recruitment of cells to the central and the peripheral conduction system. Our data represent the first report of a transcription factor showing a stage-dependent restriction to different parts of the developing conduction system, and suggest some commonality in this development between birds and mammals. This dynamic pattern of expression is consistent with the hypothesis that Nkx-2.5, and its level of expression, have a role in regulation and/or maintenance of specialized fate selection by embryonic myocardial cells. Anat Rec 263:307-313, 2001. (C) 2001 Wiley-Liss, Inc. C1 Natl Heart & Lung Inst, Dept Cardiothorac Surg, Imperial Coll Sch Med, London SW3 6LY, England. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Med Univ S Carolina, Cardiovasc Dev Biol Ctr, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Thomas, PS (reprint author), Natl Heart & Lung Inst, Dept Cardiothorac Surg, Imperial Coll Sch Med, Dovehouse St, London SW3 6LY, England. FU NHLBI NIH HHS [HL56728] NR 40 TC 46 Z9 52 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 0003-276X J9 ANAT REC JI Anat. Rec. PD JUL 1 PY 2001 VL 263 IS 3 BP 307 EP 313 DI 10.1002/ar.1106 PG 7 WC Anatomy & Morphology SC Anatomy & Morphology GA 448DT UT WOS:000169609300009 PM 11455540 ER PT J AU He, YL Seno, H Tsujimoto, S Tashiro, C AF He, YL Seno, H Tsujimoto, S Tashiro, C TI The effects of uterine and umbilical blood flows on the transfer of propofol across the human placenta during in vitro perfusion SO ANESTHESIA AND ANALGESIA LA English DT Article ID ELECTIVE CESAREAN-SECTION; INTRAVENOUS PROPOFOL; PROTEIN-BINDING; IN-VITRO; FETAL PH; ANESTHESIA; INDUCTION; THIOPENTONE; DRUG; HEMODYNAMICS AB The safety of using propofol in parturients is controversial, and little information is available on the factors that influence the placental transfer of propofol. In this study, we investigated the effects of uterine and umbilical blood flows on the placental transfer of propofol by using the dually perfused human placental cotyledon. Placental transfer was evaluated on the basis of the placental clearances at various uterine and umbilical flow rates. The placental transfer of propofol was significantly facilitated by the increased uterine flow rates over the range from 7.5 to 25 mL/min. The placental clearances of propofol were also dependent on the umbilical flow rates over the range from 0.5 to 4.0 mL/min. In contrast, the placental transfer of antipyrine was flow dependent when the umbilical flow rate was <2.0 mL/min and became permeability limited when it was >2.0 mL/min. No differences in either maternal or fetal venous concentrations of propofol were observed as umbilical flow rates varied from 0.5 to 4.0 mL/min, suggesting that an equilibrium across the placenta occurs at low flow rates. These results indicate that fetal uptake of propofol can be profoundly altered by the changes in both uterine and umbilical blood flows observed in various pathophysiologic conditions and that lipid solubility greatly influences placental transfer of drugs. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Hyogo Coll Med, Dept Anaesthesiol, Nishinomiya, Hyogo, Japan. RP He, YL (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. NR 33 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUL PY 2001 VL 93 IS 1 BP 151 EP 156 PG 6 WC Anesthesiology SC Anesthesiology GA 448TK UT WOS:000169645900030 PM 11429356 ER PT J AU Scheller, M Forman, SA AF Scheller, M Forman, SA TI The gamma subunit determines whether anesthetic-induced leftward shift is altered by a mutation at alpha(1)S270 in alpha(1)beta(2)gamma(2L) GABA(A) receptors SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting American-Society-of-Anesthesiology CY OCT 14-18, 2000 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Anesthesiol ID A RECEPTOR; VOLATILE ANESTHETICS; ACID; ISOFLURANE; PROPOFOL; SITES; CURRENTS; STOICHIOMETRY; POTENTIATION; MODULATION AB Background: A major action of volatile anesthetics is enhancement of gamma -aminobutyric acid receptor type A (GABA(A)R) currents. In recombinant GABA(A)Rs consisting of several subunit mixtures, mutating the cu, subunit serine at position 270 to isoleucine [alpha (1)(S270I)] was reported to eliminate anesthetic-induced enhancement at low GABA concentrations. In the absence of studies at high GABA concentrations, it remains unclear whether alpha (1)(S270I) affects enhancement versus inhibition by volatile anesthetics. Furthermore, the majority of GABA,Rs in mammalian brain are thought to consist of alpha (1), beta (2), and gamma (2) subunits, and the alpha (1)(S270I) mutation has not been studied in the context of this combination. Methods: Recombinant GABA(A)Rs composed of alpha (1)beta (2) or alpha (1)beta (2)gamma (21) subunit mixtures were studied electrophysiologically in whole Xenopus oocytes in the voltage clamp configuration. Currents elicited by GABA (0.03 muM to 1 mM) were measured in the absence and presence of isoflurane or halothane, Anesthetic effects on GABA concentration responses were evaluated for individual oocytes. Results: In wild-type alpha (1)beta (2)gamma (21) GABA(A), anesthetics at approximately 2 minimum alveolar concentration (MAC) shifted GABA concentration response curves to the left approximately threefold, decreased the Hill coefficient, and enhanced currents at all GABA concentrations. The alpha (1)(S270I) mutation itself rendered the GABA,R more sensitive to GABA and reduced the Hm coefficient. At low GABA concentrations (EC5), anesthetic enhancement of peak current was much smaller in alpha (1)(S270I)beta (2)gamma (21), versus wild-type channels. Paradoxically, the leftward shift of the whole GABA concentration-response relation by anesthetics was the same in both mutant and wild-type channels. At high GABA concentrations, volatile anesthetics reduced currents in alpha (1)(S270I)beta (2)gamma (21), GABA(A)Rs. In parallel studies on alpha (1)beta (2) (gamma -less) GABA,Rs, anesthetic-induced leftward shifts in wild-type receptors were more than eightfold at 2 MAC, and the alpha (1)(S270I) mutation nearly eliminated anesthetic-induced leftward shift. Conclusions The results support a role for alpha (1)S270 in alpha (1)beta (2)gamma (21) GABA(A)R gating and sensitivity to inhibition by volatile anesthetics. The alpha (1)S270 locus also modulates anesthetic enhancement in alpha (1)beta (2) GABA(A)R, The presence of the gamma (21) subunit reduces anesthetic-induced left shift of wild-type GABA,R and nullifies the impact of the alpha (1)(S270I) mutation on anesthetic modulation, Thus, the gamma (21) subunit plays a significant role in (;ABA,R modulation by volatile anesthetic compounds. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Clin 3, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Forman, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Clin 3, 55 Fruit St, Boston, MA 02114 USA. FU NIGMS NIH HHS [P01-GM58448] NR 32 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUL PY 2001 VL 95 IS 1 BP 123 EP 131 DI 10.1097/00000542-200107000-00022 PG 9 WC Anesthesiology SC Anesthesiology GA 448YN UT WOS:000169657700018 PM 11465549 ER PT J AU Woolf, CJ Max, MB AF Woolf, CJ Max, MB TI Mechanism-based pain diagnosis - Issues for analgesic drug development SO ANESTHESIOLOGY LA English DT Editorial Material ID RANDOMIZED CONTROLLED TRIAL; POSTHERPETIC NEURALGIA; DIABETIC NEUROPATHY; CENTRAL SENSITIZATION; ENRICHED ENROLLMENT; POSTOPERATIVE PAIN; HIV-INFECTION; AMITRIPTYLINE; EFFICACY; SYMPTOMS C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 149 13th St,Room 4310, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS 38253-01] NR 49 TC 158 Z9 160 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUL PY 2001 VL 95 IS 1 BP 241 EP 249 DI 10.1097/00000542-200107000-00034 PG 9 WC Anesthesiology SC Anesthesiology GA 448YN UT WOS:000169657700030 PM 11465563 ER PT J AU Cho, EY Stampfer, MJ Seddon, JM Hung, S Spiegelman, D Rimm, EB Willett, WC Hankinson, SE AF Cho, EY Stampfer, MJ Seddon, JM Hung, S Spiegelman, D Rimm, EB Willett, WC Hankinson, SE TI Prospective study of zinc intake and the risk of age-related macular degeneration SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE age-related macular degeneration; food-frequency questionnaire; health professionals follow-up study; men; nurses' health study; prospective studies; women; zinc intake ID RETINAL-PIGMENT EPITHELIUM; TOTAL-ENERGY-INTAKE; BEAVER DAM EYE; ORAL ZINC; MACULOPATHY; ANTIOXIDANT; DISEASE; HEALTH AB PURPOSE: Zinc is found in high concentrations in the retina and is hypothesized to reduce the risk of age-related macular degeneration (AMD). Any long-term benefit associated with dietary zinc intake has nor been evaluated. METHODS: We followed 66,572 women and 37,636 men who were greater than or equal to 50 years old and had no diagnosis of AMD or cancer. Zinc intake from food, multivitamins, and supplements was assessed with a semiquantitative food-frequency questionnaire at baseline (in 1984 for women and in 1986 for men) and repeated during follow-up (twice for women, once for men). RESULTS: During 10 years of follow-up for women and 8 years of follow-up for men, we confirmed 384 incident cases of AMD (195 cases of the early form and 189 cases of the late form) associated with a visual acuity loss of 20/30 or worse. After multivariate adjustment for potential risk factors, the pooled relative risk was 1.13 (95% confidence interval [CI], 0.82 to 1.57; p-value, test for trend, 0.74) among participants in the highest quintile of total zinc intake (energy-adjusted median; 25.5 mg/day for women and 40.1 mg/day for men) compared with those in the lowest quintile (energy-adjusted median; 8.5 mg/day for women and 9.9 mg/day for men). The relative risk for highest compared with lowest quintile was 1.04 (95% CI, 0.59 to 1.83; e-value, test for trend, 0.54) for zinc intake from food. Subjects who took zinc supplements had a pooled multivariate relative risk of 1.04 (95% CI, 0.75 to 1.45). CONCLUSIONS: In these two large prospective studies, moderate zinc intake, either in food or in supplements, was not associated with a reduced risk of AMD. Ann Epidemiol 2001;11:328-336, (C) 2001 Elsevier Science Inc. All rights reserved. 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 Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Epidemiol Unit, Boston, MA 02115 USA. RP Cho, EY (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA 40356, CA 55075]; NEI NIH HHS [EY 09611]; NHLBI NIH HHS [HL 35464] NR 27 TC 38 Z9 40 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JUL PY 2001 VL 11 IS 5 BP 328 EP 336 DI 10.1016/S1047-2797(01)00217-4 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 438CQ UT WOS:000169036500008 PM 11399447 ER PT J AU Au, DH Curtis, JR Psaty, BM AF Au, DH Curtis, JR Psaty, BM TI Risk of myocardial ischaemia and beta-adrenoceptor agonists SO ANNALS OF MEDICINE LA English DT Editorial Material DE beta-adrenoceptor; beta-agonists; cardiovascular disease; obstructive pulmonary disease ID PRESCRIBED FENOTEROL; CARDIAC DEATH; NEW-ZEALAND; ASTHMA; BRONCHODILATORS; DESENSITIZATION; TERBUTALINE; ASSOCIATION; SALBUTAMOL; SAFETY AB Modern therapy for both cardiovascular disease and obstructive lung disease involves diametrically opposed manipulations of the beta-adrenoceptor, Beta-agonists reduce airflow limitation and improve symptoms among patients with obstructive lung disease while beta-blockers reduce symptoms, recurrent myocardial ischaemia and all-cause mortality among patients with ischaemic heart disease. There is biological plausibility for beta-agonists leading to adverse cardiovascular outcomes, and observational trials have raised concern about the safety of beta-agonists among patients with cardiovascular disease. Although there are many potential causal and noncausal explanations for these observational findings, the implications from these studies are the same. Physicians should be careful when prescribing beta-agonists for patients at risk for ischaemic heart disease. Furthermore, careful consideration should be given to distinguish symptoms caused by cardiovascular versus respiratory aetiologies. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev 152, Dept Vet Affairs, Seattle, WA 98108 USA. Univ Washington, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA. Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98195 USA. RP Au, DH (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev 152, Dept Vet Affairs, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 30 TC 5 Z9 5 U1 0 U2 1 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1M 8AE, ENGLAND SN 0785-3890 J9 ANN MED JI Ann. Med. PD JUL PY 2001 VL 33 IS 5 BP 287 EP 290 DI 10.3109/07853890109002080 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 454GC UT WOS:000169964000001 PM 11491185 ER PT J AU Andreassen, OA Ferrante, RJ Huang, HM Dedeoglu, A Park, L Ferrante, KL Kwon, J Borchelt, DR Ross, CA Gibson, GE Beal, MF AF Andreassen, OA Ferrante, RJ Huang, HM Dedeoglu, A Park, L Ferrante, KL Kwon, J Borchelt, DR Ross, CA Gibson, GE Beal, MF TI Dichloroacetate exerts therapeutic effects in transgenic mouse models of Huntington's disease SO ANNALS OF NEUROLOGY LA English DT Article ID PYRUVATE-DEHYDROGENASE; ENERGY-METABOLISM; INTRANUCLEAR INCLUSIONS; IN-VIVO; MICE; DYSFUNCTION; IMPAIRMENT; EXPRESSION; REPEAT; BRAIN AB Dichloroacetate (DCA) stimulates pyruvate dehydrogenase complex (PDHC) activity and lowers cerebral lactate concentrations. In the R6/2 and N171-82Q transgenic mouse models of Huntington's disease (HD), DCA significantly increased survival, improved motor function, delayed loss of body weight, attenuated the development of striatal neuron atrophy, and prevented diabetes. The percentage of PDHC in the active form was significantly reduced in R6/2 mice at 12 weeks of age, and DCA ameliorated the deficit. These results provide further evidence for a role of energy dysfunction in HD pathogenesis and suggest that DCA may exert therapeutic benefits in HD. C1 Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, Dept Neurol & Neurosci, New York, NY 10021 USA. Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Bedford VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bedford, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Johns Hopkins Med Sch, Dept Pathol, Baltimore, MD USA. Burke Med Res Inst, White Plains, NY USA. RP Beal, MF (reprint author), Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, Dept Neurol & Neurosci, 525 E 68th St, New York, NY 10021 USA. RI Ross, Christopher/H-8395-2013 FU NINDS NIH HHS [NS35255, NS37102, NS38180] NR 21 TC 44 Z9 46 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUL PY 2001 VL 50 IS 1 BP 112 EP 117 DI 10.1002/ana.1085 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 447FR UT WOS:000169561300015 PM 11456300 ER PT J AU Werber, YB Wright, CD AF Werber, YB Wright, CD TI Massive hemoptysis from a lung abscess due to retained gallstones SO ANNALS OF THORACIC SURGERY LA English DT Article ID LAPAROSCOPIC CHOLECYSTECTOMY; LOST GALLSTONES; CHOLELITHOPTYSIS AB This case report describes a subhepatic abscess from spilled gallstones which eroded through the diaphragm causing a right lower lobe pulmonary abscess and presenting as massive hemoptysis. (C) 2001 by The Society of Thoracic Surgeons. C1 Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA. RP Wright, CD (reprint author), Massachusetts Gen Hosp, Dept Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. NR 6 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 2001 VL 72 IS 1 BP 278 EP 279 DI 10.1016/S0003-4975(00)02563-7 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 453FU UT WOS:000169906500076 PM 11465203 ER PT J AU Sheehan, MK Shireman, PK Littooy, FN Baker, VH AF Sheehan, MK Shireman, PK Littooy, FN Baker, VH TI Ureteral injury during aortic aneurysm repair by the retroperitoneal approach SO ANNALS OF VASCULAR SURGERY LA English DT Article ID VASCULAR-SURGERY AB Three ureteral injuries (two proximal, one middle) associated with retroperitoneal repair of aortic abdominal aneurysms are reported. The authors believe these represent traction injuries that are related to the use of stationary retractors and suggest that complete anterior mobilization of the left kidney from its posterior fossa will decrease the odds of such an injury. C1 Loyola Univ, Med Ctr, Dept Surg, Div Peripheral Vasc Surg, Maywood, IL 60153 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Surg, Hines, IL 60141 USA. RP Baker, VH (reprint author), Loyola Univ, Med Ctr, Dept Surg, Div Peripheral Vasc Surg, 2160 S 1st Ave, Maywood, IL 60153 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD JUL PY 2001 VL 15 IS 4 BP 481 EP 484 DI 10.1007/s100160010125 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 464BK UT WOS:000170512700013 PM 11525541 ER PT J AU Lewis, VO O'Reilly, MS Gehrmann, M Llinas, M Schaller, J Weissbach, L AF Lewis, VO O'Reilly, MS Gehrmann, M Llinas, M Schaller, J Weissbach, L TI Inhibition of tumor growth by plasminogen-related protein-B SO ANTICANCER RESEARCH LA English DT Article DE plasminogen-related protein-B; plasminogen-activation peptide; tumor; recombinant protein ID KRINGLE DOMAINS; HUMAN ANGIOSTATIN; ANGIOGENESIS; GENE; CARTILAGE; CANCER; CELLS; SUPPRESSION; EXPRESSION; FAMILY AB Background: Various fragments of the fibrinolytic protein plasminogen can act as antiangiogenic factors and inhibit the growth of primary and metastatic tumors in mice. Plasminogen-related gene-B encodes a putative 9 kDa protein virtually identical to the plasminogen N-terminal activation peptide, a 77-amino acid motif that is liberated from the parent plasminogen molecule during conversion to the serine proteinase plasmin. Previous data have documented enhanced transcription of plasminogen-related gene-B in neoplastic tissues. Materials and Methods: We have tested the effects of recombinant versions of plasminogen-related protein-B and the plasminogen N-terminal activation peptide on the growth of tumors in mice, employing murine tumor cell lines implanted subcutaneously. Results: The recombinant plasminogen-related protein-B significantly inhibited the growth of primary tumors in mice, while recombinant plasminogen N-terminal activation peptide elicited only a slight inhibition of tumor growth. Conclusion: These data suggest that plasminogen-related protein-B may have utility as a novel cancer therapeutic. C1 Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Cellular Biol, Boston, MA 02115 USA. Childrens Hosp, Dept Surg, Boston, MA 02114 USA. Carnegie Mellon Univ, Dept Chem, Pittsburgh, PA 15213 USA. Univ Bern, Dept Chem & Biochem, CH-3012 Bern, Switzerland. RP Weissbach, L (reprint author), Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-29409] NR 21 TC 6 Z9 6 U1 1 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JUL-AUG PY 2001 VL 21 IS 4A BP 2287 EP 2291 PG 5 WC Oncology SC Oncology GA 489GY UT WOS:000171984700006 PM 11724284 ER PT J AU Song, LX Xu, MF Lopes-Virella, MF Huang, Y AF Song, LX Xu, MF Lopes-Virella, MF Huang, Y TI Quercetin inhibits matrix metalloproteinase-1 expression in human vascular endothelial cells through extracellular signal-regulated kinase SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE metalloproteinase; expression; quercetin; endothelium ID ACUTE CORONARY SYNDROMES; PROTEIN-KINASE; ATHEROSCLEROTIC PLAQUE; TISSUE INHIBITORS; OXIDIZED LDL; FLAVONOIDS; NEOVASCULARIZATION; KERATINOCYTES; COLLAGENASE; ANTIOXIDANT AB Studies have shown that intake of quercetin was inversely associated with mortality from coronary heart disease. Since recent studies documented that disruption of atherosclerotic plaques is the key event triggering acute myocardial infarction, and vascular endothelium-derived matrix metalloproteinase-1 (MMP-1) contributes to plaque destabilization, we examined the effect of quercetin on MMP-1 expression in human vascular endothelial cells. Our results showed that quercetin significantly inhibited basal and oxidized LDL (oxLDL)-stimulated MMP-1 expression. Our data also indicated that extracellular signal-regulated kinase (ERK) mediated the basal and oxLDL-stimulated expression of MMP-1, and quercetin is a potent inhibitor of ERK, suggesting that quercetin may inhibit MMP-1 expression by blocking the ERK pathway. Finally, we showed that quercetin stimulated tissue inhibitor of metalloproteinase-l expression in oxLDL- and PMA-treated cells. In conclusion, the present study demonstrated for the first time that quercetin inhibited MMP-1 expression in vascular endothelial cells, suggesting that quercetin might contribute to plaque stabilization. (C) 2001 Academic Press. C1 Ralph H Johnson Vet Adm Med Ctr, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. RP Huang, Y (reprint author), Ralph H Johnson Vet Adm Med Ctr, Charleston, SC 29401 USA. NR 35 TC 22 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL 1 PY 2001 VL 391 IS 1 BP 72 EP 78 DI 10.1006/abbi.2001.2402 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 449RD UT WOS:000169700200010 PM 11414687 ER PT J AU Busam, KJ Hester, K Charles, C Sachs, DL Antonescu, CR Gonzalez, S Halpern, AC AF Busam, KJ Hester, K Charles, C Sachs, DL Antonescu, CR Gonzalez, S Halpern, AC TI Detection of clinically amelanotic malignant melanoma and assessment of its margins by in vivo confocal scanning laser microscopy SO ARCHIVES OF DERMATOLOGY LA English DT Article ID IN-VIVO; ROUTINE HISTOLOGY; HUMAN SKIN; CONTRAST; DISEASE AB Background: Near-infrared confocal scanning laser microscopy (CSLM) represents a novel imaging technique for in vivo microscopic analysis of skin lesions, including pigmented lesions. Objectives: To investigate the feasibility of detecting a clinically amelanotic malignant cutaneous melanoma using CSLM and to explore the use of this technique for assessing its margins. Patients and Methods: Two lesions from 2 patients were imaged and analyzed using CSLM. Sites suspected to represent melanoma or benign skin on CSLM were marked as such; then. biopsy specimens were obtained for diagnosis using conventional histological analysis. Both lesions were stained for melanin pigment and analyzed immunohistochemically for the expression of melanosomal markers. In 1 case, a biopsy specimen was also examined with electron microscopy. Results: The images obtained using CSLM allowed recognition of an abnormal intraepidermal melanocytic proliferation that was distinctly different from normal skin. Comparison of the sites examined using CSLM and subsequently using conventional histological methods revealed that CSLM correctly identified intraepidermal melanoma and benign skin. Fontana-Masson stains and immunohistochemical and ultrastructural studies showed that clinically amelanotic melanoma cells contained melanosomes and rare melanin granules. Conclusions: We demonstrated, for the first time, the detection of clinically amelanotic melanoma using CSLM. This technique ma): aid in the early detection of clinically barely visible or nonpigmented melanomas and may facilitate preoperative noninvasive assessment of their margins. C1 Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med, Dermatol Serv, New York, NY 10021 USA. Massachusetts Gen Hosp, Wellman Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Busam, KJ (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA. NR 31 TC 110 Z9 118 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUL PY 2001 VL 137 IS 7 BP 923 EP 929 PG 7 WC Dermatology SC Dermatology GA 452DC UT WOS:000169841000010 PM 11453812 ER PT J AU Brody, AL Saxena, S Stoessel, P Gillies, LA Fairbanks, LA Alborzian, S Phelps, ME Huang, SC Wu, HM Ho, ML Ho, MK Au, SC Maidment, K Baxter, LR AF Brody, AL Saxena, S Stoessel, P Gillies, LA Fairbanks, LA Alborzian, S Phelps, ME Huang, SC Wu, HM Ho, ML Ho, MK Au, SC Maidment, K Baxter, LR TI Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy - Preliminary findings SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 12-16, 1999 CL ACAPULCO, MEXICO SP Amer Coll Neuropsychopharmacol ID OBSESSIVE-COMPULSIVE DISORDER; POSITRON-EMISSION-TOMOGRAPHY; BASAL GANGLIA; PREFRONTAL CORTEX; MOOD DISORDERS; ANTIDEPRESSANT TREATMENTS; GLUCOSE-METABOLISM; FUNCTIONAL-ANATOMY; SEROTONIN RELEASE; BEHAVIOR-THERAPY AB Background: In functional brain imaging studies of major depressive disorder (MDD), regional abnormalities have been most commonly found in prefrontal cortex, anterior cingulate gyrus, and temporal lobe. We examined baseline regional metabolic abnormalities and metabolic changes from pretreatment to posttreatment in subjects with MDD. We also performed a preliminary comparison of regional changes with 2 distinct forms of treatment (paroxetine and interpersonal psychotherapy). Methods: Twenty-four subjects with unipolar MDD and 16 normal control subjects underwent resting F 18 ((18)F) fluorodeoxyglucose positron emission tomography scanning before and after 12 weeks. Between scans, subjects with MDD were treated with either paroxetine or interpersonal psychotherapy (based on patient preference). while controls underwent no treatment. Results: At baseline, subjects with MDD had higher normalized metabolism than controls in the prefrontal cortex land caudate and thalamus), and lower metabolism in the temporal lobe, With treatment, subjects with MDD had metabolic changes in the direction of normalization in these regions. After treatment, paroxetine-treated subjects had a greater mean decrease in Hamilton Depression Raring Scale score (61.4%) than did subjects treated with interpersonal psychotherapy (38.0%), but both subgroups showed decreases in normalized prefrontal cor tex (paroxetine-treated bilaterally and interpersonal psychotherapy-treated on the right) and left anterior cingulate gyrus metabolism, and increases in normalized left temporal lobe metabolism. Conclusions: Subjects with MDD had regional brain metabolic abnormalities at baseline that tended to normalize with treatment. Regional metabolic changes appeared similar with the Z forms of treatment. These results should be interpreted with caution because of study limitations (small sample size, lack of random assignment to treatment groups, and differential treatment response between treatment subgroups). C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med & Mol Pharmacol, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Toronto, Dept Psychiat, Toronto, ON M5S 1A8, Canada. Univ Alabama, Dept Psychiat & Behav Neurobiol, Birmingham, AL 35294 USA. RP Brody, AL (reprint author), 300 UCLA Med Plaza,Suite 2340, Los Angeles, CA 90095 USA. EM abrody@ucla.edu FU NIMH NIH HHS [R01 MH-53565] NR 65 TC 322 Z9 333 U1 0 U2 17 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUL PY 2001 VL 58 IS 7 BP 631 EP 640 DI 10.1001/archpsyc.58.7.631 PG 10 WC Psychiatry SC Psychiatry GA 451KN UT WOS:000169801400001 PM 11448368 ER PT J AU Sherbourne, CD Wells, KB Duan, NH Miranda, J Unutzer, J Jaycox, L Schoenbaum, M Meredith, LS Rubenstein, LV AF Sherbourne, CD Wells, KB Duan, NH Miranda, J Unutzer, J Jaycox, L Schoenbaum, M Meredith, LS Rubenstein, LV TI Long-term effectiveness of disseminating quality improvement for depression in primary care SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MANAGED PRIMARY-CARE; MAJOR DEPRESSION; RECURRENT DEPRESSION; COST-EFFECTIVENESS; COGNITIVE THERAPY; UNITED-STATES; OUTCOMES; PSYCHOTHERAPY; GUIDELINES; DISORDERS AB Background: This article addresses whether dissemination of short-term quality improvement (QI) interventions for depression to primary care practices improves patients' clinical outcomes and health-related quality of life (HRQOL) over 2 years, relative to usual care (UC). Methods: The sample included 1299 patients with current depressive symptoms and 12-month, lifetime, or no depressive disorder from 46 primary care practices in 6 managed care organizations. Clinics were randomized to UC or 1 of 2 QI programs that included training local experts and nurse specialists to provide clinician and patient education, assessment, and treatment planning, plus either nurse care managers for medication follow-up (QI-meds) or access to trained psychotherapists (QI-therapy). Outcomes were assessed every 6 months for 2 years. Results: For most outcomes, differences between intervention and UC patients were not sustained for the full 2 years. However, QI-therapy reduced overall poor outcomes compared with UC by about 8 percentage points throughout 2 years, and by 10 percentage points compared with QI-meds at 24 months. Both interventions improved patients' clinical and role outcomes, relative to UC, over 12 months (eg, a 10-11 and 6-7 percentage point difference in probable depression at 6 and 12 months, respectively). Conclusions; While most outcome improvements were not sustained over the full 2 study years, findings suggest that flexible dissemination of short-term, QI programs in managed primary care can improve patient outcomes well after program termination. Models that support integrated psychotherapy and medication based treatment strategies in primary care have the potential for relatively long-term patient benefits. C1 RAND Corp, Hlth Program, Santa Monica, CA 90407 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Biobehav Serv, Los Angeles, CA 90024 USA. Georgetown Univ, Med Ctr, Dept Psychiat, Washington, DC 20007 USA. VA Greater Los Angeles Healthcare Syst, Dept Med, Sepulveda, CA USA. RP Sherbourne, CD (reprint author), RAND Corp, Hlth Program, 1700 Main St, Santa Monica, CA 90407 USA. NR 44 TC 101 Z9 102 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUL PY 2001 VL 58 IS 7 BP 696 EP 703 DI 10.1001/archpsyc.58.7.696 PG 8 WC Psychiatry SC Psychiatry GA 451KN UT WOS:000169801400011 PM 11448378 ER PT J AU Hatch, JP Shinkai, RSA Sakai, S Rugh, JD Paunovich, ED AF Hatch, JP Shinkai, RSA Sakai, S Rugh, JD Paunovich, ED TI Determinants of masticatory performance in dentate adults SO ARCHIVES OF ORAL BIOLOGY LA English DT Article DE mastication; masticatory performance; dentate; structural equation modeling ID RANDOMIZED CLINICAL-TRIAL; COMPLETE DENTURE WEARERS; OCCLUSAL CONTACT AREA; BITE-FORCE; CHEWING PERFORMANCE; CRANIOMANDIBULAR INDEX; NATURAL DENTITION; FACIAL MORPHOLOGY; POSTCANINE TEETH; EFFICIENCY AB Masticatory performance results fi om a complex interplay of direct and indirect effects, yet most studies employ univariate models. This study tested a multivariate model of masticatory performance for dentate subjects. Explanatory variables included number of functional tooth units, bite force, sex, age, masseter cross-sectional area, presence of temporomandibular disorders. and presence of diabetes mellitus. The population-based sample consisted of 631 dentate subjects aged 37-80 years. Convariance structure analysis showed that 68%, of the variability in masticatory performance could be explained by the combined effects of the explanatory variables. Age and sex did not show a strong effect on masticatory performance, either directly or indirectly through masseter cross-sectional area, temporomandibular disorders. and bite force. Number of functional tooth units and bite force were confirmed as the key determinants of masticatory performance, which suggests that their maintenance may be of major importance for promoting healthful functional status. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Orthodont, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Dent Diagnost Sci, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. Univ Campinas, Dept Prosthodont & Periodont, BR-13414900 Piracicaba, SP, Brazil. RP Hatch, JP (reprint author), Univ Texas, Hlth Sci Ctr, Dept Orthodont, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. RI Shinkai, Rosemary/I-3510-2013 OI Shinkai, Rosemary/0000-0002-4107-5661 FU NIDCR NIH HHS [P50 DE 10756] NR 42 TC 153 Z9 172 U1 0 U2 24 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0003-9969 J9 ARCH ORAL BIOL JI Arch. Oral Biol. PD JUL PY 2001 VL 46 IS 7 BP 641 EP 648 DI 10.1016/S0003-9969(01)00023-1 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 438TR UT WOS:000169070800008 PM 11369319 ER PT J AU Karl, AI Carney, ML Kaul, MP AF Karl, AI Carney, ML Kaul, MP TI The lumbrical provocation test in subjects with median inclusive paresthesia SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE carpal tunnel syndrome; electrodiagnosis; rehabilitation ID CARPAL-TUNNEL SYNDROME; ELECTRODIAGNOSIS; DIAGNOSIS AB Objective: To investigate the value of the Lumbrical Provocation Test (LPT) in predicting carpal tunnel syndrome (CTS) among patients with symptoms suspicious for CTS. Design: Prospective unigroup technique with blinded comparison of a clinical diagnostic test with 2 commonly used methods of diagnosing CTS: electrodiagnosis and a hand diagram. Setting: Outpatient veterans referred by a heterogeneous group of specialists and generalists to a Veterans Affairs medical center electrodiagnostic laboratory. Patients: Ninety-six consecutive patients who were referred to the electrodiagnostic laboratory with median inclusive paresthesia were evaluated. Interventions: LPT: hold hand as fist for 1 minute (to evaluate changes in paresthesia); electrodiagnostic evaluations: median and ulnar mixed nerve, antidromic sensory, and motor latencies; and hand symptom diagram to describe pain. Main Outcome Measures: Evaluation of symptoms of paresthesia (with or without pain) inclusive of the median nerve distribution distal to the wrist. Prevalence sensitivity, specificity, and positive and negative predictive value of LPT, and electrodiagnosis, and hand diagram tests. Results: Compared with the findings obtained with electrodiagnosis, the sensitivity of the LPT was .37; specificity, .71; positive predictive value, .59; and negative predictive value, .50. Compared with the findings obtained with the use of the hand diagram as a clinical measure, the sensitivity of the LPT was .43, specificity,.71, positive predictive value,.59, and negative predictive value, .56. Conclusion: The LPT has minimal use in predicting CTS in patients with median inclusive paresthesia compared with 2 commonly used methods of diagnosing CTS. C1 Oregon Hlth Sci Univ, Sch Med, Portland, OR 97201 USA. Vet Adm Med Ctr, Portland, OR USA. RP Kaul, MP (reprint author), Portland Vet Affairs Med Ctr, EMG Lab, POB 1035, Portland, OR 97201 USA. NR 11 TC 1 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUL PY 2001 VL 82 IS 7 BP 935 EP 937 DI 10.1053/apmr.2001.23898 PG 3 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 450KV UT WOS:000169742800012 PM 11441381 ER PT J AU Guo, ZM Van Remmen, H Yang, HG Chen, XL Mele, J Vijg, J Epstein, CJ Ho, YS Richardson, A AF Guo, ZM Van Remmen, H Yang, HG Chen, XL Mele, J Vijg, J Epstein, CJ Ho, YS Richardson, A TI Changes in expression of antioxidant enzymes affect cell-mediated LDL oxidation and oxidized LDL-induced apoptosis in mouse aortic cells SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE LDL; transgenic mice; aortas; antioxidant enzymes ID LOW-DENSITY-LIPOPROTEIN; SMOOTH-MUSCLE CELLS; MANGANESE SUPEROXIDE-DISMUTASE; HUMAN ENDOTHELIAL-CELLS; FAT-FED MICE; GLUTATHIONE-PEROXIDASE; LIPID-PEROXIDATION; STRAND BREAKS; COMET ASSAY; STRESS AB Transgenic mice overexpressing Cu/Zn superoxide dismutase (hSod1Tg(+/0)) or catalase (hCatTg(+/0)) and knockout mice underexpressing manganese superoxide dismutase (Sod2(+/-)) or glutathione peroxidase-l (Gpx1(-/-)) were used to study the effect of antioxidant enzymes on cell-mediated low density lipoprotein (LDL) oxidation and oxidized LDL (oxLDL)-induced apoptosis. Incubation of LDL with mouse aortic segments or smooth muscle cells (SMCs) resulted in a significant increase in LDL oxidation. However, LDL oxidation was significantly reduced when LDL was incubated with aortic segments and SMCs obtained from hSod1Tg(+/0) and hCatTg(+/0) mice compared with those obtained from wild-type mice. In contrast, LDL oxidation was significantly increased when LDL was incubated with aortic segments and SMCs obtained from Sod2(+/-) and Gpx1(-/-) mice. CuSO4-oxidized LDL increased DNA fragmentation and caspase activities in the primary cultures of mouse aortic SMCs. However, oxLDL-induced DNA fragmentation and caspase activities were reduced 50% in SMCs obtained from hSod1Tg(+/0) and hCatTg(+/0) mice compared with wild-type control mice. In contrast, oxLDL-induced DNA fragmentation and caspase activities were significantly increased in SMCs obtained from Sod2(+/-) and Gpx1(-/-) mice. These findings suggest that overexpression of Cu/Zn superoxide dismutase or catalase reduces cell-mediated LDL oxidation and oxLDL-induced apoptosis, whereas underexpression of manganese superoxide dismutase or glutathione peroxidase-1 increases cell-mediated LDL oxidation and oxLDL-induced apoptosis. C1 Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Wayne State Univ, Inst Chem Toxicol, Detroit, MI 48201 USA. Wayne State Univ, Dept Biochem, Detroit, MI 48201 USA. RP Guo, ZM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Physiol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NIA NIH HHS [P01 AG-13319, P01 AG-16998] NR 41 TC 64 Z9 65 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUL PY 2001 VL 21 IS 7 BP 1131 EP 1138 DI 10.1161/hq0701.092092 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 455AK UT WOS:000170005200008 PM 11451741 ER PT J AU Yoshida, M Sawada, T Ishii, H Gerszten, RE Rosenzweig, A Gimbrone, MA Yasukochi, Y Numano, F AF Yoshida, M Sawada, T Ishii, H Gerszten, RE Rosenzweig, A Gimbrone, MA Yasukochi, Y Numano, F TI HMG-CoA reductase inhibitor modulates monocyte-endothelial cell interaction under physiological flow conditions in vitro - Involvement of Rho GTPase-dependent mechanism SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article; Proceedings Paper CT 72nd Annual Scientific Session of the American-Heart-Association CY NOV 07-10, 1999 CL ATLANTA, GA SP Amer Heart Assoc DE HMG-CoA reductase inhibitor; adhesion molecules; monocytes; atherosclerosis ID NITRIC-OXIDE SYNTHASE; LEUKOCYTE ADHESION; HYPERCHOLESTEROLEMIC RATS; VASCULAR ENDOTHELIUM; UP-REGULATION; E-SELECTIN; IN-VITRO; ATHEROSCLEROSIS; ATHEROGENESIS; EXPRESSION AB 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, have been reported to exert actions independent of their lipid-lowering effects. To critically assess the effects of statins on monocyte-endothelial cell interactions, we used an in vitro model that mimicked physiological flow conditions. Monocytic U937 cells were incubated in the presence of cerivastatin for 48 hours. Adhesive interactions of statin-treated U937 cells were then analyzed by use of activated (interleukin-1 beta 10 U/mL, 4 hours) human umbilical vein endothelial cells in an in vitro flow apparatus. Flow cytometric analysis of adhesion molecules and measurement of F-actin content in U937 cells were performed before and after statin treatment. Preincubation with cerivastatin significantly decreased U937 firm adhesion to activated human umbilical vein endothelial cells, whereas U937 rolling was not decreased. Fluorescence-activated cell sorter analysis revealed downregulation of U937 surface expression of CD11a, CD18, and VLA4 after statin treatment. Cerivastatin significantly reduced F-actin content in U937 cells and inhibited RhoA translocation, whereas preincubation with C3 exoenzyme reduced U937 adhesion under flow. Cerivastatin reduces monocyte adhesion to vascular endothelium under physiological flow conditions via downregulation of integrin adhesion molecules and inhibition of actin polymerization via RhoA inactivation. Our findings have important implications for the lipid-independent effects of statins. C1 Tokyo Med & Dent Univ, Dept Appl Genet, Bunkyo Ku, Tokyo 1138510, Japan. Tokyo Med & Dent Univ, Dept Med, Tokyo 1138510, Japan. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol,Div Vasc Res, Boston, MA 02115 USA. RP Tokyo Med & Dent Univ, Dept Appl Genet, Bunkyo Ku, 1-5-45 Yushima Bldg D-621, Tokyo 1138510, Japan. EM masamgen@tmd.ac.jp NR 32 TC 150 Z9 163 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUL PY 2001 VL 21 IS 7 BP 1165 EP 1171 DI 10.1161/hq0701.092143 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 455AK UT WOS:000170005200013 PM 11451746 ER PT J AU Gerard, HC Wang, Z Wang, GF El-Gabalawy, H Goldbach-Mansky, R Li, Y Majeed, W Zhang, H Ngai, N Hudson, AP Schumacher, HR AF Gerard, HC Wang, Z Wang, GF El-Gabalawy, H Goldbach-Mansky, R Li, Y Majeed, W Zhang, H Ngai, N Hudson, AP Schumacher, HR TI Chromosomal DNA from a variety of bacterial species is present in synovial tissue from patients with various forms of arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID POLYMERASE-CHAIN-REACTION; CHLAMYDIA-TRACHOMATIS DNA; RIBOSOMAL-RNA; REITERS-SYNDROME; NUCLEIC-ACIDS; PNEUMONIAE; FLUID; IDENTIFICATION; PATHOGENS; ANTIGENS AB Objective. We and others have reported the presence of Chlamydia and other bacterial species in joint specimens from patients with reactive arthritis (ReA). The present study was conducted to investigate whether bacteria other than those specified by diagnostic criteria for ReA could be identified in synovial fluid (SF) or tissue from patients with various arthritides, and whether the presence of such organisms corresponds to particular clinical characteristics in any patient set or subset. Methods. DNA in synovial biopsy samples and SF obtained from 237 patients with various arthritides, including ReA, rheumatoid arthritis, and undifferentiated oligoarthritis, was assayed by polymerase chain reaction (PCR) using "panbacterial" primers; we chose only samples known to be PCR negative for Chlamydia, Borrelia, and Mycoplasma species. PCR products were cloned, and cloned amplicons from each sample were sequenced; DNA sequences were compared against all others in GenBank for identification of bacterial species involved. Results. Ten percent of patient samples were PCR positive in panbacterial screening assays. Bacterial species identified belonged to the genera Neisseria, Acinetobacter, Moraxella, Salmonella, Pseudomonas, and others. Thirty-five percent of PCR-positive patients showed the presence of DNA from more than a single bacterial species in synovium; overall, however, we could identify no clear relationship between specific single or multiple bacterial species in the synovium and any general clinical characteristics of any individual or group of patients. Conclusion. This analysis provides the first systematic attempt to relate bacterial nucleic acids in the synovium to clinical characteristics, joint findings, and outcomes. Many patients with arthritis have bacterial DNA in the joint, and, in some cases, DNA from more than a single species is present. However, except for 1 case of a control patient with staphylococcal septic arthritis, it is not clear from the present study whether the synovial presence of such organisms is related to disease pathogenesis or evolution in any or all cases. C1 Wayne State Univ, Sch Med, Dept Immunol & Microbiol, Detroit, MI 48201 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Hudson, AP (reprint author), Wayne State Univ, Sch Med, Dept Immunol & Microbiol, Gordon H Scott Hall,540 E Canfield Ave, Detroit, MI 48201 USA. FU NIAMS NIH HHS [AR-42541, AR-47186] NR 35 TC 66 Z9 68 U1 0 U2 8 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 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUL PY 2001 VL 44 IS 7 BP 1689 EP 1697 DI 10.1002/1529-0131(200107)44:7<1689::AID-ART293>3.0.CO;2-K PG 9 WC Rheumatology SC Rheumatology GA 498BY UT WOS:000172491000027 PM 11465721 ER PT J AU Shito, M Kim, NH Baskaran, H Tilles, AW Tompkins, RG Yarmush, ML Toner, M AF Shito, M Kim, NH Baskaran, H Tilles, AW Tompkins, RG Yarmush, ML Toner, M TI In vitro and in vivo evaluation of albumin synthesis rate of porcine hepatocytes in a flat-plate bioreactor SO ARTIFICIAL ORGANS LA English DT Article DE bioartificial liver; flat-plate bioreactor; porcine hepatocyte culture; pharmacokinetics; albumin production; in vivo perfusion ID BIOARTIFICIAL LIVER; SANDWICH CONFIGURATION; BILIRUBIN CONJUGATION; EXTRACORPOREAL; METABOLISM; FULMINANT; PERFUSION AB Several configurations of extracorporeal bioartificial liver devices have been developed for the potential treatment of fulminant hepatic failure or as a bridge to liver transplantation. Recently, we developed a micro-channel flat-plate bioreactor with an internal membrane oxygenator in which porcine hepatocytes are cultured as a monolayer on the bottom glass surface. In the present study, we investigated synthetic function of porcine hepatocytes in the bioreactor in both in vitro and in vivo flow circuit models. In vitro, albumin synthesis was stable in the bioreactor for up to 4 days of perfusion. In vivo, with the extracorporeal connection of the bioreactor to rat vasculature, porcine albumin was detectable for 24 h in the rat plasma. We also developed a simple mathematical model to predict the in vivo porcine albumin concentration in rat plasma. These results indicate that this configuration of a microchannel flat-plate bioreactor has potential as a liver support device and warrants further investigation. C1 Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Toner, M (reprint author), Massachusetts Gen Hosp, Ctr Engn Med, Bigelow 1401,55 Fruit St, Boston, MA 02114 USA. NR 19 TC 22 Z9 24 U1 1 U2 3 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0160-564X J9 ARTIF ORGANS JI Artif. Organs PD JUL PY 2001 VL 25 IS 7 BP 571 EP 578 DI 10.1046/j.1525-1594.2001.025007571.x PG 8 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 458UK UT WOS:000170212800010 PM 11493279 ER PT J AU Radomsky, AS Rachman, S Hammond, D AF Radomsky, AS Rachman, S Hammond, D TI Memory bias, confidence and responsibility in compulsive checking SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Association-for-Advancement-of-Behavior-Therapy CY NOV 14, 1999 CL TORONTO, CANADA SP Assoc Adv Beh Therapy ID DISORDER; INFORMATION AB Recent research suggests that there is a positive memory bias for threatening information in compulsive cleaners. However, the relationship between OCD and memory is likely to be more complex when the compulsive behaviour is checking. Hence, we decided to explore this relationship in a clinical sample of people who check compulsively. Participants completed a diagnostic interview and were then asked to complete a standard 'baseline' check which normally causes distress/discomfort. Two additional checks were then completed-one under conditions of high responsibility and one under low responsibility. The order of responsibility manipulation was randomized across participants. After each check, participants completed a Memory and Confidence Interview which assessed memory for threat-relevant and threat-irrelevant aspects of the check, and also confidence in memory for the check. One week later, participants came into the laboratory to complete additional Memory and Confidence Interviews after watching a videotape of the checks completed earlier in their own homes. These videotaped checks were taken as conditions of 'no responsibility'. Results show a positive memory bias for threat-relevant information. As responsibility was inflated, this positive memory bias was amplified. Under conditions of no responsibility, no memory bias was detectable. Also, responsibility appears to have had a greater impact on confidence in memory than on memory itself in OCD. The results are discussed in terms of the mnestic deficit theory of OCD and in terms of cognitive-behavioural approaches to understanding the disorder. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Univ British Columbia, Dept Psychol, Vancouver, BC V6T 1Z4, Canada. RP Radomsky, AS (reprint author), Massachusetts Gen Hosp, ACC812-15 Parkman St, Boston, MA 02114 USA. OI Radomsky, Adam/0000-0003-2807-184X NR 24 TC 81 Z9 83 U1 0 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD JUL PY 2001 VL 39 IS 7 BP 813 EP 822 DI 10.1016/S0005-7967(00)00079-6 PG 10 WC Psychology, Clinical SC Psychology GA 442PV UT WOS:000169294900006 PM 11419612 ER PT J AU Yildiz, A Demopulos, CM Moore, CM Renshaw, PF Sachs, GS AF Yildiz, A Demopulos, CM Moore, CM Renshaw, PF Sachs, GS TI Effect of lithium on phosphoinositide metabolism in human brain: A proton decoupled P-31 magnetic resonance spectroscopy study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE lithium; inositol monophosphatase; proton decoupled P-31 MRS; inositol depletion ID MOOD-STABILIZING AGENTS; SIGNAL-TRANSDUCTION PATHWAYS; MANIC-DEPRESSIVE ILLNESS; INOSITOL METABOLISM; INVIVO P-31; MYOINOSITOL; MODULATION; MECHANISM; SPECTRA; CNS AB Background: The objective of our study was to evaluate whether lithium increases brain phosphomonoester (PME) levels in human subjects. Methods: Proton decoupled P-31 magnetic resonance spectra were obtained from eight healthy volunteers before and after the administration of lithium carbonate, 450 mg b.i.d, for 7 and 14 days. Results: Pairwise comparisons of the mole percent PME revealed a significant increase from baseline at day 7 and day 14 of lithium administration. Conclusions: An increase in PME concentration with 7 and 14 days of lithium administration in the human brain in vivo was observed. Because the inositol-1-monophosphate contributes to the PME peak, this result suggests that some of the initial actions of lithium may occur through a reduction of myo-inositol, which in turn may initiate a cascade of secondary changes at different levels of signal transduction process and gene expression in brain, effects that are ultimately responsible for the therapeutic benefits of lithium. Biol Psychiatry 2001;50: 3-7 (C) 2001 Society of Biological Psychiatry. C1 Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bipolar Program, Boston, MA USA. Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02178 USA. RP Yildiz, A (reprint author), 170 Sok Guller Apt 8-8, TR-35360 Izmir, Turkey. FU NIMH NIH HHS [MH 58681] NR 32 TC 15 Z9 15 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 1 PY 2001 VL 50 IS 1 BP 3 EP 7 DI 10.1016/S0006-3223(01)01069-1 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 455HD UT WOS:000170020700002 PM 11457417 ER PT J AU Kurtz, SM Muratoglu, OK Buchanan, F Currier, B Gsell, R Greer, K Gualtieri, G Johnson, R Schaffner, S Sevo, K Spiegelberg, S Shen, FW Yau, SS AF Kurtz, SM Muratoglu, OK Buchanan, F Currier, B Gsell, R Greer, K Gualtieri, G Johnson, R Schaffner, S Sevo, K Spiegelberg, S Shen, FW Yau, SS TI Interlaboratory reproducibility of standard accelerated aging methods for oxidation of UHMWPE SO BIOMATERIALS LA English DT Article DE ultra-high molecular weight polyethylene; UHMWPE; oxidation; accelerated aging; degradation; Fourier transform infrared spectroscopy; FTIR; repeatability; reproducibility; precision; accuracy; bias; experimental uncertainty ID POLYETHYLENE; STERILIZATION AB During accelerating aging, experimental uncertainty may arise due to variability in the oxidation process, or due to limitations in the technique that is ultimately used to measure oxidation. The purpose of the present interlaboratory study was to quantify the repeatability and reproducibility of standard accelerated aging methods for ultra-high molecular weight polyethylene (UHMWPE). Sections (200 mum thick) were microtomed from the center of an extruded rod of GUR 4150 HP, gamma irradiated in air or nitrogen, and circulated to 12 institutions in the United States and Europe for characterization of oxidation before and after accelerated aging. Specimens were aged for 3 weeks at 80 degreesC in an air circulating oven or for 2 weeks at 70 degreesC in an oxygen bomb (maintained at 503 kPa (5 atm.) of O-2) in accordance with the two standard protocols described in ASTM F 2003-00. FTIR spectra were collected from each specimen within 24 h of the start and finish of accelerated aging, and oxidation indices were calculated by normalizing the peak area of the carbonyl region by the reference peak areas at 1370 or 2022 cm(-1). The mean relative interlaboratory uncertainty of the oxidation data was 78.5% after oven aging and 129.1% after bomb aging. The oxidation index measurement technique was not found to be a significant factor in the reproducibility. Comparable relative intrainstitutional uncertainty was observed after oven aging and bomb aging, For both aging methods, institutions successfully discriminated between air-irradiated and control specimens, However, the large interinstitutional variation suggests that absolute performance standards for the oxidation index of UHMWPE after accelerated aging may not be practical at the present time. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Exponent Inc, Philadelphia, PA 19103 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Queens Univ Belfast, Belfast BT7 1NN, Antrim, North Ireland. Dartmouth Coll, Hanover, NH 03755 USA. Zimmer Inc, Warsaw, IN USA. DePuy Orthopaed, Warsaw, IN USA. Drexel Univ, Philadelphia, PA 19104 USA. Smith & Nephew, Memphis, TN USA. Sulzer Orthopaed, Winterthur, Switzerland. Wright Med Technol, Arlington, TN USA. Cambridge Polymer Grp, Cambridge, MA USA. Orthoped Hosp, Los Angeles, CA 90007 USA. Howmed Osteon Corp, Rutherford, NJ USA. RP Kurtz, SM (reprint author), Exponent Inc, 2300 Chestnut St,Suite 150, Philadelphia, PA 19103 USA. OI Currier, Barbara/0000-0003-3273-225X NR 17 TC 35 Z9 35 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD JUL PY 2001 VL 22 IS 13 BP 1731 EP 1737 DI 10.1016/S0142-9612(00)00333-1 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 435YE UT WOS:000168909100005 PM 11396876 ER PT J AU Li, ZX Gergely, J Tao, T AF Li, ZX Gergely, J Tao, T TI Proximity relationships between residue 117 of rabbit skeletal troponin-I and residues in troponin-C and actin SO BIOPHYSICAL JOURNAL LA English DT Article ID RECONSTITUTED THIN-FILAMENTS; ENERGY-TRANSFER MEASUREMENTS; TERMINAL HYDROPHOBIC POCKET; PHOTO-CROSS-LINKING; MUSCLE TROPONIN; INHIBITORY REGION; BIOLOGICAL-ACTIVITY; REGULATORY DOMAIN; CONFORMATIONAL TRANSITION; PROTEOLYTIC FRAGMENTS AB We used resonance energy transfer and site-directed photo-cross-linking to probe the Ca2+-dependent proximity relationships between residue 117 next to the C-terminus of the inhibitory region in rabbit skeletal troponin-I (TnI) and residues in troponin-C (TnC) and in actin. A mutant TnI that contains a single cysteine at position 117 (I117) was constructed, and the distance between TnI residue 117 and TnC residue 98 was measured with the following results: for both the binary TnC-TnI complex and the ternary troponin complex, this distance was 30 and 41 Angstrom in the presence and absence of Ca2+, respectively. The distance between Tnl residue 117 and Cys374 of actin was 48 and 41 Angstrom in the presence and absence of Ca2+, respectively. Six additional distances from this Tnl residue to cysteines in TnC mutants were measured and used to localize this residue with respect to the crystal structure of TnC. The results show that in the presence of Ca2+ it is localized near the B and C helices of TnC's N-terminal domain. In the absence of Ca2+ this residue moves away from this location by similar to8 Angstrom. Photo-cross-linking experiments show that I117 labeled with 4-maleimidobenzophenone photo-crosslinked to TnC but not to actin in both the presence and absence of Ca2+. Taken together these results provide independent experimental support for the proposal (Y. Luo, J. L. Wu, B. Li, K. Langsetmo, J. Gergely, and T. Tao, 2000, J. Mol. Biol. 296:899-910) that upon Ca2+ removal the region comprising Tnl residues 114-125 triggers the movements of residues 89-113 and 130-150 toward actin, but does not itself interact with actin. C1 Boston Biomed Res Inst, Muscle & Motil Grp, Watertown, MA 02472 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. RP Tao, T (reprint author), Boston Biomed Res Inst, Muscle & Motil Grp, 64 Grove St, Watertown, MA 02472 USA. FU NIAMS NIH HHS [AR21673] NR 70 TC 15 Z9 16 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 2001 VL 81 IS 1 BP 321 EP 333 PG 13 WC Biophysics SC Biophysics GA 447RZ UT WOS:000169587400028 PM 11423417 ER PT J AU Kay, NE Leong, TL Bone, N Vesole, DH Greipp, PR Van Ness, B Oken, MM Kyle, RA AF Kay, NE Leong, TL Bone, N Vesole, DH Greipp, PR Van Ness, B Oken, MM Kyle, RA TI Blood levels of immune cells predict survival in myeloma patients: results of an Eastern Cooperative Oncology Group phase 3 trial for newly diagnosed multiple myeloma patients SO BLOOD LA English DT Article ID CLINICAL-TRIAL; RESPONSES; TRANSPLANTATION; CHEMOTHERAPY; VACCINATION; GENERATION; THERAPY; ANTIGEN AB Previously, it was reported that patients with multiple myeloma (MM) who have higher baseline levels of blood CD4(+) or CD19(+) cells have longer survival. This article extends the analysis of immune cell levels and survival in a large cohort (N = 504) of patients with MM entered on Eastern Cooperative Oncology Group (ECOG) phase 3 trial (9486), Newly diagnosed patients with MM received 2 cycles of vincristine, bischloroethylnitrosourea, melphalan, cytoxan, prednisone (VBMCP) and were treated on one of 3 randomized arms: VBMCP with either interferon or high-dose cyclophosphamide, or VBMCP alone. Blood immune cell levels were studied at trial entry (baseline), after 2 cycles of chemotherapy, after 2 years of therapy, and at relapse. Baseline CD3(+), CD4(+), CD8(+), CD19(+), and CD4(+) subset cell levels were all positively associated with survival (P = .0087 to P < .0001). A multivariate analysis incorporating CD4(+) and CD19(+) cell levels defined 3 separate groups of patients with MM to survival outcome. Higher CD19(+) blood levels were positively associated with MM-patient survival at entry to the study, at year 2, and at relapse (P < .0001 at all 3 timepoints), Patients with MM had evidence of immune cell reconstitution after 2 years of therapy, but the rate and extent of recovery was greater for CD8(+), which was greater than CD4(+), which was greater than CD19(+). This latter data affirms the positive relationship between the quantitative status of the blood immune system in MM and survival. In addition, the importance of the CD19(+) blood cells to survival is evident throughout the course of MM. Therapeutic efforts to maintain an intact immune system may be crucial in maximizing chemotherapeutic and/or immunotherapy efforts in this disease. (C) 2001 by The American Society of Hematology. C1 Virginia Piper Canc Inst, Minneapolis, MN USA. Univ Minnesota, Inst Human Genet, Minneapolis, MN 55455 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. RP Kay, NE (reprint author), Mayo Med Ctr, 200 1st St SW, Rochester, MN 55905 USA. FU NCI NIH HHS [CA66636, CA15947, CA23318, CA13650, CA21115] NR 24 TC 46 Z9 49 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 2001 VL 98 IS 1 BP 23 EP 28 DI 10.1182/blood.V98.1.23 PG 6 WC Hematology SC Hematology GA 447JK UT WOS:000169568000007 PM 11418458 ER PT J AU Chen, G Shankar, P Lange, C Valdez, H Skolnik, PR Wu, LJ Manjunath, N Lieberman, J AF Chen, G Shankar, P Lange, C Valdez, H Skolnik, PR Wu, LJ Manjunath, N Lieberman, J TI CD8 T cells specific for human immunodeficiency virus, Epstein-Barr virus, and cytomegalovirus lack molecules for homing to lymphoid sites of infection SO BLOOD LA English DT Article ID TOXIC LYMPHOCYTES-T; HIGH ENDOTHELIAL VENULES; PRIMARY IMMUNE-RESPONSE; DIRECT VISUALIZATION; DISEASE PROGRESSION; SIGNALING MOLECULES; TRANSPLANT PATIENTS; IMPAIRED FUNCTION; HIV-INFECTION; IN-VIVO AB CD8 T cells are classified as naive, effector, or memory cells on the basis of CD45RA, CD62L, and CCR7 expression. Sequential engagement of cell-surface CD62L and CCR7 receptors is required for efficient trafficking to lymphoid tissue by means of high endothelial venules, Naive CD8 T cells are CCR7(+)CD62L(+) CD45RA(+), whereas long-term memory cells are CCR7(+)CD62L(+)CD45RA(-). Effector cytotoxic T cells are thought to be CCR7(-)CD45RA(+). The distribution of CD8 subsets and cytolytic protein expression in healthy donors and donors seropositive for human immunodeficiency virus (HIV) were compared. In HIV-infected subjects, CCR7(-) CD8 T cells expanded at the expense of naive and long-term memory cells. In both healthy donors and HIV-infected donors, CCR7(+) CD8 T cells were uniformly negative for perforin. In all subsets, perforin and granzyme A were not coordinately expressed, with perforirr expression being more tightly regulated. The properties of CD8 T cells specific for cytomegalovirus, Epstein-Barr virus (EBV), and HIV were studied by staining with major histocompatibility complex peptide tetramers, Antigen-specific cells for chronic infections with these viruses were uniformly CCR7- and predominantly CD62L(-). In 2 HIV-seropositive donors, 3-to 4-fold fewer EBV-tetramer-positive cells were present in lymph nodes com-pared with blood. Antigen-specific CD8 T cells are therefore preferentially excluded from lymphoid sites, even when infection is primarily in lymphoid tissue. This may protect lymphoid tissues from immunopathological changes but compromise immune defense against viruses, such as HIV and EBV, that target lymphocytes. HIV-specific CD8 T cells do not express CD45RA, whereas EBV- and CMV-specific CD8 T cells are heterogeneous in CD45RA(+) expression, Lack of CD45RA expression may indicate incomplete differentiation of HIV-specific CD8 T cells to cytotoxic T cells. (C) 2001 by The American Society of Hematalogy. C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Case Western Reserve Univ, Univ Hosp Cleveland, Dept Med, Div Infect Dis, Cleveland, OH 44106 USA. Tufts Univ, Sch Med, New England Med Ctr, Dept Med,Div Infect Dis & Geog Med, Boston, MA 02111 USA. Millennium Pharmaceut Inc, Cambridge, MA USA. RP Lieberman, J (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Lange, Christoph/J-6289-2012; Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI-42519, AI-45306, AI-45406] NR 54 TC 123 Z9 128 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 JUL 1 PY 2001 VL 98 IS 1 BP 156 EP 164 DI 10.1182/blood.V98.1.156 PG 9 WC Hematology SC Hematology GA 447JK UT WOS:000169568000024 PM 11418475 ER PT J AU Davies, FE Raje, N Hideshima, T Lentzsch, S Young, G Tai, YT Lin, B Podar, K Gupta, D Chauhan, D Treon, SP Richardson, PG Schlossman, RL Morgan, GJ Muller, GW Stirling, DI Anderson, KC AF Davies, FE Raje, N Hideshima, T Lentzsch, S Young, G Tai, YT Lin, B Podar, K Gupta, D Chauhan, D Treon, SP Richardson, PG Schlossman, RL Morgan, GJ Muller, GW Stirling, DI Anderson, KC TI Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma SO BLOOD LA English DT Article ID BONE-MARROW; IN-VITRO; INTERLEUKIN-6; APOPTOSIS; ADHESION; ANALOGS; ALPHA; TUMOR AB The antiangiogenic activity of thalidomide (Thal), coupled with an,increase In bone marrow angiogenesis in multiple myeloma (MM), provided the rationale for the use of That in MM. Previously, the direct anti-MM activity of That and its analogues (immunomodulatory drugs, IMiDs) on MM cells was demonstrated, suggesting multiple mechanisms of action. In this study, the potential immuno-modulatory effects of Thal/lMiDs in MM were examined. It was demonstrated that Thal/lMiDs do not induce T-cell proliferation alone but act as costimulators to trigger proliferation of anti-CD5-stimulated T cells from patients with MM, accompanied by an increase in interferon-gamma and IL-2 secretion. However, an increase in autologous T-cell killing of patient MM cells could not be demonstrated. A role for natural killer (NK)- and LAK-cell-mediated killing is suggested because IL-2-primed peripheral blood mononuclear cells (PBMCs) treated with Thal/ IMiDs demonstrated significantly increased lysis of MM cell lines. Cold target inhibition assays suggested NK- rather than LAK-cell-mediated killing. Furthermore, this killing was not major histocompatibility complex-class restricted, and the depletion of CD56(+) cells blocked the drug-induced MM cell lysis, It was significant that increased killing of patient MM cells by autologous PBMCs treated with Thal/lMiDs Was also observed. Although the in vivo relevance of NK-cell-mediated MM cell killing is unknown, phenotypic analysis performed in MM patients receiving Thal therapy demonstrated an increase in CD3(-)CD56(+) cells in patients responding to therapy. Thus in vitro and in vivo data support the hypothesis that That may mediate its anti-MM effect, at least in part, by modulating NK cell number and function. (C) 2001 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Jerome Lipper Multiple Myeloma C, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Celgene Corp, Warren, NJ USA. Univ Leeds, Leeds LS2 9JT, W Yorkshire, England. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Jerome Lipper Multiple Myeloma C, 44 Binney St,Rm M557, Boston, MA 02115 USA. FU PHS HHS [P0-1 78378] NR 18 TC 580 Z9 613 U1 2 U2 27 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 JUL 1 PY 2001 VL 98 IS 1 BP 210 EP 216 DI 10.1182/blood.V98.1.210 PG 7 WC Hematology SC Hematology GA 447JK UT WOS:000169568000031 PM 11418482 ER PT J AU Winston, DJ Antin, JH Wolff, SN Bierer, BE Small, T Miller, KB Linker, C Kaizer, H Lazarus, HM Petersen, FB Cowan, MJ Ho, WG Wingard, JR Schiller, GJ Territo, MC Jiao, J Petrarca, MA Tonetta, SA AF Winston, DJ Antin, JH Wolff, SN Bierer, BE Small, T Miller, KB Linker, C Kaizer, H Lazarus, HM Petersen, FB Cowan, MJ Ho, WG Wingard, JR Schiller, GJ Territo, MC Jiao, J Petrarca, MA Tonetta, SA TI A multicenter, randomized, double-blind comparison of different doses of intravenous immunoglobulin for prevention of graft-versus-host disease and infection after allogeneic bone marrow transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE immunoglobulin; graft-versus-host disease; infection ID CYTOMEGALO-VIRUS INFECTION; SERONEGATIVE BLOOD PRODUCTS; IMMUNE GLOBULIN; GANCICLOVIR PROPHYLAXIS; FUNGAL-INFECTIONS; CONTROLLED TRIAL; RECIPIENTS; EFFICACY; COMPLICATIONS; CYCLOSPORINE AB Intravenous immunoglobulin is approved for use in allogeneic bone marrow transplant recipients for prevention of graft-versus-host disease (GVHD) and infections, but the minimally effective dose has not been established. In this multicenter, randomized, double-blind trial, patients undergoing allogeneic marrow transplantation were randomized to receive 100 mg/kg, 250 mg/kg, or 500 mg/kg doses of intravenous immunoglobulin. Each dose was given weekly for 90 days and then monthly until 1 year after transplant. Six hundred and eighteen patients were evaluated. Acute GVHD (grades 2-4) occurred in 39% of the patients (80 of 206) in the 100 mg/kg group, 42% of the patients (88 of 208) in the 250 mg/kg group, and in 35% of the patients (72 of 204) in the 500 mg/kg group (P = 0.344). Among patients with unrelated marrow donors, a higher dose of intravenous immunoglobulin (500 mg/kg) was associated with less acute GVHD (P = 0.07). The incidences of chronic GVHD, infection and interstitial pneumonia were similar for all three doses of intravenous immunoglobulin. The dose of intravenous immunoglobulin also had no effect on the types of infection, relapse of hematological malignancy or survival. Except for more frequent chills (P = 0.007) and headaches (P = 0.015) in patients given the 500 mg/kg or 250 mg/kg dose of immunoglobulin, adverse events were similar for all three doses. These results suggest that 100 mg/kg, 250 mg/kg, and 500 mg/kg doses of intravenous immunoglobulin are associated with similar incidences of GVHD and infections in most allogeneic marrow transplants. These results should be considered when designing cost-effective strategies for the use of intravenous immunoglobulin in allogeneic marrow transplants receiving other current regimens for prophylaxis of GVHD and infection. C1 Univ Calif Los Angeles, Med Ctr, Dept Med, Ctr Hlth Sci, Los Angeles, CA 90095 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Tufts New England Med Ctr, Boston, MA USA. Univ Calif San Francisco, Ctr Canc Res, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Case Western Reserve Univ Hosp, Cleveland, OH 44106 USA. Univ Utah Hosp, Salt Lake City, UT USA. St Josephs Hosp, Orange, CA USA. Emory Univ, Ctr Canc, Atlanta, GA 30322 USA. Alpha Therapeut Corp, Los Angeles, CA USA. RP Winston, DJ (reprint author), Univ Calif Los Angeles, Med Ctr, Dept Med, Ctr Hlth Sci, Room 42-121 CHS, Los Angeles, CA 90095 USA. NR 32 TC 47 Z9 48 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JUL PY 2001 VL 28 IS 2 BP 187 EP 196 DI 10.1038/sj.bmt.1703109 PG 10 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 461NJ UT WOS:000170370100010 PM 11509937 ER PT J AU Rendl, M Mayer, C Weninger, W Tschachler, E AF Rendl, M Mayer, C Weninger, W Tschachler, E TI Topically applied lactic acid increases spontaneous secretion of vascular endothelial growth factor by human reconstructed epidermis SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article DE alpha-hydroxy acids; angiogenesis; lactic acid; skin equivalent; vascular endothelial growth factor ID ALPHA-HYDROXY-ACIDS; GLYCOLIC ACID; HUMAN KERATINOCYTES; CELL SURVIVAL; MESSENGER-RNA; HUMAN SKIN; EXPRESSION; ANGIOGENIN; INTERLEUKIN-8; RECEPTORS AB Background Alpha-hydroxy acids (AHAs) are widely used for the treatment of hyperkeratotic skin disorders and photodamaged skin. Objectives To investigate the effect of lactic acid (LA) on the secretion of cytokines by keratinocytes (KCs) of human reconstructed epidermis. Methods Creams containing 1.5%, 3% or 5% LA or vehicle controls were topically applied on to human epidermal equivalents (EEs). After 24 h, EEs were analysed for morphology and for the presence of apoptotic cells. Secretion of vascular endothelial growth factor (VEGF), angiogenin (ANG) and interleukin (IL)-8 was measured in the supernatants by enzyme-linked immunosorbent assay. Results LA led to a concentration-dependent increase in apoptotic cells as determined by cell morphology and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling. VEGF secretion was increased 2.5- and 2.8-fold (P < 0.05) over vehicle control after treatment with 1.5% and 3% LA, respectively. No significant increase in VEGF secretion was detected with 5% LA. In contrast to VEGF, secretion of ANG was decreased by LA in a concentration-dependent manner (0.5-fold for 5% LA; P < 0.01). No significant changes in IL-8 secretion were found with any of the concentrations tested. Conclusions Our data demonstrate that the topical application of AHAs modulates the secretion of cytokines by KCs. Regulation of KC-derived growth factors and cytokines by AHAs might represent a mechanism contributing to their therapeutic effects in disorders such as photoageing. C1 Univ Vienna, Sch Med, Dept Dermatol, Div Immunol Allergy & Infect Dis, A-1090 Vienna, Austria. Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02115 USA. Ctr Rech & Invest Epiderm Sensorielles, Neuilly, France. RP Tschachler, E (reprint author), Univ Vienna, Sch Med, Dept Dermatol, Div Immunol Allergy & Infect Dis, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. NR 36 TC 20 Z9 20 U1 2 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JUL PY 2001 VL 145 IS 1 BP 3 EP 9 DI 10.1046/j.1365-2133.2001.04274.x PG 7 WC Dermatology SC Dermatology GA 452UX UT WOS:000169879000002 PM 11453900 ER PT J AU Waber, DP Shapiro, BL Carpentieri, SC Gelber, RD Zou, GY Dufresne, A Romero, I Tarbell, NJ Silverman, LB Sallan, SE AF Waber, DP Shapiro, BL Carpentieri, SC Gelber, RD Zou, GY Dufresne, A Romero, I Tarbell, NJ Silverman, LB Sallan, SE TI Excellent therapeutic efficacy and minimal late neurotoxicity in children treated with 18 grays of cranial radiation therapy for high-risk acute lymphoblastic leukemia - A 7-year follow-up study of the Dana-Farber Cancer Institute Consortium Protocol 87-01 SO CANCER LA English DT Article DE acute lymphoblastic leukemia; cranial irradiation; neuropsychologic toxicity; central nervous system; recurrence ID LONG-TERM SURVIVORS; OSTERRIETH COMPLEX FIGURE; IQ SCORES; IRRADIATION; CHILDHOOD; CHEMOTHERAPY; PROPHYLAXIS; PERFORMANCE; SEQUELAE; SYSTEM AB BACKGROUND. In the current study, the authors evaluated late neuropsychologic effects 7 years after diagnosis and the long-term survival in a cohort of patients treated for high-risk childhood acute lymphoblastic leukemia (ALL) with cranial radiation therapy. Efficacy and toxicity were evaluated in relation to patient age at diagnosis (age < or 36 months). METHODS. Two hundred and one patients treated for high-risk ALL on the Dana-Farber Cancer Institute Consortium Protocol 87-01 were included, 147 of whom were in continuous complete disease remission and were eligible for cognitive testing. Sixty-one patients consented to undergo testing. All patients received 18 grays (Gy) of cranial radiation as a component of central nervous system treatment. RESULTS. For all 201 patients, the 5-year overall survival (% +/- the standard error) was 82% +/- 2 and the 5-year event-free survival (% +/- the standard error) was 75% +/- 3. Only two patients developed a central nervous system recurrence. Intelligence quotient (IQ) and memory were at the expected mean for age, but performance on a complex figure drawing task was found to be reduced. Children who were age < 36 months at the time of diagnosis were found to have an IQ in the average range, but showed verbal deficits. CONCLUSIONS. The results of the current study demonstrate excellent efficacy of therapy and relatively limited late neurotoxicity on a childhood ALL therapy protocol in which all evaluated patients had received 18 Gy of cranial radiation. Efficacious therapy that includes cranial radiation does not appear to necessarily incur a heightened risk for significant cognitive impairment. Cancer 2001;92: 15-22. (C) 2001 American Cancer Society. C1 Childrens Hosp, Dept Psychiat, Div Psychol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Hop St Justine, Montreal, PQ H3T 1C5, Canada. Interamer Univ Puerto Rico, San Juan, PR USA. RP Waber, DP (reprint author), Childrens Hosp, Dept Psychiat, Div Psychol, 300 Longwood Ave, Boston, MA 02115 USA. RI Zou, Guangyong/K-6408-2013 FU NCI NIH HHS [CA68484, CA06516]; NICHD NIH HHS [P30-HD18655] NR 29 TC 35 Z9 37 U1 1 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JUL 1 PY 2001 VL 92 IS 1 BP 15 EP 22 DI 10.1002/1097-0142(20010701)92:1<15::AID-CNCR1286>3.0.CO;2-W PG 8 WC Oncology SC Oncology GA 449CF UT WOS:000169666200003 PM 11443604 ER PT J AU Haiman, CA Stampfer, MJ Giovannucci, E Ma, J Decalo, NE Kantoff, PW Hunter, DJ AF Haiman, CA Stampfer, MJ Giovannucci, E Ma, J Decalo, NE Kantoff, PW Hunter, DJ TI The relationship between a polymorphism in CYP17 with plasma hormone levels and prostate cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER; RISK; GENE; 5-ALPHA-REDUCTASE AB The A2 allele of the CYP17 gene has been thought to be associated with increased functional activity of this steroidogenic enzyme. Consequently, the A2 allele has been examined as a biomarker of individual susceptibility to hormone-related diseases among men and women. We prospectively assessed the association between the A2 allele of CYP27 and prostate cancer risk among 590 cases and 782 controls in a case-control study nested within the Physicians' Health Study cohort. We also evaluated associations between CYP17 genotype and plasma steroid hormones among controls and the potential interaction between CYP27 and SRD5A2 V89L polymorphisms in relationship with prostate cancer risk and circulating steroid hormone levels. We observed a borderline significant association between the A2 aIlele and prostate cancer risk (odds ratio, 1.23; 95% confidence interval, 0.99-1.54), however, we did not observe evidence of a gene-dosage effect (versus A1/A2 genotype: A1/A2 genotype; odds ratio, 1.26; 95% confidence interval, 0.99-1.59; A2/A2 genotype: odds ratio, 1.17; 95% confidence interval, 0.85-1.61). The A2 allele was not overrepresented among cases with advanced prostate cancer. Among controls, carriers of the A2 allele had steroid hormone levels similar to noncarriers, We also found no evidence of a gene-gene interaction between CYP27 and SRD5A2 V89L polymorphisms on prostate cancer risk or endogenous steroid hormone levels, These results suggest that CYP17 genotype may possibly confer a small increased susceptibility to prostate cancer but is not a strong predictor of endogenous steroid hormone levels in men. C1 Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, 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 Publ Hlth, Harvard Ctr Canc Prevent, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90089 USA. RP Hunter, DJ (reprint author), Harvard Univ, Sch Med, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA42182, CA40360, CA57374, CA70817]; NIEHS NIH HHS [ES00002] NR 22 TC 63 Z9 68 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2001 VL 10 IS 7 BP 743 EP 748 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 451CE UT WOS:000169782900003 PM 11440959 ER PT J AU Spear, MA Breakefield, XO Beltzer, J Schuback, D Weissleder, R Pardo, FS Ladner, R AF Spear, MA Breakefield, XO Beltzer, J Schuback, D Weissleder, R Pardo, FS Ladner, R TI Isolation, characterization, and recovery of small peptide phage display epitopes selected against viable malignant glioma cells SO CANCER GENE THERAPY LA English DT Article DE phage display; vector targeting; herpes simplex virus type-1; glioma; glioblastoma multiforme; amplicon ID MAMMALIAN-CELLS; GENE-TRANSFER; TUMOR; CHEMOTHERAPY; ANTIBODIES; RECEPTOR; LIBRARY AB Phage display techniques rely on nearly random oligonucleotide sequences inserted into the protein III filament binding protein of an Escherichia coli filamentous phage M13 to generate a library of phage that express more than 10(7) different peptides. Phage that expresses a sequence having high affinity for a specific molecule, cell, or tissue can then be isolated through selective binding and recovery. Selected phage cannot only be used as gene transfer vectors in themselves, but the small peptide epitopes can be sequenced and potentially recombined into the attachment proteins of viral vectors, or used by themselves to target other therapeutic agents and diagnostic imaging radiolabels. Most phage display selections are carried out against purified and/or fixed protein targets, raising concerns as to the relevance of the selected epitopes. We have selected phage from the CMTI library against viable U87-MG human malignant glioma cells using a derivation of biopanning. The library, which initially contained phage expressing 2x10(7) different epitope sequences, collapsed after four rounds of selection such that 42% of recovered clones expressed a consensus sequence. Selective binding to viable adherent U87-MG cells was subsequently demonstrated under physiologic conditions at 167% (+/- 27%) unselected phage using a novel, viable enzyme-linked immunosorbent assay technique. In comparison, there was no difference in binding to control 9L rat gliosarcoma, PANC-1 human pancreatic adenocarcinoma, T98-MG human malignant glioma, or AST-4 human malignant glioma cells of selected compared to unselected phage. Using polymerase chain reaction, the epitope was recovered with flanking unique restriction sites for recombination into a herpes simplex virus type-1 vector. This study demonstrates and discusses optimized methodologies for using phage display to target viable cells. C1 Univ Calif San Diego, Ctr Canc, Gene Therapy Program, San Diego, CA 92103 USA. Dyax Inc, Cambridge, MA USA. Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. RP Spear, MA (reprint author), Univ Calif San Diego, Med Ctr, MC 8757,200 W Arbor Dr, San Diego, CA 92103 USA. FU NCI NIH HHS [CA69146] NR 19 TC 37 Z9 43 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD JUL PY 2001 VL 8 IS 7 BP 506 EP 511 DI 10.1038/sj.cgt.7700334 PG 6 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 460YN UT WOS:000170338300006 PM 11498772 ER PT J AU Anderson, KC AF Anderson, KC TI Novel biologically based therapies for myeloma SO CANCER JOURNAL LA English DT Article; Proceedings Paper CT 2nd National Oncology Forum CY OCT 14-15, 2000 CL CHICAGO, ILLINOIS DE allografting; angiogenesis; autografting; bone marrow stromal cells; multiple myeloma; thalidomide ID BONE-MARROW TRANSPLANTATION; RELAPSED MULTIPLE-MYELOMA; DONOR LYMPHOCYTE INFUSION; DRUG-RESISTANCE; CELLS; THALIDOMIDE; APOPTOSIS; ADHESION; TUMOR; INTERLEUKIN-6 AB Recent advances in our understanding of the molecular regulation of myeloma cells suggest novel strategies for treating multiple myeloma. Some myeloma cells express a 69 kD variant of Ku86, a heterodimer subunit that is essential for double-stranded DNA break repair. Presence of the variant impairs DNA repair; therefore normal Ku86 in myeloma cells confers resistance to therapy and may represent a therapeutic target. The upregulation of NF-kappaB-dependent interleukin-6 (IL-6) transcription and secretion that occurs following adhesion of myeloma cells to bone marrow stromal cells (BMSCs) may serve as a potential therapeutic target, as IL-6 is a growth and survival factor for myeloma cells. Accordingly, proteasome inhibitors inhibit activation of NF-KB and induce apoptosis of myeloma cells; they also inhibit the NF-KB-dependent up-regulation of IL-6 in BMSCs and related paracrine growth of adherent tumor cells. Therapeutic strategies may also target the mitogen-activated protein kinase (MAPK) pathway that is thought to mediate the IL-6-induced proliferation of myeloma cells. Vascular endothelial growth factor (VEGF) is also upregulated by adhesion of myeloma cells to BMSCs and may serve as a growth and/or survival factor for myeloma cells; preliminary studies suggest that VEGF receptor inhibitors may block proliferation of tumor cells. Thalidomide was recently used successfully to treat myeloma in patients whose disease was refractory to conventional treatment. An enhanced understanding of the mechanisms of action of thalidomide may result in the development of analogues with enhanced potency and fewer side effects. The potential mechanisms of action of thalldomide are reviewed, including antiangiogenic effects; direct effects of thalidomide on the growth and survival of myeloma cells and BMSCs; modulation of adhesive interactions; and regulation of secretion and bioactivity of cytokines. Immune-based strategies for treating multiple myeloma are also reviewed. Therapeutic obstacles include excessive toxicity after allografting, contaminating tumor cells in autografts, and the persistence of minimal residual disease (MRD) after high-dose therapy followed by allogenic or autologous stem cell transplantation. Allografting can be performed safely in myeloma, donor lympocyte infusions (DLI) may effectively treat relapsed myeloma post allografting; and use of CD4+ T cell-enriched DLI may reduce the risk of graft-versus-host disease. Treatment with autografting is frequently compromised by MRD in the autograft and in the patient post myeloablative therapy. Adenoviral purging prior to autotransplantation and in vivo and ex vivo stimulation of autoimmune cells are discussed as potential approaches to address these problems. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr, 44 Binney St,Room Mayer 557, Boston, MA 02115 USA. NR 31 TC 15 Z9 15 U1 0 U2 2 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PONE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. Sci. Am. PD JUL-AUG PY 2001 VL 7 SU 1 BP S19 EP S23 PG 5 WC Oncology SC Oncology GA 458MU UT WOS:000170198800004 PM 11504280 ER PT J AU Whedon, MB Meyer, LP Cassin, C Dahlin, C Von Roenn, JH Smolinski, KM AF Whedon, MB Meyer, LP Cassin, C Dahlin, C Von Roenn, JH Smolinski, KM TI Metastatic pancreatic cancer: Meeting palliative care needs SO CANCER PRACTICE LA English DT Editorial Material AB HC is a 73-year-old woman with pancreatic cancer. At the time of diagnosis, she also was found to have lung and liver metastases. HC is a widow and the mother of three adult children. The patient was receiving treatment on a phase II clinical trial with continuous intravenous drug infusion (using a portable volumetric infusion pump) for 14 days every 21 days. HC had also been on Medicare Hospice Benefit for approximately 6 weeks. HC was using oxygen at home intermittently, but recently she had reported increased dyspnea on exertion to her hospice care providers. She was advised to increase the use of oxygen and to continue with her current medications and dosages of controlled-release oxycodone, 20 mg every 12 hours, with oxycodone, 10 mg every 4 hours, as needed for breakthrough pain Although it is a 3-hour roundtrip drive from NC's home to the academic medical center at which her oncologist practices, she wanted to continue her appointments with the oncologist and oncology nurse practitioner. When NC and her boyfriend arrived at the medical center for a regularly scheduled appointment, she was noted to be extremely short of breath despite continuous oxygen per nasal canula. Assessment by the oncologist and oncology nurse practitioner revealed the presence of pleural effusion confirmed on chest x-ray. NC was informed of these findings and was advised that a thoracentesis was necessary for the relief of symptoms, This procedure was performed by interventional radiology later that afternoon, at which time a permanent chest tube was placed. HC was quite taxed after the procedure, but her dyspnea was significantly reduced. The patient agreed with the oncologist and nurse practitioner's recommendation that she stay overnight at the medical center rather than make the long drive home that evening. This would also allow time for teaching the patient and her boyfriend about home management of the permanent chest tube. A call was made to the director of the hospice program who informed the nurse practitioner that the program did not have a contract for inpatient admission at the medical center, although they did have a contract with the hospital in HC's home community. The director advised the patient to disenroll from the hospice benefit, which would then allow, payment for the admission under the patient's Medicare Benefit Part A. The hospice director and nurse practitioner had a further discussion regarding the need for improved symptom management in the future, House staff responsible for admitting HC to the oncology unit requested guidance from the Palliative Care Consult Service about strategies to best address this patient's needs, especially with the likelihood of discharge the next day. C1 Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. Northwestern Univ, Div Hematol Oncol, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Johns Hopkins Oncol Ctr, Baltimore, MD USA. RP Whedon, MB (reprint author), Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. NR 4 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1065-4704 J9 CANCER PRACT JI Cancer Pract. PD JUL-AUG PY 2001 VL 9 IS 4 BP 164 EP 168 DI 10.1046/j.1523-5394.2001.94003.x PG 5 WC Oncology; Health Care Sciences & Services; Nursing SC Oncology; Health Care Sciences & Services; Nursing GA 452ZG UT WOS:000169889100002 ER PT J AU Bates, RC Edwards, NS Burns, GF Fisher, DE AF Bates, RC Edwards, NS Burns, GF Fisher, DE TI A CD44 survival pathway triggers chemoresistance via lyn kinase and phosphoinositide 3-Kinase/Akt in colon carcinoma cells SO CANCER RESEARCH LA English DT Article ID ANKYRIN-BINDING DOMAIN; TYROSINE KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; MONOCLONAL-ANTIBODIES; STIMULATING FACTOR; SYNTHASE KINASE-3; SIGNALING PATHWAY; GLYCOPROTEIN CD44; COLORECTAL-CANCER; INDUCED APOPTOSIS AB A major obstacle to successful treatment of colorectal cancer is chemotherapy resistance. Enhanced expression of variant CD44 isoforms has been associated with aggressive tumor behavior, prompting the question of whether signaling from this receptor might modulate drug sensitivity. Activation of variant CD44 in colon carcinoma cell lines triggered resistance to the drug 1,3-bis(2-chloroethyl)-1-nitrosurea. Resistance was induced by monoclonal antibodies directed against epitopes independent of the hyaluronate-binding region but was not triggered by identical treatment of a carcinoma line expressing the standard CD44 isoform. We observed that variant CD44 produced activation of the src-family tyrosine kinase lyn. Moreover, overexpression of dominant-active lyn recapitulated chemoresistance via a pathway shown to involve activation of phosphoinositide 3-kinase and Akt. These results establish a novel role for CD44 in determining survival of colon carcinoma cells through lyn kinase and Akt. The ability to suppress apoptosis might play a critical role in the onset and development of colorectal malignancies. C1 Univ Newcastle, Fac Med, Canc Res Unit, Newcastle, NSW 2308, Australia. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. RP Bates, RC (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, Div Canc Biol & Angiogenesis, Res North,99 Brookline Ave, Boston, MA 02215 USA. NR 62 TC 119 Z9 121 U1 1 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 JUL 1 PY 2001 VL 61 IS 13 BP 5275 EP 5283 PG 9 WC Oncology SC Oncology GA 447GJ UT WOS:000169563300052 PM 11431370 ER PT J AU Irwin, MS Kaelin, WG AF Irwin, MS Kaelin, WG TI p53 family update: p73 and p63 develop their own identities SO CELL GROWTH & DIFFERENTIATION LA English DT Review ID TUMOR-SUPPRESSOR P53; ENDOTHELIAL GROWTH-FACTOR; SQUAMOUS-CELL CARCINOMA; P53-RELATED PROTEIN P73; WILD-TYPE P73; KINASE C-ABL; BREAST-CANCER; DNA-DAMAGE; TRANSCRIPTIONAL ACTIVITIES; HUMAN KERATINOCYTES C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, 44 Binney St,Mayer Bldg,Room 457, Boston, MA 02115 USA. NR 145 TC 194 Z9 211 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JUL PY 2001 VL 12 IS 7 BP 337 EP 349 PG 13 WC Cell Biology SC Cell Biology GA 454CG UT WOS:000169954400001 PM 11457731 ER PT J AU Kradin, RL Sakamoto, H Zhao, LH Leary, C AF Kradin, RL Sakamoto, H Zhao, LH Leary, C TI Bleomycin lung injury in interleukin-12 knockout mice SO CHEST LA English DT Article; Proceedings Paper CT 43rd Annual Thomas L Petty Aspen Lung Conference: Mechanisms of Pulmonary Fribrosis CY MAY 31-JUN 03, 2000 CL ASPEN, COLORADO C1 Massachusetts Gen Hosp, Immunopathol Unit, Boston, MA 02114 USA. RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Immunopathol Unit, 100 Blossom St,Cox 506, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 JUL PY 2001 VL 120 IS 1 SU S BP 10S EP 11S DI 10.1378/chest.120.1_suppl.S10-a PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 453LM UT WOS:000169917400014 ER PT J AU Malhotra, A Pillar, G Fogel, R Beauregard, J Edwards, J White, DP AF Malhotra, A Pillar, G Fogel, R Beauregard, J Edwards, J White, DP TI Upper-airway collapsibility - Measurements and sleep effects SO CHEST LA English DT Article DE breathing; collapsibility; critical pressure; dilator; flow limitation; genioglossus; inspiration resistive load; lung; negative pressure; obstructive sleep apnea; pharynx; resistance; upper airway ID GENIOGLOSSUS MUSCLE ACTIVATION; LUNG-VOLUME; APNEA; PRESSURE; RESISTANCE; INDUCTION; WAKEFULNESS; SNORERS; POSTURE; HUMANS AB Study objectives: Obstructive sleep apnea (OSA) is characterized by repetitive pharyngeal collapse during sleep. Several techniques have been proposed to assess the collapsibility of the upper airway in awake humans, but sleep-wake comparisons have rarely been attempted and there air? few studies comparing OSA patients to control subjects, We sought to compare two collapsibility measurement techniques between normal and apneic subjects, and between wakefulness and sleep. Design: We conducted three studies. First, we examined whether collapsibility assessed by negative pressure pulses (NPPs) during wakefulness reflected values during sleep in 21 normal subjects. Second we determined in these normal subjects whether collapsibility during sleep assessed by NPPs was predictive of collapsibility measured by inspiratory resistive loading (LRL). Finally, we compared upper-airway collapsibility between apnea patients (n = 22) and normal volunteers (n = 38) during wakefulness by MPPs, Setting: Clinical and research laboratories at the Brigham and Women's Hospital. Participants: Two populations of normal subjects (n = 21 and n 38) and OSA patients (n = 22), Measurements and results: Collapsibility during wakefulness, as measured by NPPs, correlated significantly with collapsibility during sleep (r = 0.62; p = 0.003), There was also a significant correlation between the two measures of collapsibility (IRL and NPP) during sleep (r = 0.53; p = 0.01). Both measures revealed a significant increase in pharyngeal collapsibility during sleep as comp:ucd to wakefulness. Finally, apnea patients had significantly greater pharyngeal collapsibility than control subjects during wakefulness (p = 0.017), Conclusions: These data suggest that upper-airway collapsibility measured during wakefulness does provide useful physiologic information about pharyngeal mechanics during sleep and demonstrates clear differences between individuals with and without sleep apnea. C1 Brigham & Womens Hosp, Sleep Disorders Sect, Div Endocrinol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Pulm & Crit Care Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP White, DP (reprint author), Brigham & Womens Hosp, Sleep Disorders Sect, Div Endocrinol, RF 486,221 Longwood Ave, Boston, MA 02115 USA. FU NCRR NIH HHS [M01 RR002635, RR02635]; NHLBI NIH HHS [HL 48531, HL 60292, P50 HL060292, R01 HL048531]; NIA NIH HHS [K23 AG024837] NR 27 TC 39 Z9 41 U1 1 U2 5 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 2001 VL 120 IS 1 BP 156 EP 161 DI 10.1378/chest.120.1.156 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 451YG UT WOS:000169829900030 PM 11451832 ER PT J AU George, DJ Halabi, S Shepard, TF Vogelzang, NJ Hayes, DF Small, EJ Kantoff, PW AF George, DJ Halabi, S Shepard, TF Vogelzang, NJ Hayes, DF Small, EJ Kantoff, PW TI Prognostic significance of plasma vascular endothelial growth factor levels in patients with hormone-refractory prostate cancer treated on cancer and leukemia group B 9480 SO CLINICAL CANCER RESEARCH LA English DT Article ID CARCINOMA; METASTASIS; DENSITY; TUMOR; HYDROCORTISONE; INHIBITOR; SURVIVAL; MITOGEN; TRIAL; VEGF AB Purpose: Plasma vascular endothelial growth factor (VEGF) levels are significantly elevated in patients with hormone-refractory prostate cancer (HRPC) compared with patients with localized disease and have been associated with disease progression in other cancer patient populations. Therefore, we measured VEGF levels in plasma prospectively collected from patients enrolled in Cancer and Leukemia Group B 9480, an intergroup study of suramin in patients with HRPC, to determine whether these levels had prognostic significance. Experimental Design: Pretreatment plasma was collected from patients with HRPC enrolled in Cancer and Leukemia Group B 9480, In a subset of samples representative of the entire cohort, plasma VEGF levels were determined in duplicate using a Quantiglo chemiluminescent ELISA kit (R&D Systems, Minneapolis, MN). Statistical analyses were performed to determine the correlation between pretreatment plasma VEGF levels and time of overall survival. The proportional hazards model was used to assess the prognostic significance of various cut points in multivariate models. Results: Plasma VEGF levels in this population ranged from 4-885 pg/ml, with a median level of 83 pg/ml, As a continuous variable, plasma VEGF levels inversely correlated with survival time (P = 0.002). Using various exploratory cut points, plasma VEGF levels appeared to correlate with survival. In multivariate models in which other prognostic factors (serum prostate-specific antigen, alkaline phosphatase, evidence of measurable disease, and hemoglobin) were included, plasma VEGF levels were significant at various cut points tested. Conclusion: Although these data are exploratory and need to be confirmed in an independent data set, they suggest that VEGF may have clinical significance in patients with HRPC. C1 Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Duke Univ, Med Ctr, Canc & Leukemia Grp B Stat Ctr, Durham, NC 27710 USA. Univ Chicago, Dept Med, Sect Hematol & Oncol, Canc Res Ctr, Chicago, IL 60637 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Univ Calif San Francisco, Mt Zion Med Ctr, San Francisco, CA 94115 USA. RP George, DJ (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 1230 Dana Bldg,44 Binney St, Boston, MA 02115 USA. NR 27 TC 213 Z9 221 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 JUL PY 2001 VL 7 IS 7 BP 1932 EP 1936 PG 5 WC Oncology SC Oncology GA 451BZ UT WOS:000169782400016 PM 11448906 ER PT J AU Cooper, DKC AF Cooper, DKC TI Christiaan Neethling Barnard - Profiles in cardiology SO CLINICAL CARDIOLOGY LA English DT Biographical-Item 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 149-9019,13th St, Boston, MA 02129 USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU CLINICAL CARDIOLOGY PUBL CO PI MAHWAH PA PO BOX 832, MAHWAH, NJ 07430-0832 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD JUL PY 2001 VL 24 IS 7 BP 527 EP 528 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 446MK UT WOS:000169516900010 PM 11444646 ER PT J AU Paterson, DL Singh, N Rihs, JD Squier, C Rihs, BL Muder, RR AF Paterson, DL Singh, N Rihs, JD Squier, C Rihs, BL Muder, RR TI Control of an outbreak of infection due to extended-spectrum beta-lactamase-producing Escherichia coli in a liver transplantation unit SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID KLEBSIELLA-PNEUMONIAE; RESISTANCE AB We report an outbreak of infection due to genotypically identical extended-spectrum beta -lactamase-producing Escherichia coli among patients in a liver transplantation unit. Control of the outbreak was achieved by a combination of contact isolation, feedback on hand hygiene, and gut decontamination with an orally administered fluoroquinolone. These interventions led to abrupt curtailment of the outbreak. C1 VA Pittsburgh Healthcare Syst, Vet Affairs Med Ctr, Infect Dis Sect, Pittsburgh, PA 15240 USA. RP Muder, RR (reprint author), VA Pittsburgh Healthcare Syst, Vet Affairs Med Ctr, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA. RI Paterson, David/A-9258-2010 NR 8 TC 56 Z9 61 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 JUL 1 PY 2001 VL 33 IS 1 BP 126 EP 128 DI 10.1086/320882 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 439GB UT WOS:000169101500027 PM 11389506 ER PT J AU Tapp, A Kilzieh, N Wood, AE Raskind, M Tandon, R AF Tapp, A Kilzieh, N Wood, AE Raskind, M Tandon, R TI Depression in patients with schizophrenia during an acute psychotic episode SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID NEGATIVE SYMPTOMS; FREQUENCY; DIAGNOSIS AB There is disagreement about whether depressive symptoms in schizophrenia are part of the basic disease process, or whether they represent adverse effects of treatment with antipsychotic medications. In a sample of initially antipsychotic drug-free acutely hospitalized patients with schizophrenia (N = 104), we measured change in depressive symptoms after 4 weeks of treatment. We also examined the relationship of changes in depressive symptoms to changes in positive and negative schizophrenic symptoms. Depressive symptoms improved after 4 weeks of anti-psychotic medication treatment, and their improvement corresponded with improvement in both positive and negative schizophrenic: symptoms. These results suggest that depressive symptoms in schizophrenia are related to the disease process itself, at least during acute exacerbations of schizophrenia. Depressive symptoms may be responsive to antipsychotic: medications directly or as a secondary response to improvement in positive and negative symptoms. Copyright (C) 2001 by W.B. Saunders Company. C1 Univ Washington, Mental Hlth Serv 116, Amer Lake Div, VA Puget Sound Hlth Care Syst, Tacoma, WA 98493 USA. Univ Michigan, Schizophrenia Program, Ann Arbor, MI USA. RP Tapp, A (reprint author), Univ Washington, Mental Hlth Serv 116, Amer Lake Div, VA Puget Sound Hlth Care Syst, Tacoma, WA 98493 USA. NR 27 TC 22 Z9 26 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 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JUL-AUG PY 2001 VL 42 IS 4 BP 314 EP 318 DI 10.1053/comp.2001.24577 PG 5 WC Psychiatry SC Psychiatry GA 453UM UT WOS:000169934900008 PM 11458306 ER PT J AU Miserocchi, E Baltatzis, S Foster, CS AF Miserocchi, E Baltatzis, S Foster, CS TI A case of atypical Cogan's syndrome with uncommon corneal findings SO CORNEA LA English DT Article DE Cogan's syndrome; interstitial keratitis; corneal neovascularization; penetrating keratoplasty; deafness ID INTERSTITIAL KERATITIS AB Purpose. We report a case of atypical bilateral interstitial keratitis associated with Cogan's syndrome. Methods. A 28-year-old man presented with a 2-year history of recurrent bilateral keratitis. Bilateral hearing loss preceded the ocular symptoms by 2 years. The patient also complained of skin nodules, headache, back pain, and arthritis. Corneal finding were consistent with superior stromal keratitis with stromal neovascularization and lipid deposition in the stroma. The patient's audiogram revealed cochlear pathology compatible with Cogan's syndrome (sensorineural deafness). Results. The patient was treated with topical steroids but eventually required corneal transplantation in the right eye as a consequence of progressive loss of vision secondary to progressive lipid keratopathy. Visual acuity at the patient's most recent follow-up evaluation was 20/40. Conclusion. This case represents an unusual type of interstitial keratitis associated with Cogan's disease. The absence of ocular symptoms at the time of initial ear involvement and the atypical presentation of the keratitis were responsible for the delay in diagnosis in this patient, resulting in hearing impairment. C1 Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, Dept Ophthalmol, Boston, MA 02114 USA. Univ Athens, Dept Ophthalmol, Athens, Greece. RP Foster, CS (reprint author), Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 8 TC 5 Z9 5 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD JUL PY 2001 VL 20 IS 5 BP 540 EP 542 DI 10.1097/00003226-200107000-00021 PG 3 WC Ophthalmology SC Ophthalmology GA 445FX UT WOS:000169448400021 PM 11413415 ER PT J AU Van Etten, RA AF Van Etten, RA TI Pathogenesis and treatment of Ph+ leukemia: recent insights from mouse models SO CURRENT OPINION IN HEMATOLOGY LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; PRIMITIVE HEMATOPOIETIC-CELL; ACUTE LYMPHOBLASTIC-LEUKEMIA; COLONY-STIMULATING FACTOR; BCR-ABL; TRANSGENIC MICE; CHRONIC-PHASE; BONE-MARROW; MYELOPROLIFERATIVE DISEASE AB Several methods to model human Ph+ leukemia in laboratory mice are available, including propagation of BCR/ABL-expressing cells in mice, xenotransplantation of primary Ph+ leukemia cells into immunodeficient mice, BCR/ABL transgenic mice, and BCR/ABL retroviral bone marrow transduction and transplantation. Recent studies in these different model systems have yielded important advances in our knowledge of the pathogenesis and therapy of human chronic myeloid leukemia and Ph+ B-lymphoblastic leukemia, and are the subject of this review. (C) 2001 Lippincott Williams & Wilkins, Inc. C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Van Etten, RA (reprint author), Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA90576] NR 56 TC 9 Z9 9 U1 0 U2 0 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 JUL PY 2001 VL 8 IS 4 BP 224 EP 230 DI 10.1097/00062752-200107000-00008 PG 7 WC Hematology SC Hematology GA 473WD UT WOS:000171071100008 PM 11561160 ER PT J AU Hsu, K Kanki, JP Look, AT AF Hsu, K Kanki, JP Look, AT TI Zebrafish myelopoiesis and blood cell development SO CURRENT OPINION IN HEMATOLOGY LA English DT Article ID POSITIONAL CLONING; HEMATOPOIESIS; GENES; IRON; EXPRESSION; LINEAGES; LEUKEMIA; CLOCHE; MODEL; PU.1 AB The zebrafish (Danio rerio) animal model offers a unique opportunity to discover novel genes required for the control of normal vertebrate myeloid cell development. It is well suited for both developmental and genetic analyses: eg, genome-wide chemical mutagenesis screens have fed to the identification of specific new genes affecting vertebrate erythropoiesis. Mutants defective in one or more hematopoietic functions will be useful as models of human disease and will assist in the elucidation of lineage-specific developmental programs. By using a combination of forward genetic mutagenesis screens and emerging strategies based on transgenic and antisense knockdown approaches, it should be possible to dissect the genetic programs that lead to myeloproliferative/myelodysplastic syndromes and to acute myeloid leukemia. (C) 2001 Lippincott Williams & Wilkins, Inc. C1 Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. RP Look, AT (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Pediat Oncol, 44 Binney St,Mayer 630, Boston, MA 02115 USA. FU NCI NIH HHS [CA93152, 1T32 CA81156] NR 38 TC 19 Z9 22 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 JUL PY 2001 VL 8 IS 4 BP 245 EP 251 DI 10.1097/00062752-200107000-00011 PG 7 WC Hematology SC Hematology GA 473WD UT WOS:000171071100011 PM 11561163 ER PT J AU Golub, TR AF Golub, TR TI Genomic approaches to the pathogenesis of hematologic malignancy SO CURRENT OPINION IN HEMATOLOGY LA English DT Article ID GENE-EXPRESSION; CDNA MICROARRAY; CELL-CYCLE; C-MYC; IDENTIFICATION; HYBRIDIZATION; CANCER; PATTERNS; LEUKEMIA; DIFFERENTIATION AB Recent advances in genome technologies and computational biology have facilitated genome-wide views of hematologic malignancy. In particular, comparative gene expression methods using DNA microarrays have allowed for the analysis of gene expression patterns in both primary patient material and model systems of hematopoietic development. This review provides an overview of the basic technologies underlying these approaches and provides a summary of recent progress in the genome-wide molecular classification of human acute leukemias and lymphomas and of initial attempts to define oncogene-mediated transcriptional programs using DNA microarrays. Curr Opin Hematol 2001, 81:252-261 (C) 2001 Lippincott Williams & Wilkins, Inc. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Golub, TR (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM golub@genome.wi.mit.edu NR 39 TC 17 Z9 17 U1 0 U2 0 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 JUL PY 2001 VL 8 IS 4 BP 252 EP 261 DI 10.1097/00062752-200107000-00012 PG 10 WC Hematology SC Hematology GA 473WD UT WOS:000171071100012 PM 11561164 ER PT J AU Tuveson, DA Fletcher, JA AF Tuveson, DA Fletcher, JA TI Signal transduction pathways in sarcoma as targets for therapeutic intervention SO CURRENT OPINION IN ONCOLOGY LA English DT Review ID GASTROINTESTINAL STROMAL TUMORS; NEUROFIBROMATOSIS TYPE-1 GENE; TYROSINE KINASE INHIBITOR; ROUND-CELL TUMOR; INFLAMMATORY MYOFIBROBLASTIC TUMOR; C-KIT; CONGENITAL FIBROSARCOMA; MESOBLASTIC NEPHROMA; INTERSTITIAL-CELLS; IN-VITRO AB Investigations into the molecular alterations in sarcomas have made substantial progress during the past decade. Classical linkage analysis and the direct sequencing of chromosomal translocation fusions have identified candidate genes in many different sarcomas, A large group of these genes participate in signal transduction pathways and represent potential sites of disease intervention with targeted therapies. This review will discuss five types of sarcoma that display aberrant tyrosine kinase pathway signaling: gastrointestinal stromal tumor, inflammatory myofibroblastic tumor, congenital fibrosarcoma and mesoblastic nephroma, dermatofibrosarcoma protuberans, and desmoplastic small round cell tumor; one sarcoma predisposition syndrome with specific dysregulation of the ras pathway-neurofibromatosis-will also be discussed. (C) 2001 Lippincott Williams & Wilkins, Inc. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. MIT, Ctr Canc, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fletcher, JA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 80 TC 19 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD JUL PY 2001 VL 13 IS 4 BP 249 EP 255 DI 10.1097/00001622-200107000-00007 PG 7 WC Oncology SC Oncology GA 447ZP UT WOS:000169602600007 PM 11429482 ER PT J AU Heymach, JV AF Heymach, JV TI Angiogenesis and antiangiogenic approaches to sarcomas SO CURRENT OPINION IN ONCOLOGY LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; SOFT-TISSUE SARCOMAS; TUMOR ANGIOGENESIS; KAPOSIS-SARCOMA; IONIZING-RADIATION; FUMAGILLIN ANALOG; FACTOR EXPRESSION; BREAST-CARCINOMA; FACTOR RECEPTOR; POOR-PROGNOSIS AB Established chemotherapy regimens for advanced or metastatic sarcoma generally have low response rates and substantial toxicity, and resistance often arises quickly, making sarcoma an ideal target for alternative treatment approaches. Antiangiogenic therapies have a number of potential advantages including decreased resistance, fewer side effects, and a broad spectrum of activity, This paper reviews the evidence supporting the use of antiangiogenic therapies for adult soft tissue sarcomas. Human sarcomas express a number of proangiogenic factors that may represent therapeutic targets, with vascular endothelial growth factor being the best characterized, and inhibitors of angiogenesis have antitumor activity in animal models of human sarcomas. Clinical trials are in early stages, although promising results have already been seen. In the future, improved drugs, refined molecular profiling of tumors, and new ways of combining antiangiogenic agents with cytotoxic agents may lead to more effective and tolerable therapies for sarcomas. (C) 2001 Lippincott Williams & Wilkins, Inc. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Heymach, JV (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 84 TC 26 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD JUL PY 2001 VL 13 IS 4 BP 261 EP 269 DI 10.1097/00001622-200107000-00009 PG 9 WC Oncology SC Oncology GA 447ZP UT WOS:000169602600009 PM 11429484 ER PT J AU Kachnic, LA Willett, CG AF Kachnic, LA Willett, CG TI Radiation therapy in the management of rectal cancer SO CURRENT OPINION IN ONCOLOGY LA English DT Review ID TERM FOLLOW-UP; POSTOPERATIVE ADJUVANT CHEMOTHERAPY; PROTRACTED-INFUSION FLUOROURACIL; THYMIDYLATE SYNTHASE EXPRESSION; SPHINCTER-SPARING SURGERY; TOTAL MESORECTAL EXCISION; HIGH-DOSE LEUCOVORIN; PREOPERATIVE RADIATION; LOCAL EXCISION; COLORECTAL-CANCER AB Substantial advances have been made in the adjuvant management of patients with resectable rectal cancer. Increasing interest in patient quality of life has promoted the use of radiation therapy to enhance sphincter-preserving surgical approaches as an alternative to the standard abdominoperineal resection. Because of the suggestion of enhanced sphincter preservation with preoperative therapy and the potential advantage of decreased acute morbidity, randomized trials comparing preoperative and postoperative adjuvant combined modality therapy are ongoing. Recent progress in adjuvant postoperative treatment regimens relates to the integration of systemic therapy to radiation, and redefining the techniques for both modalities. The incorporation of improved radiation planning may reduce treatment-related bower toxicity. The integration of novel chemotherapeutic agents in the adjuvant therapy of rectal cancer remains an active area of investigation. (C) 2001 Lippincott Williams & Wilkins. Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Kachnic, LA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. NR 61 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD JUL PY 2001 VL 13 IS 4 BP 300 EP 306 DI 10.1097/00001622-200107000-00014 PG 7 WC Oncology SC Oncology GA 447ZP UT WOS:000169602600014 PM 11429489 ER PT J AU Bush, AI AF Bush, AI TI Therapeutic targets in the biology of Alzheimer's disease SO CURRENT OPINION IN PSYCHIATRY LA English DT Article ID AMYLOID-BETA-PEPTIDE; PLACEBO-CONTROLLED TRIAL; A-BETA; MOUSE MODEL; SENILE PLAQUES; NEUROFIBRILLARY TANGLES; SUPEROXIDE-DISMUTASE; PRECURSOR PROTEIN; DOUBLE-BLIND; ZINC AB The cause of Alzheimer's disease is closely associated with the accumulation of beta -amyloid in the neocortex. The neurochemical factors responsible for precipitating this otherwise normal, soluble protein are contentious. Nevertheless, in the absence of any other curative treatment for Alzheimer's disease, the majority of the research effort has focussed on inhibiting the production of beta -amyloid (using secretase inhibitors) or destroying the protein (vaccination with synthetic peptide). Both approaches assume that the protein serves no purposive function, In contrast, a new alternative has recently emerged employing small metal complexing agents that inhibit the neurotoxic hydrogen peroxide produced by beta -amyloid, and which facilitate the dissolution of brain amyloid deposits in vivo in transgenic mice. Currently in clinical trials, this class of agent may interdict the Alzheimer disease process at its most generic biochemical level. Curr Opin Psychiatry 14:341-348. (C) 2001 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp East, Lab Oxidat Biol, Genet & Aging Unit, Charlestown, MA USA. Mental Hlth Res Inst Victoria, Parkville, Vic, Australia. RP Bush, AI (reprint author), Massachusetts Gen Hosp CAGN, Lab Oxidat Biol, Genet & Aging Unit, Bldg 114,16th St, Charlestown, MA 02129 USA. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 NR 58 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD JUL PY 2001 VL 14 IS 4 BP 341 EP 348 DI 10.1097/00001504-200107000-00018 PG 8 WC Psychiatry SC Psychiatry GA 455GD UT WOS:000170018400018 ER PT J AU Tekki-Kessaris, N Woodruff, R Hall, AC Gaffield, W Kimura, S Stiles, CD Rowitch, DH Richardson, WD AF Tekki-Kessaris, N Woodruff, R Hall, AC Gaffield, W Kimura, S Stiles, CD Rowitch, DH Richardson, WD TI Hedgehog-dependent oligodendrocyte lineage specification in the telencephalon SO DEVELOPMENT LA English DT Article DE telencephalon; hedgehog signalling; oligodendrocyte; rat; mouse ID SPINAL-CORD OLIGODENDROCYTES; CENTRAL-NERVOUS-SYSTEM; PDGF ALPHA-RECEPTOR; SONIC HEDGEHOG; GROWTH-FACTOR; MONOCLONAL-ANTIBODY; PROGENITOR CELLS; NEURAL-TUBE; OPTIC-NERVE; SUBVENTRICULAR ZONE AB In the caudal neural tube, oligodendrocyte progenitors (OLPs) originate in the ventral neuroepithelium under the influence of Sonic hedgehog (SHH), then migrate throughout the spinal cord and brainstem before differentiating into myelin-forming cells, We present evidence that oligodendrogenesis in the anterior neural tube follows a similar pattern, We show that OLPs in the embryonic mouse forebrain express platelet-derived growth factor alpha-receptors (PDGFRA), as they do in more caudal regions, They first appear within a region of anterior hypothalamic neuroepithelunm that co-expresses mRNA encoding SHH, its receptor PTC1 (PTCH) and the transcription factors OLIG1, OLIG2 and SOX10. Pdgfra-positive progenitors later spread through the forebrain into areas where Shh is not expressed, including the cerebral cortex, Cyclopamine inhibited OLP development in cultures of mouse basal forebrain, suggesting that hedgehog (HPI) signalling is obligatory for oligodendrogenesis in the ventral telencephalon, Moreover, Pdgfra-positive progenitors did not appear on schedule in the ventral forebrains of Nkx2.1 null mice, which lack the telencephalic domain of Shh expression. However, OLPs did develop in cultures of Nkx2.1(-/-) basal forebrain and this was blocked by cyclopamine. OLPs also developed in neocortical cultures, even though Shh transcripts could not be detected in the embryonic cortex, Here, too, the appearance of OLPs was suppressed by cyclopamine. In keeping with these findings, we detected mRNA encoding SHH and Indian hedgehog (IHH) in both Nkx2.1(-/-) basal forebrain cultures and neocortical cultures, Overall, the data are consistent with the idea that OLPs in the telencephalon, possibly even some of those in the cortex, develop under the influence of SHH in the ventral forebrain. C1 UCL, Wolfson Inst Biomed Res, London WC1E 6AE, England. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. USDA ARS, Western Reg Res Ctr, Albany, CA 94710 USA. RP Richardson, WD (reprint author), UCL, Wolfson Inst Biomed Res, Cruciform Bldg,Gower St, London WC1E 6AE, England. EM w.richardson@ucl.ac.uk RI Richardson, William/C-1762-2008 OI Richardson, William/0000-0001-7261-2485 NR 65 TC 209 Z9 214 U1 0 U2 5 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 JUL PY 2001 VL 128 IS 13 BP 2545 EP 2554 PG 10 WC Developmental Biology SC Developmental Biology GA 454JE UT WOS:000169968800012 PM 11493571 ER PT J AU Raftery, LA Sutherland, DJ AF Raftery, LA Sutherland, DJ TI BMP- and Sog-dependent thresholds of Smad activation during Drosophila dorsal-ventral patterning. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. RI Raftery, Laurel/H-1406-2012 OI Raftery, Laurel/0000-0003-4797-4163 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 5 BP 172 EP 173 PG 2 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100015 ER PT J AU Sun, T Lu, R Stiles, C Echelard, Y Rowitch, D AF Sun, T Lu, R Stiles, C Echelard, Y Rowitch, D TI Ectopic expression of Olig1 is deleterious to V3 interneuron development in the developing CNS. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 238 BP 222 EP 222 PG 1 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100217 ER PT J AU Noramly, S Houghton, L Broun, M Shimizu, H Morgan, B AF Noramly, S Houghton, L Broun, M Shimizu, H Morgan, B TI Inductive signals that initiate feather bud development. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 266 BP 228 EP 228 PG 1 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100242 ER PT J AU Huang, NN Mootz, D Walhout, AJ Vidal, M Hunter, CP AF Huang, NN Mootz, D Walhout, AJ Vidal, M Hunter, CP TI MEX-3-interacting proteins link cell polarity to asymmetric gene expression in Caenorhabditis elegans. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 276 BP 230 EP 231 PG 2 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100252 ER PT J AU de Santa Barbara, P Faure, S Whitman, M Roberts, DJ AF de Santa Barbara, P Faure, S Whitman, M Roberts, DJ TI Endogenous patterns of BMP signaling during chicken development. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 390 BP 256 EP 256 PG 1 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100355 ER PT J AU Kenyon, KL Clouser, CR Pignoni, F AF Kenyon, KL Clouser, CR Pignoni, F TI Isolation of factors that directly interact with sine oculis. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 466 BP 273 EP 273 PG 1 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100425 ER PT J AU Raftery, LA Dobens, LL AF Raftery, LA Dobens, LL TI Drosophila bunched maintains a cell fate boundary by regulating Notch signaling. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RI Raftery, Laurel/H-1406-2012 OI Raftery, Laurel/0000-0003-4797-4163 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 464 BP 273 EP 273 PG 1 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100423 ER PT J AU Roman, BL Pham, VN Childs, S Lekven, AC Neubaum, D Moon, RT Fishman, MC Weinstein, BM AF Roman, BL Pham, VN Childs, S Lekven, AC Neubaum, D Moon, RT Fishman, MC Weinstein, BM TI The zebrafish mutant violet beauregarde exhibits abnormal cranial blood vessel development due to a lesion in alk1, the gene responsible for human hereditary hemorrhagic telangiectasia type II. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NICHD, LMG, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, CVRC, Charlestown, MA 02129 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 555 BP 293 EP 294 PG 2 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100505 ER PT J AU Heller, RS Stoffers, DA Bock, T Svenstrup, K Jensen, J Horn, T Miller, CP Habener, JF Madsen, OD Serup, P AF Heller, RS Stoffers, DA Bock, T Svenstrup, K Jensen, J Horn, T Miller, CP Habener, JF Madsen, OD Serup, P TI Improved glucose tolerance and acinar dysmorphogenesis by targeted expression of transcription factor PDX-1 to the exocrine pancreas SO DIABETES LA English DT Article ID HOMEODOMAIN PROTEIN IDX-1; TRANSGENIC MICE; ARBITRARY PARTICLES; UNBIASED ESTIMATION; INSULIN GENE; ISLET CELLS; BETA; NUMBER; ONSET; DIFFERENTIATION AB The homeodomain protein PDX-1 is critical for pancreas development and is a key regulator of insulin gene expression. PDX-1 nullizygosity and haploinsufficiency in mice and humans results in pancreatic agenesis and diabetes, respectively. At embryonic day (e) 10.5, PDX-1 is expressed in all pluripotential gut-derived epithelial cells destined to differentiate into the exocrine and endocrine pancreas. At e15, PDX-1 expression is downregulated in exocrine cells, but remains high in endocrine cells. The aim of this study was to determine whether targeted overexpression of PDX-1 to the exocrine compartment; of the developing pancreas at e15 would allow for respecification of the exocrine cells. Transgenic (TG) mice were generated in which PDX-1 was expressed in the exocrine pancreas using the exocrine-specific elastase-1 promoter. These mice exhibited a marked dysmorphogenesis of the exocrine pancreas, manifested by increased rates of replication and apoptosis in acinar cells and a progressive fatty infiltration of the exocrine pancreas with age. Interestingly, the TG mice exhibited improved glucose tolerance, but absolute beta -cell mass was not increased. These findings indicate that downregulation of PDX-1 is required for the proper maintenance of the exocrine cell phenotype and that upregulation of PDX-1 in acinar cells affects beta -cell function. The mechanisms underlying these observations remain to be elucidated. C1 Hagedorn Res Inst, Dept Dev Biol, DK-2820 Gentofte, Denmark. Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. Genet Inst, Cambridge, MA 02140 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Lab Mol Endocrinol, Boston, MA USA. HS Kommunehosp, Bartholin Inst, Copenhagen, Denmark. Herlev Hosp, Dept Pathol, DK-2730 Herlev, Denmark. RP Heller, RS (reprint author), Hagedorn Res Inst, Dept Dev Biol, DK-2820 Gentofte, Denmark. RI Heller, R.Scott/A-7279-2008; Madsen, Ole/A-7415-2011; Serup, Palle/A-7407-2011; Stoffers, Doris/H-6157-2012; OI Madsen, Ole/0000-0002-2753-5203; Serup, Palle/0000-0002-0858-590X; Jensen, Jan/0000-0003-0657-4032 FU NIDDK NIH HHS [DK-30547] NR 30 TC 43 Z9 43 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2001 VL 50 IS 7 BP 1553 EP 1561 DI 10.2337/diabetes.50.7.1553 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 447LX UT WOS:000169575800006 PM 11423476 ER PT J AU Jovanovic, L Knopp, RH Brown, Z Conley, MR Park, E Mills, JL Metzger, BE Aarons, JH Holmes, LB Simpson, JL AF Jovanovic, L Knopp, RH Brown, Z Conley, MR Park, E Mills, JL Metzger, BE Aarons, JH Holmes, LB Simpson, JL CA Nalt Inst Child Hlth Human Dev Dia TI Declining insulin requirement in the late first trimester of diabetic pregnancy SO DIABETES CARE LA English DT Article ID GLUCOSE-TOLERANCE; WOMEN; INFANTS; MOTHERS AB OBJECTIVE - To investigate whether pregnancies complicated by type 1 diabetes are associated with a decrease in first-trimester insulin requirement. RESEARCH DESIGN AND METHODS - We examined the weekly insulin requirement (as units per kilogram per day) during the first trimester of pregnancy in diabetic women in the Diabetes in Early Pregnancy Study (DIEP) viith accurate gestational dating, regular glucose monitoring, daily insulin-dose recording, and monthly glycohemoglobin measurements. RESULTS - In pregnancies that resulted in live-born full-term singleton infants, a significant 18% increase in mean weekly dosage was observed between weeks 3 and 7 (P = 0.000), followed by a significant 9% decline from week 7 through week 15 (P = 0.000). Further testing localized a significant change in insulin dose in the interval beginning weeks 7-8 and ending weeks 11-12 (P = 0.014). Within this interval, the maximum decrease was between weeks 9 and 10 (mean), 10 and Il (median), and 8 and 9 (most frequent maximal decrease). To determine whether prior poor glucose control exaggerated these trends, we categorized the women based on their glycohemoglobin values: <2 SDs above the mean of a normal population (subgroup 1), 2-4 SDs (subgroup 2), and >4 SDs (subgroup 3) at baseline. Late first-trimester declines in dosage were statistically significant in subgroup 2 (P = 0.002) and subgroups 2 and 3 together (P = 0.003). Similarly, women with BMI > 27.0 had a greater initial insulin rise and then fall compared with leaner women. CONCLUSIONS - Observations in the DIEP cohort disclose a mid-first-trimester decline in insulin requirement in type 1 diabetic pregnant women. Possible explanations include over-insulinization of previously poorly controlled diabetes, a transient decline in progesterone secretion during the late first-trimester luteo-placental shift in progesterone secretion, or other hormonal shifts. Clinicians should anticipate a clinically meaningful reduction in insulin requirement in the 5-week interval between weeks 7 and 12 of gestation. C1 Sansum Med Res Inst, Santa Barbara, CA 93105 USA. Univ Washington, NW Lipid Res Clin, Seattle, WA 98195 USA. Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. NICHHD, Epidemiol Branch, Bethesda, MD 20892 USA. NICHHD, Biometry Branch, Bethesda, MD 20892 USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. Univ Pittsburgh, Magee Womens Hosp, Dept Med, Pittsburgh, PA 15213 USA. Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. RP Jovanovic, L (reprint author), Sansum Med Res Inst, 2219 Bath St, Santa Barbara, CA 93105 USA. FU NCRR NIH HHS [RR-00037-28, RR-48]; PHS HHS [CRC R0047] NR 29 TC 36 Z9 39 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2001 VL 24 IS 7 BP 1130 EP 1136 DI 10.2337/diacare.24.7.1130 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 446NU UT WOS:000169520000002 PM 11423491 ER PT J AU Galluzzi, JR Cupples, LA Meigs, JB Wilson, PWF Schaefer, EJ Ordovas, JM AF Galluzzi, JR Cupples, LA Meigs, JB Wilson, PWF Schaefer, EJ Ordovas, JM TI Association of the ala54-thr polymorphism in the intestinal fatty acid-binding protein with 2-h postchallenge insulin levels in the Framingham Offspring Study SO DIABETES CARE LA English DT Article ID CORONARY HEART-DISEASE; CANDIDATE GENES; GLUCOSE-TOLERANCE; CODON-54 POLYMORPHISM; DIABETES-MELLITUS; MEXICAN-AMERICANS; JAPANESE SUBJECTS; OBESE SUBJECTS; PIMA-INDIANS; RAT-LIVER AB OBJECTIVE - To investigate the association of variants of the intestinal fatty acid-binding protein gene (FABP2) with Easting and postchallenge glucose and insulin levers, HbA(1c), and prevalence of type 2 diabetes in a separate sample of men and women. RESEARCH DESIGN AND METHODS - Subjects were participants in the Framingham Offspring Study, a long-term community-based prospective observational study of risk factors for cardiovascular disease. The study sample consisted of 762 men and 922 women. RESULTS - In women, carriers of the thr54 allele had significantly higher 2-h postchallenge insulin levels than noncarriers (104.4 +/- 73.0 vs. 93.4 +/- 61.5 muU/ml; P = 0.0139). This relationship remained significant after adjustment for familial relationship, age, BMI, triglycerides, APOE genotype, smoking, alcohol intake, the use of P-blockers, menopausal status, and estrogen therapy. No such significant association was observed in men. In both men and women, there were no statistical associations between the FABP2 polymorphism and BMI, fasting glucose, fasting insulin, 2-h postchallenge glucose levels, HbA(1c), and prevalence of type 2 diabetes. CONCLUSIONS - These results suggest that the FABP2 thr54 allele may have a minor contribution to the insulin resistance syndrome in a white general population. C1 Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Lipid Metab Lab, Boston, MA 02111 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Gen Internal Med, Boston, MA 02114 USA. NHLBI, Framington Heart Study, Framingham, MA USA. RP Galluzzi, JR (reprint author), Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Lipid Metab Lab, 711 Washington St, Boston, MA 02111 USA. OI Ordovas, Jose/0000-0002-7581-5680 FU NHLBI NIH HHS [HL54776]; NIA NIH HHS [AG00209-09] NR 47 TC 33 Z9 33 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2001 VL 24 IS 7 BP 1161 EP 1166 DI 10.2337/diacare.24.7.1161 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 446NU UT WOS:000169520000007 PM 11423496 ER PT J AU Fineberg, SE Bergenstal, RM Bernstein, RM Laffel, LM Schwartz, SL AF Fineberg, SE Bergenstal, RM Bernstein, RM Laffel, LM Schwartz, SL TI Use of an automated device for alternative site blood glucose monitoring SO DIABETES CARE LA English DT Article ID ACCURACY AB OBJECTIVE - To evaluate the accuracy, comfort, and ease of use of a new automated device for blood glucose monitoring using the arm as an alternative sampling site. RESEARCH DESIGN AND METHODS- These studies use an automated hand-held device that applies a small vacuum, lances the skin, transfers blood onto an electrochemical test strip, and measures glucose. Patients who had type 1 or type 2 diabetes and had received no prior training using this device were recruited from five diabetes clinics. Testing was performed by the patients using this device and by trained healthcare professionals. Blood glucose was measured by 354 patients: from the arm using the device, from the finger using a laboratory reference instrument, and from the finger using the device via the secondary test port. Each patient completed a questionnaire rating the level of pain and ease of use of the device. RESULTS - Blood glucose results in samples obtained from the arm with the automated device agreed well with finger stick plasma glucose results using a reference instrument (regression slope 0.98, intercept 0.01 mmol/l [0.1 mg/dl], r = 0.96). Error grid analysis showed that 100% of the measurements fell within zones A and B. In the survey, 60% of the patients reported that arm testing with the automated device was "painless;" another 31% of the patients stated that it was "much less painful," and 6% of patients considered using the device "less painful" than finger-stick testing. In a survey containing 15 questions for rating the ease of use with a scale of 1 to 6, the overall mean rating was 5.5. CONCLUSIONS- The automated device is easy to use and provides accurate glucose results; 97% of the patients found it less painful than finger-stick testing. C1 Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. Reg Endocrinol Associates, Santa Fe, NM USA. Int Diabet Ctr, Minneapolis, MN USA. Reg Endocrinol Associates, Santa Fe, NM USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Diabet & Glandular Dis Clin, San Antonio, TX USA. RP Fineberg, SE (reprint author), Indiana Univ, Med Ctr, Wishard Hosp, W Bldg,M200, Indianapolis, IN 46202 USA. NR 11 TC 21 Z9 21 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2001 VL 24 IS 7 BP 1217 EP 1220 DI 10.2337/diacare.24.7.1217 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 446NU UT WOS:000169520000016 PM 11423505 ER PT J AU Delamater, AM Jacobson, AM Anderson, B Cox, D Fisher, L Lustman, P Rubin, R Wysocki, T AF Delamater, AM Jacobson, AM Anderson, B Cox, D Fisher, L Lustman, P Rubin, R Wysocki, T TI Psychosocial therapies in diabetes - Report of the psychosocial therapies working group SO DIABETES CARE LA English DT Review ID QUALITY-OF-LIFE; INTENSIVE INSULIN THERAPY; OB-OB MICE; METABOLIC CONTROL; GLYCEMIC CONTROL; EATING DISORDERS; CONTROLLED TRIAL; SELF-CARE; PSYCHIATRIC-DISORDERS; REGIMEN ADHERENCE AB OBJECTIVE - To review key advances in the behavioral science literature related to psychosocial issues and therapies for persons with diabetes, to discuss barriers to research progress, and to make recommendations for future research. RESEARCH DESIGN AND METHODS - Key findings from the literature on psychosocial research in diabetes are reviewed separately for children and adults. Specific issues covered include psychosocial adjustment and psychiatric disorders, neurocognitive functioning, quality of life, and psychosocial therapies. Barriers that must be addressed to allow research in this area to progress are discussed. Recommendations are then made concerning high-priority areas for advancing research in the field. CONCLUSIONS - A substantial amount of behavioral science research has demonstrated that psychosocial factors play an integral role in the management of diabetes in both children and adults. Research has also shown the efficacy of a number of psychosocial therapies that can improve regimen adherence, glycemic control, psychosocial functioning, and qualify of life. More research in this area is needed to develop psychosocial intervention programs for specific patient populations and to demonstrate the cost-effectiveness of these approaches. C1 Univ Miami, Sch Med, Dept Pediat, Miami, FL 33101 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Cambridge, MA 02138 USA. Univ Virginia, Charlottesville, VA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Washington Univ, St Louis, MO USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Nemours Clin, Jacksonville, FL USA. RP Delamater, AM (reprint author), Univ Miami, Sch Med, Dept Pediat, POB 016820, Miami, FL 33101 USA. NR 111 TC 131 Z9 139 U1 12 U2 25 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2001 VL 24 IS 7 BP 1286 EP 1292 DI 10.2337/diacare.24.7.1286 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 446NU UT WOS:000169520000027 PM 11423517 ER PT J AU Campbell, AP AF Campbell, AP TI Health benefits of dietary fiber for people with diabetes SO DIABETES EDUCATOR LA English DT Article ID CORONARY HEART-DISEASE; RISK; CANCER; MEN C1 Joslin Clin, Boston, MA 02215 USA. RP Campbell, AP (reprint author), Joslin Clin, 1 Joslin Pl, Boston, MA 02215 USA. NR 5 TC 0 Z9 0 U1 3 U2 6 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 JUL-AUG PY 2001 VL 27 IS 4 BP 511 EP 514 DI 10.1177/014572170102700406 PG 4 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 454JH UT WOS:000169969100005 PM 12212339 ER PT J AU McKee, GT Tambouret, RH Finkelstein, D AF McKee, GT Tambouret, RH Finkelstein, D TI Fine-needle aspiration cytology of the breast: Invasive vs. in situ carcinoma SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE fine-needle aspirates; breast; invasive; in situ; carcinoma ID DUCTAL CARCINOMA; IN-SITU; MAMMOGRAPHIC FEATURES; INSITU; DIAGNOSIS; CANCER; MASSES AB The surgical management of invasive breast carcinoma differs from that of in situ disease. Invasive carcinoma necessitates axillary lymph node dissection, a procedure that has associated morbidity. We studied 80 cases (66 invasive, 14 in situ) of breast carcinoma that had a histological diagnosis and a preoperative fine-needle aspirate. All slides were reviewed, with 17 cytologic features assessed. We found that six of these features showed a statistically significant difference between the invasive and in situ cases. These were infiltration of fat or stroma by malignant cells (72% of invasive cases demonstrated this feature, but it was not present in any of the in situ cases, P = 0.0002), the presence of myoepithelial cells overlying clusters of tumor cells (seen in 86% of in situ tumors and 7% of invasive cases. P < 0.00001), calcification (present in 71% of in situ and 15% of the invasive group, P = 0.001), foamy macrophages (noted in 64% of in situ tumors and 16% of invasive carcinomas, P = 0.0007), intracytoplasmic vacuoles (seen in 50% of invasive cases and 21% of in situ lesions, P = 0.08), and tubules (present in 30% of invasive and 7% of in situ tumors, P = 0.10). We demonstrate that invasion can be suggested in fine-needle aspirates of carcinomas. provided that true infiltration of fibrofatty connective tissue by neoplastic cells is present. In situ disease has characteristic features, but the presence of invasion cannot be excluded, even in the presence of stromal or adipose tissue fragments without tumor infiltration. (C) 2001 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Cytopathol, Boston, MA 02493 USA. RP McKee, GT (reprint author), Massachusetts Gen Hosp, Dept Cytopathol, WRN 2,55 Fruit St, Boston, MA 02493 USA. NR 25 TC 29 Z9 29 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 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD JUL PY 2001 VL 25 IS 1 BP 73 EP 77 DI 10.1002/dc.2006 PG 5 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 448YG UT WOS:000169657100011 PM 11466818 ER PT J AU Kobayashi, T Kishimoto, J Ge, YM Jin, W Hudson, DL Ouahes, N Ehama, R Shinkai, H Burgeson, RE AF Kobayashi, T Kishimoto, J Ge, YM Jin, W Hudson, DL Ouahes, N Ehama, R Shinkai, H Burgeson, RE TI A novel mechanism of matrix metalloproteinase-9 gene expression implies a role for keratinization SO EMBO REPORTS LA English DT Article ID CULTURED HUMAN KERATINOCYTES; IV COLLAGENASE; TISSUE INHIBITOR; TERMINAL DIFFERENTIATION; EPIDERMAL-KERATINOCYTES; INVOLUCRIN GENE; GELATINASE; APOPTOSIS; CELLS; IDENTIFICATION AB To investigate the pathophysiological role of matrix metalloproteinase (MMP)-9 in the skin, we analyzed MMP-9 expression from human keratinocytes in culture. MMP-9 and the terminal differentiation marker involucrin were co-localized in the same keratinocytes with a high concentration of Ca2+, a potent stimulator of differentiation. We identified the novel KRE-M9 element, further downstream to the previously reported TPA responsive element in the MMP-9 promoter, and both of these two elements were shown to be important for MMP-9 transcription and Ca2+ induction. The concomitant upregulation of MMP-9 and involucrin transcripts was probably due to the very similar gene regulatory elements, KRE-M9 and KRE-4 in their respective promoters. These results indicate a novel mechanism of transcriptional regulation for MMP-9 in the process of keratinization, implying the probable association of apoptosis and differentiation of keratinocytes in epidermal skin tissue. C1 Chiba Univ, Sch Med, Dept Dermatol, Chuo Ku, Chiba 2608670, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr,Dept Dermatol, Charlestown, MA 02129 USA. RP Kobayashi, T (reprint author), Chiba Univ, Sch Med, Dept Dermatol, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan. NR 25 TC 36 Z9 36 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD JUL PY 2001 VL 2 IS 7 BP 604 EP 608 DI 10.1093/embo-reports/kve129 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 454GH UT WOS:000169964500013 PM 11463743 ER PT J AU Huang, JS Grinspoon, S AF Huang, JS Grinspoon, S TI HIV and bone metabolism SO ENDOCRINOLOGIST LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; MINERAL DENSITY; INFECTION; WOMEN; MEN; OSTEOPOROSIS; DISORDERS; NECROSIS; CELLS AB Reduced bone density and abnormal bone turnover has recently been reported in HIV-infected patients receiving antiretroviral therapy. In addition, recent data suggest that individuals infected with HIV are at an increased risk for avascular necrosis. A number of factors, including potential medication toxicity, undernutrition, hypogonadism, abnormalities in calcium homeostasis, or HIV infection itself, may be contributing to the bone pathology in this population. However, the specific mechanisms of the disordered bone turnover and reduced bone density in HIV-infected patients have not yet been identified. Moreover, the associated vertebral fracture risk of this newly identified osteopenia in the HIV-infected population has yet to be fully assessed. This paper reviews the literature to date on bone metabolism in HIV-infected patients, highlighting possible etiologies and contributors to the observed reduction in bone density in this population. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL457B,55 Fruit St, Boston, MA 02114 USA. NR 39 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD JUL-AUG PY 2001 VL 11 IS 4 BP 269 EP 274 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 461CK UT WOS:000170347200004 ER PT J AU Shimizu, M Carter, PH Khatri, A Potts, JT Gardella, TJ AF Shimizu, M Carter, PH Khatri, A Potts, JT Gardella, TJ TI Enhanced activity in parathyroid hormone-(1-14) and -(1-11): Novel peptides for probing ligand-receptor interactions SO ENDOCRINOLOGY LA English DT Article ID N-TERMINAL REGION; PTH RECEPTOR; SELECTIVITY; RESIDUES AB The amino-terminal portion of PTH is critical for PTH-1 receptor (P1Rc) activation. In exploring this component of the ligand receptor interaction, we recently showed that the agonist potency of the weakly active PTH-(1-14)NH2 peptide can be enhanced by natural amino acid substitutions at several positions, including position 11 (normally leucine). Here we show that the potency of PTH-(1-14)NH2 can be enhanced by using nonnatural amino acids that increase the length and polarizability of the position 11 side-chain. Thus, in LLC-PK1 cells stably expressing high levels of the human P1Rc, [homoarginine([Har)(11)]PTH-(1-14)NH2 was 30-fold more potent for cAMP production than was native PTH-(1-14)NH2. Combining the homoarginine-11 substitution with other recently identified activity-enhancing substitutions yielded [Ala(3,12),Gln(10),Har(11),Trp(14)]PTH-(1-14)NH2, which was 1500-fold more potent than PTH-(1-14)NH2 (EC50 = 0.12 +/- 0.04 and 190 +/- 20 muM, respectively) and only 63-fold less potent than PTH-(1-34) (EC50 = 1.9 +/- 0.5 nM). The even shorter analog [Ala(3),Gln(10),Har(11)] PTH-( 1-11)NH2 was also a full cAMP agonist (EC50 = 3.1 +/- 1.5 muM) Receptor mutations at Phe(184) and Leu(187) located near the boundary of the amino-terminal domain and transmembrane domain-1 severely impaired responsiveness to the PTH(1-11) analog. Overall, these studies demonstrate that PTH analogs of only 11 amino acids are sufficient for activation of the PTH-1 receptor through interaction with its juxtamembrane region. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Biopolymer Core Facil, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Gardella, TJ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-11794] NR 26 TC 47 Z9 49 U1 0 U2 6 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 JUL PY 2001 VL 142 IS 7 BP 3068 EP 3074 DI 10.1210/en.142.7.3068 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 445XX UT WOS:000169484800042 PM 11416029 ER PT J AU Proctor, SP Rosenman, E Sparrow, D Hu, H AF Proctor, SP Rosenman, E Sparrow, D Hu, H TI Examination of a computer-assisted 'hold test' (the NES vocabulary test) as a measure of basic academic skills SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 VA Boston Healthcare Syst, Boston Environm Hazards Ctr, Boston, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. VA Boston Healthcare Syst, Normat Aging Study, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, Cambridge, MA 02138 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 347 BP S67 EP S67 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500316 ER PT J AU Shiraishi, H Watanabe, Y Watanabe, M Inoue, Y Fujiwara, T Yagi, K AF Shiraishi, H Watanabe, Y Watanabe, M Inoue, Y Fujiwara, T Yagi, K TI Interictal and ictal magnetoencephalographic study in patients with medial frontal lobe epilepsy SO EPILEPSIA LA English DT Article DE MEG; frontal lobe epilepsy; medial cortex; midline EEG spikes ID EMISSION COMPUTED-TOMOGRAPHY; INTRACRANIAL LOCALIZATIONS; MIDLINE SPIKES; MAGNETIC-FIELD; STIMULATION; SEIZURES; AGREES; BRAIN; EEG AB Purpose: To determine whether magnetoencephalography (MEG) has any clinical value for the analysis of seizure discharges in patients with medial frontal lobe epilepsy (FLE). Methods: Four patients were studied with 74-channel MEG. Interictal and ictal electroencephalographic (EEG) and MEG recordings were obtained. The equivalent current dipoles (ECDs) of the MEG spikes were calculated. Results: In two patients with postural seizures, interictal EEG spikes occurred at Cz or Fz. The ECDs of interictal MEG spikes were localized around the supplementary motor area. In the other two patients with focal motor or oculomotor seizures, interictal EEG spikes occurred at Fz or Cz. The ECDs of interictal MEG spikes were localized at the top of the medial frontal region. The ECDs detected at MEG ictal onset were also localized in the same area as those of the interictal discharges. Conclusions: In medial FLE patients, interictal and ictal MEG indicated consistent ECD localization that corresponded to the semiology of clinical seizures. Our findings demonstrate that MEG is a useful tool for detecting epileptogenic focus. C1 Shizuoka Higashi Hosp, Natl Epilepsy Ctr, Shizuoka, Japan. RP Shiraishi, H (reprint author), Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Room 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM shiraishi@nmr.mgh.harvard.edu RI Shiraishi, Hideaki/A-8427-2012 NR 22 TC 51 Z9 51 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUL PY 2001 VL 42 IS 7 BP 875 EP 882 DI 10.1046/j.1528-1157.2001.042007875.x PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 466TE UT WOS:000170661000010 PM 11488887 ER PT J AU Alvarez, B Quinn, LS Busquets, S Lopez-Soriano, FJ Argiles, JM AF Alvarez, B Quinn, LS Busquets, S Lopez-Soriano, FJ Argiles, JM TI Direct effects of tumor necrosis factor alpha (TNF-alpha) on murine skeletal muscle cell lines. Bimodal effects on protein metabolism SO EUROPEAN CYTOKINE NETWORK LA English DT Article DE cytokines; myotubes; cachexia; protein turnover ID UBIQUITIN GENE-EXPRESSION; GROWTH-FACTOR-I; INSULIN-RESISTANCE; CANCER CACHEXIA; MEDIATES CHANGES; RAT; CYTOKINES; RECEPTORS; TURNOVER; PLASMA AB Incubation of murine C2C12 myotubes with tumour necrosis factor-alpha (TNF-alpha) leads to significant changes in protein content and turnover, suggesting that the cytokine exerts direct effects in skeletal muscle. The effects of the cytokine on protein content show a clear bimodal behaviour. At low concentrations (1 U/ml or less), TNF-alpha decreases both total and myofibrillar protein content, while at relatively high concentrations (100 U/ml or more), the effects are opposite and TNF-alpha increases the total and myofibrillar protein content in C2C12 myotubes. The mechanisms responsible for this latter, unexpected anabolic effect of the cytokine on muscle cells are related to a 40% increase in the rate of protein synthesis and to a significant decrease (14%) in the rate of protein degradation. At high concentrations, TNF-alpha decreased the expression of the mRNA of components of both the ATP- (ubiquitin, E2, C8) and Call-dependent (m-calpain) proteolytic systems. The effects of TNF-alpha (10 U/ml or higher) on protein content of cultured murine myotubes (differentiated myogenic cells) were similar to those induced by insulin (1 or 5 mug/ml), but the effects of TNF-alpha and those of insulin were not additive. Experiments using inhibitors of the signalling pathways mediated by PI3K and MAP kinases (MAPKs) ERK1/2 and p38 suggest that insulin and TNF-alpha may share some intracellular signalling pathways involving MAPKs in the enhanced protein accretion observed in the muscle cell cultures. C1 Univ Barcelona, Fac Biol, Dept Bioquim & Biol Mol, Canc Res Grp, Barcelona 08028, Spain. Ctr Geriatr Res Educ & Clin, VA Puget Sound Hlth Care Syst, Tacoma, WA 98493 USA. RP Argiles, JM (reprint author), Univ Barcelona, Fac Biol, Dept Bioquim & Biol Mol, Canc Res Grp, Diagonal 645, Barcelona 08028, Spain. EM argiles@porthos.bio.ub.es NR 49 TC 29 Z9 30 U1 2 U2 5 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD JUL-SEP PY 2001 VL 12 IS 3 BP 399 EP 410 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 522VX UT WOS:000173918600003 PM 11566620 ER PT J AU Schneider, H Dias, SD Hu, H Rudd, CE AF Schneider, H Dias, SD Hu, H Rudd, CE TI A regulatory role for cytoplasmic YVKM motif in CTLA-4 inhibition of TCR signaling SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CTLA-4; YVKM motif; T cell signaling; phosphatidylinositol 3-kinase; AP-2 ID T-CELL ACTIVATION; LYMPHOCYTE-ASSOCIATED MOLECULE-4; KINASE PHOSPHATIDYLINOSITOL 3-KINASE; CLATHRIN-ASSOCIATED PROTEIN; TYROSINE PHOSPHORYLATION; ANTIGEN RECEPTOR; DISTINCT ROLES; CUTTING EDGE; IN-VIVO; CD28 AB CTLA-4 negatively regulates TCR signaling, although the molecular basis for this effect has yet to be elucidated. The cytoplasmic YVKM motif, white binding to phosphatidylinositol 3-kinase, SHP-2 and the AP-1/AP-2 clathrin adaptor complexes, has been reported to play no role in CTLA-4 function. In contrast, in this study We demonstrate that, although not essential, the YVKM motif contributes to optimal CTLA-4 blockage of TCR zeta or combined TCR zeta /CD28 signaling. Significantly, dependency on the YVKM motif varied with the mode of anti-receptor presentation, where soluble antibody ligation was more dependent on the presence of the motif than immobilized antibody. Previous studies have mainly relied on the use of immobilized, antibody. Neither SHP-2 binding, alterations in TCR zeta chain phosphorylation, nor ZAP-70 recruitment was involved in CTLA-4 wild-type or mutant inhibition. Overall, our findings clearly implicate the YVKM motif in optimal CTLA-4 function. C1 Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Dept Haematol, London W12 0NN, England. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Rudd, CE (reprint author), Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Dept Haematol, London W12 0NN, England. NR 43 TC 25 Z9 25 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 2001 VL 31 IS 7 BP 2042 EP 2050 DI 10.1002/1521-4141(200107)31:7<2042::AID-IMMU2042>3.0.CO;2-D PG 9 WC Immunology SC Immunology GA 452DJ UT WOS:000169841600012 PM 11449357 ER PT J AU Young, SH Walsh, JH Rozengurt, E Slice, LW AF Young, SH Walsh, JH Rozengurt, E Slice, LW TI Agonist-dependent immobilization of chimeric bombesin/GRP receptors: Dependence on c-Src activity and dissociation from internalization SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE bombesin receptor; GCPR; GFP; FRAP; Src ID GASTRIN-RELEASING PEPTIDE; PROTEIN-COUPLED RECEPTORS; LATERAL MOBILITY; HUMAN NEUTROPHILS; KINASE-C; TYROSINE PHOSPHORYLATION; FLUORESCENCE RECOVERY; HORMONE RECEPTOR; BINDING; ACTIVATION AB G-protein-coupled receptors (GPCRs) are membrane proteins that exhibit a decreased mobile fraction compared to a freely mobile plasma membrane protein. Recently, interest has focused on proteins other than heterotrimeric G-proteins that interact with GPCRs as scaffolding structures that affect receptor signal transduction. In order to investigate the physical state of receptors before and after agonist, we used fluorescence recovery after photobleaching of the bombesin/gastrin-releasing peptide (GRP) receptor fused to the intrinsically fluorescent green fluorescent protein (GFP-GRP receptor) expressed in KNRK cells to measure both the fraction of mobile receptors and their diffusion rate before and after agonist stimulation. In live cells at 37 degreesC, addition of GRP (100 nM) caused a rapid decrease in GFP-GRP receptor mobile fraction from 0.8 +/- 0.1 to 0.49 +/- 0.05, which was independent of endocytosis, Concurrently, the remaining mobile GFP-GRP receptors showed an increase in the diffusion rate with the halftime of fluorescent recovery, tau (1/2) = 46 +/- 7 s for untreated cells, decreasing to tau (1/2) = 30 +/- 6 s for cells treated with GRP. Prior treatment with the Src-specific inhibitor PP-2 (10 muM) blocked GFP-GRP receptor immobilization while treatment with the inactive analog PP-3 (10 muM) did not affect receptor immobilization, These data suggest that agonist-bound GPCR have increased plasma membrane diffusion rates but an increased affinity for immobilization into a multiprotein complex that is mediated by Src activity. (C) 2001 Academic Press. C1 Univ Calif Los Angeles, Greater Los Angeles VA Med Ctr, Digest Dis Res Ctr, CURE,Dept Med,Div Digest Dis, Los Angeles, CA 90095 USA. RP Slice, LW (reprint author), Univ Calif Los Angeles, Greater Los Angeles VA Med Ctr, Digest Dis Res Ctr, CURE,Dept Med,Div Digest Dis, 900 Vet Ave, Los Angeles, CA 90095 USA. FU NIDDK NIH HHS [DK35740, DK17294, DK59630] NR 37 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUL 1 PY 2001 VL 267 IS 1 BP 37 EP 44 DI 10.1006/excr.2001.5245 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 447YK UT WOS:000169599900004 PM 11412036 ER PT J AU Van Remmen, H Richardson, A AF Van Remmen, H Richardson, A TI Oxidative damage to mitochondria and aging SO EXPERIMENTAL GERONTOLOGY LA English DT Review DE aging; oxidative damage; mitochondria ID PERMEABILITY TRANSITION PORE; ADENINE-NUCLEOTIDE TRANSLOCASE; AGE-RELATED-CHANGES; CELL-DEATH; DIETARY RESTRICTION; SUBMITOCHONDRIAL PARTICLES; LIPID-PEROXIDATION; HYDROGEN-PEROXIDE; FOOD RESTRICTION; POINT MUTATIONS AB Oxidative damage has been implicated to be a major factor in the decline in physiologic function that occurs during the aging process. Because mitochondria are a primary site of generation of reactive oxygen species, they have become a major focus of research in this area. Increased oxidative damage to mitochondrial proteins, lipid and DNA has been reported to occur with age in several tissues in a variety of organisms. Decreased activity of electron transport chain complexes and increased release of reactive oxygen species from the mitochondria with age suggest that alterations in mitochondrial function occur with age as a consequence of increased oxidative damage. In addition, age-related alterations in the mitochondrial pathway of apoptosis, which could have profound affects on the physiological function of a tissue, could arise from oxidative damage to mitochondria. Alterations in mitochondrial turnover with age could also contribute to an increase in the number of dysfunctional mitochondria with age. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX 78284 USA. RP Van Remmen, H (reprint author), Audie Murphy VA Hosp, GRECC 182, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. NR 62 TC 151 Z9 156 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JUL PY 2001 VL 36 IS 7 BP 957 EP 968 PG 12 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 450AB UT WOS:000169718400003 PM 11404044 ER PT J AU Nakanishi, K Moran, A Hays, T Kuang, Y Fox, E Garneau, D de Oca, RM Grompe, M D'Andrea, AD AF Nakanishi, K Moran, A Hays, T Kuang, Y Fox, E Garneau, D de Oca, RM Grompe, M D'Andrea, AD TI Functional analysis of patient-derived mutations in the Fanconi anemia gene, FANCG/XRCC9 SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID NUCLEAR-COMPLEX; PROTEINS FANCA; GROUP-A; COMPLEMENTATION; CELLS; ACCUMULATION; DIAGNOSIS; INTERACT; XRCC9; FORM AB Objective. Fanconi anemia (FA) is an autosomal-recessive cancer susceptibility syndrome with seven complementation groups. Six of the FA genes have been cloned (corresponding to subtypes A, C, D2, E, F, and G) and the encoded proteins interact in a common pathway. Patient-derived mutations in FA genes have been helpful in delineating functional domains of FA proteins, The purpose of this work was to subtype FA patient-derived cell lines in our repository and to identify FA gene mutations. Methods. We subtyped 62 FA patients as type A, G, C, or non-ACG by using a combination of retroviral gene transfer and immunoblot analysis. Among these FA patients, we identified six FA-G patients for further analysis, We used a strategy involving amplification of FANCG/XRCC9 exons and direct sequencing to identify novel FANCG mutations in cell lines derived from these FA-G patients, We functionally analyzed FANCG mutant alleles by transducing the corresponding cDNAs into a known FA-G indicator cell line and scoring correction of MMC sensitivity, Results. Our results demonstrate a wide range of mutations in the FANCG gene (splice, nonsense, and missense mutations), Based on this mutational screen, a carboxy terminal functional domain of the FANCG protein appears to be required for complementation of FA-G cells and for normal assembly of the FANCA/FANCG/FANCC protein complex. Conclusion. The identification of patient-derived mutant alleles of FA genes can provide important insights to the function of FA proteins. FA subtyping is also a necessary precondition for gene therapy. (C) 2001 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Oregon Hlth Sci Univ, Dept Pediat, Portland, OR 97201 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [R01HL52725-04, P01HL54785-04] NR 35 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2001 VL 29 IS 7 BP 842 EP 849 DI 10.1016/S0301-472X(01)00663-4 PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 455ZJ UT WOS:000170057400005 PM 11438206 ER PT J AU Qiu, ZH Naten, DL Liston, JC Yess, J Rebeck, GW AF Qiu, ZH Naten, DL Liston, JC Yess, J Rebeck, GW TI A novel approach for studying endogenous A beta processing using cultured primary neurons isolated from APP transgenic mice SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer's disease; transgene; ELISA; immunoblot; immunoprecipitation; amyloid precursor protein ID AMYLOID PRECURSOR PROTEIN; HUMAN CEREBROSPINAL-FLUID; ALZHEIMERS-DISEASE; PRESENILIN-1 MUTATIONS; APOLIPOPROTEIN-E; PEPTIDE; A-BETA-42(43); INHIBITOR; ALPHA(1)-ANTICHYMOTRYPSIN; ALPHA-1-ANTICHYMOTRYPSIN AB The central component of senile amyloid plaques in Alzheimer's disease (AD) is the beta -amyloid peptide (A beta), derived from proteolytic processing of the amyloid precursor protein (APP). In this study, we developed an in vitro model to measure and identify soluble A beta from primary cortical neurons. Neurons were isolated from mice transgenic for human APP695 containing the K670N, M671L double mutation. We characterized soluble A beta using Western blot and ELISA assays. We found that the A beta levels in conditioned media from these neurons were readily detectable and almost five times higher than in CSF. The majority of A beta in the media was A beta1-40; however, A beta1-42 was also detectable. When the neurons were exposed to Phorbol 12-myristate 13-acetate (PMA), alpha1-antichymotrypsin, or alpha1-antitrypsin, the alterations of soluble A beta levels were consistent with other models reported. Most importantly, the soluble A beta in our model was remarkably stable, and aliquots were unchanged after prolonged incubations or repeated freeze/thaw cycles. The A beta appeared to be monomeric by Western blot analysis. Soluble A beta coimmunoprecipitated with endogenous mouse apolipoprotein E from the primary cultures. Taken together, our data demonstrated that using a Western blot assay to detect soluble A beta from transgenic mouse overexpressing APP695 is sensitive, specific, and reliable and provides an accessible model for examining the neuronal metabolism of APP and A beta. (C) 2001 Academic Press. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Alzheimer Res Unit, Boston, MA 02129 USA. RP Qiu, ZH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Alzheimer Res Unit, Boston, MA 02129 USA. FU NIA NIH HHS [AG14473, AG12406] NR 32 TC 4 Z9 4 U1 0 U2 1 PU ACADEMIC PRESS INC 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 JUL PY 2001 VL 170 IS 1 BP 186 EP 194 DI 10.1006/exnr.2001.7703 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 452CW UT WOS:000169840400018 PM 11421596 ER PT J AU Brignone, C Munoz, O Batoz, M Rouquette-Jazdanian, A Cousin, JL AF Brignone, C Munoz, O Batoz, M Rouquette-Jazdanian, A Cousin, JL TI Proteases produced by activated neutrophils release soluble CD23 fragments endowed with proinflammatory effects SO FASEB JOURNAL LA English DT Article DE polymorphonuclear neutrophils; cathepsin G; monocytes ID REGULATES MONOCYTE ACTIVATION; COLLAGEN-INDUCED ARTHRITIS; EPSILON RECEPTOR-II; RHEUMATOID-ARTHRITIS; PROTEOLYTIC ACTIVITY; CATHEPSIN-G; CELL-SURFACE; STIMULATED NEUTROPHILS; MONOCLONAL-ANTIBODY; CYTOKINE PRODUCTION AB Polymorphonuclear neutrophils (PMNs) are the major source of proteolytic activities involved mainly in tissue injuries observed in chronic inflammatory disorders. High levels of soluble forms of CD23 (the low-affinity receptor for IgE) were found in biological fluids from these patients, and recent reports focused on a CD23-mediated regulation of inflammatory response. In this context, we show here that co-culture of activated PMN with CD23(+) B cells resulted in a drastic release of soluble CD23 fragments from the cell surface. This cleavage was inhibited by serine proteases inhibitors, including alpha1-antitrypsin. We next demonstrated that purified human leukocyte elastase or cathepsin G efficiently cleaved membrane CD23 on B cells with a high specificity. Soluble fragments released by serine proteases-mediated CD23 proteolysis stimulated resting monocytes to produce oxidative burst and proinflammatory cytokine without any co-stimulatory signal. This work strongly supports the idea that the capacity of PMN-derived proteases to release soluble forms of CD23 participates in the inflammatory process mediated by these cells. C1 Hop Archet, INSERM, U343, F-06202 Nice 3, France. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cousin, JL (reprint author), Hop Archet, INSERM, U343, BP 79, F-06202 Nice 3, France. EM cousin@unice.fr NR 57 TC 11 Z9 11 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL PY 2001 VL 15 IS 9 BP 2027 EP + DI 10.1096/fj.00-0773fje PG 21 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 460PV UT WOS:000170318500015 PM 11511513 ER PT J AU Hocker, M Cramer, T O'Conner, DT Rosewicz, S Wiedenmann, B Wang, TC AF Hocker, M Cramer, T O'Conner, DT Rosewicz, S Wiedenmann, B Wang, TC TI Neuroendocrine-specific and gastrin-dependent expression of a chromogranin A-luciferase fusion gene in transgenic mice SO GASTROENTEROLOGY LA English DT Article ID HUMAN GASTROINTESTINAL-TRACT; ENDOCRINE-CELLS; REGULATORY ELEMENT; CHOLECYSTOKININ-A; SECRETOGRANIN-II; MESSENGER-RNA; RAT STOMACH; DIFFERENTIATION; IDENTIFICATION; PANCREASTATIN AB Background & Aims: Chromogranin A (CgA) is a multi-functional acidic protein specifically expressed in neuroendocrine cells. In the stomach, CgA is found predominantly in enterochromaffin-like (ECL) cells, where it is regulated by gastrin. We investigated the ability of a promoter fragment comprising 4.8 kb of 5'-flanking DNA of the mouse CgA (mCgA) gene to direct cell-specific expression as well as gastrin responsiveness in the gastroenteropancreatic neuroendocrine system. Methods Two independent lines of mCgA 4.8 kb-luc transgenic mice were created. Transgene expression was assessed by determination of luciferase activity and reverse-transcription polymerase chain reaction analysis of luciferase messenger RNA. Cell specificity of transgene expression was investigated by immunohistochemical analysis. The influence of hypergastrinemia on transgene expression was determined after repeated omeprazole injections. Results: In both transgenic lines, mCgA 4.8 kb-luc expression paralleled the expression pattern of the endogenous CgA gene. ECL cells were identified as the major gastric cell population expressing the transgene. Omeprazole treatment stimulated expression of the transgene and the endogenous CgA gene selectivity in the gastric corpus (3-4-fold). Conclusions: mCgA 5'-flanking DNA (4.8 kb) contain the major cis-regulatory element(s) required for cell-specific CgA expression in the neuroendocrine system and gastrin-responsiveness in the gastric corpus. Further analysis of the CgA promoter in transgenic studies may elucidate the general molecular mechanisms underlying cell-specific gene expression in the gastroenteropancreatic neuroendocrine system. C1 Humboldt Univ, Klinikum Charite, Med Klin Mit Schwerpunkt Hepatol & Gastroenterol, Berlin, Germany. Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. Univ Calif San Diego, Ctr Mol Genet, San Diego, CA 92103 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Wang, TC (reprint author), Univ Massachusetts, Med Ctr, Div Gastroenterol, Biotech 2,Suite 210,373 Plantat St, Worcester, MA 01605 USA. RI Cramer, Thorsten/S-2479-2016 OI Cramer, Thorsten/0000-0002-6462-239X FU NIDDK NIH HHS [2RO1 DK 48077] NR 50 TC 12 Z9 12 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 2001 VL 121 IS 1 BP 43 EP 55 DI 10.1053/gast.2001.25526 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 445YF UT WOS:000169485600009 PM 11438493 ER PT J AU Letko, E Ahmed, AR Foster, CS AF Letko, E Ahmed, AR Foster, CS TI Treatment of ocular cicatricial pemphigoid with tacrolimus (FK 506) SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article ID IMMUNOSUPPRESSIVE THERAPY; FK-506; FK506 AB Purpose: To evaluate the efficacy of tacrolimus (FK 506) therapy in patients with ocular cicatricial pemphigoid (OCP). Methods: In a cohort study, six patients with OCP, in whom the disease was not controlled by conventional immunosuppressive agents administered in high doses for an appropriate period of time, were treated with FK 506. The FK 506 was administered orally at the daily dose of 8 mg. Final clinical response to FK 506 was divided into three categories based on the difference between severity of conjunctival inflammation before and after FK 506 therapy. "Total control" of disease activity was defined as residual inflammatory activity of 0.5 or less in the final examination and an inflammation decrement of at least 0.5 between initial and final examination. "Partial control" was defined as final disease activity 1.0 or 1.5 and at least 0.5 decrement of disease activity between initial and final examination. "Uncontrolled inflammation" was defined as final disease activity above 1.5 or no improvement between initial and final activity. Results: The average age of the patients was 67.5 years (range 50-75 years). Male to female ratio was 1: 1. The average duration of OCP prior to beginning of FK 506 treatment was 6.25 years (range 3-12.5 years). The average duration of treatment with FK 506 was I I months (range 5-18 months). The average disease activity prior to the administration of FK 506 was 2.6 (range 2.0-3.0). The average disease activity at the time when FK 506 was stopped was 2.0 (range 1.0-2.5). In four patients (67%) FK 506 failed to control activity of OCP, and in two patients (33%) the activity was controlled partially. Conclusions: Although FK 506 was not used in a prospective randomized trial and although we used the drug only in patients with OCP refractory to conventional immunosuppressive agents, it is likely that FK 506 is incapable of controlling the activity of OCP and inducing a remission. C1 Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, Boston, MA 02116 USA. Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Boston, MA 02115 USA. RP Foster, CS (reprint author), Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, 3 Charles St, Boston, MA 02116 USA. NR 28 TC 14 Z9 15 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD JUL PY 2001 VL 239 IS 6 BP 441 EP 444 DI 10.1007/s004170100306 PG 4 WC Ophthalmology SC Ophthalmology GA 461AB UT WOS:000170341800009 PM 11561793 ER PT J AU Havens, L AF Havens, L TI Soundings: A psychological equivalent of medical percussion SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID PSYCHIATRY C1 McLean Hosp, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. Cambridge Hlth Alliance, Dept Psychiat, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Havens, L (reprint author), Cambridge Hlth Alliance, Dept Psychiat, 1493 Cambridge St, Cambridge, MA 02139 USA. NR 21 TC 1 Z9 1 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JUL-AUG PY 2001 VL 9 IS 4 BP 147 EP 157 PG 11 WC Psychiatry SC Psychiatry GA 447HW UT WOS:000169566700001 PM 11410538 ER PT J AU Brendel, DH Florman, J Roberts, S Solet, JM AF Brendel, DH Florman, J Roberts, S Solet, JM TI "In sleep I almost never grope": Blindness, neuropsychiatric deficits, and a chaotic upbringing SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID LOW-BIRTH-WEIGHT; TEMPORAL-LOBE EPILEPSY; INFANTS; PREMATURITY; RISK C1 Cambridge Hlth Alliance, Dept Psychiat, Cambridge, MA USA. Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. McLean Hosp, Belmont, MA 02478 USA. RP Brendel, DH (reprint author), McLean Hosp, 115 Mill St, Belmont, MA 02478 USA. NR 25 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JUL-AUG PY 2001 VL 9 IS 4 BP 178 EP 188 PG 11 WC Psychiatry SC Psychiatry GA 447HW UT WOS:000169566700004 PM 11410541 ER PT J AU Seeman, TE Lusignolo, TM Albert, M Berkman, L AF Seeman, TE Lusignolo, TM Albert, M Berkman, L TI Social relationships, social support, and patterns of cognitive aging in healthy, high-functioning older adults: MacArthur studies of successful aging SO HEALTH PSYCHOLOGY LA English DT Article DE social support; social relationships; cognition; aging ID ALZHEIMERS-DISEASE; ELDERLY POPULATION; RISK-FACTORS; DEMENTIA; NETWORK; QUESTIONNAIRE; PERFORMANCE; ASSOCIATION; MORTALITY; NIDDM AB This study examines the relationship of social ties and support to patterns of cognitive aging in the MacArthur Studies of Successful Aging (see L. F. Berkman et al., 1993), a cohort study of 1,189 initially high-functioning older adults. Baseline and longitudinal data provide information on initial levels as well as changes in cognitive performance over a 7.5-year period, Linear regression analyses revealed that participants receiving more emotional support had better baseline performance, as did those who were unmarried and those reporting greater conflict with network members. Greater baseline emotional support was also a significant predictor of better cognitive function at the 7.5-year follow-up, controlling for baseline cognitive function and known sociodemographic, behavioral, psychological, and health status predictors of cognitive aging. The findings suggest the potential value of further research on the role of the social environment in protecting against cognitive declines at older ages. C1 Univ Calif Los Angeles, Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. Ohio State Univ, Coll Med & Publ Hlth, Columbus, OH 43210 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Dept Psychiat & Gerontol, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Cambridge, MA 02138 USA. RP Seeman, TE (reprint author), Univ Calif Los Angeles, Sch Med, Div Geriatr, 10945 Le Conte Ave,Suite 2339, Los Angeles, CA 90095 USA. FU NIA NIH HHS [AG-17056, AG-17265] NR 56 TC 239 Z9 243 U1 12 U2 72 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 JUL PY 2001 VL 20 IS 4 BP 243 EP 255 DI 10.1037//0278-6133.20.4.243 PG 13 WC Psychology, Clinical; Psychology SC Psychology GA 472HC UT WOS:000170977100001 PM 11515736 ER PT J AU Takehara, T Liu, XL Fujimoto, J Friedman, SL Takahashi, H AF Takehara, T Liu, XL Fujimoto, J Friedman, SL Takahashi, H TI Expression and role of Bcl-xL in human hepatocellular carcinomas SO HEPATOLOGY LA English DT Article ID APOPTOTIC CELL-DEATH; ANTI-FAS ANTIBODY; C-MYC; HUMAN-LIVER; P53-MEDIATED APOPTOSIS; P53 GENE; PROTEIN; SURVIVAL; BCL-X(L); FAMILY AB Transformed hepatocytes survive various apoptotic insults during their growth in vivo. However, molecular mechanisms that inhibit apoptosis and support their survival are not well understood. In this study, we investigated the expression and role of Bcl-xL, an antiapoptotic member of the Bcl-2 family, in human hepatocellular carcinoma (HCC). The Bcl-xL protein was expressed in HepG2, Hep3B, and Huh7 human hepatoma cell lines at high levels, but none of these cells expressed Bcl-2. Down-modulation of Bcl-xL by antisense oligonucleotide activated apoptosis in HepG2 cells in response to cellular stresses induced by staurosporine treatment or by serum starvation. Ectopic expression of transcriptionally active p53 alone was not sufficient for the activation of apoptosis in p53-null Hep3B cells, but apoptosis was induced when endogenous Bcl-xL was simultaneously inhibited by antisense oligonucleotide in these cells. Bcl-xL was expressed in all 20 surgically resected human HCC tissues when examined by Western blot analysis and immunohistochemistry, and levels of its expression were higher in a subset of HCC tissues than those of adjacent nontumor liver tissues or normal livers. We conclude that Bcl-xL expressed in human HCC cells inhibits apoptosis produced by various cellular stresses, such as staurosporine treatment, serum starvation, and p53 activation, and may play an important role in their survival. C1 Jikei Univ, Sch Med, Inst Clin Med & Res, Kashiwa, Chiba 2278565, Japan. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Osaka Univ, Grad Sch Med, Dept Mol Therapeut, Osaka, Japan. Hyogo Coll Med, Dept Surg 1, Nishinomiya, Hyogo, Japan. Mt Sinai Med Ctr, Div Liver Dis, New York, NY 10029 USA. RP Takahashi, H (reprint author), Jikei Univ, Sch Med, Inst Clin Med & Res, 163-1 Kashiwa Shita, Kashiwa, Chiba 2278565, Japan. NR 36 TC 177 Z9 191 U1 1 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUL PY 2001 VL 34 IS 1 BP 55 EP 61 DI 10.1053/jhep.2001.25387 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 445YG UT WOS:000169485700009 PM 11431734 ER PT J AU Bobryshev, YV Taksir, T Lord, RSA Freeman, MW AF Bobryshev, YV Taksir, T Lord, RSA Freeman, MW TI Evidence that dendritic cells infiltrate atherosclerotic lesions in apolipoprotein E-deficient mice SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Article DE atherosclerosis; apolipoprotein E-deficient mice; dendritic cells ID MONOCLONAL-ANTIBODY NLDC-145; ATHERO-PRONE AREAS; LANGERHANS CELLS; PROTEIN; DEC-205; AORTA; INVOLVEMENT; EXPRESSION; TISSUE AB Earlier we reported that atherosclerotic lesions of apoE-deficient mice contained cells which stained positively with anti-S-100 antibody and that cells exhibiting the ultrastructural features of dendritic cells were present in the aortic lesions. These observations suggested that dendritic cells might be involved in mouse atherosclerosis. By employing DEC-205 and MIDC-8 antibodies specific for dendritic cells, the present study has established that dendritic cells indeed accumulate in atherosclerotic lesions of apoE-deficient mice. Finding dendritic cells infiltrating atherosclerotic lesions in apoE-deficient mice offers the possibility of investigating the migratory routes of dendritic cells and their involvement in T-cell activation. C1 Univ New S Wales, Professorial Surg Unit, St Vincent Hosp, Darlinghurst, NSW 2010, Australia. Harvard Univ, Lipid Metab Unit, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. RP Bobryshev, YV (reprint author), Univ New S Wales, Professorial Surg Unit, St Vincent Hosp, Level 17,O Brien Bldg,Victoria St, Darlinghurst, NSW 2010, Australia. RI Bobryshev, Yuri/J-2838-2013 FU NIDDK NIH HHS [5PO1 DK 50305-10] NR 27 TC 41 Z9 45 U1 0 U2 0 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD JUL PY 2001 VL 16 IS 3 BP 801 EP 808 PG 8 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 460CN UT WOS:000170288400016 PM 11510970 ER PT J AU Joseph, PM O'Sullivan, B Lapey, A Dorkin, H Oren, J Balfour, R Perricone, MA Rosenberg, M Wadsworth, SC Smith, AE St George, JA Meeker, DP AF Joseph, PM O'Sullivan, B Lapey, A Dorkin, H Oren, J Balfour, R Perricone, MA Rosenberg, M Wadsworth, SC Smith, AE St George, JA Meeker, DP TI Aerosol and lobar administration of a recombinant adenovirus to individuals with cystic fibrosis. I. Methods, safety, and clinical implications SO HUMAN GENE THERAPY LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; MEDIATED GENE-TRANSFER; HUMAN CFTR CDNA; NASAL EPITHELIUM; LUNG-DISEASE; IDENTIFICATION; SYSTEM; VECTOR; VARIABILITY; EXPRESSION AB Cystic fibrosis (CF), an autosomal recessive disorder resulting from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, is the most common lethal genetic illness in the Caucasian population. Gene transfer to airway epithelium, using adenoviruses containing normal CFTR cDNA, leads to transient production of CFTR mRNA and, in some studies, to correction of the airway epithelial ion transport defect caused by dysfunctional CFTR. Inflammatory responses to the adenoviral vector have been reported, particularly at high viral titers. We evaluated the effects of adenovirus-mediated CFTR gene transfer to airway epithelium in 36 subjects with CF (34 individuals, 2 of whom received two separate doses of vector), 20 by lobar instillation and 16 by aerosol administration. Doses ranged from 8 x 10(6) to 2.5 x 10(10) infective units (IU), in 0.5-log increments. After lobar administration of low doses there were occasional reports of cough, low-grade temperature, and myalgias. At the highest lobar dose (2.5 x 10(9) IU) two of three patients had transient myalgias, fever, and increased sputum production with obvious infiltrates on CT scan. After aerosol administration there were no significant systemic symptoms until the 2.5 x 10(10) IU dose, when both patients experienced myalgias and fever that resolved within 24 hr. There were no infiltrates seen on chest CT scans in any of the patients in the aerosol administration group. There were no consistent changes in pulmonary function tests or any significant rise in serum IgG or neutralizing antibodies in patients from either group. Serum, sputum, and nasal cytokines, measured before and after vector administration, showed no correlation with adenoviral dose. Gene transfer to lung cells was inefficient and expression was transient. Cells infected with the vector included mononuclear inflammatory cells as well as cuboidal and columnar epithelial cells. In summary, we found no consistent immune response, no evidence of viral shedding, and no consistent change in pulmonary function in response to adenovirus-mediated CFTR gene transfer. At higher doses there was a mild, nonspecific inflammatory response, as evidenced by fevers and myalgias. Overall, vector administration was tolerated but transfer of CFTR cDNA was inefficient and transgene expression was transient for the doses and method of administration used here. C1 Genzyme Corp, Framingham, MA 01701 USA. Massachusetts Gen Hosp, Cyst Fibrosis Ctr, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Pediat Pulm & Cyst Fibrosis Ctr, Worcester, MA 01655 USA. New England Med Ctr, Pediat Pulm & Cyst Fibrosis Ctr, Boston, MA 02115 USA. RP St George, JA (reprint author), Genzyme Corp, 31 New York Ave,Room 262, Framingham, MA 01701 USA. NR 32 TC 63 Z9 63 U1 0 U2 13 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUL PY 2001 VL 12 IS 11 BP 1369 EP 1382 DI 10.1089/104303401750298535 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 455MW UT WOS:000170031500001 PM 11485629 ER PT J AU Perricone, MA Morris, JE Pavelka, K Plog, MS O'Sullivan, BP Joseph, PM Dorkin, H Lapey, A Balfour, R Meeker, DP Smith, AE Wadsworth, SC St George, JA AF Perricone, MA Morris, JE Pavelka, K Plog, MS O'Sullivan, BP Joseph, PM Dorkin, H Lapey, A Balfour, R Meeker, DP Smith, AE Wadsworth, SC St George, JA TI Aerosol and lobar administration of a recombinant adenovirus to individuals with cystic fibrosis. II. Transfection efficiency in airway epithelium SO HUMAN GENE THERAPY LA English DT Article ID MEDIATED GENE-TRANSFER; TRANSMEMBRANE CONDUCTANCE REGULATOR; RESPIRATORY-TRACT; NASAL EPITHELIUM; CFTR CDNA; IN-VIVO; VECTOR; MACROPHAGES; EXPRESSION; DEPLETION AB A phase I clinical trial was conducted in which recombinant adenovirus containing the cystic fibrosis transmembrane regulator (CFTR) (Ad2/CFTR) was administered by bronchoscopic instillation or aerosolization to the lungs of cystic fibrosis (CF) patients. In this paper, we evaluate the efficiency of Ad2/CFTR-mediated transduction of bronchial airway cells. The ability of an Ad2/CFTR vector to transduce airway cells was first evaluated in patients to whom the vector was administered by bronchoscopic instillation. Cells at the administration site were collected 2 days after treatment by bronchoscopic brushing. Ad2-specific CFTR DNA was detected in four of five individuals by PCR, and Ad2-specific CFTR RNA was detected in three of five individuals by RT-PCR. Ad2/CFTR-mediated transduction of airway epithelial cells was then determined in CF individuals receiving this vector by aerosol inhalation. Ad2-specific CFTR DNA was detected in 13 of 13 individuals 2 days after aerosolization, and in 3 of 5 individuals 7 days after aerosolization. Ad2-specific RNA was detected in 4 of 13 individuals on day 2, but was not detected in the 5 individuals tested on day 7. The percentage of airway epithelial cells containing nuclear-localized vector DNA was less than or equal to2.4% as determined by fluorescence in situ hybridization (FISH). However, in some cases, a high percentage of nonepithelial mononuclear cells or squamous metaplastic epithelial cells was infected with the adenoviral vector. In conclusion, aerosol administration is a feasible means to distribute adenoviral vectors throughout the conducting airways, but improvements in adenovirus-mediated transduction of airway epithelial cells are necessary before gene therapy for CF will be effective. C1 Genzyme Corp, Framingham, MA 01701 USA. Univ Massachusetts, Cyst Fibrosis Ctr, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Cyst Fibrosis Ctr, Boston, MA 02114 USA. New England Med Ctr, Cyst Fibrosis Ctr, Boston, MA 02115 USA. RP Perricone, MA (reprint author), Genzyme Corp, 31 New York Ave, Framingham, MA 01701 USA. NR 25 TC 48 Z9 49 U1 2 U2 7 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUL PY 2001 VL 12 IS 11 BP 1383 EP 1394 DI 10.1089/104303401750298544 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 455MW UT WOS:000170031500002 PM 11485630 ER PT J AU Dipple, KM Zhang, YH Huang, BL McCabe, LL Dallongeville, J Inokuchi, T Kimura, M Marx, HJ Roederer, GO Shih, V Yamaguchi, S Yoshida, I McCabe, ERB AF Dipple, KM Zhang, YH Huang, BL McCabe, LL Dallongeville, J Inokuchi, T Kimura, M Marx, HJ Roederer, GO Shih, V Yamaguchi, S Yoshida, I McCabe, ERB TI Glycerol kinase deficiency: Evidence for complexity in a single gene disorder SO HUMAN GENETICS LA English DT Article ID SIMPLE MENDELIAN DISORDERS; MENTAL-RETARDATION; MUTATIONS; FAMILY; TRAITS; PHENOTYPE; CLONING; SYSTEM AB Glycerol kinase deficiency (GKD) occurs as part of an Xp21 contiguous gene syndrome or as isolated GKD. The isolated form can be either symptomatic with episodic metabolic and central nervous system (CNS) decompensation or asymptomatic with hyperglycerolemia and glyceroluria only. To better understand the pathogenesis of isolated GKD, we sought individuals with point mutations in the GK coding region and measured their GK enzyme activities. We identified six individuals with missense mutations: four (N288D, A305V, M428T, and Q438R) among males who were asymptomatic and two (D198G, R405Q) in individuals who were symptomatic. GK activity measured in lymphoblastoid cell lines or fibroblasts was similar for the symptomatic and the asymptomatic individuals. Mapping of the individuals' missense mutations to the three-dimensional structure of Escherichia coli GK revealed that the symptomatic individuals' mutations are in the same region as a subset of the mutations among the asymptomatic individuals, adjacent to the active-site cleft. We conclude that, like many other disorders, GK genotype does not predict GKD phenotype. We hypothesize that the phenotype of an individual with GKD is a complex trait influenced by additional, independently inherited genes. C1 Univ Calif Los Angeles, Mattel Childrens Hosp, Div Genet, Dept Pediat, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Human Genet, Los Angeles, CA USA. Inst Pasteur, F-59019 Lille, France. Kurume Univ, Sch Med, Res Inst Med Mass Spectrometry, Kurume, Fukuoka 830, Japan. Shimane Med Univ, Dept Pediat, Izumo, Shimane 693, Japan. Mary Imogene Bassett Res Inst, Cooperstown, NY USA. Inst Rech Clin Montreal, Montreal, PQ H2W 1R7, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Kurume Univ, Sch Med, Dept Pediat & Child Hlth, Kurume, Fukuoka 830, Japan. Univ Calif Los Angeles, Brain Res Inst, Mental Retardat Res Ctr, Los Angeles, CA 90024 USA. RP McCabe, ERB (reprint author), Univ Calif Los Angeles, Mattel Childrens Hosp, Div Genet, Dept Pediat, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. FU NICHD NIH HHS [P30 HD34610, R01 HD22563, T32-HD07512]; NIGMS NIH HHS [T32-GM8243-12] NR 31 TC 41 Z9 42 U1 1 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUL PY 2001 VL 109 IS 1 BP 55 EP 62 DI 10.1007/s004390100545 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 461WE UT WOS:000170386000009 PM 11479736 ER PT J AU Lopez-Rodriguez, C Aramburu, J Jin, L Rakeman, AS Michino, M Rao, A AF Lopez-Rodriguez, C Aramburu, J Jin, L Rakeman, AS Michino, M Rao, A TI Bridging the NFAT and NF-kappa B families: NFAT5 dimerization regulates cytokine gene transcription in response to osmotic stress SO IMMUNITY LA English DT Article ID CHRONIC-RENAL-FAILURE; NECROSIS-FACTOR-ALPHA; T-CELL ACTIVATION; P50 HOMODIMER; CRYSTAL-STRUCTURE; IMMUNE-RESPONSES; BETA PROMOTER; TNF-ALPHA; RECEPTOR; BINDING AB The transcription factor NFAT5/TonEBP is evolutionarily the oldest member of the NFAT/Rel family of transcription factors. We show that NFAT5 is uniquely related to NF-KB and is the only member of the Rel/NFAT family to be activated by osmotic stress. Like Rel/NF-kappaB proteins but unlike the calcium-regulated NFAT proteins, NFAT5 is constitutively dimeric, and dimerization is essential for DNA binding and transcriptional activity. Using dominant-negative proteins that inhibit NFAT5 dimerization, we show that NFAT5 regulates expression of the TNF alpha and lymphotoxin-beta genes in osmotically stressed T cells. Chromatin immunoprecipitation experiments confirm that NFAT5 binds to the TNF alpha promoter in vivo. We suggest that NFAT5 participates in specific aspects of host defense by upregulating TNF family genes and other target genes in T cells. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Pompeu Fabra, Dept Ciences Expt & Salut, Barcelona 08003, Spain. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. RI Lopez-Rodriguez, C/G-4482-2014; Aramburu, J/G-8991-2014 OI Lopez-Rodriguez, C/0000-0002-2311-2406; Aramburu, J/0000-0001-9279-9523 FU NCI NIH HHS [CA42471]; NIAID NIH HHS [AI40127] NR 55 TC 140 Z9 142 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 2001 VL 15 IS 1 BP 47 EP 58 DI 10.1016/S1074-7613(01)00165-0 PG 12 WC Immunology SC Immunology GA 457TQ UT WOS:000170153300006 PM 11485737 ER PT J AU Labrecque, N Whitfield, LS Obst, R Waltzinger, C Benoist, C Mathis, D AF Labrecque, N Whitfield, LS Obst, R Waltzinger, C Benoist, C Mathis, D TI How much TCR does a T cell need? SO IMMUNITY LA English DT Article ID MHC CLASS-II; POSITIVE SELECTION; ANTIGEN RECEPTOR; PEPTIDE LIGANDS; GENE-EXPRESSION; TRANSGENIC MICE; IN-VIVO; SURVIVAL; CD4(+); NAIVE AB Kinetic features of TCR:MHC/peptide interactions dictate their outcome in vitro, some important parameters of which include the number of molecules engaged and the duration of engagement. We explored the in vivo significance of these findings in transgenic mice expressing TCRs in a quantitatively and temporally controlled manner. As anticipated, reduced TCR levels resulted in attenuated reactivity, but response thresholds were substantially lower than expected-at as low as 1/20(th), the normal TCR numbers and with no indication of phenotypic skewing at suboptimal levels. We also studied survival of T lymphocytes stripped of their TCRs. Unlike B cells, T cells lacking antigen receptors did not die precipitously; instead, populations decayed gradually, just as previously reported in the absence of MHC molecules. C1 CNRS, INSERM, ULP, F-67404 Strasbourg, France. RP Benoist, C (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Joslin Diabet Ctr,Sect Immunol & Innunogenet, Boston, MA 02215 USA. NR 63 TC 155 Z9 157 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 2001 VL 15 IS 1 BP 71 EP 82 DI 10.1016/S1074-7613(01)00170-4 PG 12 WC Immunology SC Immunology GA 457TQ UT WOS:000170153300008 PM 11485739 ER PT J AU Homeister, JW Thall, AD Petryniak, B Maly, P Rogers, CE Smith, PL Kelly, RJ Gersten, KM Askari, SW Cheng, GY Smithson, G Marks, RM Misra, AK Hindsgaul, O von Andrian, UH Lowe, JB AF Homeister, JW Thall, AD Petryniak, B Maly, P Rogers, CE Smith, PL Kelly, RJ Gersten, KM Askari, SW Cheng, GY Smithson, G Marks, RM Misra, AK Hindsgaul, O von Andrian, UH Lowe, JB TI The alpha(1,3)fucosyltransferases FucT-IV and FucT-VII exert collaborative control over selectin-dependent leukocyte recruitment and lymphocyte homing SO IMMUNITY LA English DT Article ID P-SELECTIN; GLYCOPROTEIN LIGAND-1; DEFICIENT MICE; FUCOSYL-TRANSFERASE; ELAM-1 LIGAND; CELL-LINES; IN-VIVO; ADHESION; EXPRESSION; BINDING AB E-, P-, and L-selectin counterreceptor activities, leukocyte trafficking, and lymphocyte homing are controlled prominently but incompletely by alpha (1,3)fucosyltransferase FucT-VII-dependent fucosylation. Molecular determinants for FucT-VII-independent leukocyte trafficking are not defined, and evidence for contributions by or requirements for other FucTs in leukocyte recruitment is contradictory and incomplete. We show here that inflammation-dependent leukocyte recruitment retained in FucT-VII deficiency is extinguished in FucT-1V(-/-)/FucT-VII-/- mice. Double deficiency yields an extreme leukocytosis characterized by decreased neutrophil turnover and increased neutrophil production. FucT-IV also contributes to HEV-born L-selectin ligands, since lymphocyte homing retained in FucT-VII-/- mice is revoked in FucT-IV-/-/FucT-VII-/- mice. These observations reveal essential FucT-IV-dependent contributions to E-, P-, and L-selectin ligand synthesis and to the control of leukocyte recruitment and lymphocyte homing. C1 Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Med, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Burnham Inst, La Jolla, CA 92093 USA. RP Lowe, JB (reprint author), Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. RI von Andrian, Ulrich/A-5775-2008; Maly, Petr/H-5962-2014 FU NCI NIH HHS [1PO1CA711932]; NHLBI NIH HHS [1PO1 HL56949, 1RO1 HL54936] NR 35 TC 216 Z9 222 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 2001 VL 15 IS 1 BP 115 EP 126 DI 10.1016/S1074-7613(01)00166-2 PG 12 WC Immunology SC Immunology GA 457TQ UT WOS:000170153300012 PM 11485743 ER PT J AU Panoutsakopoulou, V Sanchirico, ME Huster, KM Jansson, M Granucci, F Shim, DJ Wucherpfennig, KW Cantor, H AF Panoutsakopoulou, V Sanchirico, ME Huster, KM Jansson, M Granucci, F Shim, DJ Wucherpfennig, KW Cantor, H TI Analysis of the relationship between viral infection and autoimmune disease SO IMMUNITY LA English DT Article ID SIMPLEX VIRUS TYPE-1; CENTRAL-NERVOUS-SYSTEM; HERPES STROMAL KERATITIS; MYELIN BASIC-PROTEIN; T-CELLS; TRANSGENIC MICE; MOLECULAR MIMICRY; BYSTANDER ACTIVATION; ENCEPHALOMYELITIS; DEMYELINATION AB The clinical association between viral infection and onset or exacerbation of autoimmune disorders remains poorly understood. Here, we examine the relative roles of molecular mimicry and nonspecific inflammatory stimuli in progression from infection to autoimmune disease. Murine herpes virus 1 (HSV-1 KOS) infection triggers T cell-dependent autoimmune reactions to corneal tissue. We generated an HSV-1 KOS point mutant containing a single amino acid exchange within the putative mimicry epitope as well as mice expressing a TOR transgene specific for the self-peptide mimic to allow dissection of two pathogenic mechanisms in disease induction. These experiments indicate that viral mimicry is essential for disease induction after low-level viral infection of animals containing limited numbers of autoreactive T cells, while innate immune mechanisms become sufficient to provoke disease in animals containing relatively high numbers of autoreactive T cells. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Cantor, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. OI Panoutsakopoulou, Vily/0000-0002-1569-1508 FU NEI NIH HHS [F32EY07032]; NIAID NIH HHS [AI37562, AI12184, AI48125]; NINDS NIH HHS [NS 39096] NR 56 TC 88 Z9 91 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 2001 VL 15 IS 1 BP 137 EP 147 DI 10.1016/S1074-7613(01)00172-8 PG 11 WC Immunology SC Immunology GA 457TQ UT WOS:000170153300014 PM 11485745 ER PT J AU Taubman, MA Holmberg, CJ Smith, DJ AF Taubman, MA Holmberg, CJ Smith, DJ TI Diepitopic construct of functionally and epitopically complementary peptides enhances immunogenicity, reactivity with glucosyltransferase, and protection from dental caries SO INFECTION AND IMMUNITY LA English DT Article ID MUTANS STREPTOCOCCAL GLUCOSYLTRANSFERASE; GLUCAN-BINDING DOMAIN; B-CELL EPITOPES; SYNTHETIC PEPTIDES; T-CELL; ACTIVE-SITE; IMMUNIZATION; SOBRINUS; ANTIGEN; COIMMUNIZATION AB Coimmunization with peptide constructs from catalytic (CAT) and glucan-binding (GLU) domains of glucosyltransferase (GTF) of mutans streptococci has resulted in enhanced levels of antibody to the CAT construct and to GTF, We designed and synthesized a diepitopic construct (CAT-GLU) containing two copies of both CAT (B epitope only) and GLU (B and T epitope) peptides, The immunogenicity of this diepitopic construct was compared with that of individual CAT and GLU constructs by immunizing groups of Sprague-Dawley rats subcutaneously in the salivary gland vicinity with the CAT-GLU, CAT, or GLU construct or by treating rats by sham immunization. Levels of serum immunoglobulin G (Igc) antibody to GTF or CAT in the CAT-GLU group were significantly greater than in GLU- or CAT-immunized groups, Immunization with CAT-GLU was compared to coimmunization with a mixture of CAT and GLU in a second rodent experiment under a similar protocol, CAT-GLU immunization resulted in serum IgG and salivary IgA responses to GTF and CAT which were greater than after coimmunization, Immunization with the diepitopic construct and communization with CAT and GLU constructs showed proliferation of T lymphocytes to GTF, Immunization with either the CAT or GLU construct has been shown to elicit significant protection in a rodent dental caries model. Similarly in this study, the enhanced response to GTF after immunization with the CAT-GLU construct resulted in protective effects on dental caries. Therefore, the CAT-GLU diepitopic construct can be a potentially important antigen for a caries vaccine, giving rise to greater immune response than after immunization with CAT, GLU, or a mixture of the two. C1 Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. RP Taubman, MA (reprint author), Forsyth Inst, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-04733, R56 DE004733, R01 DE004733] NR 35 TC 21 Z9 28 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 JUL PY 2001 VL 69 IS 7 BP 4210 EP 4216 DI 10.1128/IAI.69.7.4210-4216.2001 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 443HL UT WOS:000169335700003 PM 11401956 ER PT J AU Jacquot, S Macon-Lemaitre, L Paris, E Kobata, T Tanaka, Y Morimoto, C Schlossman, SF Tron, F AF Jacquot, S Macon-Lemaitre, L Paris, E Kobata, T Tanaka, Y Morimoto, C Schlossman, SF Tron, F TI B cell co-receptors regulating T cell-dependent antibody production in common variable immunodeficiency: CD27 pathway defects identify subsets of severely immuno-compromised patients. SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE memory B cells; T-B interactions; tumor necrosis factor receptor family ID PLASMA-CELLS; DIFFERENTIATION; CD27/CD70; ANTIGEN; COSTIMULATION; GENERATION; CD154/CD40; ACTIVATION; EXPRESSION; CD70/CD27 AB CD27 and CD134 ligand (CD134L) are two B cell co-receptors for T-h cell activation-induced ligands (i.e. CD70 and CD134) that promote differentiation of B cells into plasma cells and high-rate antibody production respectively. We explored the CD27 pathway and T cell CD134 expression in common variable immunodeficiency (CVID), a disease characterized by a lack of plasma cells and low Ig serum levels. Twelve patients were compared to seven healthy controls. We found a low percentage of circulating CD27(+) B cells in seven patients and B cell CD27 expression was not upregulated by in vitro activation in two of them. Importantly, the number of circulating CD27(+) B cells was correlated with the severity of the disease-the patients with the lowest CD27(+) B cell counts having the lowest serum Ig concentrations and the lowest total peripheral blood 13 cell counts. In contrast, CD70 and CD134 were normally expressed on in vitro activated T cells. CD134L was not detected on patient and control IS cells in our activation conditions. Functional studies of in vitro Ig production demonstrated an absence of B cell response to CD27 cross-linking, in particular in a patient with normal CD27 expression. Our results indicate that a defect in CD27 expression or function contributes to the pathogenesis of certain severe forms of CVID. C1 CHU Charles Nicolle, Fac Med & Pharm, INSERM U519,IFRMP 23, Lab Immunopathol Clin & Expt, F-76183 Rouen, France. Univ Ryukyus, Sch Med, Okinawa Asia Res Ctr Med Sci, Dept Infect Dis & Immunol, Okinawa 9030215, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Div Tumor Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Jacquot, S (reprint author), CHU Charles Nicolle, Fac Med & Pharm, INSERM U519,IFRMP 23, Lab Immunopathol Clin & Expt, 22 Blvd Gambetta, F-76183 Rouen, France. NR 29 TC 41 Z9 44 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUL PY 2001 VL 13 IS 7 BP 871 EP 876 DI 10.1093/intimm/13.7.871 PG 6 WC Immunology SC Immunology GA 457TR UT WOS:000170153400004 PM 11431417 ER PT J AU Woodruff, RH Tekki-Kessaris, N Stiles, CD Rowitch, DH Richardson, WD AF Woodruff, RH Tekki-Kessaris, N Stiles, CD Rowitch, DH Richardson, WD TI Oligodendrocyte development in the spinal cord and telencephalon: common themes and new perspectives SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article; Proceedings Paper CT ISDN 2000 Conference CY 2000 CL HEIDELBERG, GERMANY SP ISDN ID CENTRAL-NERVOUS-SYSTEM; VENTRAL MIDLINE CELLS; PDGF ALPHA-RECEPTOR; SONIC-HEDGEHOG; PROGENITOR CELLS; NEURAL-TUBE; OPTIC-NERVE; FLOOR PLATE; NG2 PROTEOGLYCAN; ORIGIN AB There are clear parallels between oligodendrocyte development in the spinal cord and forebrain. However, there is new evidence that in both of these regions oligodendrocyte lineage development may be more complex than we earlier thought. This stems from the recent identification of three new transcription factor genes. Olig1, Olig2 and Sox10, that are expressed from the early stages of oligodendrocyte lineage development. In this article, we highlight the common themes underlying specification and early development of oligodendrocytes: in the spinal cord and telencephalon. Then, we discuss recent studies of Sox10 and the Olig genes and their implications for oligodendrocyte specification. We conclude that although the mechanisms of oligodendrogenesis appear to be fundamentally similar at different rostro-caudal levels of the neuraxis, there an still many unanswered questions about the details of oligodendrocyte specification. (C) 2001 ISDN. Published by Elsevier Science Ltd. All rights reserved. C1 UCL, Wolfson Inst Biomed Res, London WC1E 6AU, England. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Oncol, Boston, MA 02115 USA. RP Richardson, WD (reprint author), UCL, Wolfson Inst Biomed Res, Cruciform Bldg,Gower St, London WC1E 6AU, England. EM w.richardson@ucl.ac.uk RI Richardson, William/C-1762-2008; OI Richardson, William/0000-0001-7261-2485; Kessaris, Nicoletta/0000-0003-1191-6009 NR 46 TC 77 Z9 78 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD JUL PY 2001 VL 19 IS 4 BP 379 EP 385 DI 10.1016/S0736-5748(00)00083-6 PG 7 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 435KY UT WOS:000168881700004 PM 11378298 ER PT J AU Shapiro, EL Ginzberg, R AF Shapiro, EL Ginzberg, R TI The persistently neglected sibling relationship and its applicability to group therapy SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article ID EXPERIENCE AB Despite the parallel between early sibling experiences and patients' experiences of their fellow group members, there is a noticeable dearth of articles directly addressing this connection as its main thesis. This article describes the fundamental applicability of sibling dynamics to a wide range of group experiences and interventions, including the introduction of new members, the special case of only children, twinning between group members, and the cotherapy relationship. We explore patient dreams, the sources of resistance within the profession to the awareness of sibling dynamics, and the therapist's management of group boundaries and norms through this lens of sibling dynamics. C1 Massachusetts Gen Hosp, Dept Psychiat, Ctr Psychoanalyt Studies, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. RP Shapiro, EL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Ctr Psychoanalyt Studies, ACC 805,15 Parkman St, Boston, MA 02114 USA. NR 26 TC 5 Z9 5 U1 0 U2 0 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0020-7284 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD JUL PY 2001 VL 51 IS 3 BP 327 EP 341 DI 10.1521/ijgp.51.3.327.49883 PG 15 WC Psychology, Clinical SC Psychology GA 447VB UT WOS:000169592200003 PM 11447783 ER PT J AU Asea, A Ara, G Teicher, BA Stevenson, MA Calderwood, SK AF Asea, A Ara, G Teicher, BA Stevenson, MA Calderwood, SK TI Effects of the flavonoid drug Quercetin on the response of human prostate tumours to hyperthermia in vitro and in vivo SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE prostate; cancer; heat; quercetin ID HEAT-SHOCK PROTEINS; CELLS; INHIBITION; ACTIVATION; SENSITIZER; INVITRO; CANCER; KINASE; INVIVO AB Tumour hyperthermia, although potentially a powerful therapeutic agent and radiation sensitizer, is hindered by a number of considerations including inhomogeneous heating of deep seated tumours due to energy deposition and perfusion issues. One solution is to design hyperthermia sensitizers to amplify the effects of hyperthermia, particularly at cold spots within the tumour undergoing treatment. This study examined the use of Quercetin, a flavonoid drug shown previously to antagonize the expression of HSP72 and induce apoptosis as a sensitizer of prostate cancer growth in vivo. Quercetin dose-dependently suppressed PC-3 tumour growth in vitro and in vivo. When combined in a treatment protocol with hyperthermia, quercetin drastically inhibited tumour growth and potently amplified the effects of hyperthermia on two prostate tumour types, PC-3 and DU-145 in vivo. These experiments, thus, suggest the use of Quercetin as a hyperthermia sensitizer in the treatment of prostate carcinoma. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Calderwood, SK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. RI Asea, Alexzander/I-4112-2013 OI Asea, Alexzander/0000-0003-3592-3481 FU NCI NIH HHS [2PO1 CA 31303-10] NR 24 TC 43 Z9 44 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0265-6736 J9 INT J HYPERTHER JI Int. J. Hyperthermia PD JUL-AUG PY 2001 VL 17 IS 4 BP 347 EP 356 DI 10.1080/02656730110053146 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 451GK UT WOS:000169792700006 PM 11471985 ER PT J AU Chastagner, P Kozin, SV Taghian, A AF Chastagner, P Kozin, SV Taghian, A TI Topotecan selectively enhances the radioresponse of human small-cell lung carcinoma and glioblastoma multiforme xenografts in nude mice SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE radiation; topotecan; human tumor xenografts; response; oxygenation ID TOPOISOMERASE-I INHIBITORS; IONIZING-RADIATION; FIBROSARCOMA INVIVO; TUMOR XENOGRAFTS; CAMPTOTHECIN; POTENTIATION; COMBINATION; EXPOSURE; INVITRO; THERAPY AB Purpose: To evaluate the therapeutic efficacy of different combinations of the DNA topoisomerase I-targeting drug, topotecan (TPT), with radiation for treatment of two human tumor xenografts, Methods and Materials: The small cell lung carcinoma 54A and glioblastoma multiforme U87 were transplanted into nude mice. Equal i,p. injections of TPT and/or equal fractions of tumor irradiation were administered daily, for 5 consecutive days. When combined, TPT was injected at different constant time intervals prior to or after each radiation fraction. The tumor growth delay and changes in skin radiation reaction by TPT were evaluated. Tumor oxygenation was measured using the Eppendorf pO(2) histography, Results: The tumor growth delay induced by such chemoradiotherapy was independent of interval and sequencing of the agents for either tumor model. The efficacy of TPT alone or in combination with radiation was always dose-dependent, although of different magnitude in the two xenografts, In 54A xenografts, TPT alone induced longer growth delay, but its combined effect with radiation was not more than additive, In contrast, U87 responded less to TPT alone, however the drug and radiation interacted synergisticly in this tumor model, Using both a radiobiological approach (tumor irradiation under normoxia vs. clamp hypoxia conditions) and the polarographic electrode measurements, it was shown that TPT did not modify tumor oxygenation and, thus, unlikely modulated oxygen-related tumor radiosensitivity. In contrast to tumors, TPT virtually unchanged skin radiation reaction. Conclusions: Our data suggest that TPT, when combined with radiation treatment of tumors, provides a therapeutic gain without substantial local and systemic adverse effects. (C) 2001 Elsevier Science Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Hop Enfants, Serv Pediat Oncol, Nancy, France. RP Taghian, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. FU NCI NIH HHS [CA-13311] NR 31 TC 14 Z9 14 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 2001 VL 50 IS 3 BP 777 EP 782 DI 10.1016/S0360-3016(01)01501-2 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 439PP UT WOS:000169126500024 PM 11395247 ER PT J AU Brogi, E Oyama, T Koerner, FC AF Brogi, E Oyama, T Koerner, FC TI Atypical cystic lobules in patients with lobular neoplasia SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE atypical cystic lobules; lobular neoplasia; ductal carcinoma; atypical ductal hyperplasia ID CARCINOMA IN-SITU; TUBULAR CARCINOMA; BREAST; INSITU AB We analyzed the frequency and anatomic distribution of atypical cystic lobules (ACLs) in patients whose index biopsy specimen contained lobular neoplasia (LN). Thirty of 54 patients (56%) had ACLs in their index biopsy specimen. Five of the patients whose index biopsy lacked ACLs under-went an additional biopsy, and 4 of these patients had ACLs in an additional specimen, bringing the total number of patients having both ACLs and LN to 34 of 54 (62.9%). ACLs involved both breasts with equal frequency and neither the extent of the involvement nor the anatomic location of the LN paralleled the distribution of the ACLs. The presence of ACLs in patients with LN might explain its increased risk for the development of ductal carcinomas and their bilateral distribution. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. Gunma Univ, Sch Med, Dept Pathol 2, Maebashi, Gumma 371, Japan. RP Brogi, E (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA. NR 14 TC 38 Z9 38 U1 0 U2 0 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD JUL PY 2001 VL 9 IS 3 BP 201 EP 206 DI 10.1177/106689690100900305 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 483NG UT WOS:000171640700004 PM 11584316 ER PT J AU Gatinel, D Hoang-Xuan, T Azar, DT AF Gatinel, D Hoang-Xuan, T Azar, DT TI Determination of corneal asphericity after myopia surgery with the excimer laser: A mathematical model SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID PHOTOREFRACTIVE KERATECTOMY; SPHERICAL-ABERRATION; REFRACTIVE SURGERY; RADIAL KERATOTOMY; TOPOGRAPHY; EYE; SURFACE; ERROR AB PURPOSE. TO determine the theoretical change of corneal asphericity within the zone of laser ablation after a conventional myopia treatment, which conforms to Munnerlyn's paraxial formula and in which the initial corneal asphericity is not taken into consideration. METHODS. The preoperative corneal shape in cross section was modeled as a conic section of apical radius R-1 and shape factor p(2). A myopia treatment was simulated, and the equation of the postoperative corneal section within the optical zone was calculated by subtracting the ablation profile conforming to a general equation published by Munnerlyn et al. The apical radius of curvature r(2) of the postoperative profile was calculated analytically. The postoperative corneal shape was fitted by a conic section, with an apical radius equal to r(2) and a shape factor p(2) equal to the value that induced the lowest sum of horizontal residuals and the lowest sum of squared residuals. These calculations were repeated for a range of different dioptric treatments, initial shape factor values, and radii of curvature to determine the change of corneal asphericity within the optical zone of treatment. RESULTS. Analytical calculation of r(2) showed it to be independent of the initial preoperative shape factor p(1). The determination of p(2) was unambiguous, because the same value induced both the lowest sum of residuals and the lowest sum of the squared residuals. For corneas initially prolate (p(1) < 1), prolateness increased (p(2) < p(2) < 1), whereas for oblate corneas (p(1) > 1), oblateness increased (p(2) > p(2) > 1) within the treated zone after myopia treatment. This trend increased with the increasing magnitude of treatment and decreased with increasing initial apical radius of curvature R-1. CONCLUSIONS. After conventional myopic excimer laser treatment conforming to Munnerlyn's paraxial formula, the postoperative theoretical corneal asphericity can be accurately approximated by a best-fit conic section. For initially prolate corneas, there is a discrepancy between the clinically reported topographic trend to oblateness after excimer laser surgery for myopia and the results of these theoretical calculations. C1 Massachusetts Eye & Ear Infirm, Corneal External Dis & Refract Surg Serv, Boston, MA 02114 USA. Rothschild Fdn, Paris, France. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. RP Azar, DT (reprint author), Massachusetts Eye & Ear Infirm, Corneal External Dis & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. NR 39 TC 61 Z9 66 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 2001 VL 42 IS 8 BP 1736 EP 1742 PG 7 WC Ophthalmology SC Ophthalmology GA 451JG UT WOS:000169798500012 PM 11431436 ER PT J AU Clark, AF Steely, HT Dickerson, JE English-Wright, S Stropki, K McCartney, MD Jacobson, N Shepard, AR Clark, JI Matsushima, H Peskind, ER Leverenz, JB Wilkinson, CW Swiderski, RE Fingert, JH Sheffield, VC Stone, EM AF Clark, AF Steely, HT Dickerson, JE English-Wright, S Stropki, K McCartney, MD Jacobson, N Shepard, AR Clark, JI Matsushima, H Peskind, ER Leverenz, JB Wilkinson, CW Swiderski, RE Fingert, JH Sheffield, VC Stone, EM TI Glucocorticoid induction of the glaucoma gene MYOC in human and monkey trabecular meshwork cells and tissues SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OPEN-ANGLE GLAUCOMA; INDUCED OCULAR HYPERTENSION; BALTIMORE EYE SURVEY; ULTRASTRUCTURAL-CHANGES; MOLECULAR-GENETICS; ORGAN-CULTURE; JUVENILE GLAUCOMA; DEXAMETHASONE; EXPRESSION; LOCALIZATION AB PURPOSE. TO examine the intracellular and extracellular expression of myocilin in the human and primate trabecular meshwork (TM) in the presence and absence of glucocorticoids. METHODS. Myocilin expression was examined in cultured human TM cells by Northern blot analysis and myocilin antibody-mediated immunoprecipitation. Myocilin expression was quantified using high-resolution two-dimensional polyacrylamide gel electrophoresis of radiolabeled proteins from human TM cells, TM tissue explants, and perfused human anterior segments cultured with and without dexamethasone (DEX) for 14 to 21 days, as well as TM tissue from pigtailed monkeys treated orally for 1 year with cortisone acetate. Immunofluorescence with anti-myocilin antibodies was used to localize cellular and extracellular expression of myocilin in cultured human TM cells. RESULTS. Glucocorticoid treatment caused a significant induction of myocilin mRNA, a tetrad of cell-associated proteins, and 8 to 20 secreted proteins (molecular mass [M-t] 56 and 59 kDa and isoelectric point [pI] 5.2 and 5.3) in some, but not all the cultured human TM cells and explanted tissues. Western immunoblot analysis using anti-myocilin peptide antibodies identified these proteins as encoded by the MYOC gene. There was significant induction of the myocilin proteins in three perfusion-cultured human eyes, in which DM-induced elevated intraocular pressure developed. Monkeys treated 1 year with cortisol acetate showed steroid glaucoma-like morphologic changes in the TM that correlated with the induction of myocilin in the TM. Immunofluorescence analysis of cultured TM cells localized myocilin intracellularly in discrete perinuclear and cytoplasmic vesicular deposits as well as extracellularly on the cell surface associated with the extracellular matrix. In several DEX-treated TM cell lines, there were significant levels of myocilin secreted into the media. Enzymatic deglycosylation of proteins in the TM media converted the higher molecular weight isoforms of myocilin (similar to 57 kDa) to the lower molecular weight isoforms (similar to 55 kDa). CONCLUSIONS. Although the function of myocilin is unknown, induction of these TM proteins was found in eyes in which glucocorticoid-induced ocular hypertension developed. Therefore, myocilin may play an important pathogenic role in ocular hypertension in addition to its role in certain forms of POAG. C1 Alcon Res Ltd, Glaucoma Res R241, Ft Worth, TX 76135 USA. Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Psychiat, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Behav Sci & Neurol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Iowa, Coll Med, Dept Pediat, Iowa City, IA USA. Univ Iowa, Coll Med, Dept Ophthalmol, Iowa City, IA USA. Univ Iowa, Coll Med, Howard Hughes Med Inst, Iowa City, IA USA. RP Clark, AF (reprint author), Alcon Res Ltd, Glaucoma Res R241, 6201 S Freeway, Ft Worth, TX 76135 USA. RI Fingert, John/F-8787-2012 OI Fingert, John/0000-0002-0377-0479 FU NEI NIH HHS [R01 EY004542, EY10564]; NIA NIH HHS [AG-O5136] NR 74 TC 89 Z9 96 U1 0 U2 7 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 2001 VL 42 IS 8 BP 1769 EP 1780 PG 12 WC Ophthalmology SC Ophthalmology GA 451JG UT WOS:000169798500017 PM 11431441 ER PT J AU Arroyo, JG Dastgheib, K Hatchell, DL AF Arroyo, JG Dastgheib, K Hatchell, DL TI Antithrombotic effect of ticlopidine in an experimental model of retinal vein occlusion SO JAPANESE JOURNAL OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT ARVO Annual Meeting CY 1997 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol DE aspirin; experimental retinal vein occlusion; laser photothrombosis; rose bengal solution; ticlopidine AB Purpose: Ticlopidine inhibits adenosine diphosphate (ADP)-induced platelet aggregation and may be effective in patients with retinal vein occlusions (RVO). This study tests the efficacy of ticlopidine in an animal model of RVO. Methods: Rose bengal-mediated argon laser photothrombosis of retinal veins was created in rabbits pretreated with oral ticlopidine, aspirin, or saline. The number of laser spots necessary to produce a partial or complete RVO was recorded and tabulated. Results: Pretreatment with ticlopidine significantly increased the number of laser spots needed to produce a partial (P = .02), or a complete (P = .002) RVO as compared to the control group. Pretreatment with ticlopidine significantly increased the number of laser spots needed to produce a partial RVO (P = .02). Pretreatment with aspirin significantly increased the number of laser spots needed to produce a complete RVO (P = .002). Conclusion: Ticlopidine may be a useful antiplatelet agent for the treatment of patients with RVO. Patients treated with ticlopidine should be monitored for the possible development of hematologic disorders. Jpn J Ophthalmol 2001;45:359-362 (C) 2001 Japanese Ophthalmological Society. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Retina Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02114 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Duke Univ, Ctr Eye, Dept Ophthalmol, Durham, NC 27710 USA. RP Arroyo, JG (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Retina Serv, 12th Floor,243 Charles St, Boston, MA 02114 USA. NR 20 TC 7 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0021-5155 J9 JPN J OPHTHALMOL JI Jpn. J. Ophthalmol. PD JUL-AUG PY 2001 VL 45 IS 4 BP 359 EP 362 DI 10.1016/S0021-5155(01)00337-9 PG 4 WC Ophthalmology SC Ophthalmology GA 457EL UT WOS:000170124100006 PM 11485766 ER PT J AU Herndon, JH Davidson, SM Apazidis, A AF Herndon, JH Davidson, SM Apazidis, A TI Recent socioeconomic trends in orthopaedic practice SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID SMALL-AREA VARIATIONS C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Partners HealthCare Syst, Boston, MA 02114 USA. Boston Univ, Sch Management, Boston, MA 02215 USA. Boston Univ, Sch Med, Randolph, MA 02368 USA. RP Herndon, JH (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Partners HealthCare Syst, 55 Fruit St,GRB 624, Boston, MA 02114 USA. NR 18 TC 13 Z9 13 U1 1 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JUL PY 2001 VL 83A IS 7 BP 1097 EP 1105 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 455HH UT WOS:000170021100018 PM 11451982 ER PT J AU Hoge, RD Pike, GB AF Hoge, RD Pike, GB TI Oxidative metabolism and the detection of neuronal activation via imaging SO JOURNAL OF CHEMICAL NEUROANATOMY LA English DT Article DE oxidative metabolism; imaging; brain structures ID CEREBRAL-BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; HUMAN VISUAL-CORTEX; OXYGEN-CONSUMPTION; STRIATE CORTEX; CORTICAL MICROCIRCULATION; FOREPAW STIMULATION; INTRINSIC SIGNALS; NEURAL ACTIVITY; FUNCTIONAL MRI AB Recent years have witnessed a great growth of interest in non-invasive imaging methods, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), permitting identification of brain structures that mediate specific cognitive and behavioural tasks in humans. Because these techniques use physiological responses such as increased perfusion or metabolism as surrogate indicators of evoked neuronal electrical activity, understanding the role of these processes in sustaining the information processing function of neurons is vital to the proper interpretation Of functional neuroimaging data. An ultimate goal of these non-invasive techniques is to approach the sensitivity and spatial resolution of earlier autoradiographic methods, which have repeatedly demonstrated exquisitely detailed delineations of neuronal response patterns using metabolic glucose uptake as a physiological tag. Although glucose is generally metabolized ill conjunction with oxygen, technical challenges in imaging tissue oxygen Consumption in vivo have limited the use of this complementary process in the detection of neuronal activation. In this article we review concepts linking cerebral blood flow and metabolism to neuronal activation, and compare functional imaging techniques that exploit these relationships. We also describe recently introduced MRI based methods for measurement of oxygen consumption and assess the relative contributions of different metabolic pathways during neuronal activation. Our calculations suggest that the bulk of the energy demand evoked during stimulation of neurons in visual cortex is met through Oxidative metabolism of glucose, supporting the use of oxygen uptake as a marker for increased neuronal electrical activity. (C) 2001 Elsevier Science B.V. All rights reserved. C1 McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ H3A 2B4, Canada. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA USA. RP Pike, GB (reprint author), McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, 3801 Univ St, Montreal, PQ H3A 2B4, Canada. EM bruce@bic.mni.mcgill.ca RI Pike, Bruce/K-5562-2014 OI Pike, Bruce/0000-0001-8924-683X NR 49 TC 33 Z9 34 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0891-0618 J9 J CHEM NEUROANAT JI J. Chem. Neuroanat. PD JUL PY 2001 VL 22 IS 1-2 BP 43 EP 52 DI 10.1016/S0891-0618(01)00114-4 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 468FC UT WOS:000170746600004 PM 11470553 ER PT J AU Bahn, S Augood, S Standaert, DG Starkey, M Emson, PC AF Bahn, S Augood, S Standaert, DG Starkey, M Emson, PC TI Gene expression profiling in the post-mortem human brain - no cause for dismay SO JOURNAL OF CHEMICAL NEUROANATOMY LA English DT Article DE post-mortem; neuropsychiatric disorders; molecular biology; expression profiling; laser-capture microdissection ID LASER-CAPTURE MICRODISSECTION; PROGRESSIVE SUPRANUCLEAR PALSY; IN-SITU HYBRIDIZATION; SUBUNIT MESSENGER-RNAS; HUMAN POSTMORTEM BRAIN; ADULT-RAT BRAIN; HUNTINGTONS-DISEASE; PARKINSONS-DISEASE; HIPPOCAMPAL-FORMATION; ALZHEIMERS-DISEASE AB Global expression profiling techniques such as microarray technology promise to revolutionize biology. Soon it will be possible to investigate alterations at the transcript level of the entire human genome. There is great hope that these techniques will at last shed light on the pathological processes involved in complex neuropsychiatric disorders such as schizophrenia. These scientific advances in turn have re-kindled a great interest and demand for post-mortem brain tissue. Good quality post-mortem tissue undoubtedly is the fundamental prerequisite to investigate complex brain disorders with Molecular profiling techniques. In this review we show that post-mortem brain tissue can yield good quality mRNA and intact protein antigens which allow the successful application of traditional molecular biology methods as well as novel profiling techniques. We also consider the use of laser-capture microdissection on post-mortem tissue. This recently developed technique allows the experimenter to explore the molecular basis of cellular function at the single cell level. The combination of laser-capture microdissection with high throughput profiling techniques offers opportunities to obtain precise genetic fingerprints of individual neurons allowing comparisons of normal and pathological states. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Babraham Inst, Dept Neurobiol, Cambridge CB2 4AT, England. K Human Genome Mapping Project, Resource Ctr, Cambridge CB10 1SB, England. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Addenbrookes Hosp, Dept Psychiat, Cambridge CB2 2QQ, England. RP Bahn, S (reprint author), Babraham Inst, Dept Neurobiol, Cambridge CB2 4AT, England. OI Standaert, David/0000-0003-2921-8348 NR 96 TC 115 Z9 121 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0891-0618 J9 J CHEM NEUROANAT JI J. Chem. Neuroanat. PD JUL PY 2001 VL 22 IS 1-2 BP 79 EP 94 DI 10.1016/S0891-0618(01)00099-0 PG 16 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 468FC UT WOS:000170746600007 PM 11470556 ER PT J AU Soman, TB Takeoka, M Dooling, EC Caviness, V AF Soman, TB Takeoka, M Dooling, EC Caviness, V TI Diffusion-weighted imaging in moyamoya disease SO JOURNAL OF CHILD NEUROLOGY LA English DT Article ID MRI AB Moyamoya disease is characterized by progressive intracranial vascular stenoses of the circle of Willis, resulting in successive ischemic events. We report serial diffusion-weighted imaging studies in a case of moyamoya disease. A 4-year-old right-handed patient presented with multiple infarcts in the right and left hemispheres. Each new infarct was unambiguously recognized as bright on diffusion-weighted imaging. previous infarcts, readily detected on other magnetic resonance imaging sequences, were not bright on diffusion-weighted imaging. The patient subsequently underwent bilateral synangiosis. In this case, the diffusion-weighted images were helpful in assessing the extent of infarcts, determining the age of the lesion, and correlation with new clinical findings. We emphasize the usefulness of diffusion-weighted imaging for following the clinical course of children with moyamoya disease, in whom new focal deficits are highly suspicious of new infarcts. C1 Massachusetts Gen Hosp, Dept Neurol, Pediat Neurol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Soman, TB (reprint author), HKUST SSQ,T3 6B,Clearwater Bay, Kowloon, Hong Kong, Peoples R China. NR 11 TC 2 Z9 2 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD JUL PY 2001 VL 16 IS 7 BP 526 EP 530 DI 10.1177/088307380101600714 PG 5 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 473EA UT WOS:000171026000013 PM 11453452 ER PT J AU Joffe, H Taylor, AE Hall, JE AF Joffe, H Taylor, AE Hall, JE TI Polycystic ovarian syndrome - Relationship to epilepsy and antiepileptic drug therapy SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID REPRODUCTIVE ENDOCRINE DISORDERS; TEMPORAL-LOBE ORIGIN; SODIUM VALPROIC ACID; PARTIAL SEIZURES; UNITED-STATES; WOMEN; MECHANISMS; PREVALENCE; GLUTAMATE; INSULIN C1 McLean Hosp, Womens Ctr Behav Endocrinol, Belmont, MA 02478 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Psychiat, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit,Sch Med, Boston, MA 02114 USA. RP Joffe, H (reprint author), McLean Hosp, Womens Ctr Behav Endocrinol, 115 Mill St, Belmont, MA 02478 USA. EM hjoffe@partners.org NR 38 TC 16 Z9 18 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2001 VL 86 IS 7 BP 2946 EP 2949 DI 10.1210/jc.86.7.2946 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 452BY UT WOS:000169838300006 PM 11443148 ER PT J AU Danila, DC Haidar, JNS Zhang, X Katznelson, L Culler, MD Klibanski, A AF Danila, DC Haidar, JNS Zhang, X Katznelson, L Culler, MD Klibanski, A TI Somatostatin receptor-specific analogs: Effects on cell proliferation and growth hormone secretion in human somatotroph tumors SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN PITUITARY-TUMORS; GTP-BINDING-PROTEINS; TYROSINE PHOSPHATASE; SELECTIVE INDUCTION; ADENYLYL-CYCLASE; GENE-EXPRESSION; SMS 201-995; IN-VITRO; ADENOMAS; SUBTYPE AB Somatostatin (ST) acts through a family of seven transmembrane domain G protein-coupled receptors to: inhibit hormone secretion and cell proliferation in a variety of neuroendocrine tissues. In normal and neoplastic human pituitary somatotroph cells, SST-specific receptor types (SSTR) 1, 2, 3, and 5 are prevalently expressed, and SST and its analogs have been shown to inhibit GH secretion. However, in somatotroph adenomas, little is known regarding: 1) effects of SST and its analogs on pituitary tumor proliferation; 2) the relationship between the effects of SST analogs on GH secretion and tumor cell proliferation; and 3) whether SSTR expression predicts the antiproliferative effects of SST analogs in human somatotroph tumors. We investigated the effects of SST-14,;lanreotide, and SSTR 2 (BIM-23190) and SSTR 5 (BIM-23268) specific analogs in 18 somatotroph pituitary adenomas in primary culture. Our results showed that cell proliferation was significantly inhibited by SST-14, lanreotide, BIM-23190, and BIM-23268 in 4, 7, 3, and 4 tumors, respectively (range of proliferation suppression 5-60%; median, 16%). Tumors that were responsive to SSTR 2- and 5-specific analogs mere also responsive to lanreotide. SST-14 inhibited GH. secretion in 8 of 13 tumors; lanreotide, BIM-231901 and BIM-23268 inhibited GH secretion in six tumors each (range of GH secretion inhibition 23-43%; median 33%). SSTR 2 and 5 messenger RNA was expressed in all tumors investigated, whereas SSTR 1 and 3 messenger RNA was expressed in II and 12 tumors, respectively. We observed a dissociation between the in vitro effects of SST-14 or lanreotide on tumor cell proliferation and the effects on GK secretion in human somatotroph tumors. Although differences in receptor concentration and the presence of other SST receptor subtypes may play a role, the presence of SSTR 2 and/of 5 did. not have a predictive value. These data suggest that inhibition of cell proliferation occurs independently of effects on GH secretory pathways. Further studies are needed to clarify the mechanism of SST induced antiproliferative effects. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Biomeasure Inc, Milford, MA 01757 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM aklibanski@partners.org FU NIDDK NIH HHS [R01-DK40947] NR 48 TC 60 Z9 62 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2001 VL 86 IS 7 BP 2976 EP 2981 DI 10.1210/jc.86.7.2976 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 452BY UT WOS:000169838300011 PM 11443154 ER PT J AU Saenger, P Wikland, KA Conway, GS Davenport, M Gravholt, CH Hintz, R Hovatta, O Hultcrantz, M Landin-Wilhelmsen, K Lin, A Lippe, B Pasquino, AM Ranke, MB Rosenfeld, R Silberbach, M AF Saenger, P Wikland, KA Conway, GS Davenport, M Gravholt, CH Hintz, R Hovatta, O Hultcrantz, M Landin-Wilhelmsen, K Lin, A Lippe, B Pasquino, AM Ranke, MB Rosenfeld, R Silberbach, M TI Recommendations for the diagnosis and management of Turner syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 5th International Turner Symposium CY MAR 23-25, 2000 CL NAPLES, ITALY ID CARDIOVASCULAR RISK-FACTORS; GROWTH-HORMONE THERAPY; MIDDLE-AGED WOMEN; AORTIC DISSECTION; BEHAVIOR PROBLEMS; LIPID-METABOLISM; BODY-COMPOSITION; REFERENCE VALUES; MOTOR FUNCTION; FINAL HEIGHT AB Comprehensive recommendations on the diagnosis of Turner syndrome (TS) and the care of affected individuals were published in 1994. In the light of recent advances in diagnosis and treatment of TS, an international multidisciplinary workshop was convened in March 2000, in Naples, Italy, in conjunction with the Fifth International Symposium on Turner Syndrome to update these recommendations. The present paper details the outcome from this workshop. The genetics and diagnosis of the syndrome are described, and practical treatment guidelines are presented. C1 Montefiore Med Ctr, Albert Einstein Coll Med, Div Pediat Endocrinol, Bronx, NY 10467 USA. Univ Gothenburg, Dept Pediat, Goteborg Pediat Growth Res Ctr, SE-41685 Gothenburg, Sweden. Middlesex Hosp, Dept Endocrinol, London W1N 8AA, England. Univ N Carolina, Div Pediat Endocrinol, Chapel Hill, NC 27599 USA. Aarhus Univ Hosp, Med Dept M, DK-8000 Aarhus C, Denmark. Stanford Univ, Med Ctr, Dept Pediat, Stanford, CA 94305 USA. Huddinge Univ Hosp, Karolinska Inst, Dept Obstet & Gynecol, SE-14186 Huddinge, Sweden. Karolinska Hosp, Dept Otorhinolaryngol, SE-17176 Stockholm, Sweden. Sahlgrens Univ Hosp, Dept Internal Med, Res Ctr Endocrinol & Metab, SE-41345 Gothenburg, Sweden. Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. Pharmacia Corp, Peptide Hormones, Los Angeles, CA 90010 USA. Univ Roma La Sapienza, Ist Clin Pediat, Fac Policlin Umberto I 1, I-00161 Rome, Italy. Univ Tubingen, Childrens Hosp, Pediat Endocrine Sect, D-72070 Tubingen, Germany. Oregon Hlth & Sci Univ, Sch Med, Dept Pediat, Div Cardiol, Portland, OR 97201 USA. RP Saenger, P (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, Div Pediat Endocrinol, 111 E 210th St, Bronx, NY 10467 USA. EM phsaenger@aol.com RI Albertsson-Wikland, Kerstin/D-3843-2012; OI Gravholt, Claus/0000-0001-5924-1720 NR 83 TC 206 Z9 228 U1 3 U2 8 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2001 VL 86 IS 7 BP 3061 EP 3069 DI 10.1210/jc.86.7.3061 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 452BY UT WOS:000169838300026 PM 11443168 ER PT J AU Palmer, JP AF Palmer, JP TI Immunomodulatory therapy of human type 1 diabetes: lessons from the mouse SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID GLUTAMIC-ACID DECARBOXYLASE; RESIDUAL INSULIN-SECRETION; BETA-CELL FUNCTION; FUNCTIONAL-STATE; MELLITUS; MICE; REVERSAL; MODEL C1 Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol & Metab, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA USA. RP Palmer, JP (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol & Metab, III,1660 S Columbian Way, Seattle, WA 98108 USA. EM jpp@u.washington.edu NR 21 TC 6 Z9 6 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 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2001 VL 108 IS 1 BP 31 EP 33 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 449HX UT WOS:000169679900005 PM 11435453 ER PT J AU Ryu, S Kodama, S Ryu, K Schoenfeld, DA Faustman, DL AF Ryu, S Kodama, S Ryu, K Schoenfeld, DA Faustman, DL TI Reversal of established autoimmune diabetes by restoration of endogenous beta cell function SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NF-KAPPA-B; UBIQUITIN-PROTEASOME PATHWAY; COMPLETE FREUND ADJUVANT; ALPHA-INDUCED APOPTOSIS; CLASS-I EXPRESSION; NOD MICE; TNF-ALPHA; ISLET GRAFTS; T-CELLS; ANTIGENS AB In NOD (nonobese diabetic) mice, a model of autoimmune diabetes, various immunomodulatory interventions prevent progression to diabetes. However, after hyperglycemia is established, such interventions rarely alter the course of disease or allow sustained engraftment of islet transplants. A proteasome defect in lymphoid cells of NOD mice impairs the presentation of self antigens and increases the susceptibility of these cells to TNF-alpha -induced apoptosis. Here, we examine the hypothesis that induction of TNF-alpha expression combined with reeducation of newly emerging T cells with self antigens carl interrupt autoimmunity. Hyperglycemic NOD mice were treated with CFA to induce TNF-alpha expression and were exposed to functional complexes of MHC class I molecules and antigenic peptides either by repeated injection of MHC class I matched splenocytes or by transplantation of islets from nonautoimmune donors. Hyperglycemia was controlled in animals injected with splenocytes by administration of insulin or, more effectively, by implantation of encapsulated islets. These interventions reversed the established beta cell-directed autoimmunity and restored endogenous pancreatic islet function to such an extent that normoglycemia was maintained in up to 75% of animals after discontinuation of treatment and removal of islet transplants. A therapy aimed at the selective elimination of autoreactive cells and the reeducation of T cells, when combined with control of glycemia, is thus able to effect an apparent cure of established type 1 diabetes in the NOD mouse. C1 Harvard Univ, Sch Med, Immunobiol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Biostat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Charlestown, MA USA. RP Faustman, DL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp E, Immunobiol Lab, Bldg 149,Room 3602,13th St,MailStop M1493601, Charlestown, MA 02129 USA. NR 41 TC 112 Z9 113 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2001 VL 108 IS 1 BP 63 EP 72 DI 10.1172/JCI12335 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 449HX UT WOS:000169679900010 PM 11435458 ER PT J AU Ribeiro, MO Carvalho, SD Schultz, JJ Chiellini, G Scanlan, TS Bianco, AC Brent, GA AF Ribeiro, MO Carvalho, SD Schultz, JJ Chiellini, G Scanlan, TS Bianco, AC Brent, GA TI Thyroid hormone-sympathetic interaction and adaptive thermogenesis are thyroid hormone receptor isoform-specific SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BROWN ADIPOSE-TISSUE; UNCOUPLING PROTEIN GENE; MESSENGER-RNA; HYPOTHYROID RATS; MALIC ENZYME; BETA; TRIIODOTHYRONINE; MICE; NOREPINEPHRINE; ADIPOCYTES AB In newborns and small tnammals, cold-induced adaptive (or nonshivering) thermogenesis is produced primarily in brown adipose tissue (BAT). Heat production is stimulated by the sympathetic nervous system, but it has an absolute requirement for thyroid hormone. We used the thyroid hormone receptor-beta -selective (TR-beta -selective) ligand, GC-1, to determine by a pharmacological approach whether adaptive thermogenesis was TR isoform-specific, Hypothyroid mice were treated for 10 days with varying doses of T3 or GC-1. The level of uncoupling protein 1 (UCP1), the key thermogenic protein in BAT, was restored by either T3 or GC-1 treatment. However, whereas interscapular BAT in T3-treated mice showed a 3.0 degreesC elevation upon infusion of not epinephrine, indicating normal thermogenesis, the temperature did not increase (<0.5C) in GC-1-treated mice. When exposed to cold (4 degreesC), GC-1-treated mice also failed to maintain core body temperature and had reduced stimulation of BAT UCP1 mRNA, indicating impaired adrenergic responsiveness. Brown adipocytes isolated from hypothyroid mice replaced with T3, but not from those replaced with GC-1, had normal cAMP production in response to adrenergic stimulation in vitro. We conclude that two distinct thyroid-dependent pathways, stimulation of UCP1 and augmentation of adrenergic responsiveness, are mediated by different TR isoforms in the same tissue. C1 VA Greater Los Angeles Healthcare Syst, Mol Endocrinol Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Brigham & Womens Hosp, Div Thyroid, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA. RP Brent, GA (reprint author), VA Greater Los Angeles Healthcare Syst, Mol Endocrinol Lab, Bldg 114,Room 230,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Bianco, Suzy/E-8892-2010; Bianco, Antonio/A-4965-2008; Ribeiro, Miriam/A-9367-2013; Ribeiro, Miriam/B-6085-2015; Ribeiro, Miriam/C-6364-2016 OI Bianco, Suzy/0000-0003-3794-9853; Bianco, Antonio/0000-0001-7737-6813; Ribeiro, Miriam/0000-0002-7870-9701; FU NIDDK NIH HHS [DK-43714, DK-52798, R01 DK052798, R56 DK052798] NR 50 TC 152 Z9 156 U1 1 U2 9 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2001 VL 108 IS 1 BP 97 EP 105 DI 10.1172/JCI12584 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 449HX UT WOS:000169679900013 PM 11435461 ER PT J AU Kim, JK Zisman, A Fillmore, JJ Peroni, OD Kotani, K Perret, P Zong, HH Dong, JY Kahn, CR Kahn, BB Shulman, GI AF Kim, JK Zisman, A Fillmore, JJ Peroni, OD Kotani, K Perret, P Zong, HH Dong, JY Kahn, CR Kahn, BB Shulman, GI TI Glucose toxicity and the development of diabetes in mice with muscle-specific inactivation of GLUT4 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID WHITE ADIPOSE-TISSUE; INSULIN-RESISTANCE; GLYCOGEN-SYNTHESIS; SKELETAL-MUSCLE; CONSCIOUS RATS; TRANSPORT; MELLITUS; METABOLISM; GLYCOLYSIS; HYPERGLYCEMIA AB Using cre/loxP gene targeting, transgenic mice with muscle-specific inactivation of the GLUT4 gene (muscle GLUT4 KO) were generated and shown to develop a diabetes phenotype. To determine the mechanism, we examined insulin-stimulated glucose uptake and metabolism during hyperinsulinemic-euglycemic clamp in control and muscle GLUT4 KO mice before and after development of diabetes. Insulin-stimulated whole body glucose uptake was decreased by 55% in muscle GLUT4 KO mice, an effect that could be attributed to a 92% decrease in insulin-stimulated muscle glucose uptake. Surprisingly, insulin's ability to stimulate adipose tissue glucose uptake and suppress hepatic glucose production was significantly impaired in muscle GLUT4 KO mice. To address whether these latter changes were caused by glucose toxicity, we treated muscle GLUT4 KO mice with phloridzin to prevent hyperglycemia and found that insulin-stimulated whole body and skeletal muscle glucose uptake were decreased substantially, whereas insulin-stimulated glucose uptake in adipose tissue and suppression of hepatic glucose production were normal after phloridzin treatment. In conclusion, these findings demonstrate that a primary defect in muscle glucose transport can lead to secondary defects in insulin action in adipose tissue and liver due to glucose toxicity. These secondary defects contribute to insulin resistance and to the development of diabetes. C1 Yale Univ, Sch Med, Howard Hughes Med Inst, Boyer Ctr Mol Med, New Haven, CT 06536 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06536 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr, Boston, MA USA. RP Shulman, GI (reprint author), Yale Univ, Sch Med, Howard Hughes Med Inst, Boyer Ctr Mol Med, 295 Congress Ave,Room 254C,Box 9812, New Haven, CT 06536 USA. RI Perret, Pascale/M-3911-2014 OI Perret, Pascale/0000-0003-0804-8247 FU NIDDK NIH HHS [R01 DK033201, P30 DK-45735, P30 DK045735, R01 DK-33201, R01 DK-40936, R01 DK-43051, R01 DK040936, R01 DK043051, R01 DK080756, U24 DK-59635, U24 DK059635] NR 35 TC 106 Z9 118 U1 1 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2001 VL 108 IS 1 BP 153 EP 160 DI 10.1172/JCI10294 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 449HX UT WOS:000169679900019 PM 11435467 ER PT J AU Thomas, MK Devon, ON Lee, JH Peter, A Schlosser, DA Tenser, MS Habener, JF AF Thomas, MK Devon, ON Lee, JH Peter, A Schlosser, DA Tenser, MS Habener, JF TI Development of diabetes mellitus in aging transgenic mice following suppression of pancreatic homeoprotein IDX-1 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID INSULIN GENE-TRANSCRIPTION; HOMEODOMAIN PROTEIN IDX-1; BETA-CELL LINE; FACTOR-I; HOMEOBOX FACTOR; ISLET CELLS; GLUCOSE-CONCENTRATION; FACTOR EXPRESSION; MAMMALIAN-CELLS; PROMOTER AB Monogenic forms of diabetes can result from mutations in genes encoding transcription factors. Mutations in the homeodomain transcription factor IDX-1, a critical regulator of pancreas development and insulin gene transcription, confer a strong predisposition to the development of diabetes mellitus in humans. To investigate the role of IDX-1 expression in the pathogenesis of diabetes, we developed a model for the inducible impairment of IDX-1 expression in pancreatic beta cells in vivo by engineering an antisense ribozyme specific for mouse IDX-1 mRNA under control of the reverse tetracycline transactivator (rtTA), Doxycycline-induced impairment of IDX-1 expression reduced activation of the Insulin promoter but activated the Idx-1 promoter, suggesting that pancreatic beta cells regulate IDX-1 transcription to maintain IDX-1 levels within a narrow range. In transgenic mice that express both rtTA and the antisense ribozyme construct, impaired IDX-1 expression elevated glycated hemoglobin levels, diminished glucose tolerance, and decreased insulin/glucose ratios. Metabolic phenotypes induced by IDX-1 deficiency were observed predominantly in male mice over 18 months of age, suggesting that cellular mechanisms to protect IDX-1 levels in pancreatic beta cells decline with aging. We propose that even in the absence of Idx-1 gene mutations, pathophysiological processes that decrease IDX-1 levels are likely to impair glucose tolerance. Therapeutic strategies to attain normal glucose homeostasis by restoring normal IDX-1 levels may be of particular importance for older individuals with diabetes mellitus. C1 Harvard Univ, Mol Endocrinol Lab, Massachusetts Gen Hosp, Howard Hughes Med Inst,Sch Med, Boston, MA 02114 USA. RP Habener, JF (reprint author), Harvard Univ, Mol Endocrinol Lab, Massachusetts Gen Hosp, Howard Hughes Med Inst,Sch Med, 55 Fruit St,WEL320, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK02476, DK30457, DK30834, R01 DK030834, DK58783] NR 62 TC 68 Z9 68 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 JUL PY 2001 VL 108 IS 2 BP 319 EP 329 DI 10.1172/JCI12029 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 452QY UT WOS:000169871300020 PM 11457885 ER PT J AU Vonderheide, RH Dutcher, JP Anderson, JE Eckhardt, SG Stephans, KF Razvillas, B Garl, S Butine, MD Perry, VP Armitage, RJ Ghalie, R Caron, DA Gribben, JG AF Vonderheide, RH Dutcher, JP Anderson, JE Eckhardt, SG Stephans, KF Razvillas, B Garl, S Butine, MD Perry, VP Armitage, RJ Ghalie, R Caron, DA Gribben, JG TI Phase I study of recombinant human CD40 ligand in cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Hematology CY DEC 03-08, 1999 CL NEW ORLEANS, LOUISIANA SP Amer Soc Hematol ID CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELL PROLIFERATION; DENDRITIC CELLS; T-CELLS; ADOPTIVE IMMUNOTHERAPY; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; ACTIVATION; CYTOKINES; GROWTH AB Purpose: To determine the toxicity, maximum-tolerated dose (MTD), and pharmacokinetics of recombinant human CD40 ligand (rhuCD40L) (Avrend; Immunex Corp, Seattle, WA), suggested in preclinical studies to mediate cytotoxicity against CD40-expressing tumors and immune stimulation. Patients and Methods: Patients with advanced solid tumors or intermediate- or high-grade non-Hodgkin's lymphoma (NHL) received rhuCD40L subcutaneously daily for 5 days in a phase I dose-escalation study. Subsequent courses were given until disease progression. Results: Thirty-two patients received rhuCD40L at three dose levels. A total of 65 courses were administered. The MTD was 0.1 mg/kg/d based on dose-related but transient elevations of serum liver transaminases. Grade 3 or 4 transaminase elevations occurred in 14%, 28%, and 57% of patients treated at 0.05, 0.10, and 0.15 mg/kg/d, respectively. Other toxicities were mild to moderate. At the MTD, the half-life of rhuCD40L was calculated at 24.8 +/- 22.8 hours. Two patients (6%) had a partial response on study (one patient with laryngeal carcinoma and one with NHL), For the patient with laryngeal cancer, a partial response was sustained for 12 months before the patient wets taken off therapy and observed on no additional therapy. Three months later, the patient was found to have a complete response and remains biospy-proven free of disease at 24 months. Twelve patients (38%) had stable disease after one course, which wets sustained in four patients through four courses. Conclusion.: The MTD of rhuCD40L when administered subcutaneously daily for 5 days was defined by transient serum elevations in hepatic transaminases, Encouraging antitumor activity, including a long-term complete remission, was observed. phase II studies are warranted. (C) 2001 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Our Lady Mercy Hosp, New York Med Coll, Ctr Canc, Bronx, NY USA. Inst Drug Dev, Canc Therapy & Res Ctr, San Antonio, TX USA. Immunex Corp, Seattle, WA USA. RP Vonderheide, RH (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 45 TC 133 Z9 138 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 1 PY 2001 VL 19 IS 13 BP 3280 EP 3287 PG 8 WC Oncology SC Oncology GA 448AX UT WOS:000169605600016 PM 11432896 ER PT J AU Thorner, AR Travis, AC Hecht, JL Conrow, DS Fisher, DC AF Thorner, AR Travis, AC Hecht, JL Conrow, DS Fisher, DC TI Unusual presentations of malignancy - Case 3. Mantle-cell lymphoma of soft tissue SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SKELETAL-MUSCLE LYMPHOMA C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Thorner, AR (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 1 PY 2001 VL 19 IS 13 BP 3291 EP 3293 PG 3 WC Oncology SC Oncology GA 448AX UT WOS:000169605600019 PM 11432899 ER PT J AU Feres, M Haffajee, AD Allard, K Som, S Socransky, SS AF Feres, M Haffajee, AD Allard, K Som, S Socransky, SS TI Change in subgingival microbial profiles in adult periodontitis subjects receiving either systemically-administered amoxicillin or metronidazole SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE microbiology; bacteria; subgingival plaque; periodontal diseases; periodontitis; metronidazole; amoxicillin; antibiotics ID ACTINOMYCETEMCOMITANS-ASSOCIATED PERIODONTITIS; MUCOID PSEUDOMONAS-AERUGINOSA; NON-SURGICAL TREATMENT; TOBRAMYCIN RESISTANCE; NONSURGICAL TREATMENT; PLUS AMOXICILLIN; THERAPY; DISEASE; BIOFILM; AMOXYCILLIN AB Aim: The current investigation evaluated changes in levels and proportions of 40 bacterial species in subgingival plaque samples during, immediately after and up to 1 year after metronidazole or amoxicillin therapy combined with SRP. Method: After baseline clinical and microbiological monitoring, 17 adult periodontitis subjects received full mouth SRP and 14 days systemic administration of either metronidazole (250 mg, TID, n=8) or amoxicillin (500 mg, TID n=9). Clinical measurements including % of sites with plaque, gingival redness, bleeding on probing and suppuration, pocket depth (PD) and attachment level (AL) were made at baseline, 90, 180 and 360 days. Subgingival plaque samples were taken from the mesial surface of all teeth in each subject at baseline, 90, 180 and 360 days and from 2 randomly selected posterior teeth at 3, 7, and 14 days during and after antibiotic administration. Counts of 40 subgingival species were determined using checkerboard DNA-DNA hybridization. Significance of differences over time was determined using the Quade test and between groups using ANCOVA. Results: Mean PD was reduced from 3.22 +/-0.12 at baseline to 2.81 +/-0.16 (p <0.01) at 360 days and from 3.38 +/-0.23 mm to 2.80 +/-0.14 mm (p <0.01) in the amoxicillin and metronidazole treated subjects respectively. Corresponding values for mean AL were 3.21 +/-0.30 to 2.76 +/-0.32 (p <0.05) and 3.23 +/-0.28 mm to 2.94 +/-0.23 mm (p <0.01). Levels and proportions of Bacteroides forsythus, Porphyromonas gingivalis and Treponema denticola were markedly reduced during antibiotic administration and were lower than baseline levels at 360 days. Counts (x10(5), +/- SEM) of B. forsythus fell from baseline levels of 0.66 +/-0.16 to 0.04 +/-0.02, 0.13 +/-0.04, 0.10 +/-0.03 and 0.42 +/-0.19 in the amoxicillin group at 14, 90, 180 and 360 days respectively (p <0.001). Corresponding values for metronidazole treated subjects were: 1.69 +/-0.28 to 0.02 +/-0.01, 0.20 +/-0.08, 0.22 +/-0.06 and 0.22 +/-0.08 (p <0.001). Counts of Campylobacter species, Eubacterium nodatum, Fusobacterium nucleatum subspecies, F, periodonticum and Prevotella nigrescens were also detected at lower mean levels during and immediately after therapy, but gradually increased after withdrawal of the antibiotics. Members of the genera Actinomyces Streptococcus and Capnocytophaga were minimally affected by metronidazole. However, amoxicillin decreased the counts and proportions of Actinomyces species during and after therapy. Conclusions: The data suggest that metronidazole and amoxicillin are useful in rapidly lowering counts of putative periodontal pathogens, but must be accompanied by other procedures to bring about periodontal stability. C1 Forsyth Inst, Dept Periodontol, Boston, MA USA. RP Haffajee, AD (reprint author), Forsyth Inst, Dept Periodontol, Boston, MA USA. RI Feres, Magda/H-7964-2012 FU NIDCR NIH HHS [DE-04881, DE-10977, DE-12108] NR 60 TC 70 Z9 74 U1 1 U2 11 PU MUNKSGAARD INT PUBL LTD 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 JUL PY 2001 VL 28 IS 7 BP 597 EP 609 DI 10.1034/j.1600-051x.2001.028007597.x PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 449HP UT WOS:000169679000001 PM 11422580 ER PT J AU Ghaemi, SN Lenox, MS Baldessarini, RJ AF Ghaemi, SN Lenox, MS Baldessarini, RJ TI Effectiveness and safety of long-term antidepressant treatment in bipolar disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID LITHIUM MAINTENANCE TREATMENT; DOUBLE-BLIND; DEPRESSION; IMIPRAMINE; CARBONATE; OUTPATIENTS; PROPHYLAXIS; LAMOTRIGINE; PREVENTION; UNIPOLAR AB Objective: We sought to review research on use of antidepressants for long-term treatment of bipolar depression. Method: We conducted a computerized literature search of the MEDLINE, HealthStar, Current Contents, PsychInfo, and National Library of Medicine databases to identify studies involving antidepressant, anticonvulsant, or lithium use in bipolar disorder or manic-depressive illness published from 1966 through 2000. Results: Only 7 blinded, controlled trials of long-term antidepressant treatment in bipolar disorders were found. The available information is not adequate to support the safety or effectiveness of long-term antidepressant treatment for bipolar depression, with or without mood-stabilizing cotherapy. Conclusion: Antidepressant treatment of bipolar depression is extraordinarily understudied. Controlled trials comparing specific antidepressants, particularly to compare mood-stabilizing agents given alone and combined with an antidepressant, are needed. C1 Harvard Univ, Sch Med, Consoidated Dept Psychit, Boston, MA USA. Harvard Univ, Sch Med, Int Consortium Bipolar Disorders Res, Boston, MA USA. Cambridge Hosp, Bipolar Disorder Res Program, Cambridge, MA 02139 USA. Cambridge Hosp, Psychopharmacol Program, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Bipolar & Psychot Disorders Program, Belmont, MA USA. Massachusetts Gen Hosp, Psychopharmacol Program, Belmont, MA USA. Massachusetts Gen Hosp, Psychiat Res Labs, McLean Div, Belmont, MA USA. RP Ghaemi, SN (reprint author), Cambridge Hosp, Dept Psychiat, 1493 Cambridge St, Cambridge, MA 02139 USA. FU NIMH NIH HHS [MH-64189, MH-47370] NR 28 TC 108 Z9 110 U1 0 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 2001 VL 62 IS 7 BP 565 EP 569 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 457KZ UT WOS:000170137400014 PM 11488370 ER PT J AU Laeng, B Caviness, VS AF Laeng, B Caviness, VS TI Prosopagnosia as a deficit in encoding curved surface SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID FACE RECOGNITION; OBJECT RECOGNITION; VISUAL RECOGNITION; TOPOGRAPHIC PARCELLATION; UNFAMILIAR FACES; TEMPORAL CORTEX; PERCEPTION; SHAPE; MRI; HEMISPHERE AB RP is a case of "developmental" prosopagnosia who, according to brain-imaging segmentation data, shows a reduction in volume of a limited set of structures of the right hemisphere. RP is as accurate as control subjects in tasks requiring the perception of nonface objects (e.g., matching subordinate labels to exemplars, naming two-tone images), with the exception of one perceptual task: The matching of different perspectives of amoebae-like stimuli (i.e.. volumes made of a single smooth surface). In terms of speed ("efficiency") of responses, RP's performance falls clearly outside the not nial limits also in other tasks that include "natural" but nonface stimuli (i.e., animals, artifacts). Specifically, RP is slow in perceptual judgements made at very low (subordinate) levels of semantic categorization and for objects and artifacts whose geometry present much curved features and surface information. We conclude from these analyses that prosopagnosia can be the result of a deficit in the representation of basic geometric volumes made of curved surface. In turn, this points to the importance (necessity) for the normal visual system of such curved and volumetric information in the identification of human faces. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Cambridge, MA 02138 USA. RP Laeng, B (reprint author), Univ Tromso, Dept Psychol, Asgardveien 9, N-9027 Tromso, Norway. NR 92 TC 26 Z9 27 U1 1 U2 2 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD JUL 1 PY 2001 VL 13 IS 5 BP 556 EP 576 DI 10.1162/089892901750363163 PG 21 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 453BZ UT WOS:000169898000002 PM 11506657 ER PT J AU Lev, MH Farkas, J Rodriguez, VR Schwamm, LH Hunter, GJ Putman, CM Rordorf, GA Buonanno, FS Budzik, R Koroshetz, WJ Gonzalez, RG AF Lev, MH Farkas, J Rodriguez, VR Schwamm, LH Hunter, GJ Putman, CM Rordorf, GA Buonanno, FS Budzik, R Koroshetz, WJ Gonzalez, RG TI CT angiography in the rapid triage of patients with hyperacute stroke to intraarterial thrombolysis: Accuracy in the detection of large vessel thrombus SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE computed tomography; computed tomography, angiography; stroke; thrombolysis ID ACUTE ISCHEMIC STROKE; MIDDLE CEREBRAL-ARTERY; TISSUE-PLASMINOGEN-ACTIVATOR; ACUTE HEMISPHERIC STROKE; CAROTID-ARTERY; INTRAVENOUS THROMBOLYSIS; THERAPY; DIAGNOSIS; PROUROKINASE; PERFUSION AB Purpose: The purpose of this work was to evaluate the accuracy of CT angiography (CTA) for the detection of large vessel intracranial thrombus in clinically suspected hyperacute (<6 h) stroke patients. Method: Forty-four consecutive intraarterial thrombolysis candidates underwent noncontrast CT followed immediately by CTA. Axial source and two-dimensional collapsed maximum intensity projection reformatted CTA images were rated for the presence or absence of large vessel occlusion. Five hundred seventy-two circle-of-Willis vessels were reviewed. arteriographic correlation was available for 224 of these. Results: Sensitivity and specificity for the detection of large vessel occlusion were 98.4 and 98.1%: accuracy, calculated using receiver operating characteristic analysis, was 99%, Mean time for acquisition, reconstruction, and analysis of CTA images was approximately 15 min. Conclusion: CTA is highly accurate for the detection and exclusion of large vessel intracranial occlusion and may therefore be valuable in the rapid triage of hyperacute stroke patients to intraarterial thrombolytic treatment. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Tufts Univ, Sch Med, New England Med Ctr, Boston, MA 02111 USA. Univ Med & Dent New Jersey, New Jersey Med Ctr Hosp, Div Neurointervent Radiol, Newark, NJ 07103 USA. RP Lev, MH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, GRB285,POB 9657, Boston, MA 02114 USA. OI Schwamm, Lee/0000-0003-0592-9145 FU NCRR NIH HHS [RR 13213]; NINDS NIH HHS [NS 34626] NR 39 TC 138 Z9 141 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JUL-AUG PY 2001 VL 25 IS 4 BP 520 EP 528 DI 10.1097/00004728-200107000-00003 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 451CZ UT WOS:000169784700003 PM 11473180 ER PT J AU Caron, C Xue, J Sun, X Simmer, JP Bartlett, JD AF Caron, C Xue, J Sun, X Simmer, JP Bartlett, JD TI Gelatinase a (MMP-2) in developing tooth tissues and amelogenin hydrolysis SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE biomineralization; MMP-2; amelogenin; enamel; dentin; cDNA ID MATRIX-METALLOPROTEINASE; EXPRESSION; MOUSE; DEGRADATION; PROTEINS; SURFACE; ENAMEL; TEETH AB Matrix metal loproteinases (MMPs) are thought to play important roles during enamel and dentin biomineralization. Previously, membrane type-1 matrix metalloproteinase (MT1-MMP) was localized to the plasma membranes of ametoblasts and odontoblasts of the developing tooth. The best-characterized function of MT1-MMP is to initiate the activation of gelatinase A (MMP-2) Thus, we hypothesized that gelatinase A may also be expressed by developing tooth tissues. A full-length porcine gelatinase A mRNA was isolated by RT-PCR homology cloning of an enamel-organ-specific cDNA library. Northern blot and in situ hybridization analyses demonstrated gelatinase A expression in developing tooth tissues. Immunohistochemical analysis localized gelatinase A close to the plasma membrane of these tissues. Furthermore, recombinant gelatinase A was demonstrated to cleave recombinant amelogenin into several fragments of differing molecular masses. Thus, gelatinase A is expressed by developing tooth tissues along with its activator MT1-MMP and may, therefore, play an important role during tooth development. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Univ Laval, Fac Dent, Laval, PQ, Canada. Harvard Forsyth Dept Oral Biol, Boston, MA 02115 USA. Univ Texas, Hlth Sci Ctr, Sch Dent, San Antonio, TX 78284 USA. RP Bartlett, JD (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE 12098, DE13237, P01 DE013237] NR 14 TC 23 Z9 25 U1 0 U2 1 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 JUL PY 2001 VL 80 IS 7 BP 1660 EP 1664 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 536CT UT WOS:000174683700012 PM 11597028 ER PT J AU Lipinski, B AF Lipinski, B TI Pathophysiology of oxidative stress in diabetes mellitus SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Review DE oxidative stress; fibrinogen; diabetes ID LOW-DENSITY-LIPOPROTEIN; ALPHA-LIPOIC ACID; C-REACTIVE PROTEIN; CORONARY HEART-DISEASE; MASS-SPECTROMETRIC QUANTIFICATION; AGED GARLIC EXTRACT; ALL-CAUSE MORTALITY; BLOOD-CELL COUNT; CARDIOVASCULAR-DISEASE; LIPID-PEROXIDATION AB Oxidative stress is believed to play an important role, albeit not fully recognized, in the development of vascular complications in diabetes mellitus (DM) particularly type 2. In the majority of studies, attention was focused on lipid oxidation, specifically on that of low-density lipoproteins (LDLs). More recent investigations have revealed that it is not only the lipid but also the apolipoprotein moiety of LDL that becomes oxidatively modified resulting in the formation of insoluble aggregates. Consequently, it has been documented that LDL aggregation was due to the hydroxyl radical-induced dityrosine crosslinking between apo B monomers. In DM patients with atherosclerotic complications, intravascular fibrous deposits were shown to contain, in addition to oxidized LDL, a fibrin-like material(FLM). This material is immunologically identical to fibrin that is normally formed as a result of intravascular activation of the blood coagulation cascade. Although DM patients with vascular disease display increased concentration of plasma fibrinogen (Fbg), the precursor of fibrin, no markers of full blown activation of blood coagulation could he found. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dept Genet & Epidemiol, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Lipinski, B (reprint author), Harvard Univ, Sch Med, Dept Genet & Epidemiol, Joslin Diabet Ctr, Room 305,1 Joslin Pl, Boston, MA 02215 USA. NR 115 TC 96 Z9 100 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD JUL-AUG PY 2001 VL 15 IS 4 BP 203 EP 210 DI 10.1016/S1056-8727(01)00143-X PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 455WR UT WOS:000170051200007 PM 11457673 ER PT J AU Kulkarni, RG Brown, DFM Nadel, ES Thomas, S Nagurney, JT Benzer, T Lyn, E Adler, J AF Kulkarni, RG Brown, DFM Nadel, ES Thomas, S Nagurney, JT Benzer, T Lyn, E Adler, J TI Altered mentation and seizure SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID HYPONATREMIA; SODIUM C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Kulkarni, RG (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, CLN-115, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD JUL PY 2001 VL 21 IS 1 BP 59 EP 62 DI 10.1016/S0736-4679(01)00350-X PG 4 WC Emergency Medicine SC Emergency Medicine GA 441LZ UT WOS:000169233000011 PM 11399390 ER PT J AU Kim, MY Lin, JS White, R Niederman, R AF Kim, MY Lin, JS White, R Niederman, R TI Benchmarking the endodontic literature on MEDLINE SO JOURNAL OF ENDODONTICS LA English DT Article ID RANDOMIZED CONTROLLED TRIALS; SEARCHES; MEDICINE; HEALTH; PAPER; READ AB The purpose of this study was to identify and quantify the endodontic literature available for clinical decision making. A search strategy based on Medical Subject Headings for endodontics was developed to examine MEDLINE. The identified articles were limited to human subjects and English. Sensitive and specific methodological search filters identified four categories of information: etiology, diagnosis, therapy, and prognosis. The results were then subdivided by year to identify trends. Between 1990 and 1998 MEDLINE identified 3,152 articles published in English on endodontics in humans. The number of articles per year (mean a SD) for sensitive and specific searches was etiology (28 +/- 10, 1 +/- 2), diagnosis (38 +/- 11, 1 +/- 1), therapy (59 +/- 15, 3 +/- 3), and prognosis (40 +/- 13, 10 +/- 5), respectively. The number of articles in each category increased by 1 to 3% each year. There were 150 articles/yr in endodontics in at least 120 journals cited on MEDLINE (see Table 5) on which to base clinical decisions. C1 Harvard Univ, Sch Dent Med, Off Evidence Based Dent, Boston, MA 02115 USA. Forsyth Inst, Boston, MA USA. Harvard Univ, Sch Dent Med, Dept Restorat Dent, Div Endodont, Boston, MA 02115 USA. RP Niederman, R (reprint author), Harvard Univ, Sch Dent Med, Off Evidence Based Dent, 188 Longwood Ave, Boston, MA 02115 USA. NR 17 TC 12 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0099-2399 J9 J ENDODONT JI J. Endod. PD JUL PY 2001 VL 27 IS 7 BP 470 EP 473 DI 10.1097/00004770-200107000-00009 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 446JH UT WOS:000169509800009 PM 11503999 ER PT J AU Weinberger, LE Sreenivasan, S Sathyavagiswaran, L Markowitz, E AF Weinberger, LE Sreenivasan, S Sathyavagiswaran, L Markowitz, E TI Child and adolescent suicide in a large, urban area: Psychological, demographic, and situational factors SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; child and adolescent suicide ID COMPLETED SUICIDE; RISK-FACTORS; YOUNG ADOLESCENTS; MENTAL-DISORDERS; SUBSTANCE-ABUSE; BEHAVIOR; DEPRESSION; PSYCHOPATHOLOGY; HOPELESSNESS; DIAGNOSIS AB We examined all completed suicides by children and adolescents in Los Angeles County who died during 1996 and 1997. There were 46 subjects, aged 11 through 16. The majority of the decedents were males and over age 14. The predominant racial group was Hispanic. There was an almost even split between firearms and hanging as the means of death. Females had a statistically significantly higher rate of prior suicide attempts than males. Over one-third left a suicide note, almost one-half were noted to be depressed, and 22% tested positive for alcohol or illicit drugs. Less than one-quarter were in mental health treatment. Eighty-seven percent had difficulty transitioning to or during adolescence; e.g., problems at home, legal and school difficulties, and relationship losses. These findings are discussed in terms of Eriksonian developmental theory. We offer recommendations for intervention and prevention of suicide. C1 Univ So Calif, Inst Psychiat Law & Behav Sci, Los Angeles, CA 90086 USA. Univ So Calif, Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. Greater Los Angeles VA Hlth Care Syst, Los Angeles, CA USA. Los Angeles Cty Dept Coroner, Los Angeles, CA USA. Univ So Calif, Dept Med, Los Angeles, CA 90086 USA. Univ So Calif, Dept Pathol, Los Angeles, CA 90086 USA. RP Weinberger, LE (reprint author), Univ So Calif, Inst Psychiat Law & Behav Sci, POB 86125, Los Angeles, CA 90086 USA. NR 44 TC 16 Z9 17 U1 5 U2 6 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD JUL PY 2001 VL 46 IS 4 BP 902 EP 907 PG 6 WC Medicine, Legal SC Legal Medicine GA 449LV UT WOS:000169686800024 PM 11451075 ER PT J AU Armstrong, K FitzGerald, G Schwartz, JS Ubel, PA AF Armstrong, K FitzGerald, G Schwartz, JS Ubel, PA TI Using survival curve comparisons to inform patient decision making - Can a practice exercise improve understanding? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE decision making; communication; patient education ID TREATMENT PREFERENCES; 5-YEAR SURVIVAL; OLDER PATIENTS; EXPLANATIONS; PHYSICIANS AB BACKGROUND: Patients often face medical decisions that involve outcomes that occur and change over time. Survival curves are a promising communication tool for patient decision support because they present information about the probability of an outcome over time in a simple graphic format. However. previous studies of survival curves did not measure comprehension, used face-to-face explanations, and focused on a VA population. METHODS: In this study, 246 individuals awaiting jury duty at the Philadelphia County Courthouse were randomized to receive one of two questionnaires. The control group received a questionnaire describing two hypothetical treatments and a graph with two survival curves showing the outcomes of each treatment. The practice group received the same questionnaire preceded by a practice exercise asking questions about a graph containing a single curve. Subjects' ability to Interpret survival from a curve and ability to calculate change In survival over time were measured. RESULTS: Understanding of survival at a single point In time from a graph containing two survival curves was high overall, and was improved by the use of a single curve practice exercise. With a practice exercise, subjects were over 80% accurate in interpreting survival at a single point in time. Understanding of changes in survival over time was lower overall, and was not improved by the use of a practice exercise. With or without a practice exercise, subjects were only 55% accurate in calculating changes in survival. CONCLUSION: The majority of the general public can interpret survival at a point in time from self-administered survival curves. This understanding is improved by a single curve practice exercise. However, a significant proportion of the general public cannot calculate change in survival over time. Further research is necessary to determine the effectiveness of survival curves in improving risk communication and patient decision making. C1 Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Armstrong, K (reprint author), 1233 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. NR 13 TC 24 Z9 25 U1 1 U2 4 PU BLACKWELL SCIENCE 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 JUL PY 2001 VL 16 IS 7 BP 482 EP 485 DI 10.1046/j.1525-1497.2001.016007482.x PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 458DV UT WOS:000170178700009 PM 11520387 ER PT J AU Faierman, E Wang, JS Jupiter, JB AF Faierman, E Wang, JS Jupiter, JB TI Secondary ulnar nerve palsy in adults after elbow trauma: A report of two cases SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE elbow trauma; ulnar neuropathy ID FRACTURES; COMPLICATIONS; HUMERUS AB Secondary ulnar nerve palsy, an unusual condition in which the onset of ulnar nerve dysfunction occurs 1 to 3 months after elbow trauma, can be the cause of sudden deterioration of elbow function. Initially recognized in 1899, this condition has not been reported often. We describe 2 patients who had no subjective or objective evidence of ulnar nerve dysfunction after elbow trauma but had a sudden loss of motion, pain, and clinical and electrophysiologic evidence of ulnar nerve compression at the elbow 4 to 5 weeks after trauma. Marked improvement occurred after ulnar nerve subcutaneous transposition and contracture release. Copyright (C) 2001 by the American Society for Surgery of the Hand. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Hand Serv, Boston, MA 02114 USA. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Hand Serv, ACC 527,15 Parkman St, Boston, MA 02114 USA. NR 29 TC 17 Z9 17 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JUL PY 2001 VL 26A IS 4 BP 675 EP 678 DI 10.1053/jhsu.2001.26186 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 454QN UT WOS:000169983400015 PM 11466643 ER PT J AU Bozic, KJ Perez, LE Wilson, DR Fitzgibbons, PG Jupiter, JB AF Bozic, KJ Perez, LE Wilson, DR Fitzgibbons, PG Jupiter, JB TI Mechanical testing of bioresorbable implants for use in metacarpal fracture fixation SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE bioresorbable implants; metacarpal fracture; fracture fixation; mechanical testing; polymers ID BIODEGRADABLE IMPLANTS; INTERFERENCE SCREWS; ORTHOPEDIC-SURGERY; STRENGTH; CHILDREN; INVITRO AB The purpose of this study was to evaluate the mechanical properties of a bioresorbable plate and screw system that was developed for the treatment of unstable metacarpal fractures and to compare the strength and stiffness of this system with those of conventional titanium plates and screws. Using a 4-point bending test, we measured the strength and stiffness of these implants over a 12-week period of in vitro degradation. Our data suggest that these implants provide stable bending strength and stiffness for 8 weeks and gradually lose their strength over a period of 12 weeks. Further research is necessary to determine whether this level of fixation is adequate to stabilize unstable metacarpal fractures. Copyright (C) 2001 by the American Society for Surgery of the Hand. C1 Beth Israel Deaconess Med Ctr, Orthopaed Biomech Lab, Boston, MA 02215 USA. Queens Univ, Dept Mech Engn, Kingston, ON K7L 3N6, Canada. Queens Univ, Human Mobil Res Ctr, Kingston, ON K7L 3N6, Canada. Massachusetts Gen Hosp, Hand & Upper Extrem Surg Serv, Boston, MA 02114 USA. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Hand Surg Serv, Dept Orthopaed Surg, 15 Parkman St,WACC 527, Boston, MA 02114 USA. NR 36 TC 28 Z9 29 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JUL PY 2001 VL 26A IS 4 BP 755 EP 761 DI 10.1053/jhsu.2001.24145 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 454QN UT WOS:000169983400026 PM 11466654 ER PT J AU Lou, JL Marzari, R Verzillo, V Ferrero, F Pak, D Sheng, M Yang, CL Sblattero, D Bradbury, A AF Lou, JL Marzari, R Verzillo, V Ferrero, F Pak, D Sheng, M Yang, CL Sblattero, D Bradbury, A TI Antibodies in haystacks: how selection strategy influences the outcome of selection from molecular diversity libraries SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE phage antibodies; selection; libraries; molecular diversity ID PHAGE DISPLAY LIBRARIES; HUMAN MONOCLONAL-ANTIBODIES; HIGH-AFFINITY ANTIBODIES; SINGLE-CHAIN ANTIBODIES; RIBOSOME DISPLAY; IN-VITRO; PROTEIN; CELLS; FRAGMENTS; GENE AB Antibodies against most antigens can be isolated from high quality phage antibody libraries. However, not all antibodies binding a particular antigen are necessarily found when standard selections are performed. Here we investigate the effect of two different selection strategies on the isolation of antibodies against a number of different antigens, and find that these different strategies tend to select different antibodies, with little overlap between them. This indicates that the full diversity of these libraries is not tapped by a single selection strategy and that each selection strategy imposes different selective criteria in addition to that of antigen binding. To fully exploit such libraries, therefore, many different selection strategies should probably be employed for each antigen. The use of alternative strategies should be considered when selection apparently fails, or when the number of different antibodies recognizing an antigen needs to be maximised. Furthermore, the microtitre selection strategy developed is likely to prove useful in the application of phage antibody libraries to the human genome project, allowing the high throughput selection of antibodies against multiple antigens simultaneously. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Calif Los Alamos Natl Lab, Biosci Div, Los Alamos, NM 87545 USA. Univ Calif San Francisco, San Francisco Gen Hosp, Dept Anesthesia 3S50, San Francisco, CA 94143 USA. Univ Trieste, Dept Biol, Trieste, Italy. SISSA, I-34014 Trieste, Italy. Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Univ Maryland Baltimore Cty, Dept Biochem & Mol Biol, Baltimore, MD 21228 USA. RP Bradbury, A (reprint author), Univ Calif Los Alamos Natl Lab, Biosci Div, MS M888, Los Alamos, NM 87545 USA. NR 41 TC 52 Z9 55 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JUL 1 PY 2001 VL 253 IS 1-2 BP 233 EP 242 DI 10.1016/S0022-1759(01)00385-4 PG 10 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 441ZE UT WOS:000169258800021 PM 11384684 ER PT J AU Yamada, A Kishimoto, K Dong, VM Sho, M Salama, AD Anosova, NG Benichou, G Mandelbrot, DA Sharpe, AH Turka, LA Auchincloss, H Sayegh, MH AF Yamada, A Kishimoto, K Dong, VM Sho, M Salama, AD Anosova, NG Benichou, G Mandelbrot, DA Sharpe, AH Turka, LA Auchincloss, H Sayegh, MH TI CD28-independent costimulation of T cells in alloimmune responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CARDIAC ALLOGRAFT-REJECTION; B7-1 CD80; IN-VIVO; CTLA-4; CD28; MICE; LIGAND; ACTIVATION; EXPRESSION AB T cell costimulation by B7 molecules plays an important role in the regulation of alloimmune responses. Although both B7-1 and B7-2 bind CD28 and CTLA-4 on T cells, the role of B7-1 and B7-2 signaling through CTLA-4 in regulating alloimmune responses is incompletely understood. To address this question, we transplanted CD28-deficient mice with fully allogeneic vascularized cardiac allografts and studied the effect of selective blockade of B7-1 or B7-2. These mice reject their grafts by a mechanism that involves both CD4(+) and CD8(+) T cells. Blockade of CTLA-4 or B7-1 significantly accelerated graft rejection. In contrast, B7-2 blockade significantly prolonged allograft survival and, unexpectedly, reversed the acceleration of graft rejection caused by CTLA-4 blockade. Furthermore, B7-2 blockade prolonged graft survival in recipients that were both CD28 and CTLA-4 deficient. Our data indicate that B7-1 is the dominant ligand for CTLA-4-mediated down-regulation of alloimmune responses in vivo and suggest that B7-2 has an additional receptor other than CD28 and CTLA-4 to provide a positive costimulatory signal for T cells. C1 Brigham & Womens Hosp, Lab Immunogenet & Transplantat, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Immunol Res, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Transplantat Unit, Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Cellular & Mol Immunol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. RP Sayegh, MH (reprint author), Brigham & Womens Hosp, Lab Immunogenet & Transplantat, 75 Francis St, Boston, MA 02115 USA. RI Salama, Alan/B-5183-2010 FU NIAID NIH HHS [AI-38397, AI-34965, AI-37691, AI-38310, AI-41521, AI-41584] NR 44 TC 86 Z9 90 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 JUL 1 PY 2001 VL 167 IS 1 BP 140 EP 146 PG 7 WC Immunology SC Immunology GA 471VJ UT WOS:000170949100020 PM 11418642 ER PT J AU Smith, RS Fedyk, ER Springer, TA Mukaida, N Iglewski, BH Phipps, RP AF Smith, RS Fedyk, ER Springer, TA Mukaida, N Iglewski, BH Phipps, RP TI IL-8 production in human lung fibroblasts and epithelial cells activated by the Pseudomonas autoinducer N-3-oxododecanoyl homoserine lactone is transcriptionally regulated by NF-kappa B and activator protein-2 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERLEUKIN-8 GENE-EXPRESSION; AERUGINOSA VIRULENCE GENES; CYSTIC-FIBROSIS; VIBRIO-FISCHERI; INFLAMMATORY CYTOKINES; FACTOR AP-2; ALPHA GENE; IN-VITRO; PNEUMONIA; INFECTION AB The destructive pulmonary inflammation associated with Pseudomonas aeruginosa colonization is caused, in part, by the production of the chemokine IL-8, which recruits neutrophils; into the lung. The Pseudomonas autoinducer, N-3-oxododecanoyl homoserine lactone (3-O-C12-HSL), is a small lipid-soluble molecule that is essential in the regulation of many P. aeruginosa virulence factors, but little is known about how it affects eukaryotic cells. In this report we demonstrate that 3-O-C12-HSL is a potent stimulator of both IL-8 mRNA and protein from human fibroblasts and epithelial cells in vitro. The IL-8 produced from these 3-O-C12-HSL-stimulated cells was found to be functionally active by inducing the chemotaxis of neutrophils. To determine a mechanism for this IL-8 induction, deletion constructs of the IL-8 promoter were examined. It was found that the DNA region between nucleotides -1481 and -546 and the transcription factor NF-KB were essential for the maximal induction of IL-8 by 3-O-C12-HSL. This was confirmed by EMSAs, where 3-O-C12-HSL induced a shift with both AP-2 and NF-KB consensus DNA. The activation of NF-kappaB and subsequent production of IL-8 were found to be regulated by a mitogen-activated protein kinase pathway. These findings support the concept that the severe lung damage that accompanies P. aeruginosa infections is caused by an exuberant neutrophil response stimulated by 3-O-C12-HSL-induced IL-8. Understanding the mechanisms of 3-O-C12-HSL activation of lung structural cells may provide a means to help control lung damage during infections with P. aeruginosa. C1 Univ Rochester, Sch Med & Dent, Ctr Canc, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Dept Microbiol & Immunol, Rochester, NY 14642 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Kanazawa Univ, Canc Res Inst, Dept Mol Oncol, Kanazawa, Ishikawa 920, Japan. RP Phipps, RP (reprint author), Univ Rochester, Sch Med & Dent, Ctr Canc, 601 Elmwood Ave,Box 704, Rochester, NY 14642 USA. RI Mukaida, Naofumi/D-7623-2011 OI Mukaida, Naofumi/0000-0002-4193-1851 FU NCI NIH HHS [CA11198, CA11051]; NHLBI NIH HHS [HL07216, HL56002]; NIAID NIH HHS [AI133713]; NIDCR NIH HHS [DE11390]; NIEHS NIH HHS [ES01247] NR 52 TC 169 Z9 175 U1 0 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2001 VL 167 IS 1 BP 366 EP 374 PG 9 WC Immunology SC Immunology GA 471VJ UT WOS:000170949100050 PM 11418672 ER PT J AU Studdert-Kennedy, M Mody, M Brady, S AF Studdert-Kennedy, M Mody, M Brady, S TI A response to Denenberg SO JOURNAL OF LEARNING DISABILITIES LA English DT Editorial Material ID SPEECH-PERCEPTION DEFICITS; PHONOLOGICAL PROCESSING PROBLEMS; POOR READERS; LANGUAGE IMPAIRMENT; CHILDREN; CRITIQUE C1 Haskins Labs Inc, New Haven, CT 06511 USA. Univ Connecticut, Storrs, CT 06269 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Univ Rhode Isl, Kingston, RI 02881 USA. RP Studdert-Kennedy, M (reprint author), Haskins Labs Inc, 270 Crown St, New Haven, CT 06511 USA. NR 12 TC 0 Z9 0 U1 1 U2 1 PU PRO-ED INC PI AUSTIN PA 8700 SHOAL CREEK BLVD, AUSTIN, TX 78757-6897 USA SN 0022-2194 J9 J LEARN DISABIL-US JI J. Learn. Disabil. PD JUL-AUG PY 2001 VL 34 IS 4 BP 302 EP 303 DI 10.1177/002221940103400402 PG 2 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 452CQ UT WOS:000169839900002 ER PT J AU Gow, DW AF Gow, DW TI Assimilation and anticipation in continuous spoken word recognition SO JOURNAL OF MEMORY AND LANGUAGE LA English DT Article DE spoken word recognition; assimilation; phonological variation; feature mismatch; anticipation ID LEXICAL ACCESS; SPEECH-PERCEPTION; PHONOLOGICAL VARIATION; COMPETITION; REPRESENTATION; INFERENCE; FORM; BIAS; MODEL AB English coronal place assimilation is one of many productive phonological processes that change the phonological form of words. It may, for example. cause speakers to pronounce green as something approximating [grin] or [grim] in different contexts. The present work examines how listeners recognize words that have undergone this modification. Current accounts are broadly differentiated by two issues: (1) whether listeners generally recognize words that have undergone word-final, single-feature modification. and (2) how context effects in the perception of assimilated speech are interpreted. Experiment 1 employs form priming to demonstrate that listeners tolerate single-feature mismatch resulting from both phonologically plausible and phonologically implausible word form modification when recognizing words heard in context. Experiments 2 and 3 employ phoneme monitoring and negative rhyme priming paradigms, respectively, to demonstrate that listeners use assimilation to anticipate upcoming context. Evidence for anticipation is contrasted with claims that listeners use context to regressively infer the underlying form of place assimilated segments. (C) 2001 Academic Press. C1 Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. Salem State Coll, Salem, MA 01970 USA. RP Gow, DW (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, 55 Fruit St,VBK 821, Boston, MA 02114 USA. NR 62 TC 79 Z9 79 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0749-596X J9 J MEM LANG JI J. Mem. Lang. PD JUL PY 2001 VL 45 IS 1 BP 133 EP 159 DI 10.1006/jmla.2000.2764 PG 27 WC Linguistics; Psychology; Psychology, Experimental SC Linguistics; Psychology GA 446ZM UT WOS:000169544100007 ER PT J AU Pole, N Best, SR Weiss, DS Metzler, T Liberman, AM Fagan, J Marmar, CR AF Pole, N Best, SR Weiss, DS Metzler, T Liberman, AM Fagan, J Marmar, CR TI Effects of gender and ethnicity on duty-related posttraumatic stress symptoms among urban police officers SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID POST-TRAUMATIC STRESS; HISPANIC VIETNAM VETERANS; DISORDER; EXPOSURE; COMBAT; WOMEN; SCALE AB We studied 655 urban police officers (21% female, 48% white, 24% black, and 28% Hispanic) to assess ethnic and gender differences in duty-related symptoms of posttraumatic stress disorder (PTSD). We obtained self-report measures of. a) PTSD symptoms, b) peritraumatic dissociation, c) exposure to duty-related critical incidents, d) general psychiatric symptoms, e) response bias due to social desirability, and f) demographic variables. We found that self-identified Hispanic-American officers evidenced greater PTSD symptoms than both self-identified European-American and self-identified African-American officers. These effects were small in size but they persisted even after controlling for differences in other relevant variables. Contrary to expectation, we found no gender differences in PTSD symptoms. Our findings are of note because: a) they replicate a previous finding of greater PTSD among Hispanic-American military personnel and b) they fail to replicate the well-established finding of greater PTSD symptoms among civilian women. C1 Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Natl Inst Justice, Washington, DC USA. Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. RP Pole, N (reprint author), Univ Michigan, Dept Psychol, 525 E Univ, Ann Arbor, MI 48109 USA. FU NIMH NIH HHS [R01-MH56350-01A1] NR 30 TC 77 Z9 78 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JUL PY 2001 VL 189 IS 7 BP 442 EP 448 DI 10.1097/00005053-200107000-00005 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 459ED UT WOS:000170237300005 PM 11504321 ER PT J AU Geller, DA Biederman, J Faraone, S Agranat, A Cradock, K Hagermoser, L Kim, G Frazier, J Coffey, BJ AF Geller, DA Biederman, J Faraone, S Agranat, A Cradock, K Hagermoser, L Kim, G Frazier, J Coffey, BJ TI Developmental aspects of obsessive compulsive disorder: Findings in children, adolescents, and adults SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID EARLY-ONSET; RELIABILITY; SCALE; PHENOMENOLOGY; COMORBIDITY; BEHAVIOR; VALIDITY; FAMILY AB Although juvenile, obsessive compulsive disorder (OCD) is increasingly recognized as a putative developmental subtype of the disorder, comparisons among children, adolescents, and adults with OCD have been lacking. We aimed to evaluate clinical correlates of OCD in three developmentally distinct groups. Subjects comprised children, adolescents, and adults meeting DSM-HI-R and DSM-IV criteria for OCD referred to separate specialized OCD clinics. All subjects were systematically evaluated with structured diagnostic interviews and clinical assessments by OCD experts. Specific clinical correlates and symptom profiles were associated with the disorder in different age groups. These findings support a hypothesis of developmental discontinuity between juvenile and adult OCD and identify age specific correlates of the disorder across the life cycle. Further work is needed to validate whether juvenile-onset OCD represents a true developmental subtype of the disorder. C1 McLean Hosp, Pediat OCD Clin, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Joint Program Pediat Psychopharmacol, Belmont, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Hadassah Med Sch, Hadassah Mt Scopus Hosp Hebrew Univ, Dept Child & Adolescent Psychiat, Jerusalem, Israel. RP Geller, DA (reprint author), McLean Hosp, Pediat OCD Clin, 115 Mill St, Belmont, MA 02178 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K08 MH01481] NR 24 TC 130 Z9 136 U1 2 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JUL PY 2001 VL 189 IS 7 BP 471 EP 477 DI 10.1097/00005053-200107000-00009 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 459ED UT WOS:000170237300009 PM 11504325 ER PT J AU Greer, DM Schaefer, PW Schwamm, LH AF Greer, DM Schaefer, PW Schwamm, LH TI Unilateral temporal lobe stroke causing ischemic transient global amnesia: Role for diffusion-weighted imaging in the initial evaluation SO JOURNAL OF NEUROIMAGING LA English DT Article DE stroke; diffusion-weighted imaging; magnetic resonance imaging; transient global amnesia ID MRI AB Ischemia has been proposed as a cause of transient global amnesia (TGA), but proof has been lacking. The authors performed magnetic resonance imaging on a 77-year-old woman with classic TGA at 4 hours and at 6 days after the onset of symptoms. Her initial diffusion-weighted imaging (DWI) and apparent diffusion coefficient imaging suggested an acute infarct in the left mesial temporal lobe. Follow-up T2-weighted imaging at 6 days confirmed the lesion as an ischemic infarct, despite resolution of her symptoms. DWI permits early detection of small ischemic lesions and may identify patients with ischemic TGA who should be evaluated for potential sources of emboli. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Schwamm, LH (reprint author), Massachusetts Gen Hosp, Dept Neurol, VBK 915,32 Fruit St, Boston, MA 02114 USA. OI Schwamm, Lee/0000-0003-0592-9145 NR 14 TC 22 Z9 22 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD JUL PY 2001 VL 11 IS 3 BP 317 EP 319 PG 3 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 455FV UT WOS:000170017600016 PM 11462302 ER PT J AU Cao, GD Pei, W Lan, J Stetler, RA Luo, YM Nagayama, T Graham, SH Yin, XM Simon, RP Chen, J AF Cao, GD Pei, W Lan, J Stetler, RA Luo, YM Nagayama, T Graham, SH Yin, XM Simon, RP Chen, J TI Caspase-activated DNase/DNA fragmentation factor 40 mediates apoptotic DNA fragmentation in transient cerebral ischemia and in neuronal cultures SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cerebral ischemia; apoptosis; programmed cell death; caspase-3; DNA fragmentation; caspase-activated deoxyribonuclease ID HIPPOCAMPAL CA1 NEURONS; GLOBAL-ISCHEMIA; RAT-BRAIN; CHROMATIN CONDENSATION; FOREBRAIN ISCHEMIA; CELL-DEATH; ICAD-S; INHIBITOR; EXPRESSION; PROTEIN AB Nuclear changes, including internucleosomal DNA fragmentation, are characteristic features of neuronal apoptosis resulting from transient cerebral ischemia and related brain insults for which the molecular mechanism has not been elucidated. Recent studies suggest that a caspase-3-mediated mechanism may be involved in the process of nuclear degradation in ischemic neurons. In this study, we cloned from rat brain a homolog cDNA encoding caspase-activated deoxyribonuclease (CAD)/DNA fragmentation factor 40 (DFF40), a 40 kDa nuclear enzyme that is activated by caspase-3 and promotes apoptotic DNA degradation. Subsequently, we investigated the role of CAD/DFF40 in the induction of internucleosomal DNA fragmentation in the hippocampus in a rat model of transient global ischemia and in primary neuronal cultures under ischemia-like conditions. At 8-72 hr after ischemia, CAD/DFF40 mRNA and protein were induced in the degenerating hippocampal CA1 neurons. CAD/DFF40 formed a heterodimeric complex in the nucleus with its natural inhibitor CAD (ICAD) and was activated after ischemia in a delayed manner (>24 hr) by caspase-3, which translocated into the nucleus and cleaved ICAD. Furthermore, an induced CAD/DFF40 activity was detected in nuclear extracts in both in vivo and in vitro models, and the DNA degradation activity of CAD/DFF40 was inhibited by purified ICAD protein. These results strongly suggest that CAD/DFF40 is the endogenous endonuclease that mediates caspase-3-dependent internucleosomal DNA degradation and related nuclear alterations in ischemic neurons. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Pittsburgh Inst Neurodegenerat Disorders, Pittsburgh, PA 15261 USA. Legacy Res, RS Dow Ctr Neurobiol, Portland, OR 97208 USA. Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA 15261 USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S-507,Biomed Sci Tower, Pittsburgh, PA 15213 USA. FU NINDS NIH HHS [NS35965, NS36736, NS38560] NR 50 TC 69 Z9 77 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 JUL 1 PY 2001 VL 21 IS 13 BP 4678 EP 4690 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 445JP UT WOS:000169454600016 PM 11425895 ER PT J AU Bothwell, S Meredith, GE Phillips, J Staunton, H Doherty, C Grigorenko, E Glazier, S Deadwyler, SA O'Donovan, CA Farrell, M AF Bothwell, S Meredith, GE Phillips, J Staunton, H Doherty, C Grigorenko, E Glazier, S Deadwyler, SA O'Donovan, CA Farrell, M TI Neuronal hypertrophy in the neocortex of patients with temporal lobe epilepsy SO JOURNAL OF NEUROSCIENCE LA English DT Article DE temporal lobe epilepsy; stereology; Brodmann's area 38; ectopia; cortical atrophy; neuronal hypertrophy; hippocampal sclerosis ID HUMAN EPILEPTOGENIC NEOCORTEX; PERINATAL BRAIN-DAMAGE; ALZHEIMERS-DISEASE; CORTICAL DYSPLASIA; CEREBRAL-CORTEX; DEVELOPMENTAL NEUROPATHOLOGY; ARBITRARY PARTICLES; TUBEROUS SCLEROSIS; MATTER LESIONS; TOTAL NUMBER AB The underlying cause of neocortical involvement in temporal lobe epilepsy (TLE) remains a fundamental and unanswered question. Magnetic resonance imaging has shown a significant loss in temporal lobe volume, and it has been proposed that neocortical circuits are disturbed functionally because neurons are lost. The present study used design-based stereology to estimate the volume and cell number of Brodmann's area 38, a region commonly resected in anterior temporal lobectomy. Studies were conducted on the neocortex of patients with or without hippocampal sclerosis (HS). Results provide the surprising finding that TLE patients have significant atrophy of neocortical gray matter but no loss of neurons. Neurons are also significantly larger, dendritic trees appear sparser, and spine density is noticeably reduced in TLE specimens compared with controls. The increase in neuronal density we found in TLE patients is therefore attributable to large neurons occupying a much smaller volume than in normal brain. Neurons in the underlying white matter are also increased in size but, in contrast to other reports, are not significantly elevated in number or density. Neuronal hypertrophy affects HS and non-HS brains similarly. The reduction in neuropil and its associated elements therefore appears to be a primary feature of TLE, which is not secondary to cell loss. In both gray and white matter, neuronal hypertrophy means more perikaryal surface area is exposed for synaptic contacts and emerges as a hallmark of this disease. C1 Univ Missouri, Sch Med, Dept Basic Med Sci, Kansas City, MO 64108 USA. Univ Dublin Trinity Coll, Dept Zool, Dublin 2, Ireland. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Royal Coll Surg Ireland, Dept Anat, Dublin 2, Ireland. Royal Coll Surg Ireland, Dept Clin Neurol Sci, Dublin 2, Ireland. Wake Forest Univ, Bowman Gray Sch Med, Dept Neurol, Winston Salem, NC 27157 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Neurosurg, Winston Salem, NC 27157 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA. RP Meredith, GE (reprint author), Univ Missouri, Sch Med, Dept Basic Med Sci, 2411 Holmes Rd,M3-C03, Kansas City, MO 64108 USA. FU NIDA NIH HHS [DA07625, DA00119] NR 83 TC 76 Z9 76 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 JUL 1 PY 2001 VL 21 IS 13 BP 4789 EP 4800 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 445JP UT WOS:000169454600027 PM 11425906 ER PT J AU Hoh, BL Putman, CM Budzik, RF Carter, BS Ogilvy, CS AF Hoh, BL Putman, CM Budzik, RF Carter, BS Ogilvy, CS TI Combined surgical and endovascular techniques of flow alteration to treat fusiform and complex wide-necked intracranial aneurysms that are unsuitable for clipping or coil embolization SO JOURNAL OF NEUROSURGERY LA English DT Article DE balloon occlusion; dissection; extracranial-intracranial bypass; proximal (vascular) occlusion; fusiform aneurysm; giant aneurysm ID INTERNAL CAROTID-ARTERY; VERTEBRAL ARTERY; BALLOON OCCLUSION; GIANT ANEURYSMS; BASILAR ARTERY; SUBARACHNOID HEMORRHAGE; UNCLIPPABLE ANEURYSMS; POSTERIOR CIRCULATION; DETACHABLE BALLOONS; CEREBRAL ANEURYSMS AB Object. Certain intracranial aneurysms, because of their fusiform or complex wide-necked structure, giant size, or involvement with critical perforating or branch vessels, are unamenable to direct surgical clipping or endovascular coil treatment. Management of such lesions requires alternative or novel treatment strategies. Proximal and distal occlusion (trapping) is the most effective strategy. In lesions that cannot be trapped, alteration in blood flow to the "inflow zone," the site most vulnerable to aneurysm growth and rupture, is used. Methods. From 1991 to 1999 the combined neurosurgical-neuroendovascular team at the Massachusetts General Hospital (MGH) managed 48 intracranial aneurysms that could not be clipped or occluded. Intracavernous internal carotid artery aneurysms were excluded from this analysis. By applying a previously described aneurysm rupture risk classification system (MGH Grades 0-5) based on the age of the patient, aneurysm size, Hunt and Hess grade, Fisher grade, and whether the aneurysm was a giant lesion located in the posterior circulation, the authors found that a significant number of patients were at moderate risk (MGH Grade 2; 31.3% of patients) and at high risk (MGH Grades 3 or 4; 22.9%) for treatment-related morbidity. The lesions were treated using a variety of strategies-surgical, endovascular, or a combination of modalities. Aneurysms that could not be trapped or occluded were treated using a paradigm of flow alteration, with flow redirected from either native collateral networks or from a surgically performed vascular bypass. Overall clinical outcomes were determined using the Glasgow Outcome Scale (GOS). A GOS score of 5 or 4 was achieved in 77.1%, a GOS score of 3 or 2 in 8.3%, and death (GOS 1) occurred in 14.6% of the patients. Procedure-related complications occurred in 27.1% of cases; the major morbidity rate was 6.3% and the mortality rate was 10.4%. Three patients experienced aneurysmal hemorrhage posttreatment; in two patients this event proved to be fatal. Aneurysms with MGH Grades 0, 1, 2, 3, and 3 were associated with favorable outcomes (GOS scores of 5 or 4) in 100%, 92.8%, 71.4%, 50%, and 0% of instances, respectively. Conclusions. Despite a high incidence of transient complications, intracranial aneurysms that cannot be clipped or occluded require alternative surgical and endovascular treatment strategies. In those aneurysms that cannot safely be trapped or occluded, one approach is the treatment strategy of flow alteration. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Intervent Neuroradiol Serv, Boston, MA 02114 USA. RP Ogilvy, CS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, VBK 710,Fruit St, Boston, MA 02114 USA. NR 49 TC 69 Z9 73 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JUL PY 2001 VL 95 IS 1 BP 24 EP 35 DI 10.3171/jns.2001.95.1.0024 PG 12 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 448JC UT WOS:000169622900004 PM 11453395 ER PT J AU Clark, RSB Chen, MZ Kochanek, PM Watkins, SC Jin, KL Draviam, R Nathaniel, PD Pinto, R Marion, DW Graham, SH AF Clark, RSB Chen, MZ Kochanek, PM Watkins, SC Jin, KL Draviam, R Nathaniel, PD Pinto, R Marion, DW Graham, SH TI Detection of single- and double-strand DNA breaks after traumatic brain injury in rats: Comparison of in situ labeling techniques using DNA polymerase 1, the Klenow fragment of DNA polymerase 1, and terminal deoxynucleotidyl transferase SO JOURNAL OF NEUROTRAUMA LA English DT Article DE apoptosis; controlled cortical impact; Klenow; PANT; TUNEL ID CORTICAL IMPACT INJURY; APOPTOTIC CELL-DEATH; CLOSED-HEAD INJURY; NEURONAL APOPTOSIS; OXIDATIVE STRESS; POLY(ADP-RIBOSE) POLYMERASE; MITOCHONDRIAL DYSFUNCTION; ENDONUCLEASE ACTIVITY; CEREBRAL-ISCHEMIA; DAMAGING AGENTS AB DNA damage is a common sequela of traumatic brain injury (TBI). Available techniques for the in situ identification of DNA damage include DNA polymerase I-mediated biotin-dATP nick-translation (PANT), the Klenow fragment of DNA polymerase I-mediated biotin-dATP nick-end labeling (Klenow), and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). While TUNEL has been widely utilized to detect primarily double-strand DNA breaks, the use of PANT to detect primarily single-strand DNA breaks and Klenow to detect both single- and double-strand DNA breaks has not been reported after TBI. Accordingly, coronal brain sections from naive rats and rats at 0, 0.5, 1, 2, 6, 24, and 72 h (n = 3-5/group) after controlled cortical impact with imposed secondary insult were processed using the PANT, Klenow, and TUNEL methods. Cells with DNA breaks were detected by PANT in the ipsilateral hemisphere as early as 0.5 h after injury and were maximal at 6 h (cortex = 66.3 +/- 15.8, dentate gyrus 58.6 +/- 12.8, CAI = 15.8 +/- 5.9, CA3 = 12.8 +/- 4.2 cells/ x 400 field, mean +/- SEM, all p < 0.05 versus naive). Cells with DNA breaks were detected by Klenow as early as 30 min and were maximal at 24 h (cortex = 56.3 +/- 14.3, dentate gyrus 78.0 +/- 16.7, CA1 = 25.8 +/- 4.7, CA3 = 29.3 +/- 15.1 cells/ x 400 field, all p < 0.05 versus naive). Cells with DNA breaks were not detected by TUNEL until 2 h and were maximal at 24 h (cortex = 47.7 +/- 21.4, dentate gyrus 63.0 +/- 11.9, CA1 = 5.6 +/- 5.4, CA3 = 6.9 +/- 3.7 cells/x400 field, cortex and dentate gyrus p < 0.05 versus naive). Dual-label immunofluorescence revealed that PANT-positive cells were predominately neurons. These data demonstrate that TBI results in extensive DNA damage, which includes both single- and double-strand breaks in injured cortex and hippocampus. The presence of multiple types of DNA breaks implicate several pathways in the evolution of DNA damage after TBI. C1 Univ Pittsburgh, Sch Med, Safar Ctr Resuscitat Res, Dept Anesthesiol & Crit Care Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Safar Ctr Resuscitat Res, Dept Pediat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Safar Ctr Resuscitat Res, Dept Cell Biol & Physiol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Safar Ctr Resuscitat Res, Dept Neurol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Safar Ctr Resuscitat Res, Dept Neurol Surg, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Brain Trauma Res Ctr, Pittsburgh, PA 15260 USA. VA Pittsburgh Hlth Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Clark, RSB (reprint author), Univ Pittsburgh, Sch Med, Safar Ctr Resuscitat Res, Dept Anesthesiol & Crit Care Med, 3434 5th Ave, Pittsburgh, PA 15260 USA. RI Kochanek, Patrick/D-2371-2015 OI Kochanek, Patrick/0000-0002-2627-913X FU NICHD NIH HHS [P30 HD28836]; NINDS NIH HHS [KO8 NS01946, P50 NS30318, R01 NS 38620] NR 56 TC 41 Z9 42 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JUL PY 2001 VL 18 IS 7 BP 675 EP 689 DI 10.1089/089771501750357627 PG 15 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 457CK UT WOS:000170119400004 PM 11497094 ER PT J AU Kales, SN Freyman, RL Hill, JM Polyhronopoulos, GN Aldrich, JM Christiani, DC AF Kales, SN Freyman, RL Hill, JM Polyhronopoulos, GN Aldrich, JM Christiani, DC TI Firefighters' hearing: A comparison with population databases from the International Standards Organization SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID NOISE AB WE investigated firefighters' hearing relative to general population data to adjust for age-expected hearing loss. For five groups of male firefighters with increasing mean ages, we compared their hearing thresholds at the 50th and 90th percentiles with normative and age-and sex-matched hearing data from the International Standards Organization (databases A and B). At the 50th percentile, from a mean age of 28 to a mean age of 53 years, relative to databases A and B, the firefighters lost an excess of 19 to 23 dB, 20 to 23 dB, and 16 to 19 dB at 3000 4000 and 6000 Hz, respectively. At the 90th percentile, from a mean age of 28 to a mean age of 53 years, relative to databases A and B, the firefighters lost an excess of 12 to 20 dB, 38 to 44 dB, 41 to 45 dB, and 22 to 28 dB at 2000 3000 4000 and 6000 Hz, respectively. The results are consistent with accelerated hearing loss in excess of age-expected loss among the firefighters, especially at or above the 90th percentile. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Cambridge, MA 02138 USA. Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Dept Commun Disorders, Amherst, MA 01003 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm Crit Care Unit, Braintree, MA USA. Massachusetts Resp Hosp, Ctr Occupat & Environm Med, Braintree, MA USA. RP Kales, SN (reprint author), Cambridge Hosp, Dept Med, 1493 Cambridge St, Cambridge, MA 02139 USA. FU NIEHS NIH HHS [ES00002, ES05947]; NIOSH CDC HHS [OH00156, OH03729] NR 19 TC 18 Z9 19 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD JUL PY 2001 VL 43 IS 7 BP 650 EP 656 DI 10.1097/00043764-200107000-00013 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 451VQ UT WOS:000169823400013 PM 11464397 ER PT J AU Miller, MC Zhang, AX Petrella, AJ Berger, RA Rubash, HE AF Miller, MC Zhang, AX Petrella, AJ Berger, RA Rubash, HE TI The effect of component placement on knee kinetics after arthroplasty with an unconstrained prosthesis SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article AB The mechanical success of a total knee replacement demands stable patellar tracking without subluxation and, stable tracking, in turn, can depend largely on the medial-lateral forces restraining the patella. Patellar button medialization has been advocated as a means of reducing subluxation, and experimental evidence has shown femoral component rotation also affects medial-lateral forces. Surgeons have choices in femoral component rotation and patellar button medialization and must frequently make intra-operative decisions concerning component placement because of anatomical variations among patients. Thus, in seeking to minimize medial-lateral patellar force, we examined the effects of patellar button medialization and external femoral component rotation. The study used an unconstrained total knee system implanted in nine cadaveric specimens tested on a knee simulator operating through flexion angles up to 100 degrees. Tests included all combinations of external femoral component rotation of 0 degrees, 2.5 degrees, and 5 degrees and patellar placement at the geometric center and at 3.75 mm medial to the geometric center. A video-based motion analysis system tracked patellar and tibial kinematics while a six-component load cell measured patellofemoral loads. Repeated measures analysis of variance revealed a statistically significant decrease in the average medial-lateral force with button medialization but no significant change with femoral component rotation. Neither femoral component rotation nor patellar button medialization had an effect on the normal component of the patellar reaction force. External femoral component rotation did cause significant increases in lateral patellar tilt, in tibial varus angle, and in external tibial rotation. Button medialization caused significant increases in lateral patellar tracking, lateral patellar tilt and external tibial rotation. The results in medial-lateral patellar forces quantify the benefit of patellar button medialization and discount any benefit of femoral rotation. The change in tibial kinematics with patellar button medialization and femoral component rotation cannot be measured in vivo with current technology, and the precise clinical implications are unknown. (C) 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. C1 Duquesne Univ, Sch Hlth Sci 129, Pittsburgh, PA 15282 USA. Natl Highway Safety Res Inst, Great Falls, VA USA. Univ Pittsburgh, Dept Mech Engn, Pittsburgh, PA 15261 USA. Rush Presbyterian St Lukes Med Ctr, Dept Orthopaed Surg, Chicago, IL 60612 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Miller, MC (reprint author), Duquesne Univ, Sch Hlth Sci 129, Pittsburgh, PA 15282 USA. EM millermark@duq.edu NR 30 TC 34 Z9 36 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD JUL PY 2001 VL 19 IS 4 BP 614 EP 620 DI 10.1016/S0736-0266(00)00043-7 PG 7 WC Orthopedics SC Orthopedics GA 461LQ UT WOS:000170366100018 PM 11518270 ER PT J AU Ring, D Waters, PM Hotchkiss, RN Kasser, JR AF Ring, D Waters, PM Hotchkiss, RN Kasser, JR TI Pediatric floating elbow SO JOURNAL OF PEDIATRIC ORTHOPAEDICS LA English DT Article DE compartment syndrome; floating elbow; fracture; humerus; radius; Volkmann contracture ID SUPRACONDYLAR; FRACTURES; CHILDREN; FOREARM AB A retrospective review of 16 patients with floating elbow injuries over a 9-year period at a tertiary care children's hospital confirms that these injuries are associated with substantial swelling and the potential to develop compartment syndrome, particularly when circumferential cast immobilization is used. Among 10 patients in whom the forearm was treated with closed reduction and plaster immobilization, a compartment syndrome developed in 2, and 4 patients had incipient compartment syndrome that responded to splitting of the: cast; 3 of these subsequently required remanipulation of the distal radius. One patient with compartment syndrome had Volkmann ischemic contracture. Six patients underwent stabilization of both the distal humeral and forearm fractures with percutaneously inserted Kirschner wires, thereby allowing postreduction immobilization in a split cast. None of these patients had problems with excessive swelling or compartment syndrome. Percutaneous Kirschner wire fixation of both the humeral and forearm fractures in pediatric flouting elbow injuries allows noncircumferential immobilization, thereby reducing the risk of compartment syndrome. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02115 USA. RP Waters, PM (reprint author), Childrens Hosp, Dept Orthopaed, 300 Longwood Ave, Boston, MA 02115 USA. NR 6 TC 9 Z9 14 U1 1 U2 1 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 JUL-AUG PY 2001 VL 21 IS 4 BP 456 EP 459 DI 10.1097/00004694-200107000-00008 PG 4 WC Orthopedics; Pediatrics SC Orthopedics; Pediatrics GA 449HM UT WOS:000169678700008 PM 11433156 ER PT J AU Gordon, CM Dougherty, DD Fischman, AJ Emans, SJ Grace, E Lamm, R Alpert, NM Majzoub, JA Rauch, SL AF Gordon, CM Dougherty, DD Fischman, AJ Emans, SJ Grace, E Lamm, R Alpert, NM Majzoub, JA Rauch, SL TI Neural substrates of anorexia nervosa: A behavioral challenge study with positron emission tomography SO JOURNAL OF PEDIATRICS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; CEREBRAL BLOOD-FLOW; SYMPTOM PROVOCATION; GLUCOSE-METABOLISM; EATING-DISORDERS; BRAIN HYPOMETABOLISM; PET; SCHIZOPHRENIA; NEUROANATOMY AB Objective: To delineate functional brain abnormalities associated with anorexia nervosa (AN). Study design: Positron emission tomographic measurements of regional cerebral blood flow (rCBF) were performed on 8 female patients with AN and 8 healthy female control subjects during exposure to 3 types of stimuli: high-calorie foods, low-calorie foods, and non-food items. Heart rate and internal state analog scale scores were also obtained. Stereotactic transformation and statistical parametric mapping techniques were used to analyze imaging data. Results: During the high-calorie condition, control subjects reported a significant desire to eat, whereas subjects with AN reported elevated anxiety and exhibited increases in heart rate. Patients with AN had elevated bilateral medial temporal lobe rCBF compared with control subjects. Planned comparisons for group-by-condition interactions demonstrated greater activation within left occipital cortex and right temporo-occipital cortex for the high-calorie versus low-calorie contrast in patients with AN compared with control subjects. Conclusions: Our finding of elevated rCBF within bilateral medial temporal lobes is similar to published results in patients with psychotic disorders and may be related to the body image distortion common to AN. The high-calorie food phobia exhibited by patients with AN appears to be associated with exaggerated responses in visual association cortex, as has been previously observed in studies of specific phobias. C1 Childrens Hosp, Div Adolescent Young Adult Med, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Gordon, CM (reprint author), Childrens Hosp, Div Adolescent Young Adult Med, 300 Longwood Ave, Boston, MA 02115 USA. OI Emans, S. Jean/0000-0002-4535-7850 FU NCRR NIH HHS [MO1 RR2172]; NIDDK NIH HHS [5T32-DK-07699]; NIMH NIH HHS [MH01215] NR 34 TC 64 Z9 64 U1 0 U2 6 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 JUL PY 2001 VL 139 IS 1 BP 51 EP 57 DI 10.1067/mpd.2001.114768 PG 7 WC Pediatrics SC Pediatrics GA 452UB UT WOS:000169877100015 PM 11445794 ER PT J AU Myrick, H Henderson, S Brady, KT Malcom, R Measom, M AF Myrick, H Henderson, S Brady, KT Malcom, R Measom, M TI Divalproex loading in the treatment of cocaine dependence SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article DE cocaine dependence; Divalproex (DVPX); GABA ID ABSTINENCE; RETENTION; BACLOFEN; RELEASE; MANIA AB The current pilot project was designed to evaluate the safety and tolerability of a loading dose of divalproex (DVPX) in subjects with cocaine dependence. Seventeen cocaine-dependent subjects were enrolled in an eight-week, open-label trial of 20 mg/kg/day DVPX. Subjects were seen weekly and urine drug screens were obtained at each visit. Over the eight-week trial, craving intensity and frequency as well as reported time using cocaine decreased significantly. Retention in the current study was 79% at week four and 50% at week eight. The medication and dosing strategy was well tolerated. This pilot study indicates that DVPX loading is well tolerated and may be efficacious in the treatment of cocaine dependence. A placebo-controlled trial would be of interest. C1 Ralph H Johnson VA Med Ctr, Subst Abuse Treatment Ctr 116, Charleston, SC 29401 USA. Med Univ S Carolina, Ctr Drug & Alcohol Programs, Charleston, SC 29425 USA. Med Univ S Carolina, Ctr Drug & Alcohol Programs, Charleston, SC 29425 USA. RP Myrick, H (reprint author), Ralph H Johnson VA Med Ctr, Subst Abuse Treatment Ctr 116, 109 Bee St, Charleston, SC 29401 USA. NR 23 TC 22 Z9 22 U1 0 U2 0 PU HAIGHT-ASHBURY PUBL PI SAN FRANCISCO PA 409 CLAYTON ST, SAN FRANCISCO, CA 94117 USA SN 0279-1072 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD JUL-SEP PY 2001 VL 33 IS 3 BP 283 EP 287 PG 5 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 484PA UT WOS:000171697700009 PM 11718321 ER PT J AU Oster, JG Steinert, RF Hogan, RN AF Oster, JG Steinert, RF Hogan, RN TI Reduction of hyperopia associated with manual excision of Salzmann's nodular degeneration SO JOURNAL OF REFRACTIVE SURGERY LA English DT Article AB PURPOSE: Removing central corneal pathology often leads to a hyperopic shift secondary to corneal flattening. A myopic shift, or reduction in hyperopia, would be expected after removal of peripheral corneal pathology with central corneal steepening. This case illustrates the refractive changes induced by Salzmann's nodular degeneration and the myopic shift associated with their excision, METHODS: A 53-year-oId female presented with a slowly progressive increase in hyperopia. Vision in the right eye was 20/40 with a refraction of +10.00 -4.00 x 90 degrees. Vision in the left eye was 20/30 with a refraction of +5.75 -2.00 x 105 degrees. Both corneas exhibited nodular subepithelial opacities in the mid-periphery. A superficial keratectomy was performed on each eye, 1 year apart. RESULTS: Twelve days postoperatively, uncorrected visual acuity in the right eye was 20/25, and 20/20 with a refraction of -0.75 -0.50 x 31 degrees, 6 months later, Six days postoperatively, uncorrected visual acuity in the left eye was 20/40, and 20/30 with a refraction of -1.25 D, 1 month later. CONCLUSION: Superficial keratectomy provides a means of restoring the original corneal contour, especially when the pathology is easily dissected from Bowman's layer, The surgeon should investigate the refractive status prior to the development of the nodules and be aware of the possible refractive change upon removal of the pathology. C1 Ophthalm Consultants Boston, Boston, MA 02114 USA. Tufts Univ, Sch Med, New England Eye Ctr, Boston, MA 02111 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Steinert, RF (reprint author), Ophthalm Consultants Boston, 50 Staniford St, Boston, MA 02114 USA. NR 6 TC 16 Z9 17 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-597X J9 J REFRACT SURG JI J. Refractive Surg. PD JUL-AUG PY 2001 VL 17 IS 4 BP 466 EP 469 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 453YG UT WOS:000169945300010 PM 11472006 ER PT J AU VanSickle, DP Cooper, RA Boninger, ML DiGiovine, CP AF VanSickle, DP Cooper, RA Boninger, ML DiGiovine, CP TI Analysis of vibrations induced during wheelchair propulsion SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE accelerations; design; instrumentation; modeling; vibrations; wheelchairs ID WHOLE-BODY VIBRATION; COEFFICIENTS; SPINE AB Little is known about how dynamic acceleration affects wheelchair-rider comfort. The current study was to test both the operation of an instrumented wheelchair by a wheelchair user over a Simulated Road Course (SRC) and the operation of the same instrumented wheelchair during normal daily activities (a field test) by test subjects. Sixteen subjects participated in the protocol. A SRC allowed collection of data from wheelchair users traversing obstacles similar to those experienced by a typical wheelchair user. The SRC consisted of eight obstacles fixed rigidly to a flat concrete surface. The field test began after the conclusion of the SRC test. Transfer functions were derived for all 16 subjects. It is clear from the results that for the SRC, the acceleration at the wheelchair frame exceeded the 8-h "fatigue-decreased performance boundary." A vertical acceleration resonant peak was evident for eight of the subjects. The average for these peaks, when present, was 8.1 Hz. This frequency is higher than the 4-6 Hz resonant peak presented in the literature for a seated human subject. This discrepancy could be due to different levels of trunk control between wheelchair users in this study and ambulatory subjects used in the literature. Subjects and their wheelchairs were exposed to a few, high-acceleration events rather than consistent, small-magnitude accelerations during the field test. This study indicates that vibration may be a contributing factor to fatigue among manual wheelchair users, which could lead to injury. C1 VA Pittsburgh Healthcare Syst, VA Rehabil Res & Dev Ctr, Human Engn Res Labs 151R1, Ctr Excellence Wheelchairs & Related Technol, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. Univ Pittsburgh, Dept Mech Engn, Pittsburgh, PA USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, VA Rehabil Res & Dev Ctr, Human Engn Res Labs 151R1, Ctr Excellence Wheelchairs & Related Technol, 7180 Highland Dr, Pittsburgh, PA 15206 USA. RI DiGiovine, Carmen/E-2982-2011; OI Boninger, Michael/0000-0001-6966-919X NR 32 TC 27 Z9 27 U1 2 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 JUL-AUG PY 2001 VL 38 IS 4 BP 409 EP 421 PG 13 WC Rehabilitation SC Rehabilitation GA 470YD UT WOS:000170899300009 PM 11563494 ER PT J AU Berkowitz, RS AF Berkowitz, RS TI Advances in the management of epithelial ovarian cancer - Editorial comments SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Editorial Material ID ORAL-CONTRACEPTIVES; RISK; BRCA1; MUTATIONS C1 Harvard Univ, Brigham & Womens Hosp, Med Sch,Dana Farber Canc Inst, Dept Obstet Gynecol & Reprod Biol,Div Gynecol Onc, Boston, MA 02115 USA. RP Berkowitz, RS (reprint author), Harvard Univ, Brigham & Womens Hosp, Med Sch,Dana Farber Canc Inst, Dept Obstet Gynecol & Reprod Biol,Div Gynecol Onc, Boston, MA 02115 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD JUL PY 2001 VL 46 IS 7 BP 629 EP 630 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 458QG UT WOS:000170205600002 ER PT J AU Karlson, EW Lee, IM Cook, NR Buring, JE Hennekens, CH Bloch, KJ AF Karlson, EW Lee, IM Cook, NR Buring, JE Hennekens, CH Bloch, KJ TI Serologic evaluation of women exposed to breast implants SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE serologic markers; connective tissue disease; antinuclear antibodies; breast implants ID CONNECTIVE-TISSUE DISEASES; SILICONE-GEL IMPLANTS; SYSTEMIC LUPUS-ERYTHEMATOSUS; RETROSPECTIVE COHORT; MULTIPLE-MYELOMA; ANTINUCLEAR ANTIBODIES; RISK; AUTOANTIBODIES; SYMPTOMS; AUGMENTATION AB Objective. There continues to be uncertainty whether women with silicone breast implants experience activation of their immune system and show increased prevalence of serologic markers of connective tissue diseases. We conducted laboratory tests in a large number of women with and without breast implants, and in diabetic patients with presumed silicone exposure via insulin syringes. Methods. Subjects were chosen from women enrolled in the run-in phase of the Women's Health Study (WHS, a randomized trial testing aspirin and vitamin E in preventing cardiovascular disease and cancer), and included 298 women without breast implants, 298 women with breast implants, and 52 diabetic patients diagnosed before age 30. Comparison groups were matched on age, race, date of blood provided to the WHS, and randomization status. We compared the proportion with abnormal results in 16 serologic tests among the 3 groups of women, stratifying by the matching factors. We also tested for monoclonal immunoglobulins by electrophoresis. Results. For 14 of the 16 serologic tests, the proportions with abnormal results among the 3 groups of women were not significantly different. Of the remaining tests, C3 levels were decreased in 8 (2.7%) women without breast implants and 22 (7.4%) women with breast implants (p = 0.003). C4 levels were decreased in 31 (10.4%) women without breast implants and 48 (16.1%) women with breast implants (p = 0.03), Women without breast implants and diabetic patients did not differ significantly in the proportions having decreased C3 and C4 levels. Women with breast implants did not have higher frequency of monoclonal immunoglobulins detected by electrophoresis. Conclusion. We found little evidence for activation of the immune system in women with breast implants. The clinical significance of isolated reductions in C3 and C4 levels, in the absence of other abnormalities such as elevated levels of antinuclear antibody, is unknown. C1 Harvard Univ, Brigham Womens Hosp,Div Prevent Med,Sch Med, RB Brigham Multipurp Arthrit Musculoskelet Dis Ctr, Dept Med,Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Med, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Massachusetts Gen Hosp, Gen Med Serv, Clin Immunol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Med Serv, Allergy Unit, Boston, MA 02114 USA. RP Karlson, EW (reprint author), Harvard Univ, Brigham Womens Hosp,Div Prevent Med,Sch Med, RB Brigham Multipurp Arthrit Musculoskelet Dis Ctr, Dept Med,Div Rheumatol Immunol & Allergy, 75 Francis St, Boston, MA 02115 USA. FU NCI NIH HHS [CA-47988, CA-81611]; NHLBI NIH HHS [HL-43851] NR 47 TC 15 Z9 15 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUL PY 2001 VL 28 IS 7 BP 1523 EP 1530 PG 8 WC Rheumatology SC Rheumatology GA 451CQ UT WOS:000169783900011 PM 11469457 ER PT J AU Choi, HK Liu, SM Merkel, PA Colditz, GA Niles, JL AF Choi, HK Liu, SM Merkel, PA Colditz, GA Niles, JL TI Diagnostic performance of antineutrophil cytoplasmic antibody tests for idiopathic vasculitides: Metaanalysis with a focus on antimyeloperoxidase antibodies SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE antineutrophil cytoplasmic antibody; antiproteinase 3; antimyeloperoxidase; Wegener's granulomatgsis; microscopic polyangiitis; Churg-Strauss syndrome; idiopathic necotizing crescentic glomerulonephritis ID RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS; WEGENERS-GRANULOMATOSIS; GBM ANTIBODIES; C-ANCA; AUTOANTIBODIES; PREVALENCE; SEROLOGY AB Objective. The diagnostic value of tests for antimyeloperoxidase antibodies (anti-MPO) for systemic vasculitis is less established than that for cytoplasmic antineutrophil cytoplasmic antibody (cANCA)/antiproteinase 3 antibodies (anti-PR3). Controversy exists regarding the optimal utilization of indirect immunofluorescence (IIF) ANCA testing versus antigen-specific ANCA testing. To summarize the pertinent data, we conducted a metaanalysis examining the diagnostic value of ANCA testing systems that include assays for anti-MPO, Methods. We performed a structured Medline search and reference list review. Target articles in the search strategy were those reporting the diagnostic value of immunoassays for anti-MPO for the spectrum of systemic necrotizing vasculitides that includes Wegener's granulomatosis, microscopic polyangiitis, the Churg-Strauss syndrome, and isolated pauci-immune necrotizing or crescentic glomerulonephritis, regardless of other types of ANCA tests. Inclusion criteria required specification of a consecutive or random patient selection method and the use of acceptable criteria for the diagnosis of vasculitis exclusive of ANCA test results. Weighted pooled summary estimates of sensitivity and specificity were calculated for anti-MPO alone, anti-MPO + perinuclear ANCA (pANCA), and anti-MPO/pANCA + anti-PR3/cANCA. Results, Of 457 articles reviewed, only 7 met the selection criteria, Summary estimates of sensitivity and specificity (against disease controls only) of assays for anti-MPO for the diagnosis of systemic necrotizing vasculitides were 37.1% (confidence interval 26.6% to 47.6%) and 96.3% (CI 94.1% to 98.5%), respectively. When the pANCA pattern by IIF was combined with anti-MPO testing, the specificity improved to 99.4%, with a lower sensitivity, 31.5%. The combined ANCA testing system (anti-PR3/cANCA + anti-MPO/pANCA) increased the sensitivity to 85.5% with a specificity of 98.6%, Conclusion. These results suggest that while anti-MPO is relatively specific for the diagnosis of systemic vasculitis, the combination system of immunoassays for anti-MPO and IIF for pANCA is highly specific and both tests should be used together given the high diagnostic precision required for these conditions. Because patients with ANCA associated vasculitis have either anti-MPO with pANCA or anti-PR3 with cANCA, and rarely both, a combined ANCA testing system including anti-PR3/cANCA and anti-MPO/pANCA is recommended to optimize the diagnostic performance of ANCA testing. C1 Massachusetts Gen Hosp, Arthrit Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Med, Arthrit Ctr, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. RP Choi, HK (reprint author), Massachusetts Gen Hosp, Arthrit Unit, Dept Med, Bulfinch 165,Fruit St, Boston, MA 02114 USA. RI Liu, Simin/I-3689-2014; Colditz, Graham/A-3963-2009 OI Liu, Simin/0000-0003-2098-3844; Colditz, Graham/0000-0002-7307-0291 NR 32 TC 81 Z9 84 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUL PY 2001 VL 28 IS 7 BP 1584 EP 1590 PG 7 WC Rheumatology SC Rheumatology GA 451CQ UT WOS:000169783900020 PM 11469466 ER PT J AU Shera, CA AF Shera, CA TI Intensity-invariance of fine time structure in basilar-membrane click responses: Implications for cochlear mechanics SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID AUDITORY-NERVE FIBERS; OUTER HAIR-CELLS; 3-DIMENSIONAL MODEL; FREQUENCY-SELECTIVITY; MOSSBAUER TECHNIQUE; CHINCHILLA COCHLEA; IMPULSE RESPONSES; WAVE-FORM; STIMULI; GLIDES AB Basilar-membrane and auditory-nerve responses to impulsive acoustic stimuli, whether measured directly in response to clicks or obtained indirectly using cross- or reverse-correlation and/or Fourier analysis, manifest a striking symmetry: near-invariance with stimulus intensity of the fine time structure of the response over almost the entire dynamic range of hearing. This paper explores the origin and implications of this symmetry for cochlear mechanics. Intensity-invariance is investigated by applying the EQ-NL theorem [de Beer, Aud. Neurosci. 3, 377-388 (1997)] to define a family of linear cochlear models in which the strength of the active force generators is controlled by a real-valued, intensity-dependent parameter, gamma (with 0 less than or equal to gamma less than or equal to1). The invariance of fine time structure is conjectured to imply that as gamma is varied the poles of the admittance of the cochlear partition remain within relatively narrow bands of the complex plane oriented perpendicular to the real frequency axis. Physically, the conjecture implies that the local resonant frequencies of the cochlear partition are nearly independent of intensity. Cochlear-model responses, computed by extending the model obtained by solution of the inverse problem in squirrel monkey at low sound levels [Zweig, J. Acoust. Sec. Am. 89, 1229-1254 (1991)] with three different forms of the intensity dependence of the partition admittance, support the conjecture. Intensity-invariance of cochlear resonant frequencies is shown to be consistent with the well-known "half-octave shift," describing the shift with intensity in the peak (or best) frequency of the basilar-membrane frequency response. Shifts in best frequency do not arise locally, via changes in the underlying resonant frequencies of the partition, but globally through the intensity dependence of the driving pressure. Near-invariance of fine time structure places strong constraints on the mechanical effects of force generation by outer hair cells. In particular, the symmetry requires that the feedback forces generated by outer hair cells (OHCs) not significantly affect the natural resonant frequencies of the cochlear partition. These results contradict many, if not most, cochlear models, in which OHC forces produce significant changes in the reactance and resonant frequencies of the partition. (C) 2001 Acoustical Society of America. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Shera, CA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. EM shera@epl.meei.harvard.edu FU NIDCD NIH HHS [R01 DC003687, R01 DC03687] NR 50 TC 64 Z9 64 U1 1 U2 3 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JUL PY 2001 VL 110 IS 1 BP 332 EP 348 DI 10.1121/1.1378349 PG 17 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 452FD UT WOS:000169846100032 PM 11508959 ER PT J AU Litvak, L Delgutte, B Eddington, D AF Litvak, L Delgutte, B Eddington, D TI Auditory nerve fiber responses to electric stimulation: Modulated and unmodulated pulse trains SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article; Proceedings Paper CT ASILOMAR Conference CY 1999 CL MONTEREY, CALIFORNIA ID COCHLEAR IMPLANTS; DISCHARGES; RECORDINGS; PATTERNS AB Many modern cochlear implants use sound processing strategies that stimulate the cochlea with modulated pulse trains. Rubinstein et al. [Hear. Res. 127, 108 (1999)] suggested that representation of the modulator in auditory nerve responses might be improved by the addition of a sustained, high-rate, desynchronizing pulse train (DPT). In addition, activity in response to the DPT may mimic the spontaneous activity (SA) in a healthy ear. The goals of this study were to compare responses of auditory nerve fibers in acutely deafened, anesthetized cats elicited by high-rate electric pulse trains delivered through an intracochlear electrode with SA, and to measure responses of these fibers to amplitude-modulated pulse trains superimposed upon a DPT. Responses to pulse trains showed variability from presentation to presentation, but differed from SA in the shape of the envelope of the interval histogram (IH) for pulse rates above 4.8 kpps (kilo pulses per second). These IHs had a prominent mode near 5 ms that was followed by a long tail, Responses to modulated biphasic pulse trains resembled responses to tones in intact ears for small (< 10%) modulation depths, suggesting that acousticlike responses to sinusoidal stimuli might be obtained with a DPT. However, realistic responses were only observed over a narrow range of levels and modulation depths. Improved coding of complex stimulus waveforms may be achieved by signal processing strategies for cochlear implants that properly incorporate a DPT. (C) 2001 Acoustical Society of America. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. MIT, Speech & Hearing Sci Program, Cambridge, MA 02139 USA. Massachusetts Eye & Ear Infirm, Conhlear Implant Res Lab, Boston, MA 02114 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Litvak, L (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. OI , /0000-0003-1349-9608 FU NIDCD NIH HHS [P01 DC000361, P01 DC000361-100005, R01 DC002258, R01 DC002258-06] NR 29 TC 75 Z9 77 U1 0 U2 5 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JUL PY 2001 VL 110 IS 1 BP 368 EP 379 DI 10.1121/1.1375140 PG 12 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 452FD UT WOS:000169846100034 PM 11508961 ER PT J AU Morrison, DA Sethi, G Sacks, J Henderson, W Grover, F Sedlis, S Esposito, R Ramanathan, K Weiman, D Saucedo, J Antakli, T Paramesh, V Pett, S Vernon, S Birjiniuk, V Welt, F Krucoff, M Wolfe, W Lucke, JC Mediratta, S Booth, D Barbiere, C Lewis, D AF Morrison, DA Sethi, G Sacks, J Henderson, W Grover, F Sedlis, S Esposito, R Ramanathan, K Weiman, D Saucedo, J Antakli, T Paramesh, V Pett, S Vernon, S Birjiniuk, V Welt, F Krucoff, M Wolfe, W Lucke, JC Mediratta, S Booth, D Barbiere, C Lewis, D CA Investigators Dept Vet Affairs Coo TI Percutaneous coronary intervention versus coronary artery bypass graft surgery for patients with medically refractory myocardial ischemia and risk factors for adverse outcomes with bypass: A multicenter, randomized trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID UNSTABLE ANGINA-PECTORIS; ASSOCIATION TASK-FORCE; FOLLOW-UP; ANGIOPLASTY; DISEASE; CARDIOLOGY; THERAPY; METAANALYSIS; GUIDELINES; MORTALITY AB BACKGROUND Percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG) are being applied to high-risk populations, but previous randomized trials comparing revascularization methods have excluded a number of important high-risk groups. OBJECTIVES This five-year, multicenter, randomized clinical trial was designed to compare long-term survival among patients with medically refractory myocardial ischemia and a high risk of adverse outcomes assigned to either a CABG or a PCI strategy, which could include stents. METHODS Patients from 16 Veterans Affairs Medical Centers were screened to identify myocardial ischemia refractory to medical management and the presence of one or more risk factors for adverse outcome with CABG, including prior open-heart surgery, age >70 years, left ventricular ejection fraction <0.35, myocardial infarction within seven days or intraaortic balloon pump required. Clinically eligible patients (n = 2,431) underwent coronary angiography; 781 were angiographically acceptable; 454 (58% of eligible) patients consented to random assignment between CABG and PCI. RESULTS A total of 232 patients was randomized to CABG and 222 to PCI. The 30-day survivals for CABG and PCI were 95% and 97%, respectively. Survival rates for CABG and PCI were 90% versus 94% at six months and 79% versus 80% at 36 months (log-rank test, p = 0.46). CONCLUSIONS Percutaneous coronary intervention is an alternative to CABG for patients with medically refractory myocardial ischemia and a high risk of adverse outcomes with CABG. (J Am Coll Cardiol 2001;38:143-9) (C) 2001 by the American College of Cardiology. C1 Univ Arizona, SAVAHCS, Dept Med & Radiol, Tucson, AZ 85723 USA. Tucson VA Med Ctr, Tucson, AZ USA. Hines CSPCC VA Hosp, Hines, IL USA. Denver VA Med Ctr, Denver, CO USA. New York VA Med Ctr, New York, NY USA. Memphis VA Med Ctr, Memphis, TN USA. Little Rock VA Med Ctr, Little Rock, AR USA. Albuquerque VA Med Ctr, Albuquerque, NM USA. W Roxbury VA Med Ctr, W Roxbury, MA USA. Durham VA Med Ctr, Durham, NC USA. Asheville VA Med Ctr, Asheville, NC USA. Lexington VA Med Ctr, Lexington, KY USA. Kansas City VA Med Ctr, Kansas City, MO USA. RP Morrison, DA (reprint author), Univ Arizona, SAVAHCS, Dept Med & Radiol, 2601 S 6th Ave, Tucson, AZ 85723 USA. NR 31 TC 159 Z9 166 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL PY 2001 VL 38 IS 1 BP 143 EP 149 DI 10.1016/S0735-1097(01)01366-3 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 448KE UT WOS:000169625400022 PM 11451264 ER PT J AU Simmons, SF Alessi, C Schnelle, JF AF Simmons, SF Alessi, C Schnelle, JF TI An intervention to increase fluid intake in nursing home residents: Prompting and preference compliance SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE nursing home; nutrition; dehydration; behavioral interventions ID DEHYDRATION AB OBJECTIVE: To evaluate a three-phase, behavioral intervention to improve fluid intake in nursing home (NH) residents. DESIGN: Controlled clinical intervention trial. SETTING: Two community NHs. PARTICIPANTS: Sixty-three incontinent NH residents INTERVENTION: Participants were randomized into intervention and control groups. The intervention consisted of three phases for a total of 32 weeks: (1) 16 weeks of four verbal prompts to drink per day, in between meals; (2) 8 weeks of eight verbal prompts per day, in between meals; and (3) 8 weeks of eight verbal prompts per day, in between meals, plus compliance with participant beverage preferences. MEASUREMENTS: Between-meal fluid intake was measured in ounces by research staff during all three phases of the intervention. Percentage of fluids consumed during meals was also estimated by research staff for a total of nine meals per participant (3 consecutive days) at baseline and at 8 and 32 weeks into the intervention. Serum osmolality, blood urea nitrogen, and creatinine values were obtained for all participants in one of the two sites at the same three time points. RESULTS: The majority (78%) of participants increased their fluid intake between meals in response to the increase in verbal prompts (phase 1 to 2). A subset of residents (21%), however, only increased their fluid intake in response to beverage preference compliance (phase 3). There was a significant reduction in the proportion of intervention participants who had laboratory values indicative of dehydration compared with the control participants. Cognitive and nutritional status were predictive of residents' responsiveness to the intervention. CONCLUSIONS: A behavioral intervention that consists of verbal prompts and beverage preference compliance was effective in increasing fluid intake among most of a sample of incontinent NH residents. Verbal prompting alone was effective in improving fluid intake in the more cognitively impaired residents, whereas preference compliance was needed to increase fluid intake among less cognitively impaired NH residents. C1 Univ Calif Los Angeles, Sch Med, Dept Geriatr, Borun Ctr Gerontol Res,Jewish Home Aging, Reseda, CA 91335 USA. Vet Adm Greater Los Angeles Healthcare Syst, Sepulveda Geriatr Res Educ & Clin Ctr, Sepulveda, CA USA. RP Simmons, SF (reprint author), Univ Calif Los Angeles, Sch Med, Dept Geriatr, Borun Ctr Gerontol Res,Jewish Home Aging, 7150 Tampa Ave, Reseda, CA 91335 USA. FU NIA NIH HHS [5R01 AG13013] NR 18 TC 55 Z9 57 U1 3 U2 4 PU BLACKWELL SCIENCE 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 JUL PY 2001 VL 49 IS 7 BP 926 EP 933 DI 10.1046/j.1532-5415.2001.49183.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 460XA UT WOS:000170332700011 PM 11527484 ER PT J AU Saunders, MJ AF Saunders, MJ TI Functional ability and oral health: Reintegrating mouth and body SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Ctr Clin, San Antonio, TX USA. RP Saunders, MJ (reprint author), Univ Texas, Hlth Sci Ctr, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE 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 JUL PY 2001 VL 49 IS 7 BP 1000 EP 1001 DI 10.1046/j.1532-5415.2001.49195.x PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 460XA UT WOS:000170332700024 PM 11527498 ER PT J AU Prady, SL Norris, D Lester, JE Hoch, DB AF Prady, SL Norris, D Lester, JE Hoch, DB TI Implementation brief - Expanding the guidelines for electronic communication with patients - Application to a specific tool SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID E-MAIL AB In 1998, the American Medical Informatics Association (AMIA) published a white paper entitled "Guidelines for the Clinical Use of Electronic Mail with patients," which outlined a practical framework for this interaction. Interest in the use of other Internet-based tools, such as the World Wide Web, to enhance clinical communication is increasing. In such systems, static information can be made centrally available to patients and interactive tools such as messaging systems, schedules, and individualized care regimens can be integrated within the site. Site-specific guidelines are needed to address potential problems inherent in the particular services being offered. This article presents advice on developing site-specific guidelines, with examples, based on experience gained in developing and refining guidelines for the use of PatientWeb tit the Massachusetts General Hospital Department of Neurology. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Prady, SL (reprint author), Massachusetts Gen Hosp, VBK 830,55 Fruit St, Boston, MA 02114 USA. NR 10 TC 20 Z9 20 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL-AUG PY 2001 VL 8 IS 4 BP 344 EP 348 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 451JM UT WOS:000169799000005 PM 11418540 ER PT J AU Salinsky, MC Storzbach, D Dodrill, CB Binder, LM AF Salinsky, MC Storzbach, D Dodrill, CB Binder, LM TI Test-retest bias, reliability, and regression equations for neuropsychological measures repeated over a 12-16-week period SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE test-retest reliability; psychometrics; stability; confidence intervals ID EPILEPSY; BATTERY; WAIS AB The interpretation of neurobehavioral change over lime requires knowledge of the test-retest characteristics of the measures. Without this information it is nor possible to distinguish a true change (i.e., one reflecting the occurrence or resolution of an intervening process) from that occurring on the basis of chance or systematic bias. We tested a group of 72 healthy young to middle aged adults twice over a 12-to-16-week interval in order to observe the change in scores over time when there was no known intervention. The test battery consisted of seven commonly used cognitive measures and the Profile of Mood States (POMS). Test-retest regression equations were calculated for each measure using initial performance, age, education, and a measure of general intellectual function (Wonderlic Personnel Test) as regressors, Test-retest correlations ranged from .39 (POMS Fatigue) to .89 (Digit Symbol). Cognitive measures generally yielded higher correlations than did the POMS. Univariate regressions based only on initial performance adequately predicted retest performance for the majority of measures. Age and education had a relatively minor influence. Practice effects and regression to the mean were common. These test-retest regression equations can be used to predict retest scores when there has been no known intervention. They can also be used to generate statistical statements regarding the significance of change in an individual's performance over a 12-to-16-week interval. C1 Oregon Hlth Sci Univ, Epilepsy Ctr, Dept Neurol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Dept Psychiat, Portland, OR USA. Univ Washington, Epilepsy Ctr, Dept Neurol, Seattle, WA 98195 USA. RP Salinsky, MC (reprint author), Oregon Hlth Sci Univ, Epilepsy Ctr, Dept Neurol, 745 SW Gaines Rd CDW-3, Portland, OR 97201 USA. NR 24 TC 50 Z9 50 U1 3 U2 11 PU CAMBRIDGE UNIV PRESS PI PORT CHESTER PA 110 MIDLAND AVE, PORT CHESTER, NY 10573-9863 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD JUL PY 2001 VL 7 IS 5 BP 597 EP 605 DI 10.1017/S1355617701755075 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 451XM UT WOS:000169827900007 PM 11459111 ER PT J AU Albert, MS Moss, MB Tanzi, R Jones, K AF Albert, MS Moss, MB Tanzi, R Jones, K TI Preclinical prediction of AD using neuropsychological tests SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE preclinical Alzheimer's disease; memory; executive function; MCI ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; MEMORY LOSS; QUESTIONABLE DEMENTIA; CINGULATE CORTEX; DEFICITS; DEGENERATION; DIAGNOSIS; ONSET AB Normals (N = 42) and patients with mild memory difficulty (N = 123) were given a neuropsychological test battery, and then followed annually for 3 years to determine which individuals developed sufficient functional change that they met clinical criteria for AD. Twenty-three of the 123 participants with mild memory difficulty converted to a diagnosis of probable Alzheimer's disease (AD) within 3 years of follow-up. Four of the 20 neuropsychological measures obtained at baseline, were useful in discriminating the groups on the basis of their status 3 years after the tests were given. The 4 discriminating tests pertained to assessments of memory and executive function. When the controls were compared to the individuals with memory impairments who ultimately developed AD (the converters), the accuracy of discrimination was 89%, based on the neuropsychological measures at baseline. The discrimination of the controls from the individuals with mild memory problems who did not progress to the point where they mel clinical criteria for probable AD over the 3 years of follow-up (the Questionables) was 74% and the discrimination of the questionables from the converters was 80%. The specific tests that contributed to these discriminations. in conjunction with recent neuropathological and neuroimaging data from preclinical cases, have implications for which brain regions may be affected during the prodromal phase of AD. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Boston Univ, Dept Anat & Neurobiol, Boston, MA 02215 USA. Brandeis Univ, Heller Sch Social Policy, Waltham, MA 02254 USA. RP Albert, MS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Psychiat Gerontol 149-9124,149 13th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [P01-AG04953] NR 61 TC 299 Z9 309 U1 1 U2 20 PU CAMBRIDGE UNIV PRESS PI PORT CHESTER PA 110 MIDLAND AVE, PORT CHESTER, NY 10573-9863 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD JUL PY 2001 VL 7 IS 5 BP 631 EP 639 DI 10.1017/S1355617701755105 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 451XM UT WOS:000169827900010 PM 11459114 ER PT J AU Smith, MR McGovern, FJ AF Smith, MR McGovern, FJ TI Gonadotropin-releasing hormone agonist failure in a man with prostate cancer SO JOURNAL OF UROLOGY LA English DT Editorial Material DE orchiectomy; prostate; prostatic neoplasms; gonadorelin; treatment failure C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 12 Z9 12 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 JUL PY 2001 VL 166 IS 1 BP 211 EP 211 DI 10.1016/S0022-5347(05)66115-0 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 442CY UT WOS:000169268700059 PM 11435862 ER PT J AU Day, CL Shea, AK Altfeld, MA Olson, DP Buchbinder, SP Hecht, FM Rosenberg, ES Walker, BD Kalams, SA AF Day, CL Shea, AK Altfeld, MA Olson, DP Buchbinder, SP Hecht, FM Rosenberg, ES Walker, BD Kalams, SA TI Relative dominance of epitope-specific cytotoxic T-lymphocyte responses in human immunodeficiency virus type 1-infected persons with shared HLA alleles SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-1 NEF PROTEIN; FINE SPECIFICITY; REVERSE-TRANSCRIPTASE; CELL RESPONSES; PRIMARY INFECTION; ENVELOPE PROTEIN; CONSERVED REGION; 3 REGIONS; IN-VIVO AB Cytotoxic T lymphocytes (CTL) target multiple epitopes in human immunodeficiency virus (HIV)-infected persons, and are thought to influence the viral set point. The extent to which HLA class I allele expression predicts the epitopes targeted has not been determined, nor have the relative contributions of responses restricted by different class I alleles within a given individual. In this study, we performed a detailed analysis of the CTL response to optimally defined CTL epitopes restricted by HLA class I A and B alleles in individuals who coexpressed HLA A2, A3, and B7. The eight HIV-l-infected subjects studied included two subjects with acute HIV infection, five subjects,vith chronic HIV infection, and one long-term nonprogressor. Responses were heterogeneous with respect to breadth and magnitude of CTL responses in individuals of the same HLA type. Of the 27 tested epitopes that are presented by A2, A3, and B7, 25 were targeted by at least one person. However, there was wide variation in the number of epitopes targeted, ranging from 2 to 17. The A2-restricted CTL response, which has been most extensively studied in infected persons, was found to be narrowly directed in most individuals, and in no cases was it the dominant contributor to the total HIV-l-specific CTL response. These results indicate that HLA type alone does not predict CTL responses and that numerous potential epitopes may not be targeted by CTL in a given individual. These data also provide a rationale for boosting both the breadth and the magnitude of HIV-l-specific CTL responses by immunotherapy in persons with chronic HIV-1 infection. C1 Massachusetts Gen Hosp, AIDS Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Dept Publ Hlth, Div Aids, AIDS Off, San Francisco, CA 94120 USA. Univ Calif San Francisco, Posit Hlth Program, San Francisco, CA 94143 USA. RP Kalams, SA (reprint author), Massachusetts Gen Hosp, AIDS Res Ctr, 149 13th St,Rm 5217, Charlestown, MA 02129 USA. RI Day, Cheryl/J-9844-2012 FU NIAID NIH HHS [AI28568, AI39966, AI42851, AI50914, P30 AI042851, R01 AI028568, R01 AI039966, R37 AI028568] NR 62 TC 51 Z9 53 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2001 VL 75 IS 14 BP 6279 EP 6291 DI 10.1128/JVI.75.14.6279-6291.2001 PG 13 WC Virology SC Virology GA 445JK UT WOS:000169454200005 PM 11413294 ER PT J AU Bluman, LG Borstelmann, NA Rimer, BK Iglehart, JD Winer, EP AF Bluman, LG Borstelmann, NA Rimer, BK Iglehart, JD Winer, EP TI Knowledge, satisfaction, and perceived cancer risk among women diagnosed with ductal carcinoma in situ SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Article ID QUALITY-OF-LIFE; NONINVASIVE BREAST-CANCER; INTRADUCTAL CARCINOMA; OVARIAN-CANCER; PSYCHOLOGICAL DISTRESS; IN-SITU; SUSCEPTIBILITY; EXPERIENCES; ADJUSTMENT; ADHERENCE AB The prevalence of ductal carcinoma in situ (DCIS) has increased through more widespread use of screening mammography. Little is known about what women with DCIS understand about their disease and future health. Although there is a wealth of information about the psychological characteristics of women with invasive breast cancer, there is virtually no information about women who have received treatment for DCIS. Seventy-six women diagnosed with DCIS who were identified through the Duke University Tumor Registry completed a mailed self-administered questionnaire including a broad range of items to measure knowledge, satisfaction with care, risk perceptions, and psychological distress. Women with DCIS have knowledge deficits about DCIS and breast cancer, as well as concerns about recurrence and misperceptions about the likelihood for DCIS metastasis. Women were generally satisfied with their care. They were less satisfied with information related to prognosis and with perceived support from their doctors. The results of this study suggest several areas of concern for women diagnosed with DCIS. Data about risk perceptions, knowledge, and attitudes in women diagnosed with DCIS provide important preliminary ideas for future studies. In view of the frequency of the DCIS diagnosis, future investigation should be conducted to build on these findings. C1 Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NCI, NIH, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, Breast Oncol Ctr, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R21 CA66228] NR 40 TC 39 Z9 41 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD JUL-AUG PY 2001 VL 10 IS 6 BP 589 EP 598 DI 10.1089/15246090152543175 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 466WB UT WOS:000170668200012 PM 11559456 ER PT J AU McNeal, MC Zareparsi, S Camicioli, R Dame, A Howieson, D Quinn, J Ball, M Kaye, J Payami, H AF McNeal, MC Zareparsi, S Camicioli, R Dame, A Howieson, D Quinn, J Ball, M Kaye, J Payami, H TI Predictors of healthy brain aging SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID FAMILIAL ALZHEIMER-DISEASE; APOLIPOPROTEIN-E GENOTYPE; E EPSILON-2 ALLELE; OLDEST-OLD; INCREASED RISK; DEMENTIA; AGE; METAANALYSIS; PREVALENCE; SURVIVAL AB To determine if superior health at old age protects against cognitive impairment (CI) and Alzheimer's disease (AD), we prospectively studied 100 optimally healthy oldest-old (greater than or equal to 85 years) individuals. Initially, subjects represented the top 3% of the oldest old for health. During 5.6 +/- 0.3 years of follow-up, 34 subjects developed CI, and 23 progressed to AD. By age 100, probability of CI and AD were. 65 +/- .09 and .49 +/- .10. Median onset age was 97 years for CI and 100 for AD. Clearly, superior health at old age does not guarantee protection against cognitive decline. Lifetime risks were similar to the general population but onset ages were later, suggesting factors that delay onset are key to improving cognitive health in the elderly. In this population, absence of apolipoprotein E-is an element of4 and male gender were associated with delayed onset, whereas estrogen use and education had no detectable effect on cognitive outcome. C1 Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Payami, H (reprint author), Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. NR 37 TC 19 Z9 19 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 2001 VL 56 IS 7 BP B294 EP B301 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 447RH UT WOS:000169585900003 ER PT J AU Kaufman, JS Reda, DJ Fye, CL Goldfarb, DS Henderson, WG Kleinman, JG Vaamonde, CA AF Kaufman, JS Reda, DJ Fye, CL Goldfarb, DS Henderson, WG Kleinman, JG Vaamonde, CA CA Vet Affairs Cooperative Study Grp TI Diagnostic value of iron indices in hemodialysis patients receiving epoetin SO KIDNEY INTERNATIONAL LA English DT Article DE anemia; parenteral iron; serum ferritin; transferrin saturation; recombinant human erythropoietin ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; SERUM FERRITIN CONCENTRATION; STAGE RENAL-DISEASE; MAINTENANCE HEMODIALYSIS; DEFICIENCY ANEMIA; THERAPY; SUPPLEMENTATION; PROTOPORPHYRIN; MANAGEMENT; EFFICACY AB Background. Iron deficiency remains a common cause of hyporesponsiveness to epoetin in hemodialysis patients. However. considerable controversy exists regarding the best strategies for diagnosis and treatment. Methods. As part of a multicenter randomized clinical trial of intravenous versus subcutaneous administration of epoetin. we made monthly determinations of serum iron, total iron binding capacity, percentage transferrin saturation. and serum ferritin. If a patient had serum ferritin < 100 ng/mL or the combination of serum ferritin < 400 ng/mL and a transferrin saturation < 20%. he/she received parenteral iron, given as iron dextran 100 mg at ten consecutive dialysis sessions. We analyzed parenteral iron use during the trial. the effect of its administration on iron indices and epoetin dose. and the ability of the iron indices to predict a reduction in epoetin dose in response to parenteral iron administration. Results. Eighty-seven percent of the 208 patients required parenteral iron to maintain adequate iron stores at an average dose of 1516 mg over 41.7 weeks, or 36 mg/week. Only two of 180 patients experienced serious reactions to intravenous iron administration. Two thirds of the patients receiving parenteral iron had a decrease in their epoetin requirement of at least 30 U/kg/week compared with 29% of patients who did not receive iron (P = 0.004). The average dose decrease 12 weeks after initiating iron therapy was 1763 U/week. A serum ferritin < 200 ng/mL had the best positive predictive value (76%) for predieting a response to parenteral iron administration, but it still had limited clinical utility. Conclusions. Iron deficiency commonly develops during epoetin therapy, and parenteral iron administration may result in a clinically significant reduction in epoetin dose. The use of transferrin saturation or serum ferritin as an indicator for parenteral iron administration has limited utility. C1 VA Boston Healthcare Syst, Renal Sect 111 RE, Boston, MA 02130 USA. Dept Vet Affairs, Cooperat Studies Program, Res & Dev Serv, Washington, DC USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Vet Affairs Cooperat Studies Program, Coordinating Ctr, Hines, IL USA. Vet Affairs Cooperat Studies Program, Clin res Pharm Coordinating Ctr, Albuquerque, NM USA. Vet Affairs Med Ctr, New York, NY USA. NYU, Sch Med, Dept Med, New York, NY USA. Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. Vet Affairs Med Ctr, Milwaukee, WI USA. Univ Miami, Sch Med, Dept Med, Miami, FL USA. Vet Affairs Med Ctr, Miami, FL 33125 USA. RP Kaufman, JS (reprint author), VA Boston Healthcare Syst, Renal Sect 111 RE, 150 S Huntington Ave, Boston, MA 02130 USA. OI Goldfarb, David/0000-0002-9215-1273 NR 27 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUL PY 2001 VL 60 IS 1 BP 300 EP 308 DI 10.1046/j.1523-1755.2001.00800.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 446CU UT WOS:000169496000035 PM 11422765 ER PT J AU Mazhar, AR Johnson, RJ Gillen, D Stivelman, JC Ryan, MJ Davis, CL Stehman-Breen, CO AF Mazhar, AR Johnson, RJ Gillen, D Stivelman, JC Ryan, MJ Davis, CL Stehman-Breen, CO TI Risk factors and mortality associated with calciphylaxis in end-stage renal disease SO KIDNEY INTERNATIONAL LA English DT Article DE hyperphosphatemia; alkaline phosphatase and calciphylaxis; serum albumin and calciphylaxix; death and calciphylaxis; skin lesions and mortality ID PROXIMAL CALCIPHYLAXIS; SKIN NECROSIS; FAILURE; HEMODIALYSIS; CALCIFICATION; DIALYSIS AB Background. We conducted a case control study to determine risk factors and mortality associated with calciphylaxis in endstage renal disease. Methods. Cases of calciphylaxis diagnosed between December 1989 and January 2000 were identified. Three controls were identified for each hemodialysis patient, with calciphylaxis matched to the date of initiation of hemodialysis. Laboratory data and medication doses were recorded during the 12 months prior to the date of diagnosis and at the time of diagnosis of calciphylaxis. Conditional logistic regression was used to identify risk factors for calciphylaxis. Cox proportional hazards models were used to estimate the risk of death associated with calciphylaxis. Results. Nineteen cases and 54 controls were identified. Eighteen patients were hemodialysis patients, and one had a functioning renal allograft. Diagnosis was confirmed by skin biopsy in 16 cases. Women were at a sixfold higher risk of developing calciphylaxis (OR = 6.04, 95% CI 1.62 to 22.6, P = 0.007). There was a 21% lower risk of calciphylaxis associated with each 0.1 g/dL increase in the mean serum albumin during the year prior to diagnosis and at the time of diagnosis of calciphylaxis (OR = 0.79. 95% CI. 0.64 to 0.99. P = 0.037, and OR = 0.80. 95% CI. 0.67 to 0.96, P = 0.019, respectively). There was a 3.51-fold increase in the risk of calciphylaxis associated with each mg/dL increase in the mean serum phosphate during the year prior to diagnosis (95% CI. 0.99 to 12.5, P = 0.052). At the time of diagnosis of calciphylaxis. for each 10 IU/L increment in alkaline phosphatase, the risk of calciphylaxis increased by 19% (OR = 1.19. 95% CI. 1.00 to 1.40, P = 0.045). Body mass index, diabetes. blood pressure, aluminum, and higher dosage of erythropoietin and iron dextran were not independent predictors of calciphylaxis. Calciphylaxis independently increased the risk of death by eightfold (OR = 8.58. 95% CI. 3.26 to 22.6. P < 0.001). Conclusions. Female gender, hyperphosphatemia. high alkaline phosphatase, and low serum albumin are risk factors For calciphylaxis. Calciphylaxis is associated with a very high mortality. C1 VA Puget Sound Hlth Care Syst, Div Nephrol, Seattle, WA 98108 USA. Univ Washington, Div Nephrol, Seattle, WA 98195 USA. Baylor Coll Med, Div Nephrol, Houston, TX USA. Univ Washington, Grad Sch Publ & Int Affairs, Dept Biostat, NW Kidney Ctr, Seattle, WA 98195 USA. RP Stehman-Breen, CO (reprint author), VA Puget Sound Hlth Care Syst, Div Nephrol, Mailstop 111A, Seattle, WA 98108 USA. FU NIDDK NIH HHS [DK07721-06] NR 20 TC 168 Z9 176 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUL PY 2001 VL 60 IS 1 BP 324 EP 332 DI 10.1046/j.1523-1755.2001.00803.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 446CU UT WOS:000169496000038 PM 11422768 ER PT J AU Hartnick, CJ Rudolph, C Willging, JP Holland, SK AF Hartnick, CJ Rudolph, C Willging, JP Holland, SK TI Functional magnetic resonance imaging of the pediatric swallow: Imaging the cortex and the brainstem SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Annual Meeting of the Middle Section of the Triological-Society CY JAN 19-21, 2001 CL CHICAGO, ILLINOIS DE functional imaging; swallow; dysphagia ID RETROSPECTIVE ESTIMATION; FMRI; PET; ACTIVATION; DISORDERS; CHILDREN; SOFTWARE; LANGUAGE; MRI AB Objective: To design and implement a functional magnetic resonance imaging (fMRI) protocol to investigate the cortical and brainstem patterns of activity in children with regard to the act of swallowing. Study Design: Pilot study to assess the clinical feasibility of the project. Methods. Using a 3T Bruker Biospec 30/60 MRI scanner, images were obtained using the Behavior Interleaved Gradient/Blood Oxygen Level Dependent (BIG-BOLD) image acquisition method. Initially, regions of interest (ROI) were developed to identify the mean time from the onset of a swallow to maximum cortical blood flow in the motor cortex. Using this data to design the BIG-BOLD acquisition method followed by postprocessing of the data, images from two volunteer adults and four volunteer children were obtained. Results: The average time from the onset of a swallow to maximum cortical blood now was 6 to 8 seconds. Regions of cortical activity include pre- and post-central gyrus (Brodmann's areas 3 and 4), superior motor cortex (B.A. 24), insula, inferior frontal cortex (B.A. 44 and 45), Heschl gyrus (B.A. 41 and 42), putamen, globus pallidus, and the superior temporal gyrus (B.A. 38), Of particular note is the first mapping of the functional activity of swallowing at the level of the brainstem; activity was seen in the region of the nucleus ambiguous. Conclusions: fMRI provides a novel means of studying the central processes of both normal swallowing and its various pathologic forms in children. Further understanding of how a child coordinates a swallow and how this coordination can be altered at the level of the brainstem and cortex may aid in the development of novel rehabilitative strategies. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. Childrens Hosp, Med Ctr, Dept Radiol, Cincinnati, OH 45229 USA. Childrens Hosp, Med Ctr, Dept Gastroenterol, Cincinnati, OH 45229 USA. RP Hartnick, CJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. OI Holland, Scott/0000-0003-3719-0875 NR 35 TC 24 Z9 25 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUL PY 2001 VL 111 IS 7 BP 1183 EP 1191 DI 10.1097/00005537-200107000-00010 PG 9 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 450VA UT WOS:000169764500009 PM 11568539 ER PT J AU Whitehead, VM Payment, C Cooley, L Lauer, SJ Mahoney, DH Shuster, JJ Vuchich, MJ Bernstein, ML Look, AT Pullen, DJ Camitta, B AF Whitehead, VM Payment, C Cooley, L Lauer, SJ Mahoney, DH Shuster, JJ Vuchich, MJ Bernstein, ML Look, AT Pullen, DJ Camitta, B TI The association of the TEL-AML1 chromosomal translocation with the accumulation of methotrexate polyglutamates in lymphoblasts and with ploidy in childhood B-progenitor cell acute lymphoblastic leukemia: a Pediatric Oncology Group study SO LEUKEMIA LA English DT Article DE methotrexate; polyglutamates; translocation; TEL-AML1; hyperdiploid; lymphoblast ID DOSE INTRAVENOUS METHOTREXATE; GAMMA-GLUTAMYL HYDROLASE; IN-SITU HYBRIDIZATION; TEL GENE; FOLYLPOLYGLUTAMATE SYNTHETASE; LINEAGE DIFFERENCES; AML1 GENE; CHILDREN; EXPRESSION; FUSION AB Lymphoblasts from children with B-progenitor cell acute lymphoblastic leukemia (BpALL) with chromosomal hyperdiploidy and with translocations affecting chromosome 12p11-13, accumulate high and low levels of methotrexate polyglutamates (MTXPGs), respectively. Recently a cryptic translocation, t(12;21) (p13;q22), has been demonstrated by molecular and fluorescence in situ hybridization techniques in this disease. The chimeric TEL-AML1 transcript, which has been associated with this translocation, can be detected in up to 25% of children with BpALL. We detected the TEL-AML1 and/or the AML1-TEL transcript in 30 (33%) of 91 patients studied. Levels of lymphoblast MTXPGs were lower in those with than in those without the TEL-AML1 translocation (P = 0.004). Hyperdiploidy was rare in lymphoblasts with the TEL-AML1 translocation (P = 0.047). Both ploidy (P = 0.0015) and TEL-AML1 status (P = 0.0043) were independently and significantly correlated with the log of the lymphoblast MTXPG level. However, the presence of TEL-AML1 or of hyperdiploidy accounted for only 22% of the variation of this value. Our results imply that each of 1.16 greater than or equal to DI and the presence of the TEL-AML1 translocation confers a 50% decrease in lymphoblast MTXPG level. When planning reduction of therapy for either of the two excellent outcome categories of hyperdiploid or TEL-AML1 BpALL, one should consider the difference between these two subgroups in the ability of lymphoblasts to accumulate MTXPGs. C1 McGill Univ, Montreal Childrens Hosp, Res Inst, Penny Cole Hematol Res Lab,Hematol Serv, Montreal, PQ H3H 1P3, Canada. McGill Univ, Dept Pediat, Montreal, PQ H3A 2T5, Canada. Baylor Coll Med, Dept Med Genet, Houston, TX 77030 USA. Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Univ Florida, Dept Stat, Gainesville, FL 32611 USA. Univ Florida, Pediat Oncol Grp, Stat Off, Gainesville, FL 32611 USA. Hop St Justine, Dept Pediat, Montreal, PQ H3T 1C5, Canada. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Mississippi, Med Ctr, Dept Pediat, Jackson, MS 39216 USA. Midw Childrens Canc Ctr, Dept Pediat, Milwaukee, WI USA. Med Coll Wisconsin, Childrens Hosp Wisconsin, Milwaukee, WI 53226 USA. RP Whitehead, VM (reprint author), McGill Univ, Montreal Childrens Hosp, Res Inst, Penny Cole Hematol Res Lab,Hematol Serv, 2300 Tupper St, Montreal, PQ H3H 1P3, Canada. FU NCI NIH HHS [CA-25408, CA-32053, CA-33587] NR 46 TC 21 Z9 21 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUL PY 2001 VL 15 IS 7 BP 1081 EP 1088 DI 10.1038/sj.leu.2402165 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 454YY UT WOS:000170000400011 PM 11455977 ER PT J AU Smalley, RV Weller, E Hawkins, MJ Oken, MM O'Connell, MJ Haase-Statz, S Borden, EC AF Smalley, RV Weller, E Hawkins, MJ Oken, MM O'Connell, MJ Haase-Statz, S Borden, EC TI Final analysis of the ECOG I-COPA trial (E6484) in patients with non-Hodgkin's lymphoma treated with interferon alfa (IFN-alpha 2a) plus an anthracycline-based induction regimen SO LEUKEMIA LA English DT Article DE interferon alfa; non-Hodgkin's lymphoma ID COOPERATIVE-ONCOLOGY-GROUP; INTENSIVE CHEMOTHERAPY; RECOMBINANT LEUKOCYTE; FOLLICULAR LYMPHOMA; CLINICAL-TRIAL; MAINTENANCE; SURVIVAL; DOXORUBICIN; REMISSION; TOXICITY AB The Eastern Cooperative Oncology Group (ECOG) performed a prospectively randomized study (E6484) evaluating the use of interferon alfa 2a (IFN-alpha 2a) in patients with aggressive low-grade or with intermediate-grade non-Hodgkin's lymphoma (NHL) accruing close to 300 patients between 1985 and 1988. patients were eligible for study if they had bulky or symptomatic low-grade lymphoma or defined intermediate-grade subtypes. Of 291 patients enrolled, 249 were eligible for analysis. Ali patients were randomized to receive a four-drug cytotoxic chemotherapy regimen including cyclophosphamide, doxorubicin, vincristine and prednisone in 4-week cycles with or without IFN-alpha 2a in addition (COPA vs I-COPA). Treatment was given for up to 8-10 months. This report, at a time when the median follow-up among survivors has reached 12 years, updates the analysis of time to treatment failure (TTF), duration of disease-free survival (DFS), and overall survival. Patients randomized to receive IFN-alpha 2a had a prolonged TTF (P = 0.008; median 2.4 vs 1.6 years), DFS for those patients who had complete responses was also longer if IFN-alpha 2a had been given (P = 0.035; median 2.1 vs 1.8 years). There was a clinically but not a statistically significant prolongation of overall survival by IFN-alpha 2a (P = 0.107; median 7.8 vs 5.7 years). There were fewer deaths over time due to lymphoma in patients receiving IFN-alpha 2a (67 vs 80 deaths). A subset analysis, based on disease histology (low-grade, follicular, intermediate-grade), revealed a significant prolongation of TTP in patients receiving IFN-alpha 2a with either low-grade (P = 0.002; median 2.4 vs 1.6 years) or follicular (P = 0.01; median 2.5 vs 1.7 years) NHL but not intermediate grade (P = 0.622; median 2.3 vs 1.6 years) NHL. This analysis, performed approximately 12 years after closure of the study to accrual, supports the addition of interferon alfa to an induction cytotoxic chemotherapy regimen including cyclophosphamide and doxorubicin in the treatment of follicular NHL. C1 Synertron Inc, Madison, WI USA. Dana Farber Canc Res Ctr, Boston, MA USA. Washington Canc Inst, Washington, DC USA. Virginia Piper Canc Inst, Minneapolis, MN USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Cleveland Clin, Cleveland, OH 44106 USA. RP Smalley, RV (reprint author), 1030 S River Landing, Edgewater, MD 21037 USA. NR 25 TC 19 Z9 19 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUL PY 2001 VL 15 IS 7 BP 1118 EP 1122 DI 10.1038/sj.leu.2402161 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 454YY UT WOS:000170000400016 PM 11455982 ER PT J AU Ubel, PA Jepson, C Baron, J Mohr, T McMorrow, S Asch, DA AF Ubel, PA Jepson, C Baron, J Mohr, T McMorrow, S Asch, DA TI Allocation of transplantable organs: Do people want to punish patients for causing their illness? SO LIVER TRANSPLANTATION LA English DT Article ID HEALTH-CARE ALLOCATION; LIVER-TRANSPLANTATION; HELPING-BEHAVIOR; RESPONSIBILITY; PRIORITIES; JUDGMENTS; MODEL; PREFERENCES; EFFICIENCY; DECISIONS AB Some people believe patients with alcoholic cirrhosis should not receive equal priority for scarce transplantable organs. This may reflect a belief that these patients (1) are personally responsible for causing their own illnesses, (2) have poop transplant prognoses, or (3) are unworthy because they have engaged in socially undesirable behavior. We explore the roles that social desirability and personal responsibility have in people's judgments about transplant allocation, We presented prospective jurors with 4 scenarios, asking them to distribute 100 transplantable organs among 2 groups of 100 patients each. In each scenario, 1 group of patients, but not the other, was described as having a history of unhealthy behavior, (alcohol or cigarette use) associated with a poorer prognosis, In some scenarios, alcohol or cigarette use was said to cause the organ failure. In others, it only contributed to the patients' transplant prognosis, We also obtained self-reports of subjects' own smoking status, Subjects allocated significantly fewer than half the organs to those with unhealthy behaviors and worse prognoses (33%; P < .001), but the specific behavior (alcohol versus cigarette use) was not significantly associated with subjects' allocation choices, Significantly fewer organs were allocated to patients with behavior responsible for causing their diseases than to other patients (P < .0001), Subjects who never smoked discriminated the most and current smokers discriminated the least against patients with a history of unhealthy behavior (P < .0001). The public's transplantation allocation preferences are influenced by whether patients' behaviors are said to have caused their organ failure. C1 Univ Michigan, Vet Affairs Med Ctr, Program Improving Hlth Care Decis, Ann Arbor, MI 48109 USA. Univ Michigan, Div Gen Internal Med, Ann Arbor, MI 48109 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. Univ Penn, Dept Sociol, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Urban Inst, Washington, DC 20037 USA. RP Ubel, PA (reprint author), Univ Michigan, Vet Affairs Med Ctr, Program Improving Hlth Care Decis, 300 N Ingalls,Rm 7C27, Ann Arbor, MI 48109 USA. OI Asch, David/0000-0002-7970-286X NR 27 TC 35 Z9 35 U1 2 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD JUL PY 2001 VL 7 IS 7 BP 600 EP 607 DI 10.1053/jlts.2001.25361 PG 8 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 452VD UT WOS:000169879600006 PM 11460227 ER PT J AU Diehr, P Patrick, DL Spertus, J Kiefe, CI McDonell, M Fihn, SD AF Diehr, P Patrick, DL Spertus, J Kiefe, CI McDonell, M Fihn, SD TI Transforming self-rated health and the SF-36 scales to include death and improve interpretability SO MEDICAL CARE LA English DT Article DE death; health-related quality of life; QALY; longitudinal; health status ID LIFE; VALIDITY; QUALITY; ADULTS AB BACKGROUND. Most measures of health-related quality of life are undefined for people who die.]Longitudinal analyses are often limited to a healthier cohort (survivors) that cannot be identified prospectively, and that may have had little change in health. OBJECTIVE. To develop and evaluate methods to transform a single self-rated health item (excellent to poor; EVGGFP) and the physical component score of the SF-36 (PCS) to new variables that include a defensible value for death. METHODS. Using longitudinal data from two large studies of older adults, health variables were transformed to the probability of being healthy in the future, conditional on the current observed value; death then has the value of 0. For EVGGFP, the new transformations were compared with some that were published earlier, based on different data. For the PCS, how well three different transformations, based on different definitions of being healthy, discriminated among groups of patients, and detected change in time were assessed. RESULTS. The new transformation for EVGGFP was similar to that published previously. Coding the 5 categories as 95, 90, 80, 30, and 15, and coding dead as 0 is recommended, The three transformations of the PCS detected group differences and change at least as well as the standard PCS. CONCLUSION. These easily interpretable transformed variables permit keeping persons who die in the analyses. Using the transformed variables for longitudinal analyses of health when deaths occur, either for secondary or primary analysis, is recommended. This approach can be applied to other measures of health. C1 Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Missouri, Dept Med, Kansas City, MO 64110 USA. Univ Alabama, Ctr Outcomes & Effectiveness Res & Educ, Birmingham, AL USA. VA Puget Sound Hlth Care Syst, NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. RP Diehr, P (reprint author), Univ Washington, Dept Biostat, Box 357232, Seattle, WA 98195 USA. FU NHLBI NIH HHS [N01-HC85086, N01-HC-85079] NR 20 TC 59 Z9 60 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUL PY 2001 VL 39 IS 7 BP 670 EP 680 DI 10.1097/00005650-200107000-00004 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 448KR UT WOS:000169626500005 PM 11458132 ER PT J AU Keating, NL Weeks, JC Landrum, MB Borbas, C Guadagnoli, E AF Keating, NL Weeks, JC Landrum, MB Borbas, C Guadagnoli, E TI Discussion of treatment options for early-stage breast cancer: Effect of provider specialty on type of surgery and satisfaction SO MEDICAL CARE LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the Society-for-General-Internal Medicine CY MAY 05-06, 2000 CL BOSTON, MASSACHUSETTS SP Soc Gen Internal Med DE breast neoplasms; mastectomy; breast-conserving surgery; patient satisfaction; referral and consultation ID COMPARING TOTAL MASTECTOMY; CONSERVING SURGERY; GEOGRAPHIC-VARIATION; OLDER WOMEN; CARE; DETERMINANTS; GUIDELINES; MANAGEMENT; CARCINOMA; PATTERNS AB OBJECTIVES. To describe the physicians with whom breast cancer patients discuss treatment options and assess whether discussing surgical options with a medical oncologist is associated with type of surgery and satisfaction. RESEARCH DESIGN. Medical record abstraction and survey. SUBJECTS. Women With early-stage breast cancer numbering 2,426 in two states - Massachusetts, where the rate of breast-conserving surgery is high, and Minnesota, where it is lower. MEASURES. Receipt of breast-conserving surgery and satisfaction. RESULTS. Women in Massachusetts discussed breast cancer treatments with more physicians than women in Minnesota (mean 3.5 vs. 2.8; P <0.001) and more often discussed surgical options with a medical oncologist (52% vs. 28%; P <0.001). Using propensity score analyses, in Massachusetts, discussing surgical options with a medical oncologist was not related to type of surgery (adjusted difference in rate of breast-conserving surgery: 3.9%, 95% CI -3.6% to 11.5%) but was associated with greater satisfaction (adjusted difference: 8.1, 95% CI 2.0% to 14.2%). In Minnesota, discussing surgical options with a medical oncologist was associated with breast-conserving surgery (adjusted difference: 12.6%, 95% CI 5.6% to 19.7%) with no difference in satisfaction (adjusted difference: -1.5%, 95% CI -6.8% to 3.8%). CONCLUSIONS. Outcomes associated with discussing surgical treatments with a medical oncologist vary with local care patterns. Where breast-conserving surgery is standard care, seeing a medical oncologist is not related to type of surgery, but is associated with greater satisfaction. Where it is not the standard, seeing a medical oncologist is associated with more breast-conserving surgery and equivalent satisfaction. These findings suggest that collaborative care may benefit women with respect to treatment selection or satisfaction. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, Sect Hlth Serv & Policy Res, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Healthcare Educ & Res Fdn Inc, St Paul, MN USA. RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA57755, CA59408] NR 32 TC 18 Z9 18 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUL PY 2001 VL 39 IS 7 BP 681 EP 691 DI 10.1097/00005650-200107000-00005 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 448KR UT WOS:000169626500006 PM 11458133 ER PT J AU Walhout, AJM Vidal, M AF Walhout, AJM Vidal, M TI High-throughput yeast two-hybrid assays for large-scale protein interaction manning SO METHODS LA English DT Article ID REVERSE 2-HYBRID; SYSTEMS; GENES AB Protein-protein interactions play fundamental roles in many biological processes. Hence, protein interaction mapping is becoming a well-established functional genomics approach to generate functional annotations for predicted proteins that so far have remained uncharacterized. The yeast two-hybrid system is currently one of the most standardized protein interaction mapping techniques. Here, we describe the protocols for a semiautomated, high-throughput, Gal4-based yeast two-hybrid system. (C) 2001 Academic Press. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Vidal, M (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 19 TC 163 Z9 166 U1 2 U2 19 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD JUL PY 2001 VL 24 IS 3 BP 297 EP 306 DI 10.1006/meth.2001.1190 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 447MJ UT WOS:000169576900011 PM 11403578 ER PT J AU Cherayil, BJ Antos, D AF Cherayil, BJ Antos, D TI Inducible nitric oxide synthase and Salmonella infection SO MICROBES AND INFECTION LA English DT Review DE Salmonella; nitric oxide; immunity ID INTESTINAL EPITHELIAL-CELLS; NADPH PHAGOCYTE OXIDASE; TYPHIMURIUM INFECTION; NUCLEAR RESPONSES; MEDIATED IMMUNOSUPPRESSION; PERITONEAL-MACROPHAGES; ANTIMICROBIAL ACTIONS; IMMUNE-RESPONSES; GAMMA-INTERFERON; REACTIVE OXYGEN AB Salmonella infection is associated with the increased expression of inducible nitric oxide synthase in macrophages and other cells. This review summarizes current knowledge of the molecular mechanisms involved in the induction process, and discusses the functional significance of nitric oxide production in the context of host defense against Salmonella. (C) 2001 Editions scientifiques et medicales Elsevier SAS. C1 Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Mucosal Immun Lab, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Cherayil, BJ (reprint author), Massachusetts Gen Hosp East, Pediat Gastroenterol Unit, Bldg 114,16th St, Charlestown, MA 02129 USA. NR 39 TC 29 Z9 29 U1 1 U2 4 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD JUL PY 2001 VL 3 IS 9 BP 771 EP 776 DI 10.1016/S1286-4579(01)01428-9 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 464JJ UT WOS:000170529200011 PM 11489426 ER PT J AU Davies, CD Melder, RJ Munn, LL Mouta-Carreira, C Jain, RK Boucher, Y AF Davies, CD Melder, RJ Munn, LL Mouta-Carreira, C Jain, RK Boucher, Y TI Decorin inhibits endothelial migration and tube-like structure formation: Role of thrombospondin-1 SO MICROVASCULAR RESEARCH LA English DT Article DE skin and cartilage decorin; protein core of decorin; thrombospondin-1; endothelial aggregation; endothelial migration; tube-like structure formation ID ANGIOGENESIS IN-VITRO; GLYCOSAMINOGLYCAN-BINDING DOMAIN; DERMATAN SULFATE PROTEOGLYCANS; C-TERMINAL DOMAIN; CELL ATTACHMENT; PLATELET THROMBOSPONDIN; PROTEIN CORE; EXPRESSION; ADHESION; GROWTH AB Interactions between endothelial cell receptors and the extracellular matrix (ECM) play a critical, yet poorly understood role in angiogenesis. Based on the anti-adhesive role of decorin, we hypothesized that decorin binding to ECM molecules such as thrombospondin-1 (TSP-1) plays a regulatory role in endothelial tube-like structure (TLS) formation. To test this hypothesis, endothelial cells were plated on TSP-1, decorin, or mixed substrates of TSP-1 plus decorin. TLS formation was induced by applying type I collagen on the confluent endothelial monolayer. Cartilage decorin inhibited the formation of TLSs in a concentration-dependent manner. On substrates of high decorin concentrations (2.5 and 5.0 mug/cm(2)) the reduction in TLSs was due either to a reduction in the number of adhering cells or to decreased cell migration. At low decorin concentrations (0.05 and 0.25 mug/cm(2)) the reduction in TLSs was independent of the number of attached cells, Time-lapse video microscopy revealed that decorin substrates facilitated homotypic aggregation and isolated cord formation at the expense of endothelial migration and TLS formation. Consistent with the reduced migration, endothelial cells formed fewer vinculin-positive focal adhesions and actin-stress fibers on decorin substrates. Endothelial migration and TLS formation were also significantly inhibited by skin decorin and the protein core of cartilage decorin. The inhibition of TLS formation by the protein core of cartilage decorin was potentiated by TSP-1. These findings suggest that decorin alone or in combination with TSP-1 interferes with the activation of endothelial cell receptors by ECM molecules, thus blocking intracellular signals that induce cytoskeletal reorganization, migration, and TLS formation, (C) 2001 Academic Press. C1 Norwegian Univ Sci & Technol, Dept Phys, N-7491 Trondheim, Norway. Human Genome Sci Inc, Dept Cell Biol, Rockville, MD USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Davies, CD (reprint author), Norwegian Univ Sci & Technol, Dept Phys, N-7491 Trondheim, Norway. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 66 TC 58 Z9 64 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0026-2862 EI 1095-9319 J9 MICROVASC RES JI Microvasc. Res. PD JUL PY 2001 VL 62 IS 1 BP 26 EP 42 DI 10.1006/mvre.2001.2311 PG 17 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 453QJ UT WOS:000169927100003 ER PT J AU Sheridan, AM Force, T Yoon, HJ O'Leary, E Choukroun, G Taheri, MR Bonventre, JV AF Sheridan, AM Force, T Yoon, HJ O'Leary, E Choukroun, G Taheri, MR Bonventre, JV TI PLIP, a novel splice variant of Tip60, interacts with group IV cytosolic phospholipase A(2), induces apoptosis, and potentiates prostaglandin production SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; GLOMERULAR MESANGIAL CELLS; PROTEIN-KINASE-C; ARACHIDONIC-ACID; NUCLEAR-ENVELOPE; FACTOR-ALPHA; HISTONE ACETYLTRANSFERASE; EXTRACELLULAR-MATRIX; SIGNAL-TRANSDUCTION; E-2 GENERATION AB The group IV cytosolic phospholipase A(2) (cPLA(2)) has been localized to the nucleus (M. R. Sierra-Honigmann, J. R. Bradley, and J. S. Pober, Lab. Investig. 74:684-695, 1996) and is known to translocate from the cytosolic compartment to the nuclear membrane CS. Clover, M. S. de Carvalho, T. Bayburt, M. Jonas, E. Chi, C. C. Leslie, and ill. H. Gelb, J. Biol. Chem. 270:15359-15367, 1995; A. R. Schievella, M. K. Regier, W L. Smith, and L. L. Lin, J. Biol. Chem. 270:30749-30754, 1995). We hypothesized that nuclear proteins interact with cPLA(2) and participate in the functional effects of this translocation. We have identified a nuclear protein, cPLA(2)-interacting protein (PLIP), a splice variant of human Tip60, which interacts with the amino terminal region of cPLA(2). Like Tip60, FLIP cDNA includes the MYST domain containing a C2HC zinc finger and well-conserved similarities to acetyltransferases, Both PLIP and Tip60 coimmunoprecipitate and colocalize with cPLA(2) within the nuclei of transfected COS cells. A polyclonal antibody raised to PLIP recognizes both FLIP and Tip60. Endogenous Tip60 and/or FLIP in rat mesangial cells is localized to the nucleus in response to serum deprivation. Nuclear localization coincides temporally with apoptosis. FLIP expression, mediated by adenoviral gene transfer, potentiates serum deprivation-induced prostaglandin E-2 (PGE(2)) production and apoptosis in mouse mesangial cells from cPLA(2)(+/+) mice but not in mesangial cells derived from cPLA(2)(-/-) mice. Thus FLIP, a splice variant of Tip60, interacts with cPLA(2) and potentiates cPLA(2)-mediated PGE(2) production and apoptosis. C1 Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. RP Massachusetts Gen Hosp, Med Serv, 149-4002 13th St, Charlestown, MA 02129 USA. EM asheridan@partners.org RI Yoon, Hyung-Jin/J-5566-2012; OI Force, Thomas/0000-0002-0450-8659 FU NIDDK NIH HHS [R01 DK039773, R37 DK039773, DK02356, P01 DK038452, DK 39773, DK 38452, DK 54741, R01 DK054741, R56 DK054741]; NINDS NIH HHS [P01 NS010828, F32 NS010828, P50 NS010828, NS 10828] NR 82 TC 48 Z9 50 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2001 VL 21 IS 14 BP 4470 EP 4481 DI 10.1128/MCB.21.14.4470-4481.2001 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 445DQ UT WOS:000169443200005 PM 11416127 ER PT J AU Bogan, JS Mckee, AE Lodish, HF AF Bogan, JS Mckee, AE Lodish, HF TI Insulin-responsive compartments containing GLUT4 in 3T3-L1 and CHO cells: Regulation by amino acid concentrations SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RAT ADIPOSE-CELLS; GLUCOSE-TRANSPORTER GLUT4; SUBCELLULAR TRAFFICKING KINETICS; ENDOCYTIC RECYCLING MECHANISM; GREEN-FLUORESCENT PROTEIN; P70 S6 KINASE; STIMULATED TRANSLOCATION; PLASMA-MEMBRANE; INTRACELLULAR GLUT4; SIGNALING PATHWAYS AB In fat and muscle, insulin stimulates glucose uptake by rapidly mobilizing the GLUT4 glucose transporter from a specialized intracellular compartment to the plasma membrane. We describe a method to quantify the relative proportion of GLUT4 at the plasma membrane, using flow cytometry to measure a ratio of fluorescence intensities corresponding to the cell surface and total amounts of a tagged GLUT4 reporter in individual living cells. Using this assay, we demonstrate that both 3T3-L1 and CHO cells contain intracellular compartments from which GLUT4 is rapidly mobilized by insulin and that the initial magnitude and kinetics of redistribution to the plasma membrane are similar in these two cell types when they are cultured identically. Targeting of GLUT4 to a highly insulin responsive compartment in CHO cells is modulated by culture conditions. In particular, we find that amino acids regulate distribution of GLUT4 to this kinetically defined compartment through a rapamycin-sensitive pathway. Amino acids also modulate the magnitude of insulin-stimulated translocation in 3T3-L1 adipocytes. Our results indicate a novel link between glucose and amino acid metabolism. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lodish, HF (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM lodish@wi.mit.edu RI Bogan, Jonathan/A-1575-2010 OI Bogan, Jonathan/0000-0001-6463-8466 FU NIDDK NIH HHS [K11 DK02371, R37 DK047618, R37 DK47618] NR 116 TC 95 Z9 99 U1 0 U2 8 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 JUL PY 2001 VL 21 IS 14 BP 4785 EP 4806 DI 10.1128/MCB.21.14.4785-4806.2001 PG 22 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 445DQ UT WOS:000169443200031 PM 11416153 ER PT J AU Hemann, MT Rudolph, KL Strong, MA DePinho, RA Chin, L Greider, CW AF Hemann, MT Rudolph, KL Strong, MA DePinho, RA Chin, L Greider, CW TI Telomere dysfunction triggers developmentally regulated germ cell apoptosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID CHROMOSOME SYNAPSIS; MOUSE TELOMERASE; MEIOSIS; YEAST; LENGTH; MICE; PROTEINS; SPERMATOCYTES; DEFICIENT; PROPHASE AB Telomere dysfunction results in fertility defects in a number of organisms. Although data from fission yeast and Caenorhabditis elegans suggests that telomere dysfunction manifests itself primarily as defects in proper meiotic chromosome segregation, it is unclear how mammalian telomere dysfunction results in germ cell death. To investigate the specific effects of telomere dysfunction on mammalian germ cell development, we examined the meiotic progression and germ cell apoptosis in late generation telomerase null mice. Our results indicate that chromosome asynapsis and missegregation are not the cause of infertility in mice with shortened telomeres. Rather, telomere dysfunction is recognized at the onset of meiosis, and cells with telomeric defects are removed from the germ cell precursor pool. This germ cell telomere surveillance may be an important mechanism to protect against the transmission of dysfunctional telomeres and chromosomal abnormalities. C1 Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Grad Program Human Genet, Baltimore, MD 21205 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Greider, CW (reprint author), Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. FU NCI NIH HHS [CA-16519, P01 CA016519]; NIAMS NIH HHS [K08-AR02104]; NICHD NIH HHS [HD-34880, HD-28317]; NIGMS NIH HHS [GM-07814, T32 GM007814] NR 42 TC 105 Z9 111 U1 2 U2 4 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUL PY 2001 VL 12 IS 7 BP 2023 EP 2030 PG 8 WC Cell Biology SC Cell Biology GA 461DU UT WOS:000170350300009 PM 11452000 ER PT J AU Kim, TY Kaelin, WG AF Kim, TY Kaelin, WG TI Differential control of transcription by DNA-bound cyclins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID RNA-POLYMERASE-II; RETINOBLASTOMA GENE-PRODUCT; CELL-CYCLE; DEPENDENT KINASES; ESTROGEN-RECEPTOR; CDK COMPLEXES; SUBSTRATE-SPECIFICITY; TAT TRANSACTIVATION; GROWTH SUPPRESSION; P300 COACTIVATOR AB Different cyclins mediate different cell-cycle transitions. Some cyclins, such as cyclin A and cyclin E, form stable complexes with proteins that bind directly or indirectly to DNA and thus might be recruited to certain regions of the genome at specific times in the cell cycle. Furthermore, cyclins contain structural motifs that are also present in known transcriptional modulators. We found that cyclin A is a potent transcriptional repressor and cyclin E is a potent transcriptional activator when bound to DNA via a heterologous DNA binding domain. The former activity was linked to the integrity of the cyclin A cyclin fold, whereas the latter activity related to the ability of cyclin E to activate cdk2 and recognize substrates. Furthermore, we found that cyclin E, but not cyclin A, activated transcription in a cell-cycle-dependent manner when present in physiological concentrations as an unfused protein. These results suggest that cyclin A and cyclin E intrinsically differ with respect to their ability to modulate transcription when tethered to DNA. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Seoul Natl Univ, Coll Med, Inst Canc Res, Seoul 110744, South Korea. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RI Kim, Tae-You/J-2750-2012 NR 62 TC 15 Z9 16 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUL PY 2001 VL 12 IS 7 BP 2207 EP 2217 PG 11 WC Cell Biology SC Cell Biology GA 461DU UT WOS:000170350300023 PM 11452014 ER PT J AU Tham, WH Wyithe, JSB Ferrigno, PK Silver, PA Zakian, VA AF Tham, WH Wyithe, JSB Ferrigno, PK Silver, PA Zakian, VA TI Localization of yeast telomeres to the nuclear periphery is separable from transcriptional repression and telomere stability functions SO MOLECULAR CELL LA English DT Article ID SACCHAROMYCES-CEREVISIAE; CENTROMERIC HETEROCHROMATIN; CHROMOSOME STABILITY; CHROMATIN STRUCTURE; SIR4 PROTEINS; CELL-CYCLE; GENE; ORGANIZATION; KU; MAINTENANCE AB The left telomere of Saccharomyces chromosome VII was often localized near the nuclear periphery, even in cells lacking the silencing proteins Sir3 or Hdf1. This association was lost in late mitotic cells and when transcription was induced through the telomeric tract. Although in silencing competent cells there was no correlation between the fraction of cells in which a telomeric gene was repressed and the fraction of cells in which it was localized to the periphery, no condition was found where the telomere was both silenced and away from the periphery. We conclude that localization of a telomere to the nuclear periphery is not sufficient for transcriptional repression nor does it affect the stability function of yeast telomeres. C1 Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. Princeton Univ, Dept Astrophys Sci, Princeton, NJ 08544 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zakian, VA (reprint author), Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. OI Tham, Wai-Hong/0000-0001-7950-8699 FU NIGMS NIH HHS [GM 43265] NR 34 TC 62 Z9 64 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JUL PY 2001 VL 8 IS 1 BP 189 EP 199 DI 10.1016/S1097-2765(01)00287-8 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 456KP UT WOS:000170081900021 PM 11511372 ER PT J AU Silver, DP Livingston, DM AF Silver, DP Livingston, DM TI Self-excising retroviral vectors encoding the Cre recombinase overcome Cre-mediated cellular toxicity SO MOLECULAR CELL LA English DT Article ID SITE-SPECIFIC RECOMBINATION; EMBRYONIC STEM-CELLS; LOXP SPACER REGION; MAMMALIAN-CELLS; HIGH-TITER; GENE-EXPRESSION; TRANSGENIC MICE; MOUSE MUTANTS; GERM-LINE; DNA AB The Cre-lox system is often used to manipulate sequences in mammalian genomes. We have observed that continuous expression of the Cre recombinase in cultured cells lacking exogenous lox sites caused decreased growth, cytopathic effects, and chromosomal aberrations. Cre mutants defective in DNA cleavage were not geno- or cytotoxic. A self-excising retroviral vector that incorporates a negative feedback loop to limit the duration and intensity of Cre expression avoided measurable toxicity, retained the ability to excise a target sequence flanked by lex sites, and may provide the basis of a less toxic strategy for the use of Cre or similar recombinases. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Livingston, DM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [K08CA82572] NR 45 TC 201 Z9 208 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JUL PY 2001 VL 8 IS 1 BP 233 EP 243 DI 10.1016/S1097-2765(01)00295-7 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 456KP UT WOS:000170081900025 PM 11511376 ER PT J AU Kanai, F Liu, H Field, SJ Akbary, H Matsuo, T Brown, GE Cantley, LC Yaffe, MB AF Kanai, F Liu, H Field, SJ Akbary, H Matsuo, T Brown, GE Cantley, LC Yaffe, MB TI The PX domains of p47phox and p40phox bind to lipid products of Pl(3)K SO NATURE CELL BIOLOGY LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHOINOSITIDE-BINDING; NADPH OXIDASE; ENDOSOMAL LOCALIZATION; HOMOLOGY DOMAINS; SORTING NEXIN; IDENTIFICATION; 3-PHOSPHATE; PLECKSTRIN; RECEPTORS AB PX domains are found in a variety of proteins that associate with cell membranes, but their molecular function has remained obscure. We show here that the PX domains in p47phox and p40phox subunits of the phagocyte NADPH oxidase bind to phosphatidylinositol-3,4-bisphosphate (Ptdlns(3,4)P-2) and phosphatidylinositol-3-phosphate (Ptdlns(3)P), respectively. We also show that an Arg-to-Gln mutation in the PX domain of p47phox, which is found in patients with chronic granulomatous disease, eliminates phosphoinositide binding, as does the analogous mutation in the PX domain of p40phox, The PX domain of p40phox localizes specifically to Ptdlns(B)P-enriched early endosomes, and this localization is disrupted by inhibition of phosphoinositide-3-OH kinase (PI(3)K) or by the Arg-to-Gln point mutation. These findings provide a molecular foundation to understand the role of PI(3)K in regulating neutrophil function and inflammation, and to identify PX domains as specific phosphoinositide-binding modules involved in signal transduction events in eukaryotic cells. C1 MIT, Ctr Canc Res, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Endocrinol, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. RP Yaffe, MB (reprint author), MIT, Ctr Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIGMS NIH HHS [R01 GM041890] NR 31 TC 400 Z9 404 U1 0 U2 6 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD JUL PY 2001 VL 3 IS 7 BP 675 EP 678 DI 10.1038/35083070 PG 4 WC Cell Biology SC Cell Biology GA 450DV UT WOS:000169727000019 PM 11433300 ER PT J AU Jain, RK AF Jain, RK TI Clearing the smoke on nicotine and angiogenesis SO NATURE MEDICINE LA English DT Editorial Material ID PROLIFERATION AB Nicotine is widely used as an aid to smoking cessation and is being evaluated to treat non-smoking related disorders. Stimulation of angiogenesis by nicotine raises many questions about its mechanism of action and use in therapy. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab Tumor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jain, RK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab Tumor Biol, Boston, MA 02114 USA. NR 11 TC 16 Z9 17 U1 1 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 2001 VL 7 IS 7 BP 775 EP 777 DI 10.1038/89889 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 451NR UT WOS:000169808600020 PM 11433337 ER PT J AU Kirn, D Martuza, RL Zwiebel, J AF Kirn, D Martuza, RL Zwiebel, J TI Replication-selective virotherapy for cancer: Biological principles, risk management and future directions SO NATURE MEDICINE LA English DT Review ID NEWCASTLE-DISEASE VIRUS; HERPES-SIMPLEX VIRUS; PHASE-I TRIAL; PROSTATE-SPECIFIC ANTIGEN; TUMOR-CELL VACCINE; GENE-THERAPY; COMPETENT ADENOVIRUS; NECK-CANCER; ATTENUATED ADENOVIRUS; ONCOLYTIC ADENOVIRUS AB In the search for novel cancer therapies that can be used in conjunction with existing treatments, one promising area of research is the use of viral vectors and whole viruses. This review describes the underlying biological principles and current status of the field, outlines approaches for improving clinical effectiveness and discusses the unique safety and regulatory issues surrounding viral therapies. C1 Univ London Imperial Coll Sci Technol & Med, Viral & Genet Therapy Programme, Sch Med, London, England. Hammersmith Hosp, Imperial Canc Res Fund, London, England. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NCI, Div Canc Treatment, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Kirn, D (reprint author), Univ London Imperial Coll Sci Technol & Med, Viral & Genet Therapy Programme, Sch Med, London, England. FU NINDS NIH HHS [NS32677] NR 78 TC 286 Z9 304 U1 8 U2 42 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 2001 VL 7 IS 7 BP 781 EP 787 DI 10.1038/89901 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 451NR UT WOS:000169808600028 PM 11433341 ER PT J AU Brown, EB Campbell, RB Tsuzuki, Y Xu, L Carmeliet, P Fukumura, D Jain, RK AF Brown, EB Campbell, RB Tsuzuki, Y Xu, L Carmeliet, P Fukumura, D Jain, RK TI In vivo measurement of gene expression, angiogenesis and physiological function in tumors using multiphoton laser scanning microscopy SO NATURE MEDICINE LA English DT Article ID IN-VIVO; VASCULAR-PERMEABILITY; BLOOD-FLOW; GROWTH AB Intravital microscopy coupled with chronic animal window models has provided stunning insight into tumor pathophysiology, including gene expression, angiogenesis, cell adhesion and migration, vascular, interstitial and lymphatic transport, metabolic microenvironment and drug delivery. However, the findings to date have been limited to the tumor surface (< 150 m). Here, we show that the multiphoton laser-scanning microscope can provide high three-dimensional resolution of gene expression and function in deeper regions of tumors. These insights could be critical to the development of novel therapeutics that target not only the tumor surface, but also internal regions. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Flanders Interuniv Inst Biotechnol, Ctr Transgene Technol & Gene Therapy, Louvain, Belgium. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. FU NCI NIH HHS [P01 CA80124, R24 CA85140, R35 CA56591, T32 CA73479] NR 21 TC 391 Z9 398 U1 0 U2 20 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 2001 VL 7 IS 7 BP 864 EP 868 DI 10.1038/89997 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 451NR UT WOS:000169808600041 PM 11433354 ER PT J AU Pascual, AA Crespo, A Tolkoff-Rubin, N AF Pascual, AA Crespo, A Tolkoff-Rubin, N TI Progress in understanding humoral rejection in kidney transplantation: implications for patient management SO NEFROLOGIA LA English DT Editorial Material ID RENAL-ALLOGRAFT REJECTION; PATHOLOGICAL FEATURES; GRAFT-SURVIVAL; ANTIBODY; RESCUE; RECIPIENTS; RECEPTOR; GLOBULIN; THERAPY; ORGAN C1 Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Transplantat Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Pascual, AA (reprint author), Massachusetts Gen Hosp, Dept Med, Renal Unit, Box MZ 70, Boston, MA 02114 USA. NR 40 TC 8 Z9 8 U1 0 U2 0 PU SOC ESPANOLA NEFROLOGIA DR RAFAEL MATESANZ PI MADRID PA HOSPITAL RAMON Y CAJAL CTR DE COLMENAR, KM 9,100, 28034 MADRID, SPAIN SN 0211-6995 J9 NEFROLOGIA JI Nefrologia PD JUL-AUG PY 2001 VL 21 IS 4 BP 327 EP + PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 489ZY UT WOS:000172024300001 ER PT J AU Cariani, PA AF Cariani, PA TI Neural timing nets SO NEURAL NETWORKS LA English DT Review DE neural timing networks; time-delay neural networks; temporal coding; spiking neurons; scene analysis; temporal correlation; auditory neurocomputation ID DIFFERENT FUNDAMENTAL FREQUENCIES; AUDITORY-NERVE FIBERS; CONCURRENT VOWELS; INFERIOR COLLICULUS; PHASE SENSITIVITY; PITCH PERCEPTION; COMPUTER-MODEL; VIRTUAL PITCH; SYSTEM; INFORMATION AB Formulations of artificial neural networks are directly related to assumptions about neural coding in the brain. Traditional connectionist networks assume channel-based rate coding, while time-delay networks convert temporally-coded inputs into rate-coded outputs. Neural timing nets that operate on time structured input spike trains to produce meaningful time-structured outputs are proposed. Basic computational properties of simple feedforward and recurrent timing nets are outlined and applied to auditory computations. Feed-forward timing nets consist of arrays of coincidence detectors connected via tapped delay lines. These temporal sieves extract common spike patterns in their inputs that can subserve extraction of common fundamental frequencies (periodicity pitch) and common spectrum (timbre). Feedforward timing nets can also be used to separate time-shifted patterns, fusing patterns with similar internal temporal structure and spatially segregating different ones. Simple recurrent timing nets consisting of arrays of delay loops amplify and separate recurring time patterns. Single- and multichannel recurrent timing nets are presented that demonstrate the separation of concurrent, double vowels. Timing nets constitute a new and general neural network strategy for performing temporal computations on neural spike trains: extraction of common periodicities, detection of recurring temporal patterns, and formation and separation of invariant spike patterns that subserve auditory objects. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. RP Cariani, PA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. EM peter@epl.meei.harvard.edu FU NIDCD NIH HHS [DC03054] NR 104 TC 25 Z9 25 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0893-6080 J9 NEURAL NETWORKS JI Neural Netw. PD JUL-SEP PY 2001 VL 14 IS 6-7 SI SI BP 737 EP 753 DI 10.1016/S0893-6080(01)00056-9 PG 17 WC Computer Science, Artificial Intelligence; Neurosciences SC Computer Science; Neurosciences & Neurology GA 479RL UT WOS:000171417300014 PM 11665767 ER PT J AU Leverenz, JB Miller, MA Dobie, DJ Peskind, ER Raskind, MA AF Leverenz, JB Miller, MA Dobie, DJ Peskind, ER Raskind, MA TI Increased alpha 2-adrenergic receptor binding in locus coeruleus projection areas in dementia with Lewy bodies SO NEUROBIOLOGY OF AGING LA English DT Article DE alpha-2 adrenergic receptor; Alzheimer's disease; dementia with Lewy bodies; locus coeruleus; agitation ID ALZHEIMERS-DISEASE; ADRENERGIC-RECEPTORS; SENILE DEMENTIA; NUCLEUS COERULEUS; CERULEUS NEURONS; RAT-BRAIN; ALPHA-2-ADRENOCEPTORS; CORTEX; ADRENOCEPTORS; HIPPOCAMPUS AB Clinical studies suggest involvement of brain noradrenergic systems in the pathophysiology of disruptive agitation in Alzheimer' s disease (AD). This behavioral problem is even more prevalent in dementia with Lewy bodies (DLB). Here we used receptor autoradiography with [I-125]para-iodoclonidine to estimate alpha-2 adrenergic receptor (A2R) density in locus coeruleus (LC) projection areas in postmortem bt ain tissue from age and gender comparable groups of DLB (n = 6). AD (n = 5) and normal (n = 7) subjects. LC neuronal loss was substantial and equivalent in DLB and AD. A2R density was greater in DLB than in normals in the deep layers of the frontal cortex. A2R density was greater in DLB than in AD in hippocampus (CA-1, CA-3 and dentate hilus) and in the granule Layer of the cerebellum Increased A2R binding in DLB is consistent with expression of presynaptic A2R on fibers from surviving LC neurons involved in reinnervation of LC projection areas. These areas develop compensatory noradrenergic hyperinnervation in a rat model of partial LC ablation. It is also consistent with upregulation of post-synaptic A2R in response to loss of LC noradrenergic innervation. Either mechanism could lower the threshold for increased agitation in response to noradrenergic outflow in these dementing disorders. (C) 2001 Elsevier Science Inc. All rights reserved. C1 VA Puget Sound Hlth Care Syst, NW Network Mental Illness Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. LifeSpan BioSci, Seattle, WA 98121 USA. RP Leverenz, JB (reprint author), VA Puget Sound Hlth Care Syst, NW Network Mental Illness Res Educ & Clin, Seattle, WA 98108 USA. FU NIA NIH HHS [AG05136] NR 34 TC 16 Z9 16 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2001 VL 22 IS 4 BP 555 EP 561 DI 10.1016/S0197-4580(01)00221-4 PG 7 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 453JF UT WOS:000169912200005 PM 11445255 ER PT J AU Leung, JC Klein, C Friedman, J Vieregge, P Jacobs, H Doheny, D Kamm, C DeLeon, D Pramstaller, PP Penney, JB Eisengart, M Jankovic, J Gasser, T Bressman, SB Corey, DP Kramer, P Brin, MF Ozelius, LJ Breakefield, XO AF Leung, JC Klein, C Friedman, J Vieregge, P Jacobs, H Doheny, D Kamm, C DeLeon, D Pramstaller, PP Penney, JB Eisengart, M Jankovic, J Gasser, T Bressman, SB Corey, DP Kramer, P Brin, MF Ozelius, LJ Breakefield, XO TI Novel mutation in the TOR1A (DYT1) gene in atypical, early onset dystonia and polymorphisms in dystonia and early onset parkinsonism SO NEUROGENETICS LA English DT Article DE early onset parkinsonism; Myoclonus-dystonia; TORIA (DYT1); Multiphor single-strand conformational polymorphism analysis; 18-bp deletion ID IDIOPATHIC TORSION DYSTONIA; TYROSINE-HYDROXYLASE GENE; DOPA-RESPONSIVE DYSTONIA; MOLECULAR-GENETICS; MYOCLONUS-DYSTONIA; ALPHA-SYNUCLEIN; GAG DELETION; HUMAN BRAIN; DISEASE; FAMILY AB Dystonia is a movement disorder involving sustained muscle contractions and abnormal posturing with a strong hereditary predisposition and without a distinct neuropathology. In this study the TOR1A (DYT1) gene was screened for mutations in cases of early onset dystonia and early onset parkinsonism (EOP), which frequently presents with dystonic symptoms. In a screen of 40 patients, we identified three variations, none of which occurred in EOP patients. Two infrequent intronic single base pair (bp) changes of unknown consequences were found in a dystonia patient and the mother of an EOP patient. An 18-bp deletion (Phe323(-)Tyr328del) in the TOR1A gene was found in a patient with early onset dystonia and myoclonic features. This deletion would remove 6 amino acids close to the carboxy terminus, including a putative phosphorylation site of torsinA. This 18-bp deletion is the first additional mutation, beyond the GAG-deletion (Glu302/303del), to be found in the TOR1A gene, and is associated with a distinct type of early onset dystonia. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. Mt Sinai Hosp, Movement Disorders Ctr, New York, NY 10029 USA. Beth Israel Med Ctr, Dept Neurol, New York, NY 10003 USA. Reg Gen Hosp, Dept Neurol, Bolzano Bozen, Italy. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RI Pramstaller, Peter/C-2357-2008; OI Corey, David/0000-0003-4497-6016 FU NINDS NIH HHS [NS28384, NS37409, NS38142] NR 54 TC 120 Z9 126 U1 0 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1364-6745 J9 NEUROGENETICS JI Neurogenetics PD JUL PY 2001 VL 3 IS 3 BP 133 EP 143 DI 10.1007/s100480100111 PG 11 WC Genetics & Heredity; Clinical Neurology SC Genetics & Heredity; Neurosciences & Neurology GA 457KM UT WOS:000170136200004 PM 11523564 ER PT J AU Gill, JS Oaklander, AL AF Gill, JS Oaklander, AL TI 10 most commonly asked questions about neuropathic pain SO NEUROLOGIST LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1074-7931 J9 NEUROLOGIST JI Neurologist PD JUL PY 2001 VL 7 IS 4 BP 263 EP 269 DI 10.1097/00127893-200107000-00007 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 457LH UT WOS:000170138300007 ER PT J AU Heiland, S Margosian, P Benner, T Reith, W Forsting, M Sartor, K AF Heiland, S Margosian, P Benner, T Reith, W Forsting, M Sartor, K TI Does the 'keyhole' technique improve spatial resolution in MRI perfusion measurements? A study in volunteers SO NEURORADIOLOGY LA English DT Article DE perfusion-weighted magnetic resonance imaging; contrast media; image processing ID CEREBRAL BLOOD-FLOW; MAGNETIC-SUSCEPTIBILITY; COMPUTED-TOMOGRAPHY; CONTRAST AGENTS; K-SPACE; ECHO AB We examined the potential of the 'keyhole' technique to improve spatial resolution in perfusion-weighted MRI on whole-body imagers with standard gradient hardware. We examined 15 healthy volunteers. We acquired a high-resolution image with 256 phase-encoding steps before a bolus-tracking procedure. For the dynamic series we collected only 34 lines in the center of k-space. Data reconstruction was performed by both zero-filling and keyhole methods. The dynamic datasets, concentration-time curves calculated from user-defined regions and maps of the cerebrovascular parameters using both reconstruction methods were compared. Using keyhole series, anatomical structures could easily be defined which were not seen on the original dynamic series because of blurring due to ringing artefacts. Comparison of signal-time curves in large regions yielded no significant difference in signal loss during bolus passage. In the parameter maps truncation artefacts were significantly reduced using keyhole reconstruction. The keyhole method is appropriate for enhancing image quality in perfusion-weighted imaging on standard imagers without sacrificing time resolution or information about transitory susceptibility changes. However, it should be applied carefully, because the spatial resolution of the dynamic signal change and the cerebrovascular parameters is less than that afforded by the spatial resolution of the reconstructed images. C1 Univ Heidelberg, Sch Med, Dept Neuroradiol, D-69120 Heidelberg, Germany. Marconi Med Syst, Highland Heights, OH 44143 USA. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Univ Saarland, Sch Med, Dept Neuroradiol, D-6650 Homburg, Germany. Univ Essen Gesamthsch, Sch Med, Dept Neuroradiol, D-4300 Essen 1, Germany. RP Heiland, S (reprint author), Univ Heidelberg, Sch Med, Dept Neuroradiol, Neuenheimer Feld 400, D-69120 Heidelberg, Germany. RI Forsting, Michael/C-6925-2013 NR 21 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-3940 J9 NEURORADIOLOGY JI Neuroradiology PD JUL PY 2001 VL 43 IS 7 BP 518 EP 524 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 457KW UT WOS:000170137100002 PM 11512578 ER PT J AU Chapman, PH AF Chapman, PH TI The Alexandrian library: Crucible of a renaissance SO NEUROSURGERY LA English DT Article DE Alexandria; Alexandrian library; Egypt; Hellenism; herophilus; scholarship AB AT THE END of the 4th century BC, the Macedonian-Greek armies of Alexander the Great swept across Asia from Egypt to the Indus River, redefining political boundaries within that vast territory at a time when important cultural changes were also taking place in the Creek world. New literary forms were beginning to emerge from the classical literature, which was then the subject of scholarly investigation. There was growing curiosity about the physical world and mathematics. Aristotle and his contemporaries were redefining scholarship at a time when Alexander was redefining the political sphere. These remarkable transformations converged in Alexandria, which became the center of a new intellectual universe. The first Ptolemaic rulers founded two unique institutions-the Alexandrian Library and the Mouseion-and the Library became the crucible within which the Hellenistic renaissance was forged. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurosurg, Cambridge, MA 02138 USA. RP Chapman, PH (reprint author), Massachusetts Gen Hosp, Neurol Serv, 55 Fruit St,GRB 502, Boston, MA 02114 USA. NR 2 TC 7 Z9 7 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUL PY 2001 VL 49 IS 1 BP 1 EP 13 DI 10.1097/00006123-200107000-00001 PG 13 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 443MV UT WOS:000169345700001 PM 11440429 ER PT J AU Barker, FG Amin-Hanjani, S Butler, WE Lyons, S Ojemann, RG Chapman, PH Ogilvy, CS AF Barker, FG Amin-Hanjani, S Butler, WE Lyons, S Ojemann, RG Chapman, PH Ogilvy, CS TI Temporal clustering of hemorrhages from untreated cavernous malformations of the central nervous system SO NEUROSURGERY LA English DT Article DE cavernous malformation; hemorrhage; natural history ID PROTON-BEAM THERAPY; OCCULT VASCULAR MALFORMATIONS; FAILURE TIME DATA; NATURAL-HISTORY; STEREOTACTIC RADIOSURGERY; ARTERIOVENOUS-MALFORMATIONS; KJELLBERGS EXPERIENCE; HARVARD CYCLOTRON; ANGIOMAS; BRAIN AB OBJECTIVE: Hemorrhages from cerebral cavernous malformations (CMs) sometimes seem to occur in closely spaced "clusters" interspersed with long hemorrhage-free intervals. Clustering of hemorrhages could affect retrospective assessments of radiosurgery efficacy in prevention of CM rehemorrhage. However, this empirical observation had not been tested quantitatively. To test whether CM hemorrhages tend to cluster, we reviewed pretreatment rebleeding rates after a first symptomatic hemorrhage in CM patients who later underwent surgery or radiosurgery. METHODS: We performed a retrospective review of 141 patients with CMs who presented with clinically overt hemorrhage, and who subsequently underwent surgery or proton beam radiosurgery during an 18-year period. Statistical models were used to analyze all events per person and identify potential variation in rebleeding risk with time after a previous hemorrhage. RESULTS: Sixty-three of 141 patients experienced a second hemorrhage before treatment; 16 had additional hemorrhages. Five hundred thirty-eight patient years elapsed between first hemorrhages and treatment. The cumulative incidence of a second hemorrhage after the first CM hemorrhage was 14% after 1 year and 56% after 5 years. During the first 2.5 years after a hemorrhage, the monthly rehemorrhage hazard was 2%. The risk then decreased spontaneously to less than 1% per month, which represents a 2.4-fold decline (P < 0.001). Rehemorrhage rates were higher in younger patients (P < 0.01), but not in females or in patients with deep lesions. Shorter intervals between successive hemorrhages did not predict higher subsequent rehemorrhage risk. CONCLUSION: The rehemorrhage rate from untreated CMs is high initially, and it decreases 2 to 3 years after a previous hemorrhage. This hazard pattern generates the observed temporal clustering of hemorrhages from untreated CMs. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Neurol Serv, Boston, MA 02114 USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, Neurol Serv, Cox 315,32 Fruit St, Boston, MA 02114 USA. NR 42 TC 77 Z9 82 U1 1 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 JUL PY 2001 VL 49 IS 1 BP 15 EP 24 DI 10.1097/00006123-200107000-00002 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 443MV UT WOS:000169345700005 PM 11440436 ER PT J AU Lagares, A Putman, CM Ogilvy, CS AF Lagares, A Putman, CM Ogilvy, CS TI Posterior fossa decompression and clot evacuation for fourth ventricle hemorrhage after aneurysmal rupture: Case report SO NEUROSURGERY LA English DT Article DE aneurysmal rupture; fourth ventricle; intraventricular hemorrhage; ventricle dilation ID ACUTE CEREBELLAR HEMORRHAGE; INTRAVENTRICULAR HEMORRHAGE; INFARCTION; PREDICTOR AB OBJECTIVE AND IMPORTANCE: Massive intraventricular hemorrhage due to aneurysmal rupture is associated with a dismal prognosis. An intraventricular clot causing fourth ventricle dilation can cause compression to the brainstem similar to other posterior fossa masses such as cerebellar hemorrhage or infarction. The presence of fourth ventricle dilation carries a very high risk of death within 48 hours. Neither ventricular drainage nor fibrinolytic infusion has been successful in eliminating clots of the fourth ventricle. Posterior fossa decompression and direct evacuation of the clot could have good results in relieving brainstem compression caused by the clot. CLINICAL PRESENTATION: A 45-year-old woman was admitted to our intensive care unit after experiencing an aneurysmal subarachnoid hemorrhage. The neurological examination at admission revealed that she was in Grade V according to the World Federation of Neurological Surgeons grading system, but brainstem reflexes were present. Computed tomographic scanning revealed a massive intraventricular hemorrhage, with fourth ventricle dilation caused by an intraventricular clot. Bilateral external ventricular drains were placed to relieve elevated intracranial pressure. Cerebral angiography revealed a 1-cm basilar tip aneurysm, which was embolized with Guglielmi detachable coils (Boston Scientific, Boston, MA) during the same procedure. INTERVENTION: Given the patient's poor neurological condition, it was decided that brainstem compression should be relieved. A posterior fossa decompressive craniectomy was performed immediately after coil therapy, with direct evacuation of the intraventricular clot. The patient experienced a clear improvement in the level of consciousness and has achieved a good neurological result at early follow-up. CONCLUSION: Dilation of the fourth ventricle by an intraventricular clot is a sign of brainstem compression that can be relieved by posterior fossa decompression and direct clot evacuation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Serv, Boston, MA 02114 USA. RP Ogilvy, CS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Serv, Vincent Burnham 710,55 Fruit St, Boston, MA 02114 USA. RI Lagares, Alfonso/B-2969-2011 OI Lagares, Alfonso/0000-0003-3996-0554 NR 13 TC 14 Z9 14 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 JUL PY 2001 VL 49 IS 1 BP 208 EP 211 DI 10.1097/00006123-200107000-00033 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 443MV UT WOS:000169345700119 PM 11440445 ER PT J AU Manson, JE Martin, KA AF Manson, JE Martin, KA TI Postmenopausal hormone-replacement therapy. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; ESTROGEN REPLACEMENT; COLORECTAL-CANCER; WOMEN; RISK; METAANALYSIS; PROGESTIN; PREVENTION; EVENTS AB Patient 1 is a 52-year-old woman at average risk for breast cancer and osteoporosis who is having menopause-related hot flashes and disturbed sleep. atient 2 is a 58-year-old woman with osteopenia whose mother had breast cancer. atient 3 is a 65-year-old woman with a history of coronary revascularization and documented osteoporosis. Each wants to know whether hormone-replacement therapy is right for her. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med,Dept Med, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit, Boston, MA USA. RP Manson, JE (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med,Dept Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. NR 35 TC 130 Z9 138 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 1 PY 2001 VL 345 IS 1 BP 34 EP U6 DI 10.1056/NEJM200107053450106 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 449QJ UT WOS:000169697600006 PM 11439947 ER PT J AU Greene, MF AF Greene, MF TI Vaginal delivery after cesarean section - Is the risk acceptable? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID UTERINE RUPTURE; LABOR; TRIAL; BIRTH; WOMEN; METAANALYSIS; MISOPROSTOL C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Greene, MF (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 15 TC 58 Z9 59 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 1 PY 2001 VL 345 IS 1 BP 54 EP 55 DI 10.1056/NEJM200107053450108 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 449QJ UT WOS:000169697600008 PM 11439949 ER PT J AU Belza, B Steele, BG Hunziker, J Lakshminaryan, S Holt, L Buchner, DM AF Belza, B Steele, BG Hunziker, J Lakshminaryan, S Holt, L Buchner, DM TI Correlates of physical activity in chronic obstructive pulmonary disease SO NURSING RESEARCH LA English DT Article DE accelerometer; chronic disease; physical activity; pulmonary disease ID FUNCTIONAL STATUS; OLDER ADULTS; TRIAXIAL ACCELEROMETER; LUNG-DISEASE; EXERCISE; REHABILITATION; DYSPNEA; LIFE; FRAMEWORK; VALIDITY AB Background: Physical activity is a key dimension of functional status in people with chronic obstructive pulmonary disease (COPD), and the central target of interventions in this group. Objectives: To determine the relationships among functional performance measured as physical activity, functional capacity, symptom experiences, and health-related quality of life in people with COPD. Method: Cross-sectional, descriptive study. Convenience Sample of 63 outpatients with COPD studied prior to entry into a pulmonary rehabilitation program. Results: Daily physical activity, as measured by an accelerometer, was strongly associated with maximal distance walked during a 6-minute walk test (r = .60, p < .00), level of airway obstruction (r = .37, p < .01), walking self-efficacy (r = .27, p < .05), and physical health status (r =.40, p < .01). Physical activity was not correlated with self-report of functional status. The only predictor of physical activity was the 6-minute walk test. 1 Conclusions: Accelerometer measurement of functional performance was most significantly related to walking abilities. This methodology represents a novel approach to measuring an important dimension of functional status not previously well quantified. C1 Univ Washington, Sch Nursing, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Orthopaed, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Med Specialties Serv, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Primary Care Serv, Seattle, WA USA. Good Samaritan Med Ctr, Puyallup, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Olders Adults, Seattle, WA USA. RP Belza, B (reprint author), Univ Washington, Sch Nursing, Box 357266, Seattle, WA 98195 USA. NR 40 TC 61 Z9 63 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD JUL-AUG PY 2001 VL 50 IS 4 BP 195 EP 202 DI 10.1097/00006199-200107000-00003 PG 8 WC Nursing SC Nursing GA 456UQ UT WOS:000170101000003 PM 11480528 ER PT J AU Garber, J AF Garber, J TI Msk of breast and ovarian cancer in women with strong family histories - The Srivastava/McKinnon/Wood article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Epidemiol & Control, Boston, MA 02115 USA. RP Garber, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Epidemiol & Control, 44 Binney St, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUL PY 2001 VL 15 IS 7 BP 912 EP 913 PG 2 WC Oncology SC Oncology GA 472HR UT WOS:000170978500018 ER PT J AU Fay, AM Pieroth, L Rubin, PA AF Fay, AM Pieroth, L Rubin, PA TI An animal model of lower eyelid spacer grafting with acellular dermis SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID LOWER-LID RETRACTION; RECONSTRUCTION; ALLOGRAFT AB Purpose. Lower eyelid retraction is common in patients with dysthyroid orbitopathy and is seen less commonly in other conditions. Treatment typically requires vertical augmentation of the posterior eyelid lamella with an interpositional graft. Several autologous, homologous, and alloplastic materials have been used. We investigated the gross and microscopic in vivo histology of acellular homologous dermis used as a structural interpositional graft in the lower eyelids of Yucatan minipigs. Methods: This prospective,. experimental study was designed as follows: Surgery was performed on the left lower eyelid of 4 Yucatan minipigs in accordance with the Massachusetts General Hospital Subcommittee on Research Animal Care guidelines. A 4 x 20-mm strip of acellular porcine dermis was prepared and sutured into place between the tarsus and conjunctiva/lower lid retractors. Tissues were harvested at 6 and 12 weeks and were evaluated histologically. Results: Gross examination revealed vertical elongation of the palpebral conjunctival surface. Histologic evaluation was performed with hematoxylin and eosin and Verhoeff elastin stains. Serial sections demonstrated incorporation of grafted dermal ma trix into native tissues without evidence of inflammation. Definitive differentiation between grafted dermis and native dermis was not possible with light microscopy. Portions of the graft appeared to be epithelialized, whereas other histologic regions showed pearly adhesive epithelium. inflammatory infiltrates including lymphocytes and polymorphonuclear leukocytes were not seen. No epithelioid or giant cells were identified in the sections examined. Conclusions: Acellular homologous dermis produced no measurable untoward effects when implanted as an interpositional graft in the lower eyelid of Yucatan minipigs. On the basis of its material characteristics, it appears to be suitable for this purpose: It is readily available, easily stored, easy to manipulate, and produces minimal in inflammation. Long-term persistence, early postoperative histology, and clinical eyelid elevation in humans remain to be evaluated. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Rubin, PA (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 25 TC 8 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHALMIC PLAST REC JI Ophthalmic Plast. Reconstr. Surg. PD JUL PY 2001 VL 17 IS 4 BP 270 EP 275 DI 10.1097/00002341-200107000-00006 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 454XN UT WOS:000169997200006 PM 11476177 ER PT J AU Ocampo, VVD Foster, CS Baltatzis, S AF Ocampo, VVD Foster, CS Baltatzis, S TI Surgical excision of iris nodules in the management of sarcoid uveitis SO OPHTHALMOLOGY LA English DT Article ID OCULAR SARCOIDOSIS; VITRECTOMY; MANIFESTATIONS; INVOLVEMENT; CELLS AB Purpose: To illustrate the role of surgical removal of iris nodules (granulomas) in the management of sarcoid uveitis, Study Design: Two interventional case reports. Methods: The authors describe the clinical course of two 10-year-old males with long-standing granulomatous uveitis refractory to medical antiinflammatory and immunomodulatory therapy. Both patients were seen with iris masses, which were excised and biopsied, with findings of sarcoidosis. Main Outcome Measures: Control of ocular inflammation as evidenced by decrease in inflammatory cells in both anterior and posterior chambers. Results: On excision of the iris masses, the ocular inflammation was controlled in both patients. Conclusions: The authors hypothesize that iris granulomas may not only be products of persistent antigenic stimulation characteristic of sarcoidosis but subsequently become foci of continued cytokine production and ocular inflammation. Total surgical removal of the iris masses may help in the diagnosis and control of sarcoid uveitis refractory to medical management. Ophthalmology 2001;108:1296-1299 (C) 2001 by the American Academy of Ophthalmology. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Immunol & Uveitis Serv, Boston, MA 02114 USA. Gen Hosp Athens, Athens Sch Med, Univ Eye Clin, 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 21 TC 5 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUL PY 2001 VL 108 IS 7 BP 1296 EP 1299 DI 10.1016/S0161-6420(01)00601-7 PG 4 WC Ophthalmology SC Ophthalmology GA 446ZZ UT WOS:000169545200037 PM 11425690 ER PT J AU Lee, DS Anderson, SF Perez, EM Townsend, JC AF Lee, DS Anderson, SF Perez, EM Townsend, JC TI Amelanotic choroidal nevus and melanoma: Cytology, tumor size, and pigmentation as prognostic indicators SO OPTOMETRY AND VISION SCIENCE LA English DT Article DE amelanotic; choroidal melanoma; choroidal nevus; epithelioid cells; metastasis; pigmentation; spindle cells ID POSTERIOR UVEAL MELANOMA; CILIARY BODY MELANOMAS; CO-60 PLAQUE RADIOTHERAPY; TRANSPUPILLARY THERMOTHERAPY; MALIGNANT MELANOMAS; I-125 PLAQUE; RISK-FACTORS; EPIDEMIOLOGIC ASPECTS; OCULAR MELANOMA; CELL-TYPE AB Background. Choroidal nevi are fairly common lesions of the posterior pole that can sometimes transform into melanoma, and it is thought that most choroidal melanomas arise from preexisting nevi. Occasionally, these lesions present as nonpigmented or amelanotic variations of their pigmented counterparts. Recent studies suggest a relationship between tumor pigmentation and risk of growth and metastasis, with a better prognosis for lightly pigmented or amelanotic lesions. Case Reports. A case of an amelanotic choroidal nevus and melanoma are presented. In Case 1, a 26-year-old white female was found to have a large amelanotic nevus in the right eye. After 7 years of periodic observation, the lesion has not changed. In Case 2, a 51-year-old white male was diagnosed with a large amelanotic melanoma in the left eye. Due to extensive involvement of the optic nerve, the patient underwent enucleation. Histological evaluation confirmed the lesion as a mixed-cell type malignant amelanotic melanoma. Conclusion. Management of choroidal nevi generally consists of periodic observation, and the most widely accepted management of choroidal melanoma is observation, radiotherapy, and transpupillary thermotherapy or enucleation. The therapeutic modality of choice for melanoma will vary depending on the size, growth, and location of the lesion. In addition, recent studies suggest an association between heavy tumor pigmentation, tumor size, cell type, and risk of metastasis. Although many variables will influence the final treatment option, pigmentation of the lesion should also be considered. C1 Sepulveda Ambulatory Care Ctr & Nursing Home, Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. RP Anderson, SF (reprint author), Sepulveda Ambulatory Care Ctr & Nursing Home, VA Greater Los Angeles Healthcare Syst, Sepulveda, CA 91343 USA. NR 85 TC 5 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-5488 J9 OPTOMETRY VISION SCI JI Optom. Vis. Sci. PD JUL PY 2001 VL 78 IS 7 BP 483 EP 491 DI 10.1097/00006324-200107000-00010 PG 9 WC Ophthalmology SC Ophthalmology GA 461BG UT WOS:000170344600015 PM 11503936 ER PT J AU Schwartz, SR Yueh, B McDougall, JK Daling, JR Schwartz, SM AF Schwartz, SR Yueh, B McDougall, JK Daling, JR Schwartz, SM TI Human papillomavirus infection and survival in oral squamous cell cancer: A population-based study SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 24-29, 2000 CL WASHINGTON, D.C. SP Amer Acad Otolaryngol Head & Neck Surg ID NECK-CANCER; HEAD; EPIDEMIOLOGY; P53; ASSOCIATION; CARCINOMAS; RADIATION; GENE; RISK; E6 AB Objective: To determine whether human papillomavirus (HPV) type 16 affects survival in oral squamous cell carcinoma. STUDY DESIGN: Two hundred fifty-four patients diagnosed with primary oral cancer were studied for survival in relation to tumor HPV type 16 status. Kaplan-Meier analysis and Cox proportional hazard models were used to assess survival and estimate hazard ratios adjusted for potential confounders. RESULTS: HPV type 16 DNA was detected in 15.1% of tumors. HPV 16 positive patients had significantly reduced all-cause mortality (hazard ratio (HR) estimates = 0.34, 95% CI = 0.14, 0.83) and disease-specific mortality (HR = 0.17, 95% CI = 0.04, 0.76) compared with HPV 16 negative patients after adjustment for age, stage, treatment, smoking, alcohol, education, and comorbid disease. CONCLUSIONS: The presence of HPV type 16 DNA is independently associated with a favorable prognosis in patients with oral squamous cell carcinoma. CLINICAL SIGNIFICANCE: Although HPV genotyping is currently not widely available, it may provide important prognostic information. C1 Univ Washington, Med Ctr, Sch Med, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98104 USA. RP Schwartz, SR (reprint author), Univ Washington, Med Ctr, Sch Med, Dept Otolaryngol Head & Neck Surg, 1959 NE Pacific St,Box 356515, Seattle, WA 98195 USA. OI Yueh, Bevan/0000-0003-1380-1053 FU NCI NIH HHS [CA48996, CN05230]; NIDCD NIH HHS [DC00018] NR 20 TC 168 Z9 171 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JUL PY 2001 VL 125 IS 1 BP 1 EP 9 DI 10.1067/mhn.2001.116979 PG 9 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 453XT UT WOS:000169944000001 PM 11458206 ER PT J AU Hadlock, TA Ferraro, NF Rahbar, R AF Hadlock, TA Ferraro, NF Rahbar, R TI Acute mastoiditis with temporomandibular joint effusion SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article C1 Childrens Hosp, Dept Otolaryngol & Commun Disorders, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Childrens Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Rahbar, R (reprint author), Childrens Hosp, Dept Otolaryngol & Commun Disorders, 300 Longwood Ave, Boston, MA 02115 USA. NR 5 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 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JUL PY 2001 VL 125 IS 1 BP 111 EP 112 DI 10.1067/mhn.2001.115664 PG 2 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 453XT UT WOS:000169944000024 PM 11458229 ER PT J AU Merchany, SN McKenna, MJ Nadol, JB Kristiansen, AG Tropitzsch, A Lindal, S Tranebjaerg, L AF Merchany, SN McKenna, MJ Nadol, JB Kristiansen, AG Tropitzsch, A Lindal, S Tranebjaerg, L TI Temporal bone histopathologic and genetic studies in Mohr-Tranebj rg syndrome (DFN-1) SO OTOLOGY & NEUROTOLOGY LA English DT Article DE sensorineural hearing loss; temporal bone ID FRIEDREICHS ATAXIA; MENTAL DEFICIENCY; DYSTONIA; DISORDERS; BLINDNESS; DEFECTS; DDP AB Objective: To describe the temporal bone histopathologic and genetic abnormalities in a case of Mohr-Tranebjaerg syndrome Background: Mohr-Tranebjaerg syndrome (DFN-I) is an X-linked, recessive, syndromic hearing loss, characterized by postlingual sensorineural hearing loss with onset in childhood, followed in adult life by progressive dystonia, spasticity, dysphagia, and optic atrophy. The syndrome is caused by mutations in the DDP (deafness/dystonia peptide) gene, which are thought to result in mitochondrial dysfunction with subsequent neurodegeneration. The temporal bone pathologic changes in this syndrome have not been reported. Methods: Hearing loss developed in the patient at age 4, blindness at age 48, and dystonia at age 57. Genetic studies on peripheral blood showed a 151delT mutation in his DDP gene. He died at age 66. The right temporal bone was subjected to Light microscopy and polymerase chain reaction-based analysis of the DDP gene sequence. Results: There was near complete loss of spiral ganglion cells with loss of nearly all peripheral and central processes. Only 1,765 spiral ganglion cells remained (8.5% of mean normal far age). The organ of Corti (including hair cells), stria vascularis, and spiral ligament were preserved. There was also a severe loss of Scarpa's ganglion cells with preservation of vestibular hair cells. The population of geniculate and trigeminal ganglion cells appeared normal. Sequence analysis from temporal bone DNA showed the 151delT DDP gene mutation. Conclusion: Sensorineural hearing loss in Mohr-Tranebjaerg syndrome is the result of a postnatal, progressive, severe auditory neuropathy. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Univ Tromso Hosp, Dept Pathol, N-9012 Tromso, Norway. Univ Tromso Hosp, Dept Med Genet, N-9012 Tromso, Norway. RP Merchany, SN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [5 R01 DC03401] NR 25 TC 26 Z9 28 U1 0 U2 2 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 JUL PY 2001 VL 22 IS 4 BP 506 EP 511 DI 10.1097/00129492-200107000-00017 PG 6 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 450KP UT WOS:000169742300018 PM 11449109 ER PT J AU Arita, S Une, S Ohtsuka, S Kawahara, T Kasraie, A Smith, CV Mullen, Y AF Arita, S Une, S Ohtsuka, S Kawahara, T Kasraie, A Smith, CV Mullen, Y TI Increased islet viability by addition of beraprost sodium to collagenase solution SO PANCREAS LA English DT Article DE dog islets; beraprost sodium; islet isolation ID VASCULAR ENDOTHELIAL-CELLS; PANCREATIC-ISLETS; PROSTACYCLIN; INJURY; TRANSPLANTATION; PRESERVATION; MYOCARDIUM; RECOVERY; ILOPROST; ISCHEMIA AB The digestion of pancreatic tissue with collagenase is an essential part of the islet isolation procedure. However, the process exposes islets to various types of harmful factors, including collagenase contaminants, enzymes released from the acinar cells, warm ischemia, and mechanical agitation. Nitrogen oxide production and cytokine release may also contribute to islet cell damage. Protection of islets from such damage would improve the islet yield, survival, and function. Beraprost sodium (BPS) is a prostaglandin I, analogue, is stable in aqueous solution. and has a cytoprotective effect on various types of cells. BPS has been shown to improve the yield and function of cryopreserved and/or cultured islets. These findings prompted us to examine its cytoprotective effect on islets during the islet isolation process. Canine islets were isolated by means of a two-step digestion method and purified on Euro-Ficoll density gradient solutions (the procedure used for human islets). BPS at a concentration of 100 nM was added to the collagenase solution. After purification, the islet yield was 434,561 +/- 35,691 islet number expressed as 150 mum equivalent size (IEQ)/pancreas or 8,799 +/- 345 IEQ/g of pancreas in the BPS group and 349,987 +/- 52,887 IEQ/pancreas or 7,998 +/- 1610 IEQ/g of pancreas in the control group (n = 8, each), The percent viability was 88.5 +/- 0.7% in the BPS group and 82.0 +/- 0.9% in the control group (P < 0.01), Therefore, the recovery of viable islets (calculated by islet number x % viability) was 384,586 +/- 46,804 IEQ/pancreas (7,743 IEQ/g) in the BPS group and 186,989 +/- 43,367 IEQ/pancreas (6,558 IEQ/g) in the control group (P < 0.02). After culture, significantly higher numbers of islets were also recovered in the BPS group than in the control group. The islet insulin content was significantly higher in the BPS group than controls (237.8 +/- 38.5 versus 92.3 +/- 25.6 muU/IEQ P < 0.02), although islets of bath groups responded with high stimulation indices (>6). These results indicate that the addition of BPS to the collagenase solution increases the recovery of viable islets, and improves beta cell function. C1 W Los Angeles Vet Affairs Med Ctr, Islet Transplant Program, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Surg, Islet Transplatn Program, Los Angeles, CA 90024 USA. RP Mullen, Y (reprint author), W Los Angeles Vet Affairs Med Ctr, Islet Transplant Program, 11301 Wilshire Blvd,Bldg 304,Rm E1-206, Los Angeles, CA 90073 USA. NR 31 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD JUL PY 2001 VL 23 IS 1 BP 62 EP 67 DI 10.1097/00006676-200107000-00009 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 446ZF UT WOS:000169543500009 PM 11451149 ER PT J AU Emmons, KM Hammond, SK Fava, JL Velicer, WF Evans, JL Monroe, AD AF Emmons, KM Hammond, SK Fava, JL Velicer, WF Evans, JL Monroe, AD TI A randomized trial to reduce passive smoke exposure in low-income households with young children SO PEDIATRICS LA English DT Article DE passive smoke; nicotine levels; low income families ID ENVIRONMENTAL TOBACCO-SMOKE; PARENTAL SMOKING; INTERVENTION; COTININE; NICOTINE; INFANCY; HEALTH AB Objective. Passive smoke exposure among children is widespread in the United States; estimates suggest that almost 40% of children who are younger than 5 years live with a smoker. Few randomized studies of passive smoke exposure reduction among children have been conducted, and the impact of interventions that have been evaluated has been limited. The objective of this study was to determine whether a motivational intervention for smoking parents of young children will lead to reduced household passive smoke exposure. Methods. Project KISS (Keeping Infants Safe From Smoke), a theory-driven exposure reduction intervention targeting low-income families with young children, was a randomized controlled study in which participants-smoking parents/caregivers (N = 291) who had children who were younger than 3 years and who were recruited through primary care settings-were randomly assigned to either the motivational intervention (MI) or a self-help (SH) comparison condition was used. Follow-up assessments were conducted at 3 and 6 months. The MI condition consisted of a 30- to 45-minute motivational interviewing session at the participant's home with a trained health educator and 4 follow-up telephone counseling calls. Feedback from baseline household air nicotine assessments and assessment of the participant's carbon monoxide level was provided as part of the intervention. Participants in the SH group received a copy of the smoking cessation manual, the passive smoke reduction tip sheet, and the resource guide in the mail. Household nicotine levels were measured by a passive diffusion monitor. Results. The 6-month nicotine levels were significantly lower in MI households. Repeated measures analysis of variance across baseline, 3-month, and 6-month time points showed a significant time-by-treatment interaction, whereby nicotine levels for the MI group decreased significantly and nicotine levels for the SH group increased but were not significantly different from baseline. Conclusions. This study targeted a large sample of racially and ethnically diverse low-income families, in whom both exposure and disease burden is likely to be significant. This is the first study to our knowledge that has been effective in reducing objective measures of passive smoke exposure in households with healthy children. These findings have important implications for pediatric health care providers, who play an important role in working with parents to protect children's health. Providers can help parents work toward reducing household passive smoke exposure using motivational strategies and providing a menu of approaches regardless of whether the parents are ready to quit. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. Univ Rhode Isl, Kingston, RI 02881 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. RP Emmons, KM (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St, Boston, MA 02115 USA. RI Travers, Mark/C-7832-2011 FU NHLBI NIH HHS [HL54351] NR 26 TC 140 Z9 140 U1 0 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 2001 VL 108 IS 1 BP 18 EP 24 DI 10.1542/peds.108.1.18 PG 7 WC Pediatrics SC Pediatrics GA 447KU UT WOS:000169571400023 PM 11433049 ER PT J AU Assil, IQ Shomali, ME Abou-Samra, AB AF Assil, IQ Shomali, ME Abou-Samra, AB TI An oxidation resistant radioligand for corticotropin-releasing factor receptors SO PEPTIDES LA English DT Article DE corticotropin-releasing factor receptors; radioligands; sauvagine; urotensin-I; chemical crosslinking; disuccinimidyl suberate ID ADENYLATE-CYCLASE ACTIVITY; PITUITARY-GLAND; UROTENSIN-I; EXPRESSION CLONING; NERVOUS-SYSTEM; HIGH-AFFINITY; CRF RECEPTOR; RAT-BRAIN; SAUVAGINE; CELLS AB The methionine residues in Tyr-corticotropin-releasing factor (CRF) and Tyr-sauvagine radioligands are subject to oxidation, which renders them biologically inactive. Therefore [Tyr(0). Gln(1). Leu(17)] sauvagine (YQLS), in which the methionine was replaced with leucine was synthesized and labeled with (125)lodine using chloramine-T. Mass spectroscopy revealed that chloramine-T-treatment did not oxidize YQLS. I-125-YQLS bound with high affinity to cells expressing the murine CRF receptor 1 (CRFR1), CRF receptor 2 (CRFR2), and the mouse brain regions known to express both CRF receptors. I-125-YQLS chemically cross-linked to CRFR1. In conclusion, I-125-YQLS is oxidation-resistant, high affinity radioligand that can be chemically cross-linked to the CRF receptors. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Abou-Samra, AB (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. OI Abou-Samra, Abdul/0000-0001-8735-1142 NR 32 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD JUL PY 2001 VL 22 IS 7 BP 1055 EP 1061 DI 10.1016/S0196-9781(01)00424-7 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 451KX UT WOS:000169802200007 PM 11445234 ER PT J AU Pekary, AE Sattin, A AF Pekary, AE Sattin, A TI Regulation of TRH and TRH-related peptides in rat brain by thyroid and steroid hormones SO PEPTIDES LA English DT Article DE rat brain; TRH-like peptides; depression; thyroxine; propylthiouracil; castration; HPLC; radioimmunoassay ID THYROTROPIN-RELEASING-HORMONE; SEIZURES INCREASE LEVELS; CENTRAL-NERVOUS-SYSTEM; INHIBITING FACTOR; PREPRO-TRH; DEPRESSION; BIOSYNTHESIS; HYPOTHALAMUS; GENE; PREPRO-TRH-(160-169) AB To investigate the possibility that TRH (pGlu-His-Pro-NH2) and EEP (pGlu-Glu-Pro-NH2) contribute to the behavioral and mood changes attending hypothyroidism, hyperthyroidism and hypogonadism, we have treated young, adult, male Sprague-Dawley rats (5/group, 250 g bw at time of sacrifice) for one week with either daily ip injections of saline, 5 mug T-4. 3 mg PTU or castration. Immunoreactivity for TRH (TRH-IR), TRH-Gly (pGlu-His-Pro-Gly, a TRH precursor), EEP and Ps4 (prepro-TRH-derived TRH -enhancing peptide) was measured in 8 brain regions by RIA. Castration reduced the Ps4-IR levels in hippocampus by 80%. High pressure liquid chromatography revealed that in many brain regions EEP-IR and TRH-IR consisted of a mixture of TRH and other TRH-like peptides including EEP, Val(2)-TRH, Tyr(2)-TRH, Leu(2)-TRH and Phe(2)-TRH. Transition from the hyperthyroid to the hypothyroid state increased the Val(2)-TRH and Tyr(2)-TRH levels: in the: accumbens by 10-fold and 15-fold, respectively, and the corresponding ratios for the pyriform cortex increased 9-fold and 12-fold, respectively. Hypothyroidism and castration reduced the levels of TRH and the majority of other TRH-like peptides in the entorhinal cortex. This is the first report that thyroid and steroid hormones alter the levels of TRH, prepro-TRH-derived peptides, and a newly discovered array of TRH-like neuropeptides in limbic brain regions. (C) 2001 Elsevier Science Inc. All rights reserved. C1 VA Greater Los Angles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. VA Greater Los Angles Healthcare Syst, Psychiat Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Inst Brain Res, Los Angeles, CA 90073 USA. RP Pekary, AE (reprint author), VA Greater Los Angles Healthcare Syst, Res Serv, Bldg 114,Rm 200,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 63 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD JUL PY 2001 VL 22 IS 7 BP 1161 EP 1173 DI 10.1016/S0196-9781(01)00429-6 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 451KX UT WOS:000169802200020 PM 11445247 ER PT J AU Fried, L Prichard, S Piraino, B Bleyer, A AF Fried, L Prichard, S Piraino, B Bleyer, A TI Peritoneal dialysis case forum SO PERITONEAL DIALYSIS INTERNATIONAL LA English DT Editorial Material ID ADYNAMIC BONE-DISEASE; RENAL-FAILURE; ALUMINUM REMOVAL; OSTEODYSTROPHY; DEFEROXAMINE; PREDIALYSIS; HEMODIALYSIS C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Royal Victoria Hosp, Montreal, PQ H3A 1A1, Canada. RP Prichard, S (reprint author), Royal Victoria Hosp, Div Nephrol, 687 Pine Ave W,M1084, Montreal, PQ H3A 1A1, Canada. NR 35 TC 1 Z9 1 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 JUL-AUG PY 2001 VL 21 IS 4 BP 420 EP 427 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 475LB UT WOS:000171164500020 PM 11587413 ER PT J AU Doukas, AG Soukos, NS Babusis, S Appa, Y Kollias, N AF Doukas, AG Soukos, NS Babusis, S Appa, Y Kollias, N TI Fluorescence excitation spectroscopy for the measurement of epidermal proliferation SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID HUMAN SKIN; IN-VIVO AB Fluorescence excitation spectroscopy was used to assess cellular turnover in human skin by monitoring changes of endogenous fluorescence. Epidermal proliferation was induced with alpha -hydroxy acids. Commercially available glycolic acid creams (8 and 4% wt/wt concentration) and a vehicle cream (placebo) were applied in a randomized double blinded fashion on subjects' forearms, twice daily for 21 days. Excitation spectra were recorded (excitation 250-360 nm, emission 380 nm) at days 0, 1, 3, 7, 10, 11, 14, 17 and 21, The 295 nm excitation band (assigned to tryptophan moieties) was used in this study as a marker for cellular proliferation, To further reduce the day-today variability of the skin fluorescence the intensity of the 295 nm band was normalized to the 334 nm band (assigned to collagen crosslinks), The fluorescence emission intensity from placebo-treated skin remained practically unchanged over the period of the measurements while the fluorescence intensity measured from the glycolic acid-treated skin increased monotonically with treatment. The rate of increase of the excitation intensity with treatment was found to be dose dependent. The epidermal 295 nm band may be used as a quantitative marker to monitor the rate of proliferation of epidermal keratinocytes noninvasively. C1 Harvard Univ, Wellman Labs Photomed, Massachusetts Gen Hosp, Sch Med,Dept Dermatol, Boston, MA 02114 USA. Neutrogena Corp, Los Angeles, CA USA. Johnson & Johnson Consumer Prod Worldwide, Skillman, NJ USA. RP Doukas, AG (reprint author), Harvard Univ, Wellman Labs Photomed, Massachusetts Gen Hosp, Sch Med,Dept Dermatol, WEL224, Boston, MA 02114 USA. NR 19 TC 24 Z9 24 U1 0 U2 2 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUL PY 2001 VL 74 IS 1 BP 96 EP 102 DI 10.1562/0031-8655(2001)074<0096:FESFTM>2.0.CO;2 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 449UJ UT WOS:000169705300014 PM 11460544 ER PT J AU Li, HS Zhang, JY Thompson, BS Deng, XY Ford, ME Wood, PG Stolz, DB Eagon, PK Whitcomb, DC AF Li, HS Zhang, JY Thompson, BS Deng, XY Ford, ME Wood, PG Stolz, DB Eagon, PK Whitcomb, DC TI Rat mitochondrial ATP synthase ATP5G3: cloning and upregulation in pancreas after chronic ethanol feeding SO PHYSIOLOGICAL GENOMICS LA English DT Article DE alcohol ingestion; chronic pancreatitis; adenosine 5 '-triphosphatase; subunit 9; messenger ribonucleic acid differential display ID UPSTREAM STIMULATORY FACTOR-2; CYTOCHROME-C-OXIDASE; EARLY MOUSE EMBRYOS; SUBUNIT-C; OXIDATIVE-PHOSPHORYLATION; PROTON TRANSLOCATION; ALPHA-SUBUNIT; GENE; CONSUMPTION; EXPRESSION AB Individuals with chronic excessive alcohol ingestion are put at the risk of acute and chronic pancreatitis. Underlying molecular mechanisms are unknown. Differential gene expression in the pancreas was profiled using mRNA differential display by comparison between control and ethanol-consuming rats. Male Wistar rats were fed with diets containing 6.7% (vol/vol) ethanol for 4 wk. A cDNA tag that was overexpressed in the pancreas of rats fed ethanol was isolated. A 723-bp cDNA was cloned from a rat pancreatic cDNA library, which encodes a novel rat mitochondrial ATP synthase subunit 9, isoform 3 (ATP5G3), which is homologous to a human ATP5G3 gene. Real-time PCR demonstrated that all three nuclear gene isoforms (ATP5G1, ATP5G2, and ATP5G3) were consistently upregulated in the pancreas of alcohol-consuming rats, parallel with mitochondrial injury. The cellular response to mitochondrial damage and metabolic stress may reflect an adaptive process for mitochondrial repair in pancreatic acinar cells during chronic ethanol ingestion. C1 Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Otolaryngol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Human Genet, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Ctr Genome Sci, Pittsburgh, PA 15213 USA. Vet Affairs Pittsburgh Hlth Care Syst, Pittsburgh, PA 15213 USA. RP Whitcomb, DC (reprint author), Univ Pittsburgh, Med Ctr, Sch Med, Dept Med, Mezzanine Level,C Wing,PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. FU NIAAA NIH HHS [NIAAA-RO1-10885-01] NR 50 TC 41 Z9 43 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD JUL PY 2001 VL 6 IS 2 BP 91 EP 98 PG 8 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 453DY UT WOS:000169902300003 PM 11459924 ER PT J AU Patenaude, AF Last, B AF Patenaude, AF Last, B TI Cancer and children: Where are we coming from? Where are we going? SO PSYCHO-ONCOLOGY LA English DT Editorial Material ID CHILDHOOD-CANCER AB The past four decades have seen remarkable progress in the treatment of childhood cancer and changes in the social environment in which cancer in the family is experienced. Current research in pediatric psycho-oncology focuses on psychosocial consequences of the disease and on differentiating which factors predict problematic versus positive outcomes in adjustment of the child and the family. The papers in this Special Issue reflect much of the recent developments in childhood psycho-oncology as well as the challenges to come. Copyright (C) 2001 John Wiley & Sons, Ltd. C1 Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Emma Childrens Hosp, Acad Med Ctr, Pediat Psychosocial Dept, Amsterdam, Netherlands. RP Patenaude, AF (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 11 TC 17 Z9 17 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JUL-AUG PY 2001 VL 10 IS 4 BP 281 EP 283 DI 10.1002/pon.518 PG 3 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 458TW UT WOS:000170211500001 PM 11462226 ER PT J AU Buckley, TC Kaloupek, DG AF Buckley, TC Kaloupek, DG TI A meta-analytic examination of basal cardiovascular activity in posttraumatic stress disorder SO PSYCHOSOMATIC MEDICINE LA English DT Article DE posttraumatic stress disorder; cardiovascular; heart rate; blood pressure ID VIETNAM COMBAT VETERANS; CORONARY HEART-DISEASE; PSYCHOPHYSIOLOGICAL ASSESSMENT; BLOOD-PRESSURE; PHYSIOLOGICAL-RESPONSES; PLASMA NOREPINEPHRINE; CARDIAC RESPONSE; RELEVANT STIMULI; STARTLING TONES; LOUD TONES AB Objective: The objective of this meta-analytic study was to determine whether individuals with posttraumatic stress disorder (PTSD) have higher levels of basal cardiovascular activity relative to comparable groups of individuals without PTSD. Methods: Meta-analytic data methods were applied to 34 studies that gathered indicators of basal cardiovascular activity including: heart rate (HR), systolic blood pressure, and diastolic blood pressure on subjects diagnosed with PTSD and two types of comparison groups. In total, cardiovascular measures were analyzed for 2670 subjects across all studies. Results: Results indicate that individuals with a current PTSD diagnosis have higher resting HR relative to both trauma-exposed individuals without a PTSD diagnosis and non-trauma-exposed individuals. The results also suggest that PTSD is associated with elevations in blood pressure; however, the effect sizes were smaller in magnitude than those obtained for heart rate. A subset analysis revealed that the effect sizes for comparisons on basal HR were greatest in studies with the most chronic PTSD samples. Conclusion: The meta-analysis supports previous qualitative reviews, finding a positive association between PTSD and basal cardiovascular activity. The discussion addresses possible mechanisms of action and the health-related implications of these findings. C1 Boston VAMC, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Buckley, TC (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B2, 150 S Huntington Ave, Boston, MA 02131 USA. NR 72 TC 143 Z9 146 U1 1 U2 5 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 JUL-AUG PY 2001 VL 63 IS 4 BP 585 EP 594 PG 10 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 457CP UT WOS:000170119800009 PM 11485112 ER PT J AU Fukunishi, I Sugawara, Y Takayama, T Makuuchi, M Kawarasaki, H Surman, OS AF Fukunishi, I Sugawara, Y Takayama, T Makuuchi, M Kawarasaki, H Surman, OS TI Psychiatric disorders before and after living-related transplantation SO PSYCHOSOMATICS LA English DT Article ID ORGAN-TRANSPLANTATION; PSYCHOPHARMACOLOGICAL ISSUES; KIDNEY-TRANSPLANTATION; FAILURE; LIVER; RECIPIENTS AB The authors examined psychiatric disorders among two samples of patients who underwent living-related transplant (LRT) for kidney and liver failure, The postoperative prevalence of psychiatric disorders for adult transplant recipients was highest the first 3 months posttransplant. The incidence of psychiatric disorders in the adult recipients with living-related liver transplant (LRLT) was higher (54%, 22 of 41) than that of adult recipients with living-related kidney transplant (LRKT) (28%, 65 of 234). Twelve (80%) of the 15 adult LRLT recipients with adult child-to-parent donors exhibited paradoxical psychiatric syndrome (PPS). Among the 12 affected recipients, guilt-based psychiatric disorders of various types occurred despite successful operative outcome for both donor and recipient. The higher rate of psychiatric disorders among adult LRLT recipients was associated with the occurrence of PPS among recipients of tin adult-child allograft. These results signal a new challenge for consultation psychiatrists working with transplant patients. C1 Univ Tokyo, Tokyo Metropolitan Org Med Res, Tokyo Inst Psychiat,Fac Med, Dept Pediat Surg,Dept Surg 2, Tokyo 156, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Fukunishi, I (reprint author), Univ Tokyo, Tokyo Metropolitan Org Med Res, Tokyo Inst Psychiat,Fac Med, Dept Pediat Surg,Dept Surg 2, 2-1-8 Kamikitazawa, Tokyo 156, Japan. EM fukunisi@prit.go.jp RI 幕内, 雅敏/A-2140-2012 NR 14 TC 63 Z9 64 U1 3 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JUL-AUG PY 2001 VL 42 IS 4 BP 337 EP 343 DI 10.1176/appi.psy.42.4.337 PG 7 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 456TB UT WOS:000170097400006 PM 11496023 ER PT J AU Gelberg, L Robertson, MJ Leake, B Wenzel, SL Bakhtiar, L Hardie, EA Sadler, N Getzug, T AF Gelberg, L Robertson, MJ Leake, B Wenzel, SL Bakhtiar, L Hardie, EA Sadler, N Getzug, T TI Hepatitis B among homeless and other impoverished US military veterans in residential care in Los Angeles SO PUBLIC HEALTH LA English DT Article DE military veterans; homeless; impoverished; infectious disease; poverty; prevention ID MENTALLY-ILL VETERANS; DRUG-USERS; VIRUS-INFECTION; RISK-FACTORS; PROGRAM; HEALTH; PREVALENCE; ADULTS; HIV AB Findings are presented for a cross-sectional study of serological markers or hepatitis B virus (HBV) infection in an underserved population-impoverished veterans of the US armed forces in a Veterans Administration (VA) residential program in the US. We examine the demographic, background, and risk factors associated with HBV infection ill this high-risk population. This paper presents a secondary analysis of cross-sectional survey and clinical data for 370 male veterans who were residents of a domiciliary care program for homeless veterans in Los Angeles, using chi (2), Fisher's Exact, and logistic regression analysis. About one-third (30.8%) of the sample tested positive for current or past HBV infection (ie, seropositive for either the HBV core antibody or surface antigen). After multivariate analysis, rates of HBV were significantly higher among veterans who were older, non-white, or who had a history of regular heroin use (a proxy measure for injection drug use), drug overdose, or drug detoxification treatment. The rate of current or past HBV infection among veterans in this sample (30.8%) was high compared to an estimated 5% to 8% of the general US population. Also, 3% or the sample were currently infected with HBV. Strategies for intervention include broader screening, immunization, and treatment interventions with this high-risk group. C1 Univ Calif Los Angeles, Dept Family Med, Los Angeles, CA 90095 USA. Inst Publ Hlth, Alcohol Res Grp, Berkeley, CA USA. Sch Nursing, Los Angeles, CA USA. Sch Med, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. Univ Calif Los Angeles, Div Digest Dis, Los Angeles, CA USA. W Los Angeles Vet Adm Domiciliary Program, Los Angeles, CA USA. RP Gelberg, L (reprint author), Univ Calif Los Angeles, Dept Family Med, 50-071 CHS Box 951683, Los Angeles, CA 90095 USA. NR 31 TC 7 Z9 7 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0033-3506 J9 PUBLIC HEALTH JI Public Health PD JUL PY 2001 VL 115 IS 4 BP 286 EP 291 DI 10.1038/sj.ph.1900783 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 465CP UT WOS:000170572300009 PM 11464302 ER PT J AU Harris, JE AF Harris, JE TI Smoke yields of tobacco-specific nitrosamines in relation to FTC tar level and cigarette manufacturer: Analysis of the Massachusetts Benchmark Study SO PUBLIC HEALTH REPORTS LA English DT Article AB Objectives. This research assessed the relationship between the deliveries of carcinogenic tobacco-specific nitrosamines (TSNAs) and the Federal Trade Commission (FTC) "tar" ratings of US commercial cigarettes. Methods. Analysis of covariance (ANCOVA) was used to assess the explanatory power of FTC tar, the particular manufacturer, and other cigarette characteristics to predict the yields of four TSNAs (N'-nitrosonornicotine [NNN], 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone [NNK], N'-nitrosoanatabine [NAT], and N'-nitrosoanabasine [NAB]) in 26 US commercial brands tested in the 1999 Massachusetts Benchmark Study. Results. When FTC tar alone was used to predict TSNA yield, the squared correlation coefficient (RI) was only 38% for NNN, 76% for NNK, 46% for NAT, and 49% for NAB. Inclusion of manufacturer-specific variables significantly (p < 0.001) increased the estimated R-2 for three of the four species of nitrosamine to: 78% for NNN, 88% for NNK, and 81% for NAT. Inclusion of other cigarette characteristics (filter type, paper permeability, tobacco weight, tip dilution) did not reduce the significance of the manufacturer-specific effects. Federal Trade Commission nicotine and carbon monoxide (CO) yields were no better at predicting TSNA levels. Conclusions. FTC ratings for tar, nicotine, and carbon monoxide do not tell the entire story about the comparative yields of toxic agents in marketed cigarette brands. The significant manufacturer-specific effects suggest that proprietary blending and processing of tobacco matter as well. Public, brand-by-brand disclosure of the yields of TSNA and possibly other smoke constituents appears to be warranted. C1 MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA USA. Massachusetts Dept Publ Hlth, Boston, MA 02111 USA. RP Harris, JE (reprint author), MIT, 77 Massachusetts Ave E52-252F, Cambridge, MA 02139 USA. NR 21 TC 18 Z9 19 U1 0 U2 3 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JUL-AUG PY 2001 VL 116 IS 4 BP 336 EP 343 DI 10.1093/phr/116.4.336 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 549UV UT WOS:000175465900010 PM 12037262 ER PT J AU Whittemore, R Chase, SK Mandle, CL AF Whittemore, R Chase, SK Mandle, CL TI Validity in qualitative research SO QUALITATIVE HEALTH RESEARCH LA English DT Article ID NURSING KNOWLEDGE; INQUIRY; DIALOGUE; DEBATE AB Much contemporary dialogue has centered on the difficulty of establishing validity criteria in qualitative research. Developing validity standards in qualitative research is challenging because of the necessity to incorporate rigor and subjectivity as well as creativity into the scientific process. This article explores the extant issues related to the science and art of qualitative research and proposes a synthesis of contemporary viewpoints. A distinction between primary and secondary validity criteria in qualitative research is made with credibility, authenticity, criticality, and integrity identified as primary validity criteria and explicitness, vividness, creativity, thoroughness, congruence, and sensitivity identified as secondary validity criteria. C1 Yale Univ, Sch Nursing, New Haven, CT 06520 USA. Boston Coll, Sch Nursing, Adult Hlth Dept, Chestnut Hill, MA 02167 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Med Symptom Reduct Clin, Boston, MA 02215 USA. Harvard Univ, Sch Med, Mind Body Med Inst, Cambridge, MA 02138 USA. RP Whittemore, R (reprint author), Yale Univ, Sch Nursing, New Haven, CT 06520 USA. RI Chase, Susan/D-3482-2012 NR 55 TC 324 Z9 328 U1 14 U2 58 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-7323 J9 QUAL HEALTH RES JI Qual. Health Res. PD JUL PY 2001 VL 11 IS 4 BP 522 EP 537 DI 10.1177/104973201129119299 PG 16 WC Information Science & Library Science; Social Sciences, Interdisciplinary; Social Sciences, Biomedical SC Information Science & Library Science; Social Sciences - Other Topics; Biomedical Social Sciences GA 445CY UT WOS:000169441600008 PM 11521609 ER PT J AU Mayo-Smith, WW Boland, GW Noto, RB Lee, M AF Mayo-Smith, WW Boland, GW Noto, RB Lee, M TI From the RSNA refresher courses - State-of-the-art adrenal imaging SO RADIOGRAPHICS LA English DT Article DE adrenal gland, biopsy; adrenal gland, CT; adrenal gland, MR; adrenal gland, neoplasms ID CONTRAST-ENHANCED CT; CHEMICAL-SHIFT; HISTOPATHOLOGIC CORRELATION; PRIMARY ALDOSTERONISM; COMPUTED-TOMOGRAPHY; ONCOLOGIC PATIENTS; MASSES; MR; ADENOMAS; GLAND AB The adrenal gland is a common site of disease, and detection of adrenal masses has increased with the expanding use of cross-sectional imaging. Radiology is playing a critical role in not only the detection of adrenal abnormalities but in characterizing them as benign or malignant. The purpose of the article is to illustrate and describe the appropriate radiologic work-up for diseases affecting the adrenal gland. The work-up of a suspected hyperfunctioning adrenal mass (pheochromocytoma and aldosteronoma) should start with appropriate biochemical screening tests followed by thin-collimation computed tomography (CT). If results of CT are not diagnostic, magnetic resonance (MR) and nuclear medicine imaging examinations should be performed. CT has become the study of choice to differentiate a benign adenoma from a metastasis in the oncology patient. If the attenuation of the adrenal gland is over 10 HU at nonenhanced CT, contrast material-enhanced CT should be performed and washout calculated. Over 50% washout of contrast material on a 10-minute delayed CT scan is diagnostic of an adenoma. For adrenal lesions that are indeterminate at CT in the oncology patient, chemical shift MR imaging or adrenal biopsy should be performed. Certain features can be used by the radiologist to establish a definitive diagnosis for most adrenal masses (including carcinoma, infections, and hemorrhage) based on imaging findings alone. C1 Brown Univ, Rhode Isl Hosp, Dept Radiol, Providence, RI 02903 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. Beaumont Hosp, Royal Coll Surg Ireland, Dept Radiol, Dublin 9, Ireland. RP Mayo-Smith, WW (reprint author), Brown Univ, Rhode Isl Hosp, Dept Radiol, 593 Eddy St, Providence, RI 02903 USA. NR 65 TC 160 Z9 174 U1 1 U2 2 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 JUL-AUG PY 2001 VL 21 IS 4 BP 995 EP 1012 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 471KN UT WOS:000170928700023 PM 11452074 ER PT J AU Connolly, SA Connolly, LP Jaramillo, D AF Connolly, SA Connolly, LP Jaramillo, D TI Imaging of sports injuries in children and adolescents SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID OS TRIGONUM SYNDROME; STRESS-FRACTURES; BONE-SCINTIGRAPHY; DISCOID MENISCI; MR; FEATURES; SPONDYLOLYSIS; APPEARANCE; COALITION; DIAGNOSIS AB Imaging plays an important role in the diagnosis and management of sports injuries of childhood and adolescence. This article reviews imaging of injuries that are encountered in the skeletally immature athlete. Use of plain film radiography, skeletal scintigraphy, MR imaging, and CT are discussed and illustrated. C1 Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Connolly, SA (reprint author), Childrens Hosp, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. NR 37 TC 19 Z9 19 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 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JUL PY 2001 VL 39 IS 4 BP 773 EP + DI 10.1016/S0033-8389(05)70310-9 PG 19 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 485NL UT WOS:000171760400010 PM 11549170 ER PT J AU Ecklund, K Jaramillo, D AF Ecklund, K Jaramillo, D TI Imaging of growth disturbance in children SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID PHYSEAL FRACTURES; DISTAL TIBIA; PLATE; ARREST; RABBITS; FIBULA AB Growth disturbance is frequently post-traumatic, but it also occurs because of other physeal, epiphyseal, and metaphyseal insults. This article discusses the mechanisms of growth disorders and their imaging features that depend more on the anatomic site involved than cause. The article also reviews the process of enchondral ossification and the anatomy of the ends of long bones. An understanding of these topics is essential for accurate interpretation of MR images in children with growth disturbance. C1 Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ecklund, K (reprint author), Childrens Hosp, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. NR 22 TC 25 Z9 27 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JUL PY 2001 VL 39 IS 4 BP 823 EP + DI 10.1016/S0033-8389(05)70313-4 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 485NL UT WOS:000171760400013 PM 11549173 ER PT J AU Livraghi, T Goldberg, SN Solbiati, L Meloni, F Ierace, T Gazelle, GS AF Livraghi, T Goldberg, SN Solbiati, L Meloni, F Ierace, T Gazelle, GS TI Percutaneous radio-frequency ablation of liver metastases from breast cancer: Initial experience in 24 patients SO RADIOLOGY LA English DT Article DE breast neoplasms, metastases; liver, CT; liver neoplasms, secondary; radiofrequency (RF) ablation ID RADIOFREQUENCY ABLATION; HEPATOCELLULAR-CARCINOMA; HEPATIC RESECTION; THERMAL ABLATION; SURGICAL MARGIN; ELECTRODE; NEEDLE AB PURPOSE: To evaluate the authors' initial experience in a consecutive series of 24 patients with breast cancer liver metastases treated with radio-frequency (RF) ablation. MATERIALS AND METHODS: Twenty-four consecutive patients with 64 metastases measuring 1.0-6.6 cm in diameter (mean, 1.9 cm) underwent ultrasonography-guided percutaneous RF ablation with 18-gauge, internally cooled electrodes. Treatment was performed with the patient under conscious sedation and analgesia or general anesthesia. A single lesion was treated in 16 patients, and multiple lesions were treated in eight patients. Follow-up with serial computed tomography ranged from 4 to 44 months (mean, 10 months; median, 19 months). RESULTS: Complete necrosis was achieved in 59 (92%) of 64 lesions. Among the 59 lesions, complete necrosis required a single treatment session in 58 lesions (92%) and two treatment sessions in one lesion (2%). In 14 (58%) of 24 patients, new metastases developed during follow-up. Ten (71%) of these 14 patients developed new liver metastases. Currently, 10 (63%) of 16 patients whose lesions were initially confined to the liver are free of disease. One patient died of progressive brain metastases. No major complications occurred. Two minor complications were observed. CONCLUSION: On the basis of preliminary study results, percutaneous RF ablation appears to be a simple, safe, and effective treatment for focal liver metastases in selected patients with breast cancer. C1 Massachusetts Gen Hosp, Dept Radiol, Decis Anal & Technol Assessment Grp, Boston, MA 02114 USA. Osped Civile, Dept Radiol, Vimercate, Italy. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Osped Gen, Dept Radiol, Busto Arsizio, Italy. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Gazelle, GS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Decis Anal & Technol Assessment Grp, Zero Emerson Pl,Suite 2H, Boston, MA 02114 USA. OI meloni, maria franca/0000-0001-7485-7400; Solbiati, Luigi/0000-0002-3109-1449 NR 19 TC 108 Z9 112 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 2001 VL 220 IS 1 BP 145 EP 149 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 445QH UT WOS:000169468400023 PM 11425987 ER PT J AU Marcou, Y D'Andrea, A Jeggo, PA Plowman, PN AF Marcou, Y D'Andrea, A Jeggo, PA Plowman, PN TI Normal cellular radiosensitivity in an adult Fanconi anaemia patient with marked clinical radiosensitivity SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Fanconi anaemia; severe acute reaction; cellular radiosensitivity ID NORMAL TISSUE-DAMAGE; IN-VITRO; CHROMOSOMAL RADIOSENSITIVITY; BREAST-CANCER; ANEMIA; RADIOTHERAPY; FIBROBLASTS; DIAGNOSIS; RADIATION; THERAPY AB Background: Fanconi anaemia is a rare disease associated with cellular sensitivity to chemicals (e.g. mitomycin C and diepoxybutane); variable but mild cellular radiosensitivity has also been reported. Materials and methods: A 32-year-old patient with Fanconi anaemia and tonsillar carcinoma, treated by radiotherapy, was found to exhibit profound clinical radiosensitivity. Confluent, ulcerating oropharyngeal mucositis developed after a conventionally fractionated dose of 34 Gy and healing was incomplete by 2 months after cessation of therapy. Results: Cellular radiosensitivity assays and RPLD studies from this patient did not suggest any major detectable radiosensitivity. Conclusion: There is a discrepancy between the observed clinical radiosensitivity and the usual 'predictive' radiosensitivity assays in this patient with Fanconi anaemia. (C) 2001 Elsevier Science ireland Ltd. All rights reserved. C1 St Bartholomews Hosp, Dept Clin Oncol, London EC1A 7BE, England. Harvard Univ, Childrens Hosp, Sch Med, Dana Farber Canc Inst,Dept Pediat Oncol, Boston, MA 02115 USA. Univ Sussex, MRC, Cell Mutat Unit, Brighton BN1, E Sussex, England. RP Plowman, PN (reprint author), St Bartholomews Hosp, Dept Clin Oncol, London EC1A 7BE, England. NR 22 TC 57 Z9 57 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD JUL PY 2001 VL 60 IS 1 BP 75 EP 79 DI 10.1016/S0167-8140(01)00370-X PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 451TD UT WOS:000169816600010 PM 11410307 ER PT J AU Arbuckle, MR James, JA Kohlhase, KF Rubertone, MV Dennis, GJ Harley, JB AF Arbuckle, MR James, JA Kohlhase, KF Rubertone, MV Dennis, GJ Harley, JB TI Development of anti-dsDNA autoantibodies prior to clinical diagnosis of systemic lupus erythematosus SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID DNA ANTIBODIES; COMPLEMENT PROFILES; REVISED CRITERIA; DISEASE-ACTIVITY; CLASSIFICATION; SLE AB Anti-double stranded (dsDNA) antibodies are of considerable diagnostic value and are thought to be involved in the pathogenesis of systemic lupus erythematosus (SLE). Fluctuations in anti-dsDNA antibody levels are also used as markers for disease activity and exacerbations. In this study we sought to evaluate the anti-dsDNA antibody level in serum samples collected before the onset of SLE diagnosis. A total of 130 SLE patients were identified with stored serum samples available prior to diagnosis within the US Department of Defense serum repository. All 633 sera available from these patients were screened for anti-dsDNA antibodies using an enzyme linked immunosorbant assay (ELISA). Within this cohort 55% of cases had detectable anti-dsDNA antibodies prior to SLE diagnosis. The onset of anti-dsDNA antibodies ranged from 9.3 years before to within the same month as diagnosis (with a mean onset 2.7 years before diagnosis). In order to assess for fluctuations in anti-dsDNA levels relative to diagnosis, cases were selected with at least two positive samples, one within 6 months and a second greater than 6 months prior to diagnosis (n = 26). Seven of these cases also had samples available shortly after diagnosis (less than or equal to 6 months) for comparison. Fifty eight percent of the 26 cases developed a significant rise in anti-dsDNA antibody levels within 6 months of diagnosis. A significant decline in anti-dsDNA levels ensued after diagnosis (and following treatment with corticosteroids) in all seven cases with samples available. Patients with a significant rise in anti-dsDNA antibodies at diagnosis were more likely to have renal disease than those who did not (66.7% compared to 27.3%, chi (2) =3.94, P<0.05). These data suggest that anti-dsDNA antibodies are present in SLE patient sera much earlier than previously suspected. In addition, the data are consistent with increases in anti-dsDNA levels contributing to the onset of clinical illness in some patients with SLE. C1 Oklahoma Med Res Fdn, Arthrit & Immunol Program, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK 73104 USA. Henry M Jackson Fdn Advancement Mil Med, Rockville, MD 20852 USA. USA, Ctr Hlth Promot & Prevent Med, Army Med Surveillance Act, Washington, DC 20307 USA. Walter Reed Army Med Ctr, Dept Rheumatol, Washington, DC 20307 USA. US Dept Vet Affairs, Oklahoma City, OK 73104 USA. RP James, JA (reprint author), Oklahoma Med Res Fdn, Arthrit & Immunol Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. FU NIAID NIH HHS [AI24717, AI31584]; NIAMS NIH HHS [AR42460, AR01981, AR42474, AR45084, AR45231] NR 25 TC 69 Z9 77 U1 1 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD JUL-AUG PY 2001 VL 54 IS 1-2 BP 211 EP 219 DI 10.1046/j.1365-3083.2001.00959.x PG 9 WC Immunology SC Immunology GA 452ZT UT WOS:000169890300029 PM 11439169 ER PT J AU Weiss, AP Heckers, S AF Weiss, AP Heckers, S TI Neuroimaging of declarative memory in schizophrenia SO SCANDINAVIAN JOURNAL OF PSYCHOLOGY LA English DT Review DE schizophrenia; memory; neuroimaging ID CEREBRAL-BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; MONOZYGOTIC TWINS DISCORDANT; TEMPORAL-LOBE ABNORMALITIES; FIRST-EPISODE SCHIZOPHRENIA; VERBAL-LEARNING TASK; COGNITIVE DYSMETRIA; PREFRONTAL CORTEX; WORKING-MEMORY; NEUROPSYCHOLOGICAL PERFORMANCE AB The past three decades have seen tremendous growth in our understanding of the cerebral underpinnings of schizophrenia, including the neural correlates of the cognitive impairment seen in this syndrome. In this article we review the role that structural and functional neuroimaging has played in elucidating the cerebral basis for the declarative memory deficits associated with schizophrenia. Memory impairment in schizophrenia appears to involve abnormal connectivity between the prefrontal cortex and three regions important in normal learning and memory: the hippocampus, thalamus, and cerebellum. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Weiss, AP (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Wang ACC 812, Boston, MA 02114 USA. EM aweiss@partners.org RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 NR 109 TC 82 Z9 83 U1 2 U2 4 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0036-5564 J9 SCAND J PSYCHOL JI Scand. J. Psychol. PD JUL PY 2001 VL 42 IS 3 BP 239 EP 250 DI 10.1111/1467-9450.00234 PG 12 WC Psychology, Multidisciplinary SC Psychology GA 454JT UT WOS:000169970000008 PM 11501738 ER PT J AU Shinaberger, JH AF Shinaberger, JH TI Quantification of dialysis: Historical perspective SO SEMINARS IN DIALYSIS LA English DT Article ID HIGH-EFFICIENCY HEMODIALYSIS; KINETIC-MODELS; MASS-TRANSFER; UREA REMOVAL; SINGLE-POOL; KT/V; BLOOD; HEMODIAFILTRATION; RECIRCULATION; CLEARANCE AB This article is an attempt to provide a historical perspective to the ongoing attempts to quantify dialysis therapy. It is immediately apparent that motivated chemists, physicists, engineers, mathematicians, and other scientists from all over the world have greatly aided this effort. Dialysis, described by Graham in 1861, was furthered by Abel et al. and Hass before World War I. Willem Kolff attempted to evaluate mass removed and Alwall used a solute extraction ratio. However, the concept of "clearance" and "dialysance" awaited the studies of Wolf et al. in 1951. This classic work describes most of the information concerning actual dialyzer performance known today. A. S. Michaels provided the equations leading to the KoA/Ro/A concept in 1966 which only very recently required updating. The interaction of diffusion and convection is complex and was studied by Villarroel in 1977 and recently by Jaffrin. L. W. Henderson studied and described hemofiltration and hemodiafiltration from 1967-1975. Efforts to relate the patient's outcome to the dialyzer's performance have been difficult and ongoing since 1971; the Babb-Scribner Square meter-hour (which included the expression "Kt/ the Kopp et al. Liter-Kilogram concept; 1972 Kjellstrand clearance * time/kg or Liter. A NIH sponsored conference on the Adequacy of Dialysis in Monterey, California in March of 1974 was focused somewhat on the "middle molecule" theory of uremic toxicity, but contained a presentation by Sargent and Gotch on the possibilities of urea kinetic modeling. They developed iterative computer programs to obtain the best estimates of the required variables. At about this same time, Teschan, Ginn et al. published a series of neurofunctional tests and EEG power spectra analyses which most convincingly showed that dialysis two times a week was inadequate, and that dialysis delivered three times a week at urea clearance equal to body water volume was required to normalize these abnormalities: a major contribution! The National Cooperative Dialysis Study reported in Kidney International, 1983, was either misunderstood or ignored by most practitioners. The mechanistic analysis of the study by Gotch and Sargent appeared in 1985 and indicated that at adequate protein intake a Kt/V >0.8 yielded better patient survival. In 1982 Malchesky reported the Direct Dialysis Quantification (DDQ) based on calculations from the total mass removed in the dialysate. Although cumbersome, it avoids many errors including the effect of hematocrit and other factors on dialyzer clearance and many consider it to be "the gold standard." The 1990s were characterized by the development of many simple logarithmic equations to estimate Kt/V and eKt/V suitable for spreadsheets which could be used for CQI by individual units. These are primarily by J. T. Daugirdas and coworkers, Smye and Tattersall. In 1991 the Urea Reduction Ratio (URR) was introduced by Lowrie, who in 1999 suggested that Kt and V (as indicator of lean body mass) were independent predictors of survival, Peritoneal dialysis: Although performed before and immediately after World War II, almost all of the basic quantification mechanistics and data are found in the publications of S. T. Boen (1964). Now quantifiers, the Mass Transport Area Coefficient (MTAC) or Pyle-Popovich model, the Henderson-Nolph, and Garred models, were compared by Waniewski. Gotch announced a PD modeling program which suggested that a weekly PKt/V at 2.1 was needed to supply the same urea removal as a Kt/V of 3.6, but warned that both were sensitive to decreased time. C1 W Los Angeles DVA Med Ctr, Med Serv, Nephrol Sect, Los Angeles, CA 90074 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. RP Shinaberger, JH (reprint author), W Los Angeles DVA Med Ctr, Med Serv, Nephrol Sect, W 111L,Wadsworth Bldg 500,11301 Wilshire Blvd, Los Angeles, CA 90074 USA. NR 82 TC 12 Z9 13 U1 0 U2 3 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD JUL-AUG PY 2001 VL 14 IS 4 BP 238 EP 245 DI 10.1046/j.1525-139X.2001.00063.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 459HK UT WOS:000170244800002 PM 11489196 ER PT J AU Stone, RM AF Stone, RM TI Postremission therapy in adults with acute myeloid leukemia SO SEMINARS IN HEMATOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; HIGH-DOSE CYTARABINE; ACUTE MYELOGENOUS LEUKEMIA; STEM-CELL TRANSPLANTATION; ACUTE MYELOBLASTIC-LEUKEMIA; GRAFT-VERSUS-LEUKEMIA; FIRST REMISSION; INTENSIVE CHEMOTHERAPY; CYTOSINE-ARABINOSIDE; PHASE-I C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Stone, RM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 43 TC 11 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JUL PY 2001 VL 38 IS 3 SU 6 BP 17 EP 23 DI 10.1016/S0037-1963(01)90152-0 PG 7 WC Hematology SC Hematology GA 460AX UT WOS:000170284600004 PM 11474493 ER PT J AU Callander, NS Roodman, GD AF Callander, NS Roodman, GD TI Myeloma bone disease SO SEMINARS IN HEMATOLOGY LA English DT Article ID HORMONE-RELATED PROTEIN; ADVANCED MULTIPLE-MYELOMA; GALLIUM NITRATE; GROWTH-FACTOR; IN-VIVO; PERCUTANEOUS VERTEBROPLASTY; BIOCHEMICAL MARKERS; OSTEOLYTIC LESIONS; PROGNOSTIC VALUE; SKELETAL EVENTS C1 Audie L Murphy Mem Vet Adm Med Ctr, Res Serv 151, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med Hematol, San Antonio, TX 78284 USA. RP Roodman, GD (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, Res Serv 151, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NCI NIH HHS [CA40035] NR 98 TC 96 Z9 97 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JUL PY 2001 VL 38 IS 3 BP 276 EP 285 DI 10.1053/shem.2001.26007 PG 10 WC Hematology SC Hematology GA 458TG UT WOS:000170210200011 PM 11486316 ER PT J AU Anderson, KC AF Anderson, KC TI Targeted therapy for multiple myeloma SO SEMINARS IN HEMATOLOGY LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; BONE-MARROW TRANSPLANTATION; NF-KAPPA-B; DONOR LYMPHOCYTE INFUSION; ENDOTHELIAL GROWTH-FACTOR; PROTEIN-KINASE CASCADE; VERSUS-HOST DISEASE; CELL-LINES; INDUCED APOPTOSIS; STROMAL CELLS C1 Dana Farber Canc Inst, Dept Adult Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Jerome Lipper Multiple Myeloma Ctr, Room 557,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA50947, CA78378] NR 100 TC 35 Z9 35 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JUL PY 2001 VL 38 IS 3 BP 286 EP 294 DI 10.1053/shem.2001.26010 PG 9 WC Hematology SC Hematology GA 458TG UT WOS:000170210200012 PM 11486317 ER PT J AU Daniels, GH AF Daniels, GH TI Atypical subacute thyroiditis: Preliminary observations SO THYROID LA English DT Article ID TRANSIENT THYROTOXICOSIS; AUTOIMMUNE-THYROIDITIS; HIGH PREVALENCE; HYPOTHYROIDISM; DYSFUNCTION; AMIODARONE; THERAPY; HYPERTHYROIDISM AB Nine patients with painless or minimally painful subacute thyroiditis were seen between late June and October 2000. Six had a history of antecedant viral symptoms. Thyroid peroxidase antibodies were negative in eight patients tested; none had a family history of autoimmune thyroid disease. It is possible that these patients represent examples of postviral painless subacute thyroiditis (atypical subacute thyroiditis). In order to establish the nature of the syndrome, cytological examination, HLA typing, and long-term follow-up are necessary. C1 Massachusetts Gen Hosp, Thyroid Unit ACC 730, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Daniels, GH (reprint author), Massachusetts Gen Hosp, Thyroid Unit ACC 730, Boston, MA 02114 USA. NR 47 TC 16 Z9 22 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 JUL PY 2001 VL 11 IS 7 BP 691 EP 695 DI 10.1089/105072501750362772 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 455MT UT WOS:000170031200012 PM 11484899 ER PT J AU Rajsbaum, R Fici, D Fraser, PA Flores-Villanueva, PO Awdeh, ZL AF Rajsbaum, R Fici, D Fraser, PA Flores-Villanueva, PO Awdeh, ZL TI Polymorphism of the human retinoid X receptor beta and linkage disequilibrium with HLA-DPB1 SO TISSUE ANTIGENS LA English DT Article DE retinoic acid receptor; RXRB; polymorphism; linkage disequilibrium; PCR-RFLP; HLA; HLA-DPB1 ID MAJOR HISTOCOMPATIBILITY COMPLEX; DEPENDENT DIABETES-MELLITUS; NUCLEAR RECEPTORS; HLA-DP; GENES; SUSCEPTIBILITY; ASSOCIATIONS; POPULATION; ARTHRITIS; RXRB AB The human retinoid X receptor beta (RXRB) gene is localized in the major histocompatibility complex (MHC) region between DPB1 and RING2. The RXRB gene sequence reported by different investigators suggests that the gene may be polymorphic. In this study, we confirmed one polymorphism, by sequencing genomic DNA from four Caucasian individuals. We also developed a restriction fragment length polymorphism. (RFLP) analysis to detect this specific polymorphism. Linkage analysis studies between RXRB alleles and a number of HLA markers showed significant linkage disequilibrium. between RXRB*T and BLA-DPB1*0401. C1 Ctr Blood Res, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Awdeh, ZL (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Rajsbaum, Ricardo/F-2046-2014 FU NHLBI NIH HHS [HL-29583, HL29883-13]; NIAID NIH HHS [AI42374-02]; NIAMS NIH HHS [AR-43523-03] NR 26 TC 7 Z9 7 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD JUL PY 2001 VL 58 IS 1 BP 24 EP 29 DI 10.1034/j.1399-0039.2001.580104.x PG 6 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 485AL UT WOS:000171729900004 PM 11580852 ER PT J AU Vamvakas, EC Carven, JH AF Vamvakas, EC Carven, JH TI Allogeneic blood transfusion and postoperative duration of mechanical ventilation SO TRANSFUSION LA English DT Article ID MULTIPLE ORGAN FAILURE; BYPASS GRAFT-SURGERY; INDEPENDENT RISK FACTOR; ACUTE LUNG INJURY; LEUKOCYTE DEPLETION; CARDIAC-SURGERY; BACTERIAL-INFECTION; PULMONARY-FUNCTION; THALASSEMIA MAJOR; OXYGEN DELIVERY AB BACKGROUND: In patients having open heart surgery, allogeneic blood transfusion (ABT) may be related to an enhanced inflammatory response and impaired pulmonary function, resulting in the need for prolonged mechanical ventilation. STUDY DESIGN AND METHODS: The records of 416 consecutive patients undergoing coronary artery bypass graft surgery at Massachusetts General Hospital were reviewed. Possible predictors and the number of days of postoperative ventilation, as well as the number of RBC units transfused and the length of their storage, were recorded. The association between mechanical ventilation after the day of operation and the number of RBC units transfused was calculated by logistic regression analysis. RESULTS: The number of RBC units transfused, but not the length of their storage, differed (p <0.0001) among patients ventilated for 0, 1, 2, 3, or 4 or more days after the day of operation. Patients taken off ventilation on the day of operation received (mean +/- SE) 2.01 +/- 0.14 RBC units; patients kept on ventilation for 4 or more days received 9.45 +/- 1.83 units. After adjusting for the effects of 18 confounding factors, the number of RBC units transfused was not a significant predictor of ventilation past the day of operation. There was, however, a trend suggesting that the likelihood of such ventilation might increase by 26 percent per RBC unit transfused (p = 0.0628). CONCLUSIONS: Future studies of the outcomes of ABT should examine further the possibility of a relationship between the number of transfused RBCs and the likelihood of postoperative ventilation after the day of operation. C1 NYU, Sch Med, Dept Pathol, New York, NY USA. Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. RP Vamvakas, EC (reprint author), NYU, Med Ctr, Blood Bank & Transfus Serv, RRG-17,400 E 34th St, New York, NY 10016 USA. NR 39 TC 8 Z9 8 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 JUL PY 2001 VL 41 IS 7 BP 885 EP 892 DI 10.1046/j.1537-2995.2001.41070885.x PG 8 WC Hematology SC Hematology GA 451PH UT WOS:000169810100006 PM 11452156 ER PT J AU Gardella, TJ Juppner, H AF Gardella, TJ Juppner, H TI Molecular properties of the PTH/PTHrP receptor SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID HUMAN PARATHYROID-HORMONE; PROTEIN-COUPLED RECEPTOR; PTH-RELATED PEPTIDE; FIRST EXTRACELLULAR LOOP; N-TERMINAL REGION; TUBEROINFUNDIBULAR PEPTIDE; 39 RESIDUES; BLOMSTRAND-CHONDRODYSPLASIA; TRANSMEMBRANE RESIDUES; INACTIVATING MUTATION AB The receptor for parathyroid hormone (PTH) and PTH-related protein (PTHrP) is a G protein-coupled receptor (GPCR) that plays a key role in controlling blood Ca2+ concentration and endochondral bone formation. This review focuses on the molecular mechanisms by which the receptor recognizes the PTH and PTHrP peptide ligands and transmits their signal across the cell membrane. The available data suggest that there are two principal components to the ligand-receptor interaction. First, a docking interaction between the C-terminal portion of PTH(1-34) and the N-terminal extracellular domain of the receptor; and second, a weaker interaction between the N-terminal portion of the ligand and the juxtamembrane region of the receptor, which induces signal transduction. A full understanding of these processes could lead to new PTH/PTHrP receptor ligands that are effective in controlling diseases of bone and mineral metabolism, such as osteoporosis. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Gardella, TJ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 99 TC 96 Z9 99 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD JUL PY 2001 VL 12 IS 5 BP 210 EP 217 DI 10.1016/S1043-2760(01)00409-X PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 445ME UT WOS:000169460600006 PM 11397646 ER PT J AU D'Amico, AV AF D'Amico, AV TI Combined modality staging for clinically localized adenocarcinoma of the prostate as the basis for patient selection for randomized trials of neoadjuvant chemotherapy SO UROLOGIC ONCOLOGY LA English DT Article ID RADICAL PROSTATECTOMY; CANCER; SURVIVAL C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASBI,L2, Boston, MA 02115 USA. NR 6 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1078-1439 J9 UROL ONCOL JI Urol. Oncol. PD JUL-AUG PY 2001 VL 6 IS 4 BP 171 EP 172 DI 10.1016/S1078-1439(01)00126-0 PG 2 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 447ZF UT WOS:000169601800007 ER PT J AU Ohman, T King, SL Krithivas, A Cunningham, J Dickeson, SK Santoro, SA Bergelson, JM AF Ohman, T King, SL Krithivas, A Cunningham, J Dickeson, SK Santoro, SA Bergelson, JM TI Echoviruses 1 and 8 are closely related genetically, and bind to similar determinants within the VLA-2 I domain SO VIRUS RESEARCH LA English DT Article DE echoviruses; VLA-2; human picornavirus ID ACCELERATING FACTOR CD55; INTEGRIN VLA-2; RECEPTOR; IDENTIFICATION; SEQUENCE; SEROTYPE; VIRUS AB Echoviruses (EV) 1 and 8 were originally considered to be distinct serotypes, but more recently have been considered strains of the same virus. In experiments with chimeric recombinant fusion proteins, both viruses bound to the I domain of the integrin VLA-2, and both required the same receptor residues for attachment. A full-length, infectious cDNA clone encoding EV1 was obtained; its nucleotide sequence was determined, as were the sequences encoding the EV8 capsid. EV1 and 8 show 94% amino acid identity within the capsid region and are more similar to each other than to any other human picornavirus. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Childrens Hosp Philadelphia, Div Immunol & Infect Dis, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Infect Dis Lab, Boston, MA 02115 USA. Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. RP Bergelson, JM (reprint author), Childrens Hosp Philadelphia, Div Immunol & Infect Dis, 3516 Civ Ctr Blvd,1202 Abramson, Philadelphia, PA 19104 USA. FU PHS HHS [A135667] NR 21 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD JUL PY 2001 VL 76 IS 1 BP 1 EP 8 DI 10.1016/S0168-1702(01)00226-X PG 8 WC Virology SC Virology GA 442BT UT WOS:000169265900001 PM 11376841 ER PT J AU Washington, DL AF Washington, DL TI Charting the path from lack of insurance to poor health outcomes SO WESTERN JOURNAL OF MEDICINE LA English DT Editorial Material ID CARE; QUALITY C1 Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. RP Washington, DL (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, 11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA. NR 9 TC 1 Z9 1 U1 1 U2 1 PU B M J PUBLISHING INC PI SAN FRANCISCO PA 221 MAIN ST, PO BOX 7690, SAN FRANCISCO, CA 94120-7690 USA SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD JUL PY 2001 VL 175 IS 1 BP 23 EP 23 DI 10.1136/ewjm.175.1.23 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 448NG UT WOS:000169632500014 PM 11431395 ER PT J AU Carlson, KJ AF Carlson, KJ TI Women's primary health care and the search for quality SO WOMENS HEALTH ISSUES LA English DT Article; Proceedings Paper CT Margaret E Mahoney Annual Symposium CY SEP 21-22, 2000 CL WASHINGTON, D.C. ID BREAST C1 Massachusetts Gen Hosp, Womens Hlth Associates, Boston, MA 02114 USA. RP Carlson, KJ (reprint author), Massachusetts Gen Hosp, Womens Hlth Associates, Boston, MA 02114 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2001 VL 11 IS 4 BP 300 EP 305 DI 10.1016/S1049-3867(01)00097-4 PG 6 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 459KT UT WOS:000170250100005 PM 11479076 ER PT J AU Mort, EA AF Mort, EA TI Patient-centered decision making: Empowering women to make informed choices - Experience in the United States SO WOMENS HEALTH ISSUES LA English DT Article; Proceedings Paper CT Margaret E Mahoney Annual Symposium CY SEP 21-22, 2000 CL WASHINGTON, D.C. ID HORMONE REPLACEMENT THERAPY; POSTMENOPAUSAL WOMEN; BREAST-CANCER; ESTROGEN; TRIAL C1 Massachusetts Gen Hosp, Decis Support Unit & Operat Improvement, Boston, MA 02114 USA. RP Mort, EA (reprint author), Massachusetts Gen Hosp, Decis Support Unit & Operat Improvement, Boston, MA 02114 USA. NR 23 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2001 VL 11 IS 4 BP 319 EP 325 DI 10.1016/S1049-3867(01)00119-0 PG 7 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 459KT UT WOS:000170250100011 PM 11479082 ER PT J AU Schneyer, A Tortoriello, D Sidis, Y Keutmann, H Matsuzaki, T Holmes, W AF Schneyer, A Tortoriello, D Sidis, Y Keutmann, H Matsuzaki, T Holmes, W TI Follistatin-related protein (FSRP): a new member of the follistatin gene family SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT International Workshop on Inhibins Activins and Follistatins CY OCT 26-28, 2000 CL MELBOURNE, AUSTRALIA DE follistatin; follistatin related protein; activin; reproduction; binding protein ID ACTIVIN-BINDING PROTEIN; FOLLICULAR-FLUID; HUMAN SERUM; INHIBIN; MICE; DEFECTS AB The identification and characterization of follistatin related protein (FSRP) suggests that the follistatin (FS) gene family may actually contain two sub-families. The first includes FS and FSRP by virtue of their high degree of structural homology and comparable activin-binding activity. while the second sub-family contains extracellular matrix proteins that possess one or more 10-cysteine FS domains, but do not bind activin or related TGF-beta family members. Characterization of FSRP indicates that it binds activin with similar affinity and selectivity as FS, but does not bind heparin. Furthermore, although FSRP inhibits activin-mediated gene transcription in heterologous assays, FSRP is much less active than FS in the rat pituitary bioassay. When overexpressed in transgenic mice. FSRP may lead to interruption of follicular development and fertility in females but appears to have only a modest effect on males. These results suggest that FSRP is a structural, but not necessarily a functional homologue of FS. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Millennium Pharmaceut Inc, Dept Mol Biol, Cambridge, MA USA. RP Schneyer, A (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX-519, Boston, MA 02114 USA. FU NICHD NIH HHS [U54HD29164]; NIDDK NIH HHS [R01DK53828, R01DK55838] NR 27 TC 50 Z9 53 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JUN 30 PY 2001 VL 180 IS 1-2 BP 33 EP 38 DI 10.1016/S0303-7207(01)00501-9 PG 6 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 457AU UT WOS:000170115600005 PM 11451569 ER PT J AU Sheng, M Lee, SH AF Sheng, M Lee, SH TI AMPA receptor trafficking and the control of synaptic transmission SO CELL LA English DT Review ID LONG-TERM POTENTIATION; PLASTICITY; SYNAPSES; MEMBRANE; LTP C1 Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sheng, M (reprint author), MIT, Ctr Learning & Memory, 77 Massachusetts Ave, Cambridge, MA 02139 USA. NR 20 TC 136 Z9 139 U1 2 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUN 29 PY 2001 VL 105 IS 7 BP 825 EP 828 DI 10.1016/S0092-8674(01)00406-8 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 449BK UT WOS:000169664300003 PM 11439178 ER PT J AU Sun, ZYJ Kim, HS Wagner, G Reinherz, EL AF Sun, ZYJ Kim, HS Wagner, G Reinherz, EL TI Mechanisms contributing to T cell receptor signaling and assembly revealed by the solution structure of an ectodomain fragment of the CD3 epsilon gamma heterodimer SO CELL LA English DT Article ID CD3 GAMMA-CHAIN; TCR-ALPHA-BETA; MHC CLASS-II; ANTIGEN RECEPTOR; CRYSTAL-STRUCTURE; TCR/CD3 COMPLEX; SURFACE EXPRESSION; ZETA-CHAIN; T3-MOLECULAR COMPLEX; ACTIVATION MOTIFS AB The T cell receptor (TCR) consists of genetically diverse disulfide-linked ru and beta chains in noncovalent association with the invariant CD3 subunits. CD3 epsilon and CD3 gamma are integral components of both the TCR and pre-TCR. Here, we present the solution structure of a heterodimeric CD3 epsilon gamma ectodomain complex. A unique side-to-side hydrophobic interface between the two C2-set immunoglobulin-like domains and parallel pairing of their respective C-terminal beta strands are revealed. Mutational analysis confirms the importance of the distinctive linkage as well as the membrane proximal stalk motif (RxCxxCxE) for domain-domain association. These biochemical and structural analyses offer insights into the modular pairwise association of CD3 invariant chains. More importantly, the findings suggest how the rigidified CD3 elements participate in TCR-based signal transduction. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Wagner, G (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI19807, AI37581] NR 84 TC 116 Z9 119 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUN 29 PY 2001 VL 105 IS 7 BP 913 EP 923 DI 10.1016/S0092-8674(01)00395-6 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 449BK UT WOS:000169664300011 PM 11439187 ER PT J AU Tse, WT Tang, J Jin, O Korsgren, C John, KM Kung, AL Gwynn, B Peters, LL Lux, SE AF Tse, WT Tang, J Jin, O Korsgren, C John, KM Kung, AL Gwynn, B Peters, LL Lux, SE TI A new spectrin, beta IV, has a major truncated isoform that associates with promyelocytic leukemia protein nuclear bodies and the nuclear matrix SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COMPLEMENTATION GROUP-A; PORE COMPLEX PROTEIN; FANCONI-ANEMIA; ERYTHROCYTE-MEMBRANE; PREMATURE SENESCENCE; BINDING PROTEINS; ONCOGENIC RAS; CELL-GROWTH; PML GENE; IN-VITRO AB We isolated cDNAs that encode a 77-kDa peptide similar to repeats 10-16 of beta -spectrins, Its gene localizes to human chromosome 19q13.13-q13.2 and mouse chromosome 7, at 7.5 centimorgans, A 289-kDa isoform, similar to full-length beta -spectrins, was partially assembled from sequences in the human genomic DNA data base and completely cloned and sequenced. RNA transcripts are seen predominantly in the brain, and Western analysis shows a major peptide that migrates as a 72-kDa band. This new gene, spectrin beta IV, thus encodes a full-length minor isoform (Sp beta IV Sigma1) and a truncated major isoform (Sp beta IV Sigma5), Immunostaining of cells shows a micropunctate pattern in the cytoplasm and nucleus. In mesenchymal stem cells, the staining concentrates at nuclear dots that stain positively for the promyelocytic leukemia protein (PML). Expression of Sp beta IV Sigma5 fused to green fluorescence protein in cells produces nuclear dots that include all PML bodies, which double in number in transfected cells. Deletion analysis shows that partial repeats 10 and 16 of Sp beta IV Sigma5 are necessary for nuclear dot formation. Immunostaining of whole-mount nuclear matrices reveals diffuse positivity with accentuation at PML bodies, Spectrin beta IV is the first beta -spectrin associated with a subnuclear structure and may be part of a nuclear scaffold to which gene regulatory machinery binds. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP Tse, WT (reprint author), Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA34196]; NHLBI NIH HHS [HL64885, HL55321, HL33262, R01 HL055321, R01 HL064885]; NICHD NIH HHS [P30-HD18655]; NIDDK NIH HHS [DK34083] NR 91 TC 39 Z9 41 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 29 PY 2001 VL 276 IS 26 BP 23974 EP 23985 DI 10.1074/jbc.M009307200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 446TW UT WOS:000169531100100 PM 11294830 ER PT J AU Smith, KM Van Etten, RA AF Smith, KM Van Etten, RA TI Activation of c-Abl kinase activity and transformation by a chemical inducer of dimerization SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POSITIVE HUMAN LEUKEMIAS; TYROSINE KINASE; NUCLEAR-LOCALIZATION; GLUCOCORTICOID RECEPTOR; SIGNAL-TRANSDUCTION; CELLULAR-RESPONSE; BINDING DOMAIN; GENE-PRODUCT; DNA-DAMAGE; IN-VITRO AB c-Abl is a non-receptor tyrosine kinase that is activated in human leukemias by the fusion of Bcr or Tel sequences to the Abl NH, terminus. Although Bcr and Tel have little in common, both contain oligomerization domains. To determine whether oligomerization alone is sufficient to activate c-Abl, we have generated and characterized an Abl protein that can be activated selectively with the chemical inducer of dimerization, AP1510. Mutant Abl proteins with one (c4F1) or two (c4F2) copies of the AP1510 binding motif (FKBP) transformed NIH 3T3 cells in a ligand-dependent manner with the c4F2 protein 60-fold more potent than c4F1, Both chimeric proteins exhibited ligand-dependent dimerization in vivo, suggesting that the increased transformation efficiency of the c4F2 mutant reflects more effective dimerization rather than formation of higher order oligomers. In the absence of ligand, c4F2-expresssing fibroblasts morphologically reverted and arrested in G(1) In Ba/F3 cells, the c4F2 chimera exhibited Ligand-dependent kinase activation, transformation to interleukin S-independent growth, and relocalization of the fusion protein from nucleus to cytoplasm. These results demonstrate that dimerization alone is sufficient to activate the Abl kinase and provide a method to regulate conditionally c-Abl activity that will be useful for studying the normal physiological role of c-Abl and the mechanism of transformation and leukemogenesis. C1 Harvard Univ, Sch Med, Dept Genet, Ctr Blood Res, Boston, MA 02115 USA. RP Smith, KM (reprint author), Harvard Univ, Sch Med, Dept Genet, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA72465]; NHLBI NIH HHS [T32-HL07623] NR 53 TC 29 Z9 29 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 29 PY 2001 VL 276 IS 26 BP 24372 EP 24379 DI 10.1074/jbc.M100786200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 446TW UT WOS:000169531100151 PM 11320088 ER PT J AU Yu, QY Geng, Y Sicinski, P AF Yu, QY Geng, Y Sicinski, P TI Specific protection against breast cancers by cyclin D1 ablation SO NATURE LA English DT Article ID TRANSGENIC MICE; CELL-PROLIFERATION; SIGNALING PATHWAY; NEU ONCOGENE; EXPRESSION; RAS; OVEREXPRESSION; TRANSFORMATION; PROGRESSION; GENE AB Breast cancer is the most common malignancy among women. Most of these cancers overexpress cyclin D1, a component of the core cell-cycle machinery. We previously generated mice lacking cyclin D1 using gene targeting. Here we report that these cyclin D1-deficient mice are resistant to breast cancers induced by the neu and ras oncogenes. However, animals lacking cyclin D1 remain fully sensitive to other oncogenic pathways of the mammary epithelium, such as those driven by c-myc or Wnt-1. Our analyses revealed that, in mammary epithelial cells, the Neu-Ras pathway is connected to the cell-cycle machinery by cyclin D1, explaining the absolute dependency on cyclin D1 for malignant transformation in this tissue. Our results suggest that an anti-cyclin D1 therapy might be highly specific in treating human breast cancers with activated Neu-Ras pathways. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Sicinski, P (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. NR 31 TC 645 Z9 666 U1 0 U2 16 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 28 PY 2001 VL 411 IS 6841 BP 1017 EP 1021 DI 10.1038/35082500 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 446TF UT WOS:000169528500038 PM 11429595 ER PT J AU O'Donnell, CJ Larson, MG Feng, DL Sutherland, PA Lindpaintner, K Myers, RH D'Agostino, RA Levy, D Tofler, GH AF O'Donnell, CJ Larson, MG Feng, DL Sutherland, PA Lindpaintner, K Myers, RH D'Agostino, RA Levy, D Tofler, GH TI Genetic and environmental contributions to platelet aggregation - The Framingham Heart Study SO CIRCULATION LA English DT Article DE platelets; genetics; glycoproteins; fibrinogen ID CORONARY-ARTERY DISEASE; MYOCARDIAL-INFARCTION; ALPHA(2)BETA(1) DENSITY; CARDIOVASCULAR-DISEASE; SYSTEMIC HYPERTENSION; HEMOSTATIC RESPONSES; RISK; POLYMORPHISMS; RECEPTOR; AGGREGABILITY AB Background-Platelet aggregation plays an important role in arterial thrombosis in coronary heart disease, stroke, and peripheral arterial disease. However, the contribution of genetic versus environmental influences on interindividual variation in platelet aggregability is poorly characterized. Methods and Results-We studied the heritability of platelet aggregation responses in 2413 participants in the Framingham Heart Study. The threshold concentrations of epinephrine and ADP required to produce biphasic platelet aggregation and collagen lag time were determined. Mixed-model linear regression was used to calculate correlation coefficients within sibships and within spouse pairs. Variance and covariance component methods were used to estimate the proportion of platelet aggregation attributable to measured covariates versus additive genetic effects. After accounting for environmental covariates, the adjusted sibling correlations for epinephrine, ADP, and collagen lag time were 0.24, 0.22, and 0.31, respectively (P=0.0001 for each). In contrast, adjusted correlations for spouse-pairs were -0.01, 0.05, and -0.02, respectively (all P>0.30). The estimated heritabilities were 0.48, 0.34, and 0.62, respectively. Measured covariates accounted for only 4% to 7% of the overall variance in platelet aggregation, and heritable factors accounted for 20% to 30%. The platelet glycoprotein Illa Pl(A2) polymorphism and the fibrinogen Hind III beta -148 polymorphism contributed <1% to the overall variance. Conclusions-In our large, population-based sample, heritable factors play a major role in determining platelet aggregation, and measured covariates play a lesser role. Future studies are warranted to identify the key genetic variants that regulate platelet function and to lay the groundwork for rational pharmacogenetic approaches. C1 Framingham Heart Study, NHLBI, Framingham, MA 01701 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Inst Prevent Cardiovasc Dis, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Epidemiol & Prevent Med, Boston, MA 02118 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. NHLBI, NIH, Bethesda, MD 20892 USA. RP O'Donnell, CJ (reprint author), Framingham Heart Study, NHLBI, 5 Thurber St, Framingham, MA 01701 USA. FU NHLBI NIH HHS [HL NO1-38038] NR 37 TC 137 Z9 139 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 26 PY 2001 VL 103 IS 25 BP 3051 EP 3056 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 449NK UT WOS:000169692200013 PM 11425767 ER PT J AU Kuhlencordt, PJ Chen, JQ Han, F Astern, J Huang, PL AF Kuhlencordt, PJ Chen, JQ Han, F Astern, J Huang, PL TI Genetic deficiency of inducible nitric oxide synthase reduces atherosclerosis and lowers plasma lipid peroxides in apolipoprotein E-knockout mice SO CIRCULATION LA English DT Article DE atherosclerosis; nitric oxide; nitric oxide synthase ID LOW-DENSITY-LIPOPROTEIN; IN-VITRO; SUPEROXIDE; PEROXYNITRITE; ATHEROGENESIS; MACROPHAGES; OXIDATION; MONOCYTE; RELEASE; LESIONS AB Background-inducible nitric oxide synthase (iNOS) is expressed by leukocytes and smooth muscle cells in atherosclerotic lesions. To test whether NO produced by INOS deficiency affects atherosclerosis, we studied apoE/iNOS-double knockout (dKO) and apoE-knockout (KO) control animals fed a "Western-type" diet. Methods and Results-After 16 weeks of Western-type diet, the aortic lesion area in apoE/iNOS-dKO males and females was significantly reduced, by 228 and 21%, respectively, compared with apoE-KO males and females. This effect was more pronounced after 24 weeks of Western-type diet, after which lesion formation in male and female dKO mice was reduced by 38% and 40%. respectively. Plasma levels of lipoperoxides in apoE/iNOS-dKO mice (2.0 +/-0.23 mu mol/L) were significantly lower than in apoE-KO control animals (3.2 +/-0.14 mu mol/L; P=0.02), To test whether substrate deficiency plays a role in the proatherogenic actions of INOS, we administered L-arginine to apoE-KO animals for 16 and 24 weeks. L-Arginine treatment did not affect lesion formation in apoE-KO animals fed a Western-type diet. Conclusions-Genetic deficiency of INOS decreases diet-induced atherosclerosis and lowers plasma levels of lipoperoxides, a marker for oxidative stress, in apoE-KO animals. Reduction in iNOS-mediated oxidative stress could partly explain protection from lesion formation in dKO animals. L-Arginine supplementation did not change lesion area in apoE-KO mice, indicating that substrate deficiency is not a likely cause for iNOS-mediated injury in this model of atherosclerosis. C1 Massachusetts Gen Hosp, Cardiovasc Res Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Huang, PL (reprint author), Massachusetts Gen Hosp E, Cardiovasc Res Ctr, 149 E 13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL-52818]; NINDS NIH HHS [NS-33335] NR 33 TC 163 Z9 169 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 26 PY 2001 VL 103 IS 25 BP 3099 EP 3104 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 449NK UT WOS:000169692200021 PM 11425775 ER PT J AU Ranganathan, V Heine, WF Ciccone, DN Rudolph, KL Wu, XH Chang, S Hai, H Ahearn, IM Livingston, DM Resnick, I Rosen, F Seemanova, E Jarolim, P DePinho, RA Weaver, DT AF Ranganathan, V Heine, WF Ciccone, DN Rudolph, KL Wu, XH Chang, S Hai, H Ahearn, IM Livingston, DM Resnick, I Rosen, F Seemanova, E Jarolim, P DePinho, RA Weaver, DT TI Rescue of a telomere length defect of Nijmegen breakage syndrome cells requires NBS and telomerase catalytic subunit SO CURRENT BIOLOGY LA English DT Article ID DNA-DAMAGE RESPONSE; ATAXIA-TELANGIECTASIA; SACCHAROMYCES-CEREVISIAE; HUMAN FIBROBLASTS; REPAIR PROTEINS; PHOSPHORYLATION; TRF2; P53; INSTABILITY; DISORDER AB Nijmegen breakage syndrome (NBS) is a rare human disease displaying chromosome instability, radiosensitivity, cancer predisposition, immunodeficiency, and other defects [1, 2]. NBS is complexed with MRE11 and RAD50 in a DNA repair complex [3-5] and is localized to telomere ends in association with TRF proteins [6, 7]. We show that blood cells from NBS patients have shortened telomere DNA ends. Likewise, cultured NBS fibroblasts that exhibit a premature growth cessation were observed with correspondingly shortened telomeres. Introduction of the catalytic subunit of telomerase, TERT, was alone sufficient to increase the proliferative capacity of NBS fibroblasts. However, Has, but not TERT, restores the capacity of NBS cells to survive gamma irradiation damage. Strikingly, NBS promotes telomere elongation in conjunction with TERT in NBS fibroblasts. These results suggest that NBS is a required accessory protein for telomere extension. Since NBS patients have shortened telomeres, these defects may contribute to the chromosome instability and disease associated with NBS patients. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. Res Inst Pediat Hematol, Dept Clin Immunol, Moscow, Russia. Charles Univ, Sch Med, Dept Med Genet, Prague, Czech Republic. Inst Hematol & Blood Transfus, CR-12820 Prague, Czech Republic. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Weaver, DT (reprint author), Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA54326, CA79658]; NIA NIH HHS [K08 AG001019] NR 39 TC 88 Z9 94 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUN 26 PY 2001 VL 11 IS 12 BP 962 EP 966 DI 10.1016/S0960-9822(01)00267-6 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 448EA UT WOS:000169612900020 PM 11448772 ER PT J AU Lu, CX Schwartzbauer, G Sperling, MA Devaskar, SU Thamotharan, S Robbins, PD McTiernan, CF Liu, JL Jiang, J Frank, SJ Menon, RK AF Lu, CX Schwartzbauer, G Sperling, MA Devaskar, SU Thamotharan, S Robbins, PD McTiernan, CF Liu, JL Jiang, J Frank, SJ Menon, RK TI Demonstration of direct effects of growth hormone on neonatal cardiomyocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMPROVES CARDIAC-FUNCTION; FACTOR-I; DILATED CARDIOMYOPATHY; GLUCOSE TRANSPORTERS; HEART-FAILURE; TYROSINE PHOSPHORYLATION; MYOCARDIAL-INFARCTION; DISULFIDE LINKAGE; SKELETAL-MUSCLE; GH RECEPTOR AB The cellular and molecular basis of growth hormone (GH) actions on the heart remain poorly defined, and it is unclear whether GH effects on the myocardium are direct or mediated at least in part via insulin-like growth factor (IGF-1). Here, we demonstrate that the cultured neonatal cardiomyocyte is not an appropriate model to study the effects of GH because of artifactual loss of GH receptors (GHRs). To circumvent this problem, rat neonatal cardiomyocytes were infected with a recombinant adenovirus expressing the murine GHR, Functional integrity of GHR was suggested by GH-induced activation of the cognate JAK2/STAT5, MAPK, and Akt intracellular pathways in the cells expressing GHR. Although exposure to GH resulted in a significant increase in the size of the cardiomyocyte and increased expression of c fos, myosin light chain 2, and skeletal a-actin mRNAs, there were no significant changes in IGF-1 or atrial natriuretic factor mRNA levels in response to GH stimulation. In this model, GH increased incorporation of leucine, uptake of palmitic acid, and abundance of fatty acid transport protein mRNA. In contrast, GH decreased uptake of a-deoxy-D-glucose and levels of Glut1 protein. Thus, in isolated rat neonatal cardiomyocytes expressing GHR, GH induces hypertrophy and causes alterations in cellular metabolic profile in the absence of demonstrable changes in IGF-1 mRNA, suggesting that these effects may be independent of IGF-1. C1 Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Cardiol, Pittsburgh, PA 15213 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. McGill Univ, Dept Med, Montreal, PQ H3A 1A1, Canada. RP Menon, RK (reprint author), Childrens Hosp Pittsburgh, Dept Pediat, Div Endocrinol, 3705 5th Ave, Pittsburgh, PA 15213 USA. FU NICHD NIH HHS [HD33997, HD25024]; NIDDK NIH HHS [DK46395, DK49845, T32DK07729] NR 67 TC 51 Z9 53 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 22 PY 2001 VL 276 IS 25 BP 22892 EP 22900 DI 10.1074/jbc.M011647200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 444RE UT WOS:000169412700122 PM 11303022 ER PT J AU Cannon, CP Weintraub, WS Demopoulos, LA Vicari, R Frey, MJ Lakkis, N Neumann, FJ Robertson, DH DeLucca, PT DiBattiste, PM Gibson, CM Braunwald, E AF Cannon, CP Weintraub, WS Demopoulos, LA Vicari, R Frey, MJ Lakkis, N Neumann, FJ Robertson, DH DeLucca, PT DiBattiste, PM Gibson, CM Braunwald, E CA TACTICS Thrombolysis Myocardial TI Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID WAVE MYOCARDIAL-INFARCTION; ST-SEGMENT ELEVATION; TROPONIN-I LEVELS; ARTERY DISEASE; RECEPTOR INHIBITION; BALLOON ANGIOPLASTY; RANDOMIZED TRIAL; ANGINA; MANAGEMENT; STRATIFICATION AB Background: There is continued debate as to whether a routine, early invasive strategy is superior to a conservative strategy for the management of unstable angina and myocardial infarction without ST-segment elevation. Methods: We enrolled 2220 patients with unstable angina and myocardial infarction without ST-segment elevation who had electrocardiographic evidence of changes in the ST segment or T wave, elevated levels of cardiac markers, a history of coronary artery disease, or all three findings. All patients were treated with aspirin, heparin, and the glycoprotein IIb/IIIa inhibitor tirofiban. They were randomly assigned to an early invasive strategy, which included routine catheterization within 4 to 48 hours and revascularization as appropriate, or to a more conservative (selectively invasive) strategy, in which catheterization was performed only if the patient had objective evidence of recurrent ischemia or an abnormal stress test. The primary end point was a composite of death, nonfatal myocardial infarction, and rehospitalization for an acute coronary syndrome at six months. Results: At six months, the rate of the primary end point was 15.9 percent with use of the early invasive strategy and 19.4 percent with use of the conservative strategy (odds ratio, 0.78; 95 percent confidence interval, 0.62 to 0.97; P=0.025). The rate of death or nonfatal myocardial infarction at six months was similarly reduced (7.3 percent vs. 9.5 percent; odds ratio, 0.74; 95 percent confidence interval, 0.54 to 1.00; P<0.05). Conclusions: In patients with unstable angina and myocardial infarction without ST-segment elevation who were treated with the glycoprotein IIb/IIIa inhibitor tirofiban, the use of an early invasive strategy significantly reduced the incidence of major cardiac events. These data support a policy involving broader use of the early inhibition of glycoprotein IIb/IIIa in combination with an early invasive strategy in such patients. (N Engl J Med 2001;344:1879-87.) Copyright (C) 2001 Massachusetts Medical Society. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Emory Univ, Atlanta, GA 30322 USA. Holmes Reg Med Ctr, Melbourne, FL USA. Heart Ctr Sarasota, Sarasota, FL USA. Baylor Coll Med, Houston, TX 77030 USA. Tech Univ Munich, Med Klin, D-8000 Munich, Germany. Harvard Clin Res Inst, Boston, MA USA. RP Cannon, CP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. NR 41 TC 1272 Z9 1357 U1 2 U2 16 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 21 PY 2001 VL 344 IS 25 BP 1879 EP 1887 DI 10.1056/NEJM200106213442501 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 443VJ UT WOS:000169362100001 PM 11419424 ER PT J AU Thompson, DA Zacny, V Belinsky, GS Classon, M Jones, DL Schlegel, R Munger, K AF Thompson, DA Zacny, V Belinsky, GS Classon, M Jones, DL Schlegel, R Munger, K TI The HPV E7 oncoprotein inhibits tumor necrosis factor alpha-mediated apoptosis in normal human fibroblasts SO ONCOGENE LA English DT Article DE apoptosis; tumor necrosis factor-alpha; caspase 8; human papillomavirus ID HUMAN-PAPILLOMAVIRUS TYPE-16; SIGNALING COMPLEX DISC; TNF RECEPTOR; CELL-DEATH; GROWTH ARREST; KAPPA-B; KINASE RIP; PROTEIN; ACTIVATION; PATHWAY AB Tumor necrosis factor-alpha (TNF) is a cytokine that induces programmed cell death, apoptosis, in a number of cell types and is employed by cytotoxic T cells to eliminate virus infected cells. Consequently, many viruses have acquired mechanisms to undermine these host cell defense mechanisms and cause resistance to TNF-mediated apoptosis, Here we show that normal human diploid fibroblasts that express the human papillomavirus type 16 E7 oncoprotein have a decreased propensity to undergo apoptosis in response to TNF treatment. The ability of E7 to undermine TNF-mediated apoptosis correlates with cellular transformation. While E7 does not generally subvert signaling by tumor necrosis factor receptor I, pro-caspase 8 activation is decreased in E7-expressing cells, E7 also provides some protection from apoptosis caused by stimulation of the TNF receptor 1-related cytokine receptor Fas, where induction of apoptosis occurs much slower in this cell type. Hence, E7-expressing normal human fibroblasts exhibit specific defect that obstructs cytokine-mediated activation of pro-caspase 8 and apoptosis. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Ctr Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Canc Cell BIol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Munger, K (reprint author), Harvard Univ, Sch Med, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. OI Thompson, David/0000-0003-2372-7766 FU NCI NIH HHS [T32 CA72320, R01 CA81135] NR 55 TC 34 Z9 40 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 21 PY 2001 VL 20 IS 28 BP 3629 EP 3640 DI 10.1038/sj.onc.1204483 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 444LD UT WOS:000169400200004 PM 11439326 ER PT J AU Maysinger, D Berezovska, O Savic, R Soo, PL Eisenberg, A AF Maysinger, D Berezovska, O Savic, R Soo, PL Eisenberg, A TI Block copolymers modify the internalization of micelle-incorporated probes into neural cells SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE block copolymer micelle; DiI; neuron; glia; confocal microscopy ID DRUG-DELIVERY; DIBLOCK COPOLYMERS; ENDOCYTOSIS; DYNAMIN; OLIGONUCLEOTIDE; MORPHOLOGIES; CARRIERS; NEURONS; BRAIN; DNA AB An important therapeutic concern is rate and extent of internalization of drugs into cells. Hydrophilic agents often internalize poorly and slowly, and highly lipophilic ones too rapidly. The incorporation of drugs into micelles allows regulation of their internalization parameters, and newly-described block copolymers can be selectively tailored to suit specific drugs. This report compares internalization of Cell Tracker CM-DiI (DiI), a highly lipophilic non-cytotoxic fluorescent probe in common use in biology, from the freely-presented (non-micelle-incorporated) and micelle-incorporated states. DiI was effectively incorporated (> 60%) into 25-50 nm diameter spherical micelles made from polycaprolactone-b-polyethylene oxide block copolymer. Confocal microscopy was used to evaluate the internalization of DiI into mixed neuron-glia cultures (2-14 days in vitro, 2DIV-14DIV). Incorporation of DiI into micelles strikingly reduced the rate and extent of its internalization in both 2DIV and 14DIV cultures. Both the age of the cultures and the block copolymer employed to construct the micelles significantly influence the internalization of micelle-incorporated probe. (C) 2001 Elsevier Science B.V. All rights reserved. C1 McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3G 1Y6, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Alzheimers Res Lab, Boston, MA 02129 USA. McGill Univ, Dept Chem, Montreal, PQ H3A 2T5, Canada. RP Maysinger, D (reprint author), McGill Univ, Dept Pharmacol & Therapeut, 3655 Promenade Sir William Osler,McIntyre Bldg,Ro, Montreal, PQ H3G 1Y6, Canada. EM dmaysing@pharma.mcgill.ca RI Eisenberg, Adi/B-8676-2008 NR 30 TC 28 Z9 29 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD JUN 20 PY 2001 VL 1539 IS 3 BP 205 EP 217 DI 10.1016/S0167-4889(01)00110-0 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 449TZ UT WOS:000169704400003 PM 11420118 ER PT J AU Bertone, ER Willett, WC Rosner, BA Hunter, DJ Fuchs, CS Speizer, FE Colditz, GA Hankinson, SE AF Bertone, ER Willett, WC Rosner, BA Hunter, DJ Fuchs, CS Speizer, FE Colditz, GA Hankinson, SE TI Prospective study of recreational physical activity and ovarian cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID OLDER WOMEN; RISK; EXERCISE; VALIDITY; BREAST AB Background: It has been hypothesized that physical activity may reduce the risk of ovarian cancer by decreasing estrogen levels, reducing body fat, and reducing the frequency of ovulation. Epidemiologic studies of this relationship have obtained inconsistent results. The only prospective study to date reported a positive association between frequent vigorous exercise and ovarian cancer risk. We further evaluated this relationship in the Nurses' Health Study cohort. Methods: Participation in recreational physical activity was assessed by questionnaire in 1980, 1982, 1986, 1988, 1992, and 1994, with questions assessing exercise frequency, duration, and intensity. Results were adjusted for age, parity, oral contraceptive use, tubal ligation, and other risk factors for ovarian cancer. All statistical tests were two-sided. Results: During a 16-year follow-up (from 1980 to 1996), 1.2 million person-years were accrued by 92 825 cohort members, and 377 cases of epithelial ovarian cancer were confirmed. The relative risk (RR) of ovarian cancer for women engaging in recreational physical activity for 7 hours or more per week compared with those reporting less than 1 hour per week was 0.80 (95% confidence interval [CI] = 0.49 to 1.32; P-trend =.59). When both the frequency and intensity of activity were taken into account, activity level was also not associated with a reduced risk of ovarian cancer. Compared with inactive women, participants reporting high activity in terms of metabolic equivalent task hours (MET hours) were at greater risk of ovarian cancer (RR for 20 to <30 MET hours/week = 1.84 [95% CI = 1.12 to 3.02]; RR for,30 MET hours/week = 1.27 [95% CI = 0.75 to 2.14]). Conclusions: Overall, results did not suggest an inverse association between recreational physical activity and ovarian cancer. The possibility of a modest increase in risk with frequent vigorous activity requires further investigation. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Amherst, MA 01003 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hankinson, SE (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Amherst, MA 01003 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA40356]; NIEHS NIH HHS [T32ES07069] NR 29 TC 52 Z9 59 U1 2 U2 4 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 20 PY 2001 VL 93 IS 12 BP 942 EP 948 DI 10.1093/jnci/93.12.942 PG 7 WC Oncology SC Oncology GA 442UX UT WOS:000169304300015 PM 11416116 ER PT J AU Kohen, R Fashingbauer, LA Heidmann, DEA Guthrie, CR Hamblin, MW AF Kohen, R Fashingbauer, LA Heidmann, DEA Guthrie, CR Hamblin, MW TI Cloning of the mouse 5-HT6 serotonin receptor and mutagenesis studies of the third cytoplasmic loop SO MOLECULAR BRAIN RESEARCH LA English DT Article DE 5-HT6 receptor; serotonin receptor; G-protein coupled receptor; constitutive activity; site-directed mutagenesis; structure-function relationship ID INVERSE AGONIST ACTIVITY; CONSTITUTIVELY ACTIVATED STATE; SITE-DIRECTED MUTAGENESIS; PROTEIN-COUPLED RECEPTORS; ALPHA(1B)-ADRENERGIC RECEPTOR; BETA(2)-ADRENERGIC RECEPTOR; RAT-BRAIN; LOCALIZATION; BINDING; TRANSCRIPTION AB We have cloned the mouse 5-HT6 serotonin receptor and examined structure-function relationships in the C-terminal end of the third cytoplasmic (Cm) loop, introducing point mutations by site-directed mutagenesis at positions 264 to 268. We examined the ability of 5-HT6 wild type and receptor mutants to activate a cAMP responsive reporter gene when transiently expressed in JEG-3 or COS-7 cells. The wild type 5-HT6 receptor showed strong constitutive activity even when expressed at very low levels and which increased in proportion to the amount of receptor cDNA transfected. Three of the five mutants investigated (K264I, K267A and A268R) showed reduction in constitutive activity compared to wild type. These data suggest that constitutive activity may be important to 5-HT6 receptor activity in vivo and that, unlike some other G-protein coupled receptors, alteration in the BBXXB CIII-loop motif reduces rather than further activates basal activity of the murine 5-HT6 receptor. C1 VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Hamblin, MW (reprint author), VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, GRECC-182B,1660 S Columbian Way, Seattle, WA 98108 USA. NR 34 TC 65 Z9 67 U1 0 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 JUN 20 PY 2001 VL 90 IS 2 BP 110 EP 117 DI 10.1016/S0169-328X(01)00090-0 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 444YD UT WOS:000169426900003 ER PT J AU Sheng, M AF Sheng, M TI Molecular organization of the postsynaptic specialization SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on Molecular Kinesis in Cellular Function and Plasticity CY DEC 07-09, 2000 CL IRVINE, CALIFORNIA SP Natl Acad Sci ID METABOTROPIC GLUTAMATE RECEPTORS; DOMAIN-CONTAINING PROTEIN; LONG-TERM DEPRESSION; AMPA RECEPTOR; SYNAPTIC TRANSMISSION; EXCITATORY SYNAPSES; DENSITY PROTEIN; PDZ DOMAINS; C-TERMINUS; IN-VIVO AB A specific set of molecules including glutamate receptors is targeted to the postsynaptic specialization of excitatory synapses in the brain, gathering in a structure known as the postsynaptic density (PSD). Synaptic targeting of glutamate receptors depends on interactions between the C-terminal tails of receptor subunits and specific: PDZ domain-containing scaffold proteins in the PSD. These scaffold proteins assemble a specialized protein complex around each class of glutamate receptor that functions in signal transduction, cytoskeletal anchoring, and trafficking of the receptors. Among the glutamate receptor subtypes. the N-methyl-D-aspartate receptor is relatively stably integrated in the PSD, whereas the alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor moves in and out of the postsynaptic membrane in highly dynamic fashion. The distinctive cell biological behaviors of N-methyl-D-aspartate a nd alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors can be explained by their differential interactions with cytoplasmic proteins. C1 Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sheng, M (reprint author), Massachusetts Gen Hosp, Dept Neurobiol, 50 Blossom St Wel 423, Boston, MA 02114 USA. FU NINDS NIH HHS [NS35050, R01 NS035050] NR 71 TC 251 Z9 261 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 JUN 19 PY 2001 VL 98 IS 13 BP 7058 EP 7061 DI 10.1073/pnas.111146298 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 445KL UT WOS:000169456600016 PM 11416187 ER PT J AU Fossett, N Tevosian, SG Gajewski, K Zhang, Q Orkin, SH Schulz, RA AF Fossett, N Tevosian, SG Gajewski, K Zhang, Q Orkin, SH Schulz, RA TI The Friend of GATA proteins U-shaped, FOG-1, and FOG-2 function as negative regulators of blood, heart, and eye development in Drosophila SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ZINC-FINGER PROTEIN; TRANSCRIPTION FACTORS; COFACTOR; GENE; PANNIER; DOMAIN; ACTS; DIFFERENTIATION; SPECIFICATION; REPRESSOR AB Friend of GATA (FOG) proteins regulate GATA factor-activated gene transcription. During vertebrate hematopoiesis. FOG and GATA proteins cooperate to promote erythrocyte and megakaryocyte differentiation. The Drosophila FOG homologue U-shaped (Ush) is expressed similarly in the blood cell anlage during embryogenesis. During hematopoiesis, the acute myeloid leukemia 1 homologue Lozenge and Glial cells missing are required for the production of crystal cells and plasmatocytes, respectively. However, additional factors have been predicted to control crystal cell proliferation. In this report, we show that Ush is expressed in hemocyte precursors and plasmatocytes throughout embryogenesis and larval development, and the GATA factor Serpent is essential for Ush embryonic expression. Furthermore, loss of ush function results in an overproduction of crystal cells, whereas forced expression of Ush reduces this cell population. Murine FOG-1 and FOG-2 also can repress crystal cell production, but a mutant version of FOG-2 lacking a conserved motif that binds the corepressor C-terminal binding protein fails to affect the cell lineage. The GATA factor Pannier (Pnr) is required for eye and heart development in Drosophila. When Ush, FOG-1, FOG-2, or mutant FOG-2 is coexpressed with Pnr during these developmental processes, severe eye and heart phenotypes result, consistent with a conserved negative regulation of Pnr function. These results indicate that the fly and mouse FOG proteins function similarly in three distinct cellular contexts in Drosophila, but may use different mechanisms to regulate genetic events in blood vs. cardial or eye cell lineages. C1 Univ Texas, MD Anderson Canc Ctr, Grad Program Genes & Dev, Dept Biochem & Mol Biol, Houston, TX 77030 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Schulz, RA (reprint author), Univ Texas, MD Anderson Canc Ctr, Grad Program Genes & Dev, Dept Biochem & Mol Biol, Box 117,1515 Holcombe Blvd, Houston, TX 77030 USA. FU NHLBI NIH HHS [HL59151, R01 HL059151] NR 35 TC 109 Z9 110 U1 1 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 19 PY 2001 VL 98 IS 13 BP 7342 EP 7347 DI 10.1073/pnas.131215798 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 445KL UT WOS:000169456600064 PM 11404479 ER PT J AU Flier, SN Kulkarni, RN Kahn, CR AF Flier, SN Kulkarni, RN Kahn, CR TI Evidence for a circulating islet cell growth factor in insulin-resistant states SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PANCREATIC BETA-CELLS; TYPE-2 DIABETES-MELLITUS; FACTOR-I; ADULT-RATS; MICE; GLUCOSE; RECEPTOR; MOUSE; GENE; PROLIFERATION AB Insulin resistance is a feature of many common disorders including obesity and type 2 diabetes mellitus. In these disorders, the beta -cells compensate for the insulin resistance for long periods of time with an increase in secretory capacity. an increase in beta -cell mass, or both. To determine whether the beta -cell response might relate to a circulating growth factor, we have transplanted normal islets under the kidney capsule of normoglycemic insulin-resistant mice with two different models of insulin resistance: lean mice that have a double heterozygous deletion of the insulin receptor and insulin receptor substrate-1 (DH) or the obese, hyperglycemic ob/ob mice. In the grafts transplanted into both hosts, there was a marked increase in beta -cell mitotic activity and islet mass that was comparable with that observed in the endogenous pancreas. By contrast, islets of the DH mouse transplanted into normal mice showed reduced mitotic index. These data suggest the insulin resistance is associated with a circulating islet cell growth factor that is independent of glucose and obesity. C1 Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Res Div, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Res Div, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-09825-02, DK-55545, F32 DK009825, P30 DK-36836, P30 DK036836, R01 DK055545] NR 41 TC 91 Z9 93 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 JUN 19 PY 2001 VL 98 IS 13 BP 7475 EP 7480 DI 10.1073/pnas.131192998 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 445KL UT WOS:000169456600087 PM 11404474 ER PT J AU Wong, AK Alfert, M Castrillon, DH Shen, Q Holash, J Yancopoulos, GD Chin, L AF Wong, AK Alfert, M Castrillon, DH Shen, Q Holash, J Yancopoulos, GD Chin, L TI Excessive tumor-elaborated VEGF and its neutralization define a lethal paraneoplastic syndrome SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; PELIOSIS HEPATIS; BACILLARY ANGIOMATOSIS; COLORECTAL-CARCINOMA; UP-REGULATION; CANCER; CELLS; EXPRESSION; RAS AB Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen and key regulator of both physiologic and pathologic (e.g.. tumor) angiogenesis. In the course of studies designed to assess the ability of constitutive VEGF to block tumor regression in an inducible RAS melanoma model, mice implanted with VEGF-expressing tumors sustained high morbidity and mortality that were out of proportion to the tumor burden. Documented elevated serum levels of VEGF were associated with a lethal hepatic syndrome characterized by massive sinusoidal dilation and endothelial cell proliferation and apoptosis. systemic levels of VEGF correlated with the severity of liver pathology and overall clinical compromise. A striking reversal of VEGF-induced liver pathology and prolonged survival were achieved by surgical excision of VEGF secreting tumor or by systemic administration of a potent VEGF antagonist (VEGF-TRAP(R1R2)), thus defining a paraneoplastic syndrome caused by excessive VEGF activity. Moreover, this VEGF-induced syndrome resembles peliosis hepatis, a rare human condition that is encountered in the setting of advanced malignancies, high-dose androgen therapy, and Bartonella henselae infection. Thus, our findings in the mouse have suggested an etiologic role for VEGF in this disease and may lead to diagnostic and therapeutic options for this debilitating condition in humans. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Chin, L (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. FU NCI NIH HHS [K08 CA084044, U01 CA084313, U01CA84313-01, KO8CA84044]; NIAMS NIH HHS [K08AR02104-01] NR 37 TC 52 Z9 60 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 JUN 19 PY 2001 VL 98 IS 13 BP 7481 EP 7486 DI 10.1073/pnas.121192298 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 445KL UT WOS:000169456600088 PM 11404464 ER PT J AU Yang, XF Wu, CJ McLaughlin, S Chillemi, A Wang, KS Canning, C Alyea, EP Kantoff, P Soiffer, RJ Dranoff, G Ritz, J AF Yang, XF Wu, CJ McLaughlin, S Chillemi, A Wang, KS Canning, C Alyea, EP Kantoff, P Soiffer, RJ Dranoff, G Ritz, J TI CML66, a broadly immunogenic tumor antigen, elicits a humoral immune response associated with remission of chronic myelogenous leukemia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BONE-MARROW TRANSPLANTATION; GRAFT-VERSUS-LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; STEM-CELL TRANSPLANTATION; DONOR LYMPHOCYTE INFUSION; HOST DISEASE; CANCER; IDENTIFICATION; NY-ESO-1; MELANOMA AB This report describes a tumor-associated antigen, termed CML66, initially cloned from a chronic myelogenous leukemia (CML) cDNA expression library. CML66 encodes a 583-aa protein with a molecular mass of 66 kDa and no significant homology to other known genes. CML66 gene is localized to human chromosome 8q23, but the function of this gene is unknown. CML66 is expressed in leukemias and a variety of solid tumor cell lines. When examined by Northern blot, expression in normal tissues was restricted to testis and heart, and no expression was found in hematopoietic tissues. When examined by quantitative reverse transcription-PCR, expression in CML cells was 1.5-fold higher than in normal peripheral blood mononuclear cells. The presence of CML66-specific antibody in patient serum was confirmed by Western blot and the development of high titer IgG antibody specific for CML66 correlated with immune induced remission of CML in a patient who received infusion of normal donor lymphocytes for treatment of relapse. CML66 antibody also was found in sera from 18-38% of patients with lung cancer, melanoma, and prostate cancer. These findings suggest that CML66 may be immunogenic in a wide variety of malignancies and may be a target for antigen-specific immunotherapy. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Med,Ctr Hematol Oncol, Boston, MA 02115 USA. RP Ritz, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Med,Ctr Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA66996, P01 CA066996]; NHLBI NIH HHS [K08 HL004293, KO8 HL04293]; NIAID NIH HHS [AI29530, P01 AI029530, U19 AI029530] NR 30 TC 67 Z9 79 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 JUN 19 PY 2001 VL 98 IS 13 BP 7492 EP 7497 DI 10.1073/pnas.131590998 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 445KL UT WOS:000169456600090 PM 11416219 ER PT J AU Philbin, EF Dec, GW Jenkins, PL DiSalvo, TG AF Philbin, EF Dec, GW Jenkins, PL DiSalvo, TG TI Socioeconomic status as an independent risk factor for hospital readmission for heart failure SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID INVASIVE CARDIAC PROCEDURES; MEDICARE BENEFICIARIES; MYOCARDIAL-INFARCTION; ELDERLY PATIENTS; CARE; MORTALITY; RACE; REVASCULARIZATION; UNDERUSE; OUTCOMES AB The management of heart failure is characterized by high rates of hospital admission as well as rehospitalization after inpatient treatment of this disorder, whereas skillful medical care may reduce the risk of hospital admission. The purpose of this study was to examine the relation between income (as a measure of socioeconomic status) and the frequency of hospital readmission among a large and diverse group of persons treated for heart failure. We analyzed administrative discharge data from 236 nonfederal acute-care hospitals in New York State, involving 41,776 African-American or Caucasian hospital survivors with international Classification of Diseases, Ninth Revision, Clinical Modification codes for heart failure in the principal diagnosis position between January 1 and December 31, 1995. Household income was derived from postal ZIP codes and census data. We found that patients residing in lower income neighborhoods were more often women or African-Americans, had more comorbid illness, had higher use of Medicaid insurance, and were more often admitted to rural hospitals. There was a stepwise decrease in the crude frequency of readmission from the lowest quartile of income (23.2%) to the highest (20.0%) (p < 0.0001 for Mantel-Haenszel chi-square test for trend across all quartiles; p < 0.0001 for comparison between quartiles 1 and 4). After adjustment for baseline differences and process of care, income remained a significant predictor, with an increase in the risk of readmission noted in association with lower levels of income (adjusted odds ratio for quartile 1:4 comparison, 1.18; 95% confidence interval, 1.10 to 1.26, p < 0.0001), We conclude that lower income patients hospitalized for treatment of heart failure in New York differ from higher income patients in important clinical and demographic comparisons. Even after adjustment for these fundamental differences and other potential confounding factors, lower income is a positive predictor of readmission risk. (C) 2001 by Excerpta Medica, Inc. C1 Albany Med Coll, Div Cardiol, Albany, NY 12208 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Bassett Healthcare, Bassett Res Inst, Cooperstown, NY USA. RP Philbin, EF (reprint author), Albany Med Coll, Div Cardiol, Mail Code 44,47 New Scotland Ave, Albany, NY 12208 USA. NR 22 TC 109 Z9 113 U1 1 U2 12 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 JUN 15 PY 2001 VL 87 IS 12 BP 1367 EP 1371 DI 10.1016/S0002-9149(01)01554-5 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 441NW UT WOS:000169237300007 PM 11397355 ER PT J AU Sweadner, KJ Donnet, C AF Sweadner, KJ Donnet, C TI Structural similarities of Na,K-ATPase and SERCA, the Ca(2+)-ATPase of the sarcoplasmic reticulum SO BIOCHEMICAL JOURNAL LA English DT Review DE cross-linking; crystal structure; membrane protein; protein folding; P-type ATPases ID P-TYPE ATPASES; SITE-DIRECTED MUTAGENESIS; H,K-ATPASE ALPHA-SUBUNIT; GASTRIC H+/K+-ATPASE; C-TERMINAL DOMAIN; CONFERS OUABAIN RESISTANCE; CHEMICAL CROSS-LINKING; NA+-K+-ATPASE; BETA-SUBUNIT; MONOCLONAL-ANTIBODY AB The crystal structure of SERCA1a (skeletal-muscle sarcoplasmic-reticulum /endoplasmic-reticulum Ca(2+)-ATPase) has recently been determined at 2.6 Angstrom (note 1 Angstrom = 0.1nm) resolution [Toyoshima, Nakasako, Nomura and Ogawa (2000) Nature (London) 405, 647-655]. Other P-type ATPases are thought to share key features of the ATP hydrolysis site and a central core of transmembrane helices. Outside of these most-conserved segments, structural similarities are less certain, and predicted transmembrane topology differs between subclasses. In the present review the homologous regions of several representative P-type ATPases are aligned with the SERCA sequence and mapped on to the SERCA structure for comparison. Homology between SERCA and the Na,K-ATPase is more extensive than with any other ATPase, even PMCA, the Ca(2+)-ATPase of plasma membrane. Structural features of the Na,K-ATPase are projected on to the Ca(2+)-ATPase crystal structure to assess the likelihood that they share the same fold. Homology extends through all ten transmembrane spans, and most insertions and deletions are predicted to be at the surface. The locations of specific residues are examined, such as proteolytic cleavage sites, intramolecular cross-linking sites. and the binding sites of certain other proteins. On the whole, the similarity supports a shared fold, with some particular exceptions. C1 Massachusetts Gen Hosp, Ctr Neurosci, Boston, MA 02129 USA. RP Sweadner, KJ (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, 149-6118,149 13th St, Boston, MA 02129 USA. EM sweadner@helix.mgh.harvard.edu NR 148 TC 149 Z9 149 U1 1 U2 9 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUN 15 PY 2001 VL 356 BP 685 EP 704 DI 10.1042/0264-6021:3560685 PN 3 PG 20 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 446LK UT WOS:000169514600002 PM 11389677 ER PT J AU Spencer, TJ Biederman, J Wozniak, J Faraone, SV Wilens, TE Mick, E AF Spencer, TJ Biederman, J Wozniak, J Faraone, SV Wilens, TE Mick, E TI Parsing pediatric bipolar disorder from its associated comorbidity with the disruptive behavior disorders SO BIOLOGICAL PSYCHIATRY LA English DT Article DE bipolar disorder; child; comorbidity ID DEFICIT HYPERACTIVITY DISORDER; ADOLESCENT SUBSTANCE-ABUSERS; CONDUCT DISORDER; DOUBLE-BLIND; EARLY-ONSET; PHARMACOLOGICAL TREATMENT; PSYCHIATRIC COMORBIDITY; PREPUBERTAL CHILDREN; AGGRESSIVE-CHILDREN; JUVENILE MANIA AB The unique pattern of comorbidity: found in pediatric mania greatly complicates accurate diagnosis, the course of the disorder; and its treatment. The pattern of comorbidity is unique by adult standards, especially its overlap with attention-deficit/hyperactivity: disorder (ADHD), aggression and conduct disorder. Clinically, symptoms of mania have been discounted as severe ADHD or ignored in the context of aggressive conduct disorder. This atypicality may lead to neglect of the mood component. The addition of high rates of additional disorders contributes to the severe morbidity, dysfunction, and incapacitation frequently observed in these children. A comprehensive approach to diagnostic evaluate is the keystone to establishing an effective treatment program because response to treatment differs with individual disorders. Recognition of the multiplicity of disorders guides therapeutic options in these often refractory conditions. What was previously considered refractory ADHD, oppositionality; aggression, and conduct disorder may respond after mood stabilization. We review these issues in this article. (C) 2001 Society of Biological Psychiatry. C1 Massachusetts Gen Hosp, Pediac Psychopharmacol Unit ACC 725, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Spencer, TJ (reprint author), Massachusetts Gen Hosp, Pediac 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 65 TC 40 Z9 40 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 15 PY 2001 VL 49 IS 12 BP 1062 EP 1070 DI 10.1016/S0006-3223(01)01155-6 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 447JV UT WOS:000169568900013 PM 11430848 ER PT J AU Braziel, RM Arber, DA Slovak, ML Gulley, ML Spier, C Kjeldsberg, C Unger, J Miller, TP Tubbs, R Leith, C Fisher, RI Grogan, TM AF Braziel, RM Arber, DA Slovak, ML Gulley, ML Spier, C Kjeldsberg, C Unger, J Miller, TP Tubbs, R Leith, C Fisher, RI Grogan, TM TI The Burkitt-like lymphomas: a Southwest Oncology Group study delineating phenotypic, genotypic, and clinical features SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMA; EPSTEIN-BARR-VIRUS; LARGE-CELL LYMPHOMA; INTERCELLULAR-ADHESION MOLECULE-1; IN-SITU HYBRIDIZATION; PROGNOSTIC-SIGNIFICANCE; PROTEIN EXPRESSION; GENE REARRANGEMENT; MALIGNANT-LYMPHOMA; BCL-2 GENE AB The Revised European-American Lymphoma classification gives Burkitt-like lymphoma (BLL) provisional status, leaving unresolved the differential diagnosis with Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). This study compared the biologic features of adult BLL and DLBCL. The phenotypic distinction between BLL and DLBCL was determined by immunohistochemical staining of frozen tissue from 13 patients with BLL and 55 patients with DLBCL by using an extensive antibody panel including Ki-67, CD10, CD11a/lymphocyte function-associated antigen 1 alpha (LFA-1 alpha), CD18/LFA-1 beta, CD58/LFA-3, and CD54/intercellular adhesion molecule, CD8 for tumor-infiltrating cytotoxic T cells (T-TILs), CD44 homing receptor, and p53 and Bcl-2 oncogenic proteins. Compared with DLBCL, BLL had a higher proliferative rate (mean Ki-67, 88% versus 53%), greater expression of CD10 and p53 antigens, and decreased expression of Bcl-2, BLL cases had a consistent absence of one or more cell adhesion molecules (92% versus 27%), low T-TIL numbers, and absence of CD44 homing receptor (92% versus 14%), The t(8;14) translocation was identified in 80% of BLL cases, but no patients with BLL had the t(14;18) translocation, In a 10-year analysis, median survival of patients with BLL was 1.2 years, and that of patients with DLBCL was 2.5 years. Although the proportion of patients cured was similar in the 2 groups, BLL patients had an increased risk of early death. We conclude that BLL can be recognized by its combined morphologic and phenotypic features and that it represents a high-grade lymphoma much closer to BL than DLBCL, Retention of the BLL category or inclusion of BLL as a variant of BL is biologically and clinically more appropriate than absorbing the category of BLL into DLBCL. (C) 2001 by The American Society of Hematology. C1 Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Audie Murphy Vet Hosp, San Antonio, TX USA. Univ Arizona, SWOG Cent Lymphoma Repository, Tucson, AZ USA. Univ Utah, Salt Lake City, UT USA. SWOG Stat Ctr, Seattle, WA USA. Cleveland Clin, Cleveland, OH 44106 USA. Univ New Mexico, Albuquerque, NM 87131 USA. Loyola Univ, Med Ctr, Ctr Canc, Maywood, IL 60153 USA. RP Braziel, RM (reprint author), Oregon Hlth Sci Univ, Dept Pathol, L471,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. FU NCI NIH HHS [CA 32101] NR 47 TC 62 Z9 65 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 2001 VL 97 IS 12 BP 3713 EP 3720 DI 10.1182/blood.V97.12.3713 PG 8 WC Hematology SC Hematology GA 440FB UT WOS:000169164300009 PM 11389007 ER PT J AU Wang, KS Zorn, E Ritz, J AF Wang, KS Zorn, E Ritz, J TI Specific down-regulation of interleukin-12 signaling through induction of phospho-STAT4 protein degradation SO BLOOD LA English DT Article ID RECOMBINANT HUMAN INTERLEUKIN-12; IFN-GAMMA PRODUCTION; T-CELLS; TYROSINE-PHOSPHATASE; INTERFERON-GAMMA; NATURAL-KILLER; RECEPTOR COMPONENT; NEGATIVE REGULATOR; T-HELPER-1 CELLS; TUMOR-REGRESSION AB Interleukin-12 (IL-12) plays a critical role in modulating the function of T lymphocytes and natural killer cells. IL-12 has potent antitumor effects in animal models, mediated primarily by its ability to enhance cytolytic activity and secretion of interferon-gamma (IFN-gamma), Unfortunately, the antitumor effect of IL-12 has not been demonstrated in clinical trials. Repeated administration of IL-12 in humans results in decreasing levels of IFN-gamma secretion. To understand the mechanism underlying this loss of responsiveness, the effect of IL-12 on its own signaling in activated human T cells was examined. These experiments demonstrate that the level of the signal transducer and activator of transcription 4 (STAT4) protein, a critical IL-12 signaling component, is dramatically decreased 24 hours after IL-12 stimulation, whereas levels of STAT4 messenger RNA are not affected. The decrease of STAT4 protein appears to be due to specific degradation of phospho-STAT4, possibly through the proteasome degradation pathway. Decreased levels of STAT4 protein lead to decreased STAT4 DNA-binding activity and reduced proliferation and secretion of IFN-gamma, This down-regulation of STAT4 is specific for IL-12 signaling, presumably owing to the prolonged activation of STAT4 induced by IL-12, IFN-a stimulation, which leads to transient phosphorylation of STAT4, does not reduce the level of STAT4 protein. These findings provide new insights into the regulation of IL-12 signaling in human T cells, where IL-12 promotes T(H)1 responses, but persistent IL-12 stimulation may also limit this response. The cellular depletion of STAT4 following prolonged IL-12 stimulation may also explain the loss of responsiveness following the repeated administration of IL-12 in clinical trials. (C) 2001 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dept Med,Dept Adult Oncol,Dana Farber Canc Inst, Brigham & Womens Hosp,Ctr Hematol Oncol, Boston, MA USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA41619] NR 36 TC 31 Z9 31 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 JUN 15 PY 2001 VL 97 IS 12 BP 3860 EP 3866 DI 10.1182/blood.V97.12.3860 PG 7 WC Hematology SC Hematology GA 440FB UT WOS:000169164300030 PM 11389027 ER PT J AU Smith, MR McGovern, FJ Fallon, MA Schoenfeld, D Kantoff, PW Finkelstein, JS AF Smith, MR McGovern, FJ Fallon, MA Schoenfeld, D Kantoff, PW Finkelstein, JS TI Low bone mineral density in hormone-naive men with prostate carcinoma SO CANCER LA English DT Article DE prostatic neoplasms; bone; osteoporosis; androgen-deprivation therapy ID MIDDLE-AGED MEN; QUANTITATIVE COMPUTED-TOMOGRAPHY; ANDROGEN DEPRIVATION THERAPY; X-RAY ABSORPTIOMETRY; VITAMIN-D; LUTEINIZING-HORMONE; OLDER MEN; SEX-HORMONES; CANCER; OSTEOPOROSIS AB BACKGROUND. The objective of this study was to determine the prevalence of low bone mineral density in men with prostate carcinoma and no history of androgen-deprivation therapy. METHODS. The authors conducted a cross-sectional study in 41 hormone-naive men with locally advanced, lymph node positive, or recurrent prostate carcinoma and no radiographic evidence of bone metastases. Bone mineral density of the total hip, posterior-anterior (PA) lumbar spine, and lateral lumbar spine was determined by dual-energy X-ray absorptiometry (DXA) using a densitometer. Trabecular bone mineral density of the lumbar spine was determined by quantitative computed tomography (QCT). Bone mineral density results were expressed in standard deviation units relative to young adult men (T score) and relative to age-matched men (Z score). RESULTS. Fourteen of 41 men [34%; 95%] confidence interval [95% CI], 20-51%) had T scores < -1.0 at one or more skeletal sites by DXA, 12 of 41 men (29%; 95% CI, 16-42%) had T scores between -1.0 and -2.5, and 12 of 41 men (5%; 95% CI, 1-17%) had T scores < -2.5. Thirty-nine of 41 men (95%; 95% CI, 83-99%) had T scores < -1.0 by QCT, 13 of 41 men (31%; 95% CI 18-48%) had T scores between -1.0 and -2.5, and 26 of 41 men (63%; 95% CI, 47-78%) had T scores < -2.5. T scores for trabecular bone mineral density of the lumbar spine were significantly lower than T scores for either the total hip (P < 0.001) or the PA lumbar spine (P ( 0.001). The mean Z score for trabecular bone mineral density of the lumbar spine was -0.7 +/- 0.9. Hypogonadism, hypovitaminosis D, and dietary calcium intakes below the Recommended Daily Allowance were observed in 20%, and 17%, and 59% of study participants, respectively. CONCLUSIONS. Many hormone-naive men with prostate carcinoma have low bone mineral density. QCT is a more sensitive method than DXA for diagnosing low bone mineral density in this patient population. Trabecular bone mineral density is lower than expected for age and risk factors for osteoporosis are common. (C) 2001 American Cancer Society. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Cox 640,100 Blossom St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu FU NCRR NIH HHS [RR-1066]; NIDDK NIH HHS [K24 DK02759] NR 55 TC 90 Z9 93 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JUN 15 PY 2001 VL 91 IS 12 BP 2238 EP 2245 PG 8 WC Oncology SC Oncology GA 443NX UT WOS:000169348200005 PM 11413511 ER PT J AU Barry, MJ Albertsen, PC Bagshaw, MA Blute, ML Cox, R Middleton, RG Gleason, DF Zincke, H Bergstralh, EJ Jacobsen, SJ AF Barry, MJ Albertsen, PC Bagshaw, MA Blute, ML Cox, R Middleton, RG Gleason, DF Zincke, H Bergstralh, EJ Jacobsen, SJ TI Outcomes for men with clinically nonmetastatic prostate carcinoma managed with radical prostactectomy, external beam radiotherapy, or expectant management - A retrospective analysis SO CANCER LA English DT Article DE prostatic neoplasms; prostatectomy; radiotherapy; survival; treatment outcome ID LONG-TERM SURVIVAL; CO-MORBIDITY; CANCER; DIAGNOSIS; ANTIGEN; DISEASE AB BACKGROUND. With a lack of data from randomized trials, the optimal management of men with nonmetastatic prostate carcinoma is controversial. The authors sought to define the outcomes of three common strategies for managing patients with nonmetastatic prostate carcinoma: expectant management, radiotherapy, and radical prostatectomy. METHODS. The authors conducted a retrospective cohort study with standardized collection of key prognostic data, including centralized assignment of Gleason grades from original biopsy specimens. Participants included all Connecticut hospitals (the expectant management cohort) and three academic medical centers in other states (the radiotherapy and surgery cohorts). Two thousand three hundred eleven consecutive men ages 55-74 years who were diagnosed during 1971-1984 with nonmetastatic prostate carcinoma and were treated at the participating sites were included. RESULTS. Kaplan-Meier estimates with 95% confidence intervals (95% CI) of overall survival at 10 years for each cohort were as follows: expectant management cohort, 42% of patients (95% CI, 38-46%); radiotherapy cohort, 52% of patients (95% Ct, 46-58%); and radical prostatectomy cohort, 69% of patients (95% CI, 67-71%); for disease specific mortality, the estimates were as follows: expectant management cohort, 75% of patients (95% CI, 71-79%); radiotherapy cohort, 67% of patients (95% CI, 61-73%); and radical prostatectomy cohort, 86% of patients (95% CI, 84-88%). There were large differences in distributions of important prognostic factors among men in the different treatment groups. CONCLUSIONS. These data provide precise estimates of the outcomes of patients who have been treated with different modalities for nonmetastatic prostate carcinoma in the recent past. Direct comparisons of outcomes between treatment groups are inadvisable because of the different characteristics of patients who select these alternative management strategies. (C) 2001 American Cancer Society. C1 Massachusetts Gen Hosp, Div Gen Med, Med Practices Evaluat Ctr, Boston, MA 02114 USA. Univ Connecticut, Sch Med, Div Urol, Farmington, CT USA. Stanford Univ, Sch Med, Dept Radiat Oncol, Stanford, CA 94305 USA. Mayo Clin, Dept Urol, Rochester, MN USA. Univ Utah, Sch Med, Div Urol, Salt Lake City, UT USA. Mayo Clin, Biostat Sect, Dept Hlth Sci Res, Rochester, MN USA. Mayo Clin, Clin Epidemiol Sect, Dept Hlth Sci Res, Rochester, MN USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Div Gen Med, Med Practices Evaluat Ctr, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU AHRQ HHS [HS 08397] NR 17 TC 88 Z9 89 U1 0 U2 3 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 15 PY 2001 VL 91 IS 12 BP 2302 EP 2314 DI 10.1002/1097-0142(20010615)91:12<2302::AID-CNCR1262>3.0.CO;2-P PG 13 WC Oncology SC Oncology GA 443NX UT WOS:000169348200013 PM 11413519 ER PT J AU Kozin, SV Shkarin, P Gerweck, LE AF Kozin, SV Shkarin, P Gerweck, LE TI The cell transmembrane pH gradient in tumors enhances cytotoxicity of specific weak acid chemotherapeutics SO CANCER RESEARCH LA English DT Article ID X-RAY-IRRADIATION; IN-VIVO; EXTRACELLULAR PH; INTERSTITIAL PH; SOLID TUMORS; MURINE TUMOR; BLOOD-FLOW; CHLORAMBUCIL; PERFUSION; TOXICITY AB The extracellular pH is lower in tumor than in normal tissue, whereas their intracellular pH is similar, In this study, we show that the tumor-specific pH gradient may be exploited for the treatment of cancer by weak acid chemotherapeutics, i,v,-injected glucose substantially decreased the electrode estimated extracellular pH in a xenografted human tumor while its intracellular pH, evaluated by P-31 magnetic resonance spectroscopy, remained virtually unchanged. The resulting increase in the average cell pH gradient caused a parallel increase in tumor growth delay by the weak acid chlorambucil (CHL). Regardless of glucose administration, the effect of CHL was significantly greater in tumors preirradiated with a large dose of ionizing radiation. This suggests that CHL was especially pronounced in radioresistant hypoxic cells possessing a larger transmembrane pH gradient. These results indicate that the naturally occurring cell pH gradient difference between tumor and normal tissue is a major and exploitable determinant of the uptake of weak acids in the complex tumor microenvironment, The use of such drugs may be especially effective in combination with radiation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Yale Univ, Sch Med, Magnet Resonance Ctr, New Haven, CT 06520 USA. RP Kozin, SV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Cox 7, Boston, MA 02114 USA. FU NCI NIH HHS [CA 13311, CA-22860] NR 28 TC 67 Z9 73 U1 1 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 JUN 15 PY 2001 VL 61 IS 12 BP 4740 EP 4743 PG 4 WC Oncology SC Oncology GA 443ZU UT WOS:000169374100016 PM 11406545 ER PT J AU Trojan, A Witzens, M Schultze, JL Vonderheide, RH Harig, S Krackhardt, AM Stahel, RA Gribben, JG AF Trojan, A Witzens, M Schultze, JL Vonderheide, RH Harig, S Krackhardt, AM Stahel, RA Gribben, JG TI Generation of cytotoxic T lymphocytes against native and altered peptides of human leukocyte antigen-A*0201 restricted epitopes from the human epithelial cell adhesion molecule SO CANCER RESEARCH LA English DT Article ID MHC CLASS-I; PULSED DENDRITIC CELLS; LUNG-CANCER; EP-CAM; CARCINOEMBRYONIC ANTIGEN; MONOCLONAL-ANTIBODY; HUMAN-MELANOMA; COLORECTAL-CANCER; RANDOMIZED TRIAL; IDENTIFICATION AB A growing number of human tumor antigens have been described that can be recognized by CTLs in a MHC class I restricted Fashion. The epithelial cell adhesion molecule (Ep-CAM) is expressed in a variety of human tumors and has attracted attention as a therapeutic target for monoclonal antibody serotherapy. We have identified immunogenic peptides derived from Ep-CAM, that bind to human leukocyte antigen-A*0201 and elicit strong peptide-specific human CTL responses, demonstrating that there is an effective T-cell repertoire against these Ep-CAM-derived peptides that can be recruited. Alterations to these peptides were made to increase their binding affinity to MHC class I molecules. The use of such "heteroclitic" peptides allowed generation of cytotoxic T cells that demonstrated increased killing of target cells pulsed not only with the heteroclitic but also with the native peptide. Most important, CTL cell lines that are generated against these peptides specifically Lyse epithelial tumor cells expressing Ep-CAM but not normal hematopoietic or bronchial epithelial cells. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02114 USA. Univ Zurich Hosp, Div Oncol, CH-8044 Zurich, Switzerland. RP Gribben, JG (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 FU NCI NIH HHS [CA 66996] NR 43 TC 47 Z9 47 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 JUN 15 PY 2001 VL 61 IS 12 BP 4761 EP 4765 PG 5 WC Oncology SC Oncology GA 443ZU UT WOS:000169374100020 PM 11406549 ER PT J AU Arango, D Corner, GA Wadler, S Catalano, PJ Augenlicht, LH AF Arango, D Corner, GA Wadler, S Catalano, PJ Augenlicht, LH TI c-myc/p53 interaction determines sensitivity of human colon carcinoma cells to 5-fluorouracil in vitro and in vivo SO CANCER RESEARCH LA English DT Article ID C-MYC GENE; HUMAN CANCER-CELLS; BETA-CATENIN; THERAPEUTIC AGENTS; CYCLE ARREST; APOPTOSIS; EXPRESSION; P53; AMPLIFICATION; PATHWAY AB Colon carcinoma cells overexpress c-myc due to defective Wnt signaling, but only patients whose tumors have an amplified c-myc gene show improved disease-free and overall survival in response to 5-fluoruracil (5FU), Here we show that in two colon carcinoma cell lines that do not have an amplified c-myc gene but differ in their p53 status, high c-myc levels can be further elevated by introducing a c-myc expression vector. Whereas sensitivity to low serum-induced apoptosis was imposed on the parental lines independent of p53 status and was unaffected by further elevation of c-myc, sensitivity to 5FU-induced apoptosis was dependent on both the higher c-myc levels due to the expression vector and wild-type p53 function, The elevated c-myc levels led to higher c-myc transactivation activity in the p53 wild-type cell line, but not in the mutant p53 cell line, The requirement for both elevated c-myc and p53 for 5FU sensitivity was confirmed using antisense c-myc and pifithrin-alpha, a specific inhibitor of p53, Finally, the in vitro data predicted that only patients with both amplified c-myc and wild-type p53 in their primary tumors would be responsive to 5FU-based therapy, which was borne out by analysis of tumors from 135 patients entered into a Phase III clinical trial of 5FU-based adjuvant therapy, The data provide significant insight into mechanisms that establish colon tumor cell sensitivity to 5FU, clearly demonstrate the necessity of exercising caution in considering combining novel strategies that target elevated c-myc with standard 5FU-based therapy, and suggest alternative therapeutic strategies that target c-myc and/or p53 mutations in the treatment of colon cancer. C1 Montefiore Med Ctr, Albert Einstein Canc Ctr, Dept Oncol, Bronx, NY 10467 USA. Dana Farber Canc Inst, Dept Biostat Sci, Ctr Stat, Eastern Cooperat Oncol Grp, Boston, MA 02115 USA. RP Arango, D (reprint author), Montefiore Med Ctr, Albert Einstein Canc Ctr, Dept Oncol, Hofheimer 509,111 E 210Th St, Bronx, NY 10467 USA. RI Arango, Diego/M-5667-2016 OI Arango, Diego/0000-0003-2953-3284 FU NCI NIH HHS [CA81328, CA88104]; PHS HHS [P30-13330] NR 30 TC 85 Z9 88 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 JUN 15 PY 2001 VL 61 IS 12 BP 4910 EP 4915 PG 6 WC Oncology SC Oncology GA 443ZU UT WOS:000169374100041 PM 11406570 ER PT J AU Cohen, DE Walker, BD AF Cohen, DE Walker, BD TI Human immunodeficieny virus pathogenesis and prospects for immune control in patients with established infection SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID CYTOTOXIC T-LYMPHOCYTES; ACTIVE ANTIRETROVIRAL THERAPY; INACTIVATED HIV-1 IMMUNOGEN; LONG-TERM NONPROGRESSORS; MATURE DENDRITIC CELLS; HUMAN LANGERHANS CELLS; CHEMOKINE RECEPTOR 5; BLOOD-BANK COHORT; TYPE-1 INFECTION; DISEASE PROGRESSION AB Infection with human immunodeficiency virus (HIV) results in inevitable progressive deterioration of the immune system in the majority of untreated patients. Prospects for virus eradication are remote, because HIV establishes long-lived reservoirs during the earliest stages of infection that are impervious to available antiviral therapies. Understanding how the immune system copes with this illness and other chronic viral infections is the key to designing future strategies for long-term control of viremia. Valuable insights have been gained from 2 populations in particular: patients with chronic, long-term, nonprogressing infections, in whom viremia is controllable in the absence of antiviral medications, and acutely infected patients, in whom the initial HIV-specific immune response might be preserved and augmented by timely intervention. These cases of immune control of HIV provide hope for the development of improved vaccine products that may eventually produce vaccine-induced immunity that will enhance durable control of HIV infection. C1 Fenway Community Hlth Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fenway Community Hlth Ctr, 7 Haviland St, Boston, MA 02114 USA. EM dcohen@fenwayhealth.org NR 129 TC 23 Z9 28 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 15 PY 2001 VL 32 IS 12 BP 1756 EP 1768 DI 10.1086/320759 PG 13 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 436WT UT WOS:000168959400018 PM 11360218 ER PT J AU Chan, J Mably, JD Serluca, FC Chen, JN Goldstein, NB Thomas, MC Cleary, JA Brennan, C Fishman, MC Roberts, TM AF Chan, J Mably, JD Serluca, FC Chen, JN Goldstein, NB Thomas, MC Cleary, JA Brennan, C Fishman, MC Roberts, TM TI Morphogenesis of prechordal plate and notochord requires intact Eph/ephrin B signaling SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Eph; ephrin B; zebrafish; gastrulation; prechordal plate; notochord; morphogenesis; cell movement ID RECEPTOR TYROSINE KINASES; EPH RECEPTORS; CONVERGENT EXTENSION; NEURAL-TUBE; PARAXIAL PROTOCADHERIN; TRANSMEMBRANE LIGANDS; CELL MOVEMENTS; TAIL FORMATION; ZEBRAFISH; GASTRULATION AB Eph receptors and their ligands, the ephrins, mediate cell-to-cell signals implicated in the regulation of cell migration processes during development. We report the molecular cloning and tissue distribution of zebrafish transmembrane ephrins that represent all known members of the mammalian class B ephrin family. The degree of homology among predicted ephrin B sequences suggests that, similar to their mammalian counterparts, zebrafish B-ephrins can also bind promiscuously to several Eph receptors. The dynamic expression patterns for each zebrafish B-ephrin support the idea that these ligands are confined to interact with their receptors at the borders of their complementary expression domains. Zebrafish B-ephrins are expressed as early as 30% epiboly and during gastrula stages: in the germ ring, shield, prechordal plate, and notochord. Ectopic overexpression of dominant-negative soluble ephrin B constructs yields reproducible defects in the morphology of the notochord and prechordal plate by the end of gastrulation. Notably disruption of Eph/ephrin B signaling does not completely destroy structures examined, suggesting that cell fate specification is not altered. Thus abnormal morphogenesis of the prechordal plate and the notochord is likely a consequence of a cell movement defect. Our observations suggest Eph/ephrin B signaling plays an essential role in regulating cell movements during gastrulation. (C) 2001 Academic Press. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ London Queen Mary Coll, Sch Biol Sci, Dept Genet, London E1 4NS, England. RP Chan, J (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Smith 970,1 Jimmy Fund Way, Boston, MA 02115 USA. OI Chen, Jau-Nian/0000-0001-8807-3607 FU NHLBI NIH HHS [HL49579]; NICHD NIH HHS [HD24926] NR 52 TC 62 Z9 63 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 2001 VL 234 IS 2 BP 470 EP 482 DI 10.1006/dbio.2001.0281 PG 13 WC Developmental Biology SC Developmental Biology GA 443XC UT WOS:000169367200016 PM 11397014 ER PT J AU Sharif-Askari, E Alam, A Rheaume, E Beresford, PJ Scotto, C Sharma, K Lee, D DeWolf, WE Nuttall, ME Lieberman, J Sekaly, RP AF Sharif-Askari, E Alam, A Rheaume, E Beresford, PJ Scotto, C Sharma, K Lee, D DeWolf, WE Nuttall, ME Lieberman, J Sekaly, RP TI Direct cleavage of the human DNA fragmentation factor-45 by granzyme B induces caspase-activated DNase release and DNA fragmentation SO EMBO JOURNAL LA English DT Article DE caspace; CTLs; DFF45; granzyme B ID LYMPHOCYTE-MEDIATED APOPTOSIS; BACULOVIRUS P35 PROTEIN; CELL-DEATH PROTEASE; CYTOTOXIC T-CELLS; IN-VIVO; TARGET-CELLS; NUCLEAR-LOCALIZATION; PREVENT APOPTOSIS; FAMILY PROTEASES; CPP32 CASPASE-3 AB The protease granzyme B (GrB) plays a key role in the cytocidal activity during cytotoxic T lymphocyte (CTL)-mediated programmed cell death. Multiple caspases have been identified as direct substrates for GrB, suggesting that the activation of caspases constitutes an important event during CTL-induced cell death. However, recent studies have provided evidence for caspase-independent pathway(s) during CTL-mediated apoptosis, In this study, we demonstrate caspase-independent and direct cleavage of the 45 kDa unit of DNA fragmentation factor (DFF45) by GrB both in vitro and in vivo. Using a novel and selective caspase-3 inhibitor, we show the ability of GrB to process DFF45 directly and mediate DNA fragmentation in the absence of caspase-3 activity. Furthermore, studies with DFF45 mutants reveal that both caspase-3 and GrB share a common cleavage site, which is necessary and sufficient to induce DNA fragmentation in target cells during apoptosis. Together, our data suggest that CTLs possess alternative mechanism(s) for inducing DNA fragmentation without the requirement for caspases. C1 Univ Montreal, Dept Microbiol & Immunol, Immunol Lab, Montreal, PQ H3C 3J7, Canada. McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3A 2B4, Canada. McGill Univ, Dept Expt Med, Montreal, PQ H3A 2B4, Canada. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. SmithKline Beecham Pharmaceut, Dept Med Chem, King Of Prussia, PA 19406 USA. SmithKline Beecham Pharmaceut, Dept Mechanist Enzymol, King Of Prussia, PA 19406 USA. SmithKline Beecham Pharmaceut, Dept Bone & Cartilage Biol, King Of Prussia, PA 19406 USA. RP Sekaly, RP (reprint author), Univ Montreal, Dept Microbiol & Immunol, Immunol Lab, Montreal, PQ H3C 3J7, Canada. RI Lieberman, Judy/A-2717-2015; OI Rheaume, Eric/0000-0002-0554-0984 FU NIAID NIH HHS [AI 45587, R01 AI045587, R56 AI045587] NR 75 TC 90 Z9 102 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 15 PY 2001 VL 20 IS 12 BP 3101 EP 3113 DI 10.1093/emboj/20.12.3101 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 445GP UT WOS:000169450000013 PM 11406587 ER PT J AU Dohadwala, M Luo, J Zhu, L Lin, Y Dougherty, GJ Sharma, S Huang, M Pold, N Batra, RK Dubinett, SM AF Dohadwala, M Luo, J Zhu, L Lin, Y Dougherty, GJ Sharma, S Huang, M Pold, N Batra, RK Dubinett, SM TI Non-small cell lung cancer cyclooxygenase-2-dependent invasion is mediated by CD44 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INCREASED EXPRESSION; CARCINOMA CELLS; TUMOR INVASION; HUMAN PROSTATE; UP-REGULATION; TGF-BETA; IN-VIVO; APOPTOSIS; INHIBITION; GROWTH AB Elevated tumor cyclooxygenase (COX-2) expression is associated with increased angiogenesis, tumor invasion, and suppression of host immunity. We have previously shown that genetic inhibition of tumor COX-2 expression reverses the immunosuppression induced by nonsmall cell lung cancer (NSCLC). To assess the impact of COX-2 expression in lung cancer invasiveness, NSCLC cell lines were transduced with a retroviral vector expressing the human COX-2 cDNA in the sense (COX-2-S) and antisense (COX-2-AS) orientations. COX-2-S clones expressed significantly more COX-2 protein, produced 10-fold more prostaglandin E-2, and demonstrated an enhanced invasive capacity compared with control vector-transduced or parental cells. CD44, the cell surface receptor for hyaluronate, was overexpressed in COX-2-S cells, and specific blockade of CD44 significantly decreased tumor cell invasion. In contrast, COX-2-AS clones had a very limited capacity for invasion and showed diminished expression of CD44. These findings suggest that a COX-2-mediated, CD44-dependent pathway is operative in NSCLC invasion. Because tumor COX-2 expression appears to have a multifaceted role in conferring the malignant phenotype, COX-2 may be an important target for gene or pharmacologic therapy in NSCLC. C1 Univ Calif Los Angeles, Sch Med, Dept Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Radiat Oncol, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Lung Canc Res Program, Los Angeles, CA 90095 USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, Sch Med, Dept Med, Div Pulm & Crit Care Med, 37-131 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. FU NCI NIH HHS [R01 CA078654, R01 CA71817, P50 CA090388, 1P50 CA90388, R01 CA78654] NR 50 TC 175 Z9 190 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 15 PY 2001 VL 276 IS 24 BP 20809 EP 20812 DI 10.1074/jbc.C100140200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 442RC UT WOS:000169297900002 PM 11320076 ER PT J AU Dickson, LM Lingohr, MK McCuaig, J Hugl, SR Snow, L Kahn, BB Myers, MG Rhodes, CJ AF Dickson, LM Lingohr, MK McCuaig, J Hugl, SR Snow, L Kahn, BB Myers, MG Rhodes, CJ TI Differential activation of protein kinase B and p70(S6K) by glucose and insulin-like growth factor 1 in pancreatic beta-cells (INS-1) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID P70 S6 KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION; IGF-I; 3T3-L1 ADIPOCYTES; MAMMALIAN TARGET; PHOSPHORYLATION; AKT; TRANSLATION; IDENTIFICATION AB It has been shown that IGF-1-induced pancreatic beta -cell proliferation is glucose-dependent; however, the mechanisms responsible for this glucose dependence are not known. Adenoviral mediated expression of constitutively active phosphatidylinositol 3-kinase (PI3K) in the pancreatic beta -cells, INS-1, suggested that PI3K was not necessary for glucose-induced beta -cell proliferation but was required for IGF-1-induced mitogenesis, Examination of the signaling components downstream of PI3K, 3-phosphoinositide-dependent kinase 1, protein kinase B (PKB), glycogen synthase kinase-3, and p70-kDa-S6-kinase (p70(S6K)), suggested that a major part of glucose-dependent beta -cell proliferation requires activation of mammalian target of rapamycin/p70(S6K), independent of phosphoinositide-dependent kinase 1/PKB activation. Adenoviral expression of the kinase-dead form of PKB in INS-1 cells decreased IGF-1-induced beta -cell proliferation. However, a surprisingly similar decrease was also observed in adenoviral wild type and constitutively active PKB-infected cells. Upon analysis of extracellular signal-regulated protein kinase 1 and 2 (ERK1/ERK2), an increase in ERK1/ERK2 phosphorylation activation by glucose and IGF-1 was observed in kinase-dead PKB-infected cells, but this phosphorylation activation was inhibited in the constitutively active PKB-infected cells. Hence, there is a requirement for the activation of both ERK1/ERK2 and mammalian target of rapamycin/p70(S6K) signal transduction pathways for a full commitment to glucose-induced pancreatic beta -cell mitogenesis. However, for IGF-1-induced activation, these pathways must be carefully balanced, because chronic activation of one (PI3K/PKB) can lead to dampening of the other (ERK1/2), reducing the mitogenic response. C1 Pacific NW Res Inst, Seattle, WA 98122 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98122 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol & Metab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Program Cell & Dev Biol, Boston, MA 02215 USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Rhodes, CJ (reprint author), Pacific NW Res Inst, 720 Broadway, Seattle, WA 98122 USA. FU NIDDK NIH HHS [DK 55267]; PHS HHS [R01 43051] NR 49 TC 90 Z9 94 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 15 PY 2001 VL 276 IS 24 BP 21110 EP 21120 DI 10.1074/jbc.M101257200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 442RC UT WOS:000169297900044 PM 11274216 ER PT J AU Chen, LJ Haider, K Ponda, M Cariappa, A Rowitch, D Pillai, S AF Chen, LJ Haider, K Ponda, M Cariappa, A Rowitch, D Pillai, S TI Protein kinase C-associated kinase (PKK), a novel membrane-associated, ankyrin repeat-containing protein kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LEUKEMIA-CELLS; BETA; ACTIVATION; FAMILY; DIFFERENTIATION; PHOSPHORYLATION; SUBSTRATE; ISOTYPES; RESIDUES; CLONING AB A novel murine membrane-associated protein kinase, PKK ((p) under bar rotein (k) under bar inase C-associated <(kunder bar>inase), was cloned on the basis of its physical association with protein kinase C beta (PKC beta), The regulated expression of PKK in mouse embryos is consistent with a role for this kinase in early embryogenesis, The human homolog of PKK has over 90% identity to its murine counterpart, has been localized to chromosome 21q22,3, and is identical to the PKC<()under bar>-(i) under bar nteracting (k) under bar inase, DIK (Bahr, C., Rohwer, A., Stempka, L., Rincke, G., Marks, F., and Gschwendlt, M. (2000) J. Biol, Chem. 275, 36350-36357). PKK comprises an N-terminal kinase domain and a C-terminal region containing 11 ankyrin repeats. PKK exhibits protein kinase activity in vitro and associates with cellular membranes. PKK exists in three discernible forms at steady state: an underphosphorylated form of 100 kDa; a soluble, cytosolic, phosphorylated form of 110 kDa; and a phosphorylated, detergent-insoluble form of 112 kDa, PKK is initially synthesized as an underphosphorylated soluble 100-kDa protein that is quantitatively converted to a detergent-soluble 110-kDa form. This conversion requires an active catalytic domain. Although PKK physically associates with PKC beta, it does not phosphorylate this PKC isoform, However, PKK itself mag be phosphorylated by PKC beta, PKK represents a developmentally regulated protein kinase that can associate with membranes. The functional significance of its association with PKC beta remains to be ascertained. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pillai, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA 69618]; NIAID NIH HHS [AI 33507] NR 27 TC 32 Z9 33 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 15 PY 2001 VL 276 IS 24 BP 21737 EP 21744 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 442RC UT WOS:000169297900124 PM 11278382 ER PT J AU Kantoff, PW Halabi, S Farmer, DA Hayes, DF Vogelzang, NA Small, EJ AF Kantoff, PW Halabi, S Farmer, DA Hayes, DF Vogelzang, NA Small, EJ TI Prognostic significance of reverse transcriptase polymerase chain reaction for prostate-specific antigen in men with hormone-refractory prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RECURRENCE; CELLS AB Purpose: To evaluate the prognostic significance of reverse transcriptase polymerase chain reaction (RT-PCR) detection of prostate-specific antigen (PSA) mRNA in the blood of men with hormone-refractory prostate cancer (HRPC). Patients and Methods: Peripheral blood was obtained from 193 men enrolled on Cancer and Leukemia Group B Study 9480, a prospective randomized comparison of three doses of suramin. RNA was isolated from the samples and assayed for the presence of PSA transcripts by RT-PCR. Results: RNA could be isolated in 156 (83%) of samples. PSA transcripts as measured by RT-PCR were detectable in 75 (48%) of the 156 patients. The median survival far those patients in whom no transcripts were detectable was 18 months (95% confidence interval [CI], 14 to 22 months) compared with 13 months (95% CI, 11 to 15 months) (P = .004) for those in whom transcripts were detectable. In a multivariate analysis in which other factors predictive of survival were used, RT-PCR for PSA provided independent prognostic information. Conclusion: RT-PCR for PSA predicts survival duration in a population of men with HRPC. J Clin Oncol 19:3025-3028. (C) 2001 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Dept Adult Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Duke Univ, Med Ctr, Ctr Stat, Canc & Leukemia Grp B, Durham, NC USA. Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. RP Kantoff, PW (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. NR 11 TC 40 Z9 41 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 15 PY 2001 VL 19 IS 12 BP 3025 EP 3028 PG 4 WC Oncology SC Oncology GA 442UT UT WOS:000169303900006 PM 11408497 ER PT J AU Strauss, AJ Su, JT Dalton, WMK Gelber, RD Sallan, SE Silverman, LB AF Strauss, AJ Su, JT Dalton, WMK Gelber, RD Sallan, SE Silverman, LB TI Bony morbidity in children treated for acute lymphoblastic leukemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INDUCED OSTEOPOROSIS; MENINGEAL LEUKEMIA; AVASCULAR NECROSIS; MINERAL DENSITY; CHILDHOOD; DEXAMETHASONE; OSTEONECROSIS; CHEMOTHERAPY; PREDNISONE; PATHOGENESIS AB Purpose: Corticosteroids are widely used in the treatment of acute lymphoblastic leukemia (ALL), To determine the frequency of corticosteroid-associated bony morbidity in children with ALL, we retrospectively evaluated the incidence of fractures and osteonecrosis (ON) on two consecutive pediatric ALL protocols. Patients and Methods: One hundred seventy-six consecutive children were treated for ALL between 1987 and 1995 at the Dana-Farber Cancer Institute and Children's Hospital. Prednisone was used as the corticosteroid during postremission therapy from 1987 to 1991, and dexamethasone was used from 1991 to 1995; Medical records for all patients were reviewed to assess the occurrence of fractures and ON. Results; With a median follow-up of 7.6 years, the 5-year cumulative incidence (CI) +/- SE of any bony morbidity for the 176 patients was 30% +/- 4%, with a 5-year CI of fractures of 28% +/- 3% and of ON of 7% +/- 2%, With multivariate analysis, independent predictors of bony morbidity included age 9 to 18 years at diagnosis (P < .01), male sex (P < .01), and treatment with dexamethasane (P = .01). Dexamethasone was associated with a higher risk of fractures (5-year CI, 36% +/- 5% v 20% +/- 4% with prednisone; P = .04), but not ON (P = .40). The 5-year event-free survival for the 176 patients was 79% +/- 3%. Conclusion: Children treated for ALL had a high incidence of fractures and ON. Older children, boys, and patients receiving dexamethasone were at increased risk for the development of bony morbidity, Future studies should attempt to minimize corticosteroid-associated bony morbidity without compromising clinical efficacy. J Clin Oncol 19:3066-3072. (C) 2001 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Qual Control Ctr, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Silverman, LB (reprint author), Dana Farber Canc Inst, Qual Control Ctr, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA06516, CA68484] NR 38 TC 137 Z9 139 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 15 PY 2001 VL 19 IS 12 BP 3066 EP 3072 PG 7 WC Oncology SC Oncology GA 442UT UT WOS:000169303900012 PM 11408503 ER PT J AU Fife, BT Kennedy, KJ Paniagua, MC Lukacs, NW Kunkel, SL Luster, AD Karpus, WJ AF Fife, BT Kennedy, KJ Paniagua, MC Lukacs, NW Kunkel, SL Luster, AD Karpus, WJ TI CXCL10 (IFN-gamma-inducible protein-10) control of encephalitogenic CD4(+) T cell accumulation in the central nervous system during experimental autoimmune encephalomyelitis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; MYELIN PROTEOLIPID PROTEIN; CHEMOKINE RECEPTORS; LEWIS RAT; DIFFERENTIAL EXPRESSION; MICE LACKING; SPINAL-CORD; SJL/J MICE; IP-10 AB Experimental autoimmune encephalomyelitis (EAE) is a CD4(+) Th1-mediated demyelinating disease of the CNS that serves as a model for multiple sclerosis. A critical event in the pathogenesis of EAE is the entry of both Ag-specific and Ag-nonspecific T lymphocytes into the CNS. In the present report, we investigated the role of the CXC chemokine CXCL10 (IFN-gamma -inducible protein-10) in the pathogenesis of EAE. Production of CXCL10 in the CNS correlated with the development of clinical disease. Administration of anti-CXCL10 decreased clinical and histological disease incidence, severity, as well as infiltration of mononuclear cells into the CNS. Anti-CXCL10 specifically decreased the accumulation of encephalitogenic PLP139-151 Ag-specific CD4(+) T cells in the CNS compared with control-treated animals. Anti-CXCL10 administration did not affect the activation of encephalitogenic T cells as measured by Ag-specific proliferation and the ability to adoptively transfer EAE. These results demonstrate an important role for the CXC chemokine CXCL10 in the recruitment and accumulation of inflammatory mononuclear cells during the pathogenesis of EAE. C1 Northwestern Univ, Sch Med, Robert H Lurie Canc Ctr, Immunol Ctr,Dept Pathol, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Inst Neurosci, Chicago, IL 60611 USA. Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. RP Karpus, WJ (reprint author), Northwestern Univ, Sch Med, Robert H Lurie Canc Ctr, Immunol Ctr,Dept Pathol, 303 E Chicago Ave,W127, Chicago, IL 60611 USA. RI Fife, Brian/D-2042-2013 OI Fife, Brian/0000-0001-9826-5637 FU NCI NIH HHS [CA69212]; NIAID NIH HHS [AI07476]; NINDS NIH HHS [NS34510] NR 46 TC 182 Z9 190 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2001 VL 166 IS 12 BP 7617 EP 7624 PG 8 WC Immunology SC Immunology GA 471VH UT WOS:000170949000077 PM 11390519 ER PT J AU Ntziachristos, V Weissleder, R AF Ntziachristos, V Weissleder, R TI Experimental three-dimensional fluorescence reconstruction of diffuse media by use of a normalized Born approximation SO OPTICS LETTERS LA English DT Article ID HETEROGENEOUS TURBID MEDIA; CONTRAST AGENTS; DENSITY WAVES; TOMOGRAPHY; PHOTON; LIFETIME AB We present a normalized Born expansion that facilitates fluorescence reconstructions in turbid, tissue-like media. The algorithm can be particularly useful for tissue investigations of fluorochrome distribution in vivo, since it does not require absolute photon-field measurements or measurements before contrast-agent administration. This unique advantage can be achieved only in fluorescence mode. We used this algorithm to three-dimensionally image and quantify an indocyanine fluorochrome phantom, using a navel fluorescence tomographic imager developed for animals. (C) 2001 Optical Society of America. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ntziachristos, V (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02129 USA. NR 14 TC 379 Z9 382 U1 1 U2 19 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 JUN 15 PY 2001 VL 26 IS 12 BP 893 EP 895 DI 10.1364/OL.26.000893 PG 3 WC Optics SC Optics GA 440QN UT WOS:000169185900011 PM 18040483 ER PT J AU Littner, M Johnson, SF McCall, WV Anderson, WD Davila, D Hartse, K Kushida, CA Wise, MS Hirshkowitz, M Woodson, BT AF Littner, M Johnson, SF McCall, WV Anderson, WD Davila, D Hartse, K Kushida, CA Wise, MS Hirshkowitz, M Woodson, BT CA Stand Practice Comm TI Practice parameters for the treatment of narcolepsy: An update for 2000 SO SLEEP LA English DT Article ID EXCESSIVE DAYTIME SLEEPINESS; DOUBLE-BLIND; SCHEDULED NAPS; MODAFINIL; CATAPLEXY; PLACEBO; APNEA; PERFORMANCE; AMPHETAMINE; SELEGILINE AB Successful treatment of narcolepsy requires an accurate diagnosis to exclude patients with other sleep disorders, which have different treatments, and to avoid unnecessary complications of drug treatment. Treatment objectives should be tailored to individual circumstances. Modafinil, amphetamine, methamphetamine, dextroamphetamine, methylphenidate, selegiline, pemoline, tricyclic antidepressants, and fluoxetine are effective treatments for narcolepsy, but the quality of published clinical evidence supporting them varies. Scheduled naps can be beneficial to combat sleepiness, but naps seldom suffice as primary therapy. Regular follow up of patients with narcolepsy is necessary to educate patients and their families, monitor for complications of therapy and emergent of other sleep disorders, and help the patient adapt to the disease. C1 VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Med, Sepulveda, CA USA. St Patricks Hosp, Sleep Ctr, Missoula, MT USA. Wake Forest Univ, Sch Med, Dept Psychiat & Behav Med, Winston Salem, NC USA. Univ S Florida, Coll Med, Tampa, FL USA. Baptist Med Ctr, Little Rock, AR USA. Sleep Consultants Inc, Ft Worth, TX USA. Stanford Univ, Ctr Excellence Sleep Disorders, Stanford, CA USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Houston VAMC Sleep Disorders & Res, Houston, TX USA. Med Coll Wisconsin, Dept Otolaryngol & Commun Sci, Milwaukee, WI USA. RP Littner, M (reprint author), Amer Acad Sleep Med, Stand Practice Comm, 6301 Bandel Rd,Suite 101, Rochester, MN 55901 USA. NR 58 TC 82 Z9 86 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD JUN 15 PY 2001 VL 24 IS 4 BP 451 EP 466 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 440QB UT WOS:000169184800011 PM 11403530 ER PT J AU Tatarkiewicz, K Garcia, M Lopez-Avalos, M Bonner-Weir, S Weir, GC AF Tatarkiewicz, K Garcia, M Lopez-Avalos, M Bonner-Weir, S Weir, GC TI Porcine neonatal pancreatic cell clusters in tissue culture: Benefits of serum and immobilization in alginate hydrogel SO TRANSPLANTATION LA English DT Article ID HIGH GLUCOSE-CONCENTRATIONS; LARGE-SCALE ISOLATION; LONG-TERM FUNCTION; NUDE-MICE; INSULIN-SECRETION; RAT ISLETS; BETA-CELLS; IN-VITRO; EXTRACELLULAR-MATRIX; FETAL PANCREAS AB Porcine neonatal pancreatic cell clusters (NPCCs) may be a suitable source of insulin producing tissue for transplantation in diabetic patients. The possible beneficial effect of serum on maturation of NPCCs in vitro is difficult to achieve because of cell clumping, which can be avoided by immobilization in alginate hydrogel matrix, Collagenase treated pancreata, cultured for 4 days, formed NPCCs that were embedded in alginate cross-linked with CaCl2 and cultured in modified Ham's F10 medium with 10% fetal calf serum (FCS) for 10 days. NPCCs cultured as suspension in F10+ with 0.5% bovine serum albumin or with 10% FCS were used as control. To prevent the aggregation when cultured with serum, NPCCs were kept as a very diluted suspension. At the beginning and end of the culture, samples were taken for insulin and DNA content and immunostained for beta and non-beta cells. The culture of NPCCs immobilized in alginate resulted with 3-fold increase in insulin content and 9-fold increase in insulin/DNA ratio. Histology revealed evident increase of number of insulin- and other hormone-positive cells compared with the control. Even though 2 weeks in culture resulted in impaired glucose-induced insulin release, the amount of insulin secreted by clusters cultured in the presence of serum was 4-fold higher than in serum-free conditions. After transplantation, NPCCs retrieved from alginate reversed hyperglycemia similarly to NPCCs cultured in standard conditions. In conclusion, this study shows the feasibility of in vitro immobilization of NPCCs in alginate three-dimensional matrix, allowing cell clusters to be cultured at least two times higher density compared with culture in suspension. C1 Joslin Diabet Ctr, Div Res, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Div Res, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-36836, DK R01 DK50657, P01 DK-53087] NR 47 TC 15 Z9 15 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 JUN 15 PY 2001 VL 71 IS 11 BP 1518 EP 1526 DI 10.1097/00007890-200106150-00007 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 444VN UT WOS:000169420900007 PM 11435959 ER PT J AU Ohdan, H Yang, YG Swenson, KG Kitamura, H Sykes, M AF Ohdan, H Yang, YG Swenson, KG Kitamura, H Sykes, M TI T cell and B cell tolerance to Gal alpha 1,3Gal-expressing heart xenografts is achieved in alpha 1,3-galactosyltransferase-deficient mice by nomyeloablative induction of mixed chimerism SO TRANSPLANTATION LA English DT Article ID NONLETHAL PREPARATIVE REGIMEN; ACUTE VASCULAR REJECTION; BONE-MARROW ENGRAFTMENT; CLASS II+ CELLS; NATURAL ANTIBODIES; MONOCLONAL-ANTIBODIES; IN-VIVO; LYMPHOHEMATOPOIETIC CHIMERISM; XENOGENEIC CHIMERAS; EPITOPES AB Background. We have previously demonstrated that mixed xenogeneic chimerism and donor-specific T-cell tolerance can be induced in the rat-to-mouse species combination by using a relatively nontoxic, nonmyeloablative conditioning regimen. However, natural antibodies (NAbs) against Gal alpha1,3Gal (Gal) pose an additional major barrier to pig-to-human vascularized xenograft acceptance. Methods, To determine whether the mixed chimerism approach could also overcome this humoral barrier, T cell-depleted rat (GalT(+/+)) bone marrow cells (BMC) were transplanted to alpha1,3-galactosyltransferase deficient (GalT(-/-)) mice conditioned with a nonmyeloablative regimen, consisting of transient T cell and natural killer (NK) cell depletion, 3 Gy whole body irradiation, and 7 Gy thymic irradiation. Results. By giving a high dose (180x10(6)) of rat BMC, persistent mixed chimerism could be induced in GalT(-/-) mice, although the level of donor-type hematopoietic repopulation declined over time. Induction of mixed chimerism was associated with a rapid disappearance of anti-Gal and anti-rat NAb in the sera. Both anti-Gal Ab-producing cells and B cells with receptors recognizing Gal were undetectable in mixed chimeras, even when the chimerism levels declined, suggesting that a very low level of chimerism could effectively maintain B-cell tolerance to Gal, probably by clonal deletion and/or receptor editing. Mixed chimeras accepted subsequently transplanted donor-type rat hearts (>100 days) without immunosuppressive therapy, whereas delayed vascular and even hyperacute rejection of rat hearts occurred in conditioned control GalT(-/-) mice, Cellular rejection occurred by 5-6 days in conditioned control wild-type mice. Conclusions, These findings demonstrate that induction of mixed chimerism with a nonmyeloablative regimen can prevent vascularized xenograft rejection by cellular and anti-Gal Ab-dependent pathways in GalT(+/+)-to-GalT(-/-) species combinations. C1 Harvard Univ, Sch Med,Massachusetts Gen Hosp, Surg Serv,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Sch Med,Massachusetts Gen Hosp, Surg Serv,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [R0I HL 49915, P0I HL 18646] NR 52 TC 46 Z9 48 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 JUN 15 PY 2001 VL 71 IS 11 BP 1532 EP 1542 DI 10.1097/00007890-200106150-00009 PG 11 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 444VN UT WOS:000169420900009 PM 11435961 ER PT J AU Alwayn, IPJ Buhler, L Appel, JZ Goepfert, C Csizmadia, E Correa, L Harper, D Kitamura, H Down, J Awwad, M Sackstein, R Cooper, DKC Robson, SC AF Alwayn, IPJ Buhler, L Appel, JZ Goepfert, C Csizmadia, E Correa, L Harper, D Kitamura, H Down, J Awwad, M Sackstein, R Cooper, DKC Robson, SC TI Mechanisms of thrombotic microangiopathy following xenogeneic hematopoietic progenitor cell transplantation SO TRANSPLANTATION LA English DT Article ID P-SELECTIN; BONE-MARROW; ALLOGRAFT TOLERANCE; MIXED CHIMERISM; INDUCTION; ADHESION; BABOONS; PIG; ANTIBODY; REGIMEN AB Introduction. Attempts to induce tolerance though mixed hematopoietic chimerism in the discordant pig-to-baboon xenotransplantation model are sometimes complicated by a potentially fatal thrombotic microangiopathy in the recipient baboons. This state develops immediately after the infusion of porcine mobilized peripheral blood leukocytes, containing progenitor cells (PBPC), In our study, we examined the interaction of infused porcine PBPC with recipient platelets in vivo in baboons and investigated the underlying mechanisms using an in vitro model. Methods. Two naive baboons and six baboons preconditioned with irradiation and immunosuppression that received porcine PBPC were evaluated in vivo. The interaction of porcine and baboon PBPC with baboon platelets was investigated by an in vitro platelet aggregation assay. Fresh and cryopreserved PBPC were evaluated as well as PBPC obtained from growth-factor mobilized and unmobilized pigs. Furthermore, cellular subsets of PBPC were assessed for potential to induce platelet aggregation. Immunohistochemical staining was performed on platelet-leukocyte aggregates and potential inhibition of aggregation with anti-P-selectin and anti-CD154 mAbs, or eptifibatide (a GPIIb/IIIa receptor antagonist), was tested. Results. All baboons that received porcine PBPC rapidly developed marked thrombocytopenia (<20,000/L), elevated serum lactate dehydrogenase (>1,500U/Liter), schistocytosis, and platelet aggregates on blood smear. Three baboons died (two untreated and one preconditioned), and substantive platelet aggregates containing porcine leukocytes were observed in the microvasculature of lungs and kidneys, In vitro, porcine, but not baboon, PBPC induced aggregation of baboon platelets in a dose-dependent manner. Immunohistological examination of these aggregates confirmed the incorporation of porcine leukocytes, Cryopreserved PBPC caused less aggregation than fresh PBPC, and growth-factor-mobilized PBPC induced less aggregation than unmobilized PBPC, Aggregation was fully abrogated by the addition of eptifibatide, and modulated by anti-P-selectin and anti-CD154 monoclonal antibodies that recognize adhesion receptors on activated platelets. Purified fractions (granulocytes, CD2+, and CD- cells) of porcine PBPC did not initiate aggregation, whereas addition of exogenous porcine PBPC membranes (erythrocytes, dead cells, and/or platelets) to the purified fractions exacerbated the aggregation response, Conclusions, These data indicate that porcine PBPC mediate aggregation of baboon platelets, This process likely contributes to the thrombotic microangiopathy observed after PBPC transplantation in the pig-to-baboon model. Eptifibatide can fully abrogate platelet aggregation induced by porcine PBPC in vitro. Purification of the progenitor cells from porcine PBPC and/or treatment of baboons with eptifibatide may be beneficial. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Immunol, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. Biotransplant Inc, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Robson, SC (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Immunol, 99 Brookline Ave,Room 370, Boston, MA 02215 USA. FU NIAID NIH HHS [AI 45897-O1A1] NR 29 TC 29 Z9 30 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 JUN 15 PY 2001 VL 71 IS 11 BP 1601 EP 1609 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 444VN UT WOS:000169420900020 PM 11435972 ER PT J AU Lee, TH Boucher, CA AF Lee, TH Boucher, CA TI Noninvasive tests in patients with stable coronary artery disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID AMERICAN-HEART-ASSOCIATION; PHARMACOLOGICAL STRESS ECHOCARDIOGRAPHY; MYOCARDIAL PERFUSION SPECT; TASK-FORCE; RISK STRATIFICATION; PRACTICE GUIDELINES; PROGNOSTIC VALUE; EXERCISE ECHOCARDIOGRAPHY; ACC/AHA GUIDELINES; COST-EFFECTIVENESS C1 Partners Healthcare Syst, Boston, MA 02199 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lee, TH (reprint author), Partners Healthcare Syst, Prudential Tower,11th Fl,800 Boylston St, Boston, MA 02199 USA. NR 24 TC 77 Z9 80 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 14 PY 2001 VL 344 IS 24 BP 1840 EP 1845 DI 10.1056/NEJM200106143442406 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 441LC UT WOS:000169231000006 PM 11407346 ER PT J AU Block, SD AF Block, SD TI Psychological considerations, growth, and transcendence at the end of life - The art of the possible SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ILL CANCER-PATIENTS; TERMINALLY ILL; PSYCHIATRIC MORBIDITY; BIOPSYCHOSOCIAL MODEL; PATIENTS PERSPECTIVES; DOUBLE-BLIND; GOOD DEATH; ILLNESS; DEPRESSION; DELIRIUM C1 Dana Farber Canc Inst, Dept Adult Psychosocial Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Block, SD (reprint author), Dana Farber Canc Inst, Dept Adult Psychosocial Oncol, 44 Binney St, Boston, MA 02115 USA. NR 99 TC 145 Z9 146 U1 1 U2 8 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 JUN 13 PY 2001 VL 285 IS 22 BP 2898 EP 2905 DI 10.1001/jama.285.22.2898 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 440BP UT WOS:000169156300030 PM 11401612 ER PT J AU Fischer, H Tillfors, M Furmark, T Fredrikson, M AF Fischer, H Tillfors, M Furmark, T Fredrikson, M TI Dispositional pessimism and amygdala activity: a PET study in healthy volunteers SO NEUROREPORT LA English DT Article DE affective style; attributional style; brain; emotion; human; negative affect; neuroimaging; positron emission tomography ID POSITRON-EMISSION-TOMOGRAPHY; NEGATIVE AFFECT; DEPRESSION; SADNESS; PROJECTIONS; VALIDATION; SCANS; FEAR AB The present study used scores from Seligman's Attribution Style Questionnaire and [O-15] water positron emission tomographic measurements of regional cerebral blood flow (rCBF) to investigate the relation between individual differences in dispositional pessimism and amygdala activity. During scanning 13 healthy non-snake-phobic females passively viewed a snake videotape. Using one-tailed tests, significant negative correlations were evident between pessimism scores, with low scores reflecting relatively more pessimism, and right (r=-0.60; p=0.014) and left amygdala rCBF (r=-0.53;p=0.032). These results extend previous neuroimaging findings in healthy subjects indicating a role for the amygdala in transient negative emotional states, and suggest that this multimodal brain region also is involved in more durable negative affects such as dispositional pessimism. NeuroReport 12:1635-1638 (C) 2001 Lippincott Williams & Wilkins. C1 Uppsala Univ, Dept Psychol, Uppsala, Sweden. Massachusetts Gen Hosp, Psychiat Neuroimaging Res Grp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Uppsala Hosp, PET Ctr, SE-75142 Uppsala, Sweden. RP Fredrikson, M (reprint author), Uppsala Univ, Dept Psychol, Uppsala, Sweden. NR 28 TC 20 Z9 20 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUN 13 PY 2001 VL 12 IS 8 BP 1635 EP 1638 DI 10.1097/00001756-200106130-00024 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 440QH UT WOS:000169185400020 PM 11409730 ER PT J AU Mittleman, MA Lewis, RA Maclure, M Sherwood, JB Muller, JE AF Mittleman, MA Lewis, RA Maclure, M Sherwood, JB Muller, JE TI Triggering myocardial infarction by marijuana SO CIRCULATION LA English DT Article DE cannabis; myocardial infarction; epidemiology; cross-over studies ID CASE-CROSSOVER DESIGN; PHYSICAL EXERTION; RISK; MECHANISMS; CANNABIS; ONSET AB Background-Marijuana use in the age group prone to coronary artery disease is higher than it was in the past. Smoking marijuana is known to have hemodynamic consequences, including a dose-dependent increase in heart rate, supine hypertension, and postural hypotension; however, whether it can trigger the onset of myocardial infarction is unknown. Methods and Results - In the Determinants of Myocardial Infarction Onset Study, we interviewed 3882 patients (1258 women) with acute myocardial infarction an average of 4 days after infarction onset. We used the case-crossover study design to compare the reported use of marijuana in the hour preceding symptoms of myocardial infarction onset to its expected frequency using self-matched control data. Of the 3882 patients, 124 (3.2%) reported smoking marijuana in the prior year, 37 within 24 hours and 9 within 1 hour of myocardial infarction symptoms. Compared with nonusers, marijuana users were more likely to be men (94% versus 67%, P <0.001), current cigarette smokers (68% versus 32%, P <0.001), and obese (43% versus 32%, P=0.008). They were less likely to have a history of angina (12% versus 25%, P <0.001) or hypertension (30% versus 44%, P=0.002). The risk of myocardial infarction onset was elevated 4.8 times over baseline (95% confidence interval, 2.4 to 9.5) in the 60 minutes after marijuana use. The elevated risk rapidly decreased thereafter. Conclusions - Smoking marijuana is a rare trigger of acute myocardial infarction, Understanding the mechanism through which marijuana causes infarction may provide insight into the triggering of myocardial infarction by this and other, more common stressors. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Cardiovasc Div, Inst Prevent Cardiovasc Dis,Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA. RP Mittleman, MA (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Cardiovasc Div, Inst Prevent Cardiovasc Dis,Dept Med, 1 Autumn St,5th Floor, Boston, MA 02215 USA. FU NHLBI NIH HHS [HL41016] NR 35 TC 241 Z9 249 U1 5 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 12 PY 2001 VL 103 IS 23 BP 2805 EP 2809 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 443RF UT WOS:000169353600019 PM 11401936 ER PT J AU Peters, A Dockery, DW Muller, JE Mittleman, MA AF Peters, A Dockery, DW Muller, JE Mittleman, MA TI Increased particulate air pollution and the triggering of myocardial infarction SO CIRCULATION LA English DT Article DE myocardial infarction; air pollution; heart disease; epidemiology ID HEART-RATE-VARIABILITY; DAILY TIME-SERIES; HOSPITAL ADMISSIONS; CASE-CROSSOVER; CARDIOVASCULAR-DISEASE; PHYSICAL EXERTION; EXPOSURES; MORTALITY; PROJECT; EPISODE AB Background - Elevated concentrations of ambient particulate air pollution have been associated with increased hospital admissions for cardiovascular disease. Whether high concentrations of ambient particles can trigger the onset of acute myocardial infarction (MI), however, remains unknown. Methods and Results - We interviewed 772 patients with MI in the greater Boston area between January 1995 and May 1996 as part of the Determinants of Myocardial Infarction Onset Study. Hourly concentrations of particle mass (2.5 mum (PM2.5), carbon black, and gaseous air pollutants were measured. A case-crossover approach was used to analyze the data for evidence of triggering. The risk of MI onset increased in association with elevated concentrations of fine particles in the previous 2-hour period. In addition, a delayed response associated with 24-hour average exposure 1 day before the onset of symptoms was observed. Multivariate analyses considering both time windows jointly revealed an estimated odds ratio of 1.48 associated with an increase of 25 mug/m(3) PM2.5 during a 2-hour period before the onset and an odds ratio of 1.69 for an increase of 20 mug/m(3) PM2.5 in the 24-hour period 1 day before the onset (95% CIs 1.09, 2.02 and 1.13, 2.34, respectively). Conclusions - The present study suggests that elevated concentrations of fine particles in the air may transiently elevate the risk of MIs within a few hours and 1 day after exposure. Further studies in other locations are needed to clarify the importance of this potentially preventable trigger of MI. C1 GSF, Natl Res Ctr Environm & Hlth, Inst Epidemiol, D-85758 Neuherberg, Germany. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med,Inst Prevent Cardiovasc Dis, Div Cardiovasc,Dept Med, Boston, MA 02215 USA. RP Peters, A (reprint author), GSF, Natl Res Ctr Environm & Hlth, Inst Epidemiol, POB 1129, D-85758 Neuherberg, Germany. RI Peters, Annette/A-6117-2011 FU NHLBI NIH HHS [HL-41016]; NIEHS NIH HHS [ES 00002] NR 33 TC 791 Z9 829 U1 10 U2 134 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 12 PY 2001 VL 103 IS 23 BP 2810 EP 2815 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 443RF UT WOS:000169353600020 PM 11401937 ER PT J AU Johnson, KA Lopera, F Jones, K Becker, A Sperling, R Hilson, J Londono, J Siegert, I Arcos, M Moreno, S Madrigal, L Ossa, J Pineda, N Ardila, A Roselli, M Albert, MS Kosik, KS Rios, A AF Johnson, KA Lopera, F Jones, K Becker, A Sperling, R Hilson, J Londono, J Siegert, I Arcos, M Moreno, S Madrigal, L Ossa, J Pineda, N Ardila, A Roselli, M Albert, MS Kosik, KS Rios, A TI Presenilin-1-associated abnormalities in regional cerebral perfusion SO NEUROLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; MILD ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; HIPPOCAMPAL-FORMATION; SPECT; CORTEX; ALLELE; DEGENERATION; ASSOCIATION; DIAGNOSIS AB Objective: To investigate the influence of the presenilin-1 gene (PS-1) mutation on regional cerebral perfusion, SPECT was evaluated in 57 individuals. The subjects were members of a large pedigree from Colombia, South America, many of whom carry a PS-1 mutation for early-onset AD. Methods: Members of this large kindred who were cognitively normal and did not carry the PS-1 mutation (n = 23) were compared with subjects who were carriers of the mutation but were asymptomatic (n = 18) and with individuals with the mutation and a clinical diagnosis of AD (n = 16). Cerebral perfusion was measured in each subject using hexamethylpropyleneamine oxime SPECT. The data were analyzed in two ways: 1) Mean cerebral perfusion in each of 4320 voxels in the brain was compared among the groups using t-tests (t-maps); and 2) each individual received a weighted score on 20 vectors (factors), based on a large normative sample (n = 200), using a method known as singular value decomposition (SVD). Results: Based on t-maps, subjects with the PS-1 mutation who were asymptomatic demonstrated reduced perfusion in comparison with the normal control subjects in the hippocampal complex, anterior and posterior cingulate, posterior parietal lobe, and anterior frontal lobe. The AD patients demonstrated decreased perfusion in the posterior parietal and superior frontal cortex in comparison with the normal control subjects. Discriminant function analysis of the vector scores derived from SVD (adjusted for age and gender) accurately discriminated 86% of the subjects in the three groups (p < 0.0005). Conclusion: Regional cerebral perfusion abnormalities based on SPECT are detectable before development of the clinical symptoms of AD in carriers of the PS-1 mutation. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Antioquia Univ, Sch Med, Medellin, Colombia. Brandeis Univ, Waltham, MA 02254 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Johnson, KA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, 75 Francis St, Boston, MA 02115 USA. OI Pineda Trujillo, Nicolas/0000-0002-8342-2510 FU NIA NIH HHS [P01-AG04953] NR 45 TC 49 Z9 51 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 JUN 12 PY 2001 VL 56 IS 11 BP 1545 EP 1551 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 440RB UT WOS:000169187100019 PM 11402113 ER PT J AU Dimitroff, CJ Lee, JY Rafii, S Fuhlbrigge, RC Sackstein, R AF Dimitroff, CJ Lee, JY Rafii, S Fuhlbrigge, RC Sackstein, R TI CD44 is a major E-selectin ligand on human hematopoietic progenitor cells SO JOURNAL OF CELL BIOLOGY LA English DT Article DE hematopoietic stem cells; E-selectin; CD44; PSGL-1; CLA ID CUTANEOUS LYMPHOCYTE ANTIGEN; HUMAN BONE-MARROW; LEUKOCYTE ADHESION MOLECULE-1; HOMING T-CELLS; P-SELECTIN; ENDOTHELIAL SELECTINS; CD34(+) CELLS; GROWTH-FACTOR; BINDING; EXPRESSION AB E-selectin plays a critical role in mediating tissue-specific homing of T cells into skin, and of primitive hematopoietic progenitor cells (HPCs) into bone marrow (BM). Though it is known that a glycoform of PSGL-1 (CLA) functions as the principal E-selectin ligand on human T lymphocytes, the E-selectin Ligand(s) of human HPCs has not been identified. We used a shear-based adherence assay to analyze and define the E-selectin ligand activity of membrane proteins from human HPCs, Our data show that PSGL-1 expressed on human HPCs is an E-selectin ligand, and that HPCs also express a previously unrecognized E-selectin ligand, CD44, The E-selectin ligand activity of CD44 is conferred by the elaboration of sialylated, fucosylated binding determinants on N-glycans. This glycoform of CD44 is expressed on primitive CD34+ human HPCs, but not on more mature hematopoietic cells. Under physiologic flow conditions, this molecule mediates E-selectin-dependent rolling interactions over a wider shear range than that of PSGL-1, and promotes human HPC rolling interactions on E-selectin expressed on human BM endothelial cells. These findings offer new insights into the structural biology and physiology of CD44, and into the molecular basis of E-selectin-dependent adhesive interactions that direct homing of human HPC to BM. C1 Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Bone Marrow Transplant Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Skin Dis Res Ctr, Boston, MA 02115 USA. Cornell Univ, Med Ctr, New York Hosp, Div Hematol Oncol, New York, NY 10021 USA. RP Sackstein, R (reprint author), Harvard Univ, Inst Med, 77 Ave Louis Pasteur,Room 671, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA084156, R01 CA84156]; NHLBI NIH HHS [R01 HL060528, R01 HL60528] NR 41 TC 170 Z9 176 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUN 11 PY 2001 VL 153 IS 6 BP 1277 EP 1286 DI 10.1083/jcb.153.6.1277 PG 10 WC Cell Biology SC Cell Biology GA 443AX UT WOS:000169318100014 PM 11402070 ER PT J AU Arterburn, D Noel, PH AF Arterburn, D Noel, PH TI Extracts from "Clinical Evidence" - Obesity SO BRITISH MEDICAL JOURNAL LA English DT Review ID PRIMARY PULMONARY-HYPERTENSION; WEIGHT-LOSS; CONTROLLED TRIAL; DOUBLE-BLIND; APPETITE-SUPPRESSANT; UNITED-STATES; ORLISTAT; SIBUTRAMINE; EFFICACY; PLACEBO C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. US Dept Vet Affairs, S Texas Vet Hlth Care Syst, VERDICT, San Antonio, TX 78284 USA. RP Arterburn, D (reprint author), Univ Texas, Hlth Sci Ctr, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 48 TC 23 Z9 25 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD JUN 9 PY 2001 VL 322 IS 7299 BP 1406 EP 1409 DI 10.1136/bmj.322.7299.1406 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 442KN UT WOS:000169284600020 PM 11397749 ER PT J AU Kontrogianni-Konstantopoulos, A Frye, CS Benz, EJ Huang, SC AF Kontrogianni-Konstantopoulos, A Frye, CS Benz, EJ Huang, SC TI The prototypical 4.1R-10-kDa domain and the 4.1G-10-kDa paralog mediate fodrin-actin complex formation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RED-CELL MEMBRANE; BRAIN SPECTRIN FODRIN; PRE-MESSENGER-RNA; PROTEIN-4.1 FAMILY; BETA-SPECTRIN; CYTOSKELETAL PROTEIN-4.1; ERYTHROCYTE SPECTRIN; SKELETAL PROTEIN-4.1; NONERYTHROID CELLS; PC12 CELLS AB A complex family of 4.1R isoforms has been identified in non-erythroid tissues. In this study we characterized the exonic composition of brain 4.1R-10-kDa or spectrin/actin binding (SAB) domain and identified the minimal sequences required to stimulate fodrin/F-actin association. Adult rat brain expresses predominantly 4.1R mRNAs that carry an extended SAB, consisting of the alternative exons 14/15/16 and part of the constitutive exon 17. Exon 16 along with sequences carried by exon 17 is necessary and sufficient to induce formation of fodrin-actin-4.1R ternary complexes. The ability of the respective SAB domains of 4.1 homologs to sediment fodrin/actin was also investigated. 4.1G-SAB stimulates association of fodrin/actin, although with an similar to2-fold reduced efficiency compared with 4.1R-10-kDa, whereas 4.1N and 4.1B do not. Sequencing of the corresponding domains revealed that 4.1G-SAB carries a cassette that shares significant homology with 4.1R exon 16, whereas the respective sequence is divergent in 4.1N and absent from brain 4.1B. An similar to 150-kDa 4.1R and an similar to 160-kDa 4.1G isoforms are present in PC12 lysates that occur in vivo in a supramolecular complex with fodrin and F-actin. Moreover, proteins 4.1R and 4.1G are distributed underneath the plasma membrane in PC12 cells. Collectively, these observations suggest that brain 4.1R and 4.1G may modulate the membrane mechanical properties of neuronal cells by promoting fodrin/actin association. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. RP Huang, SC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, D1420B,44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL 44985] NR 53 TC 25 Z9 26 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 8 PY 2001 VL 276 IS 23 BP 20679 EP 20687 DI 10.1074/jbc.M010581200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 439UC UT WOS:000169135100134 PM 11274145 ER PT J AU Xin, Y Fong, YT Wolf, G Wolf, D Cao, W AF Xin, Y Fong, YT Wolf, G Wolf, D Cao, W TI Protective effect of XY99-5038 on hydrogen peroxide induced cell death in cultured retinal neurons SO LIFE SCIENCES LA English DT Article DE XY99-5038; oxidative stress; hydrogen peroxide; apoptosis; neuroprotection; retinal neuronal culture; Yan Xin qigong; traditional Chinese medicine; external qi ID OXIDATIVE STRESS; ASCORBIC-ACID; LIGHT DAMAGE; APOPTOSIS; EPITHELIUM; PROTEIN; REPAIR AB XY99-5038 is a preparation from a specific formula provided by Dr. Yan Xin, a renowned Traditional Chinese Medicine specialist. This formulation has proven to be effective without side effects but has not been studied under rigorous laboratory conditions. In order to investigate the role of XY99 -5038 in protecting neurons from degeneration, we used retinal neuronal culture as a model system to study the protective effects of XY99-5038 against hydrogen peroxide (H2O2) induced cytotoxicity. Basic fibroblast growth factor (bFGF), a potent neurotrophic factor, was employed as comparable agent. Retinas of 0-2 days old Sprague-Dawley rats were isolated, dissociated, and the neurons maintained for 2 weeks in a synthetic serum-free media, Cytotoxicity was determined by MTT (3,(4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide) and LDH (Lactate dehydrogenase) assays, whereas apoptotic cell death was evaluated by the TUNEL (TdT-mediated digoxigenin-dUTP nick-end labeling) assay. Treatment with H2O2 significantly induced death of retinal neurons. Pretreatment with XY99-5038 prior to insult greatly inhibited or attenuated H2O2 induced cytotoxicity and apoptosis. These effects were shown to be dose-dependent. Our data also show that the protective effect of XY99-5038 is more potent than that of bFGF. Our data suggest that XY99-5038 could be a potential agent in the treatment of disorders associated with oxidative damage. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Univ Oklahoma, Dept Ophthalmol, Dean A McGee Eye Inst, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. Inst Chongchi Tradit Chinese Med, Chongchi, Sichuang, Peoples R China. Amer Biol Engn Sci Res Inst, Glendale, CA 91201 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Cao, W (reprint author), Univ Oklahoma, Dept Ophthalmol, Dean A McGee Eye Inst, Hlth Sci Ctr, 608 Stanton L Young Blvd, Oklahoma City, OK 73104 USA. FU NEI NIH HHS [EY12190] NR 27 TC 10 Z9 10 U1 1 U2 17 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 JUN 8 PY 2001 VL 69 IS 3 BP 289 EP 299 DI 10.1016/S0024-3205(01)01122-5 PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 441CY UT WOS:000169214500006 PM 11441920 ER PT J AU Mullen, AC High, FA Hutchins, AS Lee, HW Villarino, AV Livingston, DM Kung, AL Cereb, N Yao, TP Yang, SY Reiner, SL AF Mullen, AC High, FA Hutchins, AS Lee, HW Villarino, AV Livingston, DM Kung, AL Cereb, N Yao, TP Yang, SY Reiner, SL TI Role of T-bet in commitment of T(H)1 cells before IL-12-dependent selection SO SCIENCE LA English DT Article ID CYTOKINE GENE-EXPRESSION; TRANSCRIPTION FACTOR; SIGNAL TRANSDUCER; TH2 CELLS; ACTIVATION; RESPONSES; STAT6; IL-4; DIFFERENTIATION; INTERLEUKIN-4 AB How cytokines control differentiation of helper T (T-H) cells is controversial. We show that T-bet, without apparent assistance from interleukin 12 (IL-12)/ STAT4, specifies T(H)1 effector fate by targeting chromatin remodeling to individual interferon-gamma (IFN-gamma) alleles and by inducing IL-12 receptor beta2 expression. Subsequently, it appears that IL-12/STAT4 serves two essential functions in the development of T(H)1 cells: as growth signal, inducing survival and cell division; and as trans-activator, prolonging IFN-gamma synthesis through a genetic interaction with the coactivator, CREB-binding protein. These results suggest that a cytokine does not simply induce T-H fate choice but instead may act as an essential secondary stimulus that mediates selective survival of a lineage. C1 Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Histogenet Inc, Hawthorne, NY 10532 USA. Ctr Genet Polymorphism, Hawthorne, NY 10532 USA. Duke Univ, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. RP Reiner, SL (reprint author), Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. OI Villarino, Alejandro/0000-0001-8068-2176 FU NEI NIH HHS [EY-07131]; NIAID NIH HHS [AI-42370] NR 28 TC 555 Z9 586 U1 0 U2 8 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 8 PY 2001 VL 292 IS 5523 BP 1907 EP 1910 DI 10.1126/science.1059835 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 440WY UT WOS:000169200700048 PM 11397944 ER PT J AU Grupe, A Germer, S Usuka, J Aud, D Belknap, JK Klein, RF Ahluwalia, MK Higuchi, R Peltz, G AF Grupe, A Germer, S Usuka, J Aud, D Belknap, JK Klein, RF Ahluwalia, MK Higuchi, R Peltz, G TI In silico mapping of complex disease-related traits in mice SO SCIENCE LA English DT Article ID ALCOHOL PREFERENCE; ALLERGIC-ASTHMA; INBRED MICE; LOCI; MOUSE; GENES; IDENTIFICATION; DISCOVERY; DRINKING; MODELS AB Experimental murine genetic models of complex human disease show great potential for understanding human disease pathogenesis. To reduce the time required for analysis of such models from many months down to milliseconds, a computational method for predicting chromosomal regions regulating phenotypic traits and a murine database of single nucleotide polymorphisms were developed. After entry of phenotypic information obtained from inbred mouse strains, the phenotypic and genotypic information is analyzed in silico to predict the chromosomal regions regulating the phenotypic trait. C1 Roche Biosci, Dept Genet & Genome, Palo Alto, CA 94303 USA. Roche Mol Syst, Alameda, CA 94501 USA. Stanford Univ, Dept Chem, Stanford, CA 94305 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. RP Peltz, G (reprint author), Roche Biosci, Dept Genet & Genome, Palo Alto, CA 94303 USA. FU NHGRI NIH HHS [T32HG-00044, 1 R01 HG02322-01]; NIAAA NIH HHS [P60 AA010760]; NIAMS NIH HHS [R01 AR044659, R01 AR044659-07] NR 22 TC 222 Z9 234 U1 0 U2 7 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 8 PY 2001 VL 292 IS 5523 BP 1915 EP 1918 DI 10.1126/science.1058889 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 440WY UT WOS:000169200700050 PM 11397946 ER PT J AU Tilles, AW Baskaran, H Roy, P Yarmush, ML Toner, M AF Tilles, AW Baskaran, H Roy, P Yarmush, ML Toner, M TI Effects of oxygenation and flow on the viability and function of rat hepatocytes cocultured in a microchannel flat-plate bioreactor SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE bioartificial liver; microfabrication; flat plate; perfusion; shear stress ID BIOARTIFICIAL LIVER; NONPARENCHYMAL CELLS; SHEAR-STRESS; PERFUSION; DEVICES; TRANSPORT; CULTURES; FAILURE; DESIGN; TRIAL AB The goal of this study was to investigate the viability and synthetic function of rat hepatocytes cocultured with 3T3-J2 fibroblasts in a small-scale microchannel flat-plate bioreactor with and without an internal membrane oxygenator under flow. Bioreactor channel heights ranged between 85 and 500 mum and medium flow rates ranged between 0.06 and 4.18 mL/min. The results showed that the bioreactor without the oxygenator resulted in significantly decreased viability and function of hepatocytes, whereas hepatocytes in the bioreactor with internal membrane oxygenator were able to maintain their viability and function. The shear stress calculations showed that, at lower wall shear stresses (0.01 to 0.33 dyn/cm(2)), hepatocyte functions, measured as albumin and urea synthesis rates, were as much as 2.6- and 1.9-fold greater, respectively, than those at higher wall shear stresses (5 to 21 dyn/cm(2)). Stable albumin and urea synthesis rates for 10 days of perfusion were also demonstrated in the bioreactor with internal membrane oxygenator. These results are relevant in the design of hepatocyte bioreactors and the eventual scaling-up to clinical devices. (C) 2001 John Wiley & Sons, Inc. C1 Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Toner, M (reprint author), Massachusetts Gen Hosp, Ctr Engn Med, Bigelow 1401,55 Fruit St, Boston, MA 02114 USA. RI Yu, weiting/I-7417-2013 FU NCRR NIH HHS [RR 13322]; NIDDK NIH HHS [DK 43371] NR 32 TC 190 Z9 195 U1 1 U2 22 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD JUN 5 PY 2001 VL 73 IS 5 BP 379 EP 389 DI 10.1002/bit.1071 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 431BR UT WOS:000168612500006 PM 11320508 ER PT J AU Pujol, N Link, EM Liu, LX Kurz, CL Alloing, G Tan, MW Ray, KP Solari, R Johnson, CD Ewbank, JJ AF Pujol, N Link, EM Liu, LX Kurz, CL Alloing, G Tan, MW Ray, KP Solari, R Johnson, CD Ewbank, JJ TI Reverse genetic analysis of components of the Toll signaling pathway in Caenorhabditis elegans SO CURRENT BIOLOGY LA English DT Article ID DROSOPHILA HOST-DEFENSE; INSECT PATHOGENIC PROPERTIES; IMMUNE-RESPONSE REQUIRES; PHAGE-RESISTANT MUTANTS; C-ELEGANS; INNATE IMMUNITY; SERRATIA-MARCESCENS; RECEPTOR FAMILY; PROTEIN; NEMATODES AB Background: Both animals and plants respond rapidly to pathogens by inducing the expression of defense-related genes. Whether such an inducible system of innate immunity is present in the model nematode Caenorhabditis elegans is currently an open question. Among conserved signaling pathways important for innate immunity, the Toll pathway is the best characterized. In Drosophila, this pathway also has an essential developmental role. C, elegans possesses structural homologs of components of this pathway, and this observation raises the possibility that a Toll pathway might also function in nematodes to trigger defense mechanisms or to control development. Results: We have generated and characterized deletion mutants for four genes supposed to function in a nematode Toll signaling pathway. These genes are tol-1, trf-1, pik-1, and ikb-1 and are homologous to the Drosophila melanogaster Toll, dTraf pelle, and cactus genes, respectively. Of these four genes, only tol-l is required for nematode development, None of them are important for the resistance of C. elegans to a number of pathogens. On the other hand, C. elegans is capable of distinguishing different bacterial species and has a tendency to avoid certain pathogens, including Serratia marcescens, The tol-1 mutants are defective in their avoidance of pathogenic S. marcescens, although other chemosensory behaviors are wild type. Conclusions: In C, elegans, tol-1 is important for development and pathogen recognition, as is Toll in Drosophila, but remarkably for the latter role, it functions in the context of a behavioral mechanism that keeps worms away from potential danger. C1 Univ Aix Marseille 2, CNRS, INSERM, Ctr Immunol Marseille Luminy, F-13288 Marseille, France. Univ Aix Marseille 2, Lab Genet & Physiol Dev, F-13288 Marseille, France. Glaxo Wellcome Res, Stevenage SG1 2NY, Herts, England. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. NemaPharm Inc, Cambridge, MA 02139 USA. RP Ewbank, JJ (reprint author), Univ Aix Marseille 2, CNRS, INSERM, Ctr Immunol Marseille Luminy, F-13288 Marseille, France. EM ewbank@ciml.univ-mrs.fr RI Ewbank, Jonathan/G-4948-2010; Pujol, Nathalie/K-3880-2012; Marion-Poll, Frederic/D-8882-2011; Kurz, Cyril/L-7615-2016; Tang, Amy/L-3226-2016 OI Ewbank, Jonathan/0000-0002-1257-6862; Pujol, Nathalie/0000-0001-8889-3197; Marion-Poll, Frederic/0000-0001-6824-0180; Tang, Amy/0000-0002-5772-2878 NR 76 TC 244 Z9 258 U1 2 U2 25 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUN 5 PY 2001 VL 11 IS 11 BP 809 EP 821 DI 10.1016/S0960-9822(01)00241-X PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 440WV UT WOS:000169200400014 PM 11516642 ER PT J AU Shi, FD Flodstrom, M Balasa, B Kim, SH Van Gunst, K Strominger, JL Wilson, SB Sarvetnick, N AF Shi, FD Flodstrom, M Balasa, B Kim, SH Van Gunst, K Strominger, JL Wilson, SB Sarvetnick, N TI Germ line deletion of the CD1 locus exacerbates diabetes in the NOD mouse SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID KILLER T-CELLS; NKT CELLS; INTERFERON-GAMMA; TRANSGENIC MICE; GENETIC-CONTROL; AUTOIMMUNITY; EXPRESSION; MELLITUS; PROLIFERATION; SECRETION AB Quantitative and qualitative defects in CD1-restricted natural killer T cells have been reported in several autoimmune-prone strains of mice, including the nonobese diabetic (NOD) mouse. These defects are believed to be associated with the emergence of spontaneous autoimmunity. Here we demonstrate that both CD1d-null NOD and CD1d-null NOD/BDC2.5 T cell receptor transgenic mice have an accelerated onset and increased incidence of diabetes when compared with CD1d(+/-) and CD1d(+/+) littermates, The acceleration of disease did not seem to result from changes in the T helper (Th)1/Th2 balance because lymphocytes purified from lymphoid organs and pancreatic islets of wild-type and CD1d-null mice secreted equivalent amounts of IFN-gamma and IL-4 after stimulation. In contrast, the pancreata of CD1d-null mice harbored significantly higher numbers of activated memory T cells expressing the chemokine receptor CCR4, Notably, the presence of these T cells was associated with immunohistochemical evidence of increased destructive insulitis, Thus, CD1d-restricted T cells are critically important for regulation of the spontaneous disease process in NOD mice. C1 Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sarvetnick, N (reprint author), Scripps Res Inst, Dept Immunol, IMM-23,10555 N Torrey Pines Rd, La Jolla, CA 92037 USA. NR 31 TC 138 Z9 140 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 JUN 5 PY 2001 VL 98 IS 12 BP 6777 EP 6782 DI 10.1073/pnas.121169698 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 440AT UT WOS:000169151500046 PM 11390999 ER PT J AU Jun, CD Shimaoka, M Carman, CV Takagi, J Springer, TA AF Jun, CD Shimaoka, M Carman, CV Takagi, J Springer, TA TI Dimerization and the effectiveness of ICAM-1 in mediating LFA-l-dependent adhesion SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-1; MOLECULE-1 ICAM-1; BINDING-SITE; I-DOMAIN; T-CELL; TRANSENDOTHELIAL MIGRATION; CRYSTAL-STRUCTURE; CROSS-LINKING; RECEPTOR; INTEGRIN AB Dimeric intercellular adhesion molecule-1 (ICAM-1) binds more efficiently to lymphocyte function-associated antigen-1 (LFA-1) than monomeric ICAM-1. However, it is unknown whether dimerization enhances binding simply by providing two ligand-binding sites and thereby increasing avidity, or whether it serves to generate a single "fully competent" LFA-1-binding surface. Domain 1 of ICAM-1 contains both the binding site for LFA-1, centered on residue E34, and a homodimerization interface. Whether the LFA-1-binding site extends across the homodimerization interface has not been tested. To address this question, we constructed four different heterodimeric soluble forms of ICAM-1 joined at the C terminus via an cu-helical coiled coil (ACID-BASE). These heterodimeric ICAM-1 constructs include, (i) E34/E34 (two intact LFA-1-binding sites), (ii) E34/K34 tone disrupted LFA-1-binding site), (iii) E34/Delta D1-2 (one deleted LFA-1-binding site), and (iv) K34/K34 (two disrupted LFA-1-binding sites). Cells bearing activated LFA-1 bound similarly to surfaces coated with either E34/K34 or E34/Delta D1-2 and with an approximate to2-fold reduction in efficiency compared with E34/E34, suggesting that D1 dimerization. which is precluded in E34/Delta D1-D2. is not necessary for optimal LFA-1 binding. Furthermore, BIAcore (BIAcore, Piscataway, NJ) affinity measurements revealed that soluble open LFA-1 I domain bound to immobilized soluble ICAM-1, E34/E34. E34/K34, and E34/Delta D1-D2 with nearly identical affinities. These studies demonstrate that a single ICAM-1 monomer, not dimeric ICAM-1, represents the complete, "fully competent" LFA-1-binding surface. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. RI Carman, Christopher/L-8108-2016 OI Carman, Christopher/0000-0001-7358-2548 FU NCI NIH HHS [CA31798, R01 CA031798, R37 CA031798] NR 47 TC 46 Z9 58 U1 1 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 5 PY 2001 VL 98 IS 12 BP 6830 EP 6835 DI 10.1073/pnas.121186998 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 440AT UT WOS:000169151500055 PM 11391003 ER PT J AU Stair, TO Reed, CR Radeos, MS Koski, G Camargo, CA AF Stair, TO Reed, CR Radeos, MS Koski, G Camargo, CA CA MARC Investigators TI Variation in institutional review board responses to a standard protocol for a multicenter clinical trial SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE clinical trials; human subjects; institutional review board; multicenter research ID RESEARCH ETHICS COMMITTEES; INFORMED CONSENT; APPROVAL; SUGGESTIONS; READABILITY; PROTECTIONS; CHALLENGES AB Multicenter clinical trials require approval by multiple local institutional review boards (IRBs). The Multicenter Airway Research Collaboration mailed a clinical trial protocol to its U.S. investigators and 44 IRBs ultimately reviewed it. Objective: To describe IRE responses to one standard protocol and thereby gain insight into the advantages and disadvantages of local IRE review. Methods: Two surveys were mailed to participants, with telephone follow-up of nonrespondents. Survey 1 was mailed to 82 investigators across North America. Survey 2 was mailed to investigators from 44 medical centers in 17 U.S. states. Survey 1 asked about each investigator's local IRE (e.g., frequency of meetings, membership), whereas survey 2 asked about IRE queries and concerns related to the submitted clinical trial. Results: Both surveys had 100% response rate. Investigators submitted applications a median of 58 days (interquartile range [IQR], 40-83) after receipt of the protocol, and IRE approval took an additional 38 days (IQR, 26-62). Although eight applications were approved with little or no changes, IRBs requested an average of 3.5 changes per site. Changes involved study logistics and supervision for 45%, the research process for 43%, and the consent form for 91%. Despite these numerous requests, all eventually approved the basic protocol, including inclusion criteria, intervention, and data collection. Conclusions: The IRBs showed extreme variability in their initial responses to a standard protocol, but ultimately all gave approval. Almost all IRBs changed the consent form. A national, multicenter IRE process might streamline ethical review and warrants further consideration. C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Stair, TO (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-63253, HL-07427, HL-03533] NR 40 TC 88 Z9 89 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD JUN PY 2001 VL 8 IS 6 BP 636 EP 641 DI 10.1111/j.1553-2712.2001.tb00177.x PG 6 WC Emergency Medicine SC Emergency Medicine GA 441FM UT WOS:000169220400007 PM 11388939 ER PT J AU Waxmonsky, J Beresin, EV AF Waxmonsky, J Beresin, EV TI Taking professional wrestling to the mat - A look at the appeal and potential effects of professional wrestling on children SO ACADEMIC PSYCHIATRY LA English DT Editorial Material AB Professional wrestling (PW) has gained a firm foothold in American culture and appears to be here to stay. Children comprise a large portion of its audience, much to the dismay of many parents and clinicians. Society has struggled with how to respond to their children's fascination with PW, a novel hybrid between sports and entertainment. Parents expose children to sports, thinking they will learn healthy ways of managing conflict and aggression. However, PW is not a sport. Its values are the exact opposite of traditional sportsmanship; it demonstrates to children that cheating and verbal intimidation are effective problem-solving techniques. Because PW resembles sports, children risk applying its values to legitimate sports, as well as other realms of life. Parents can prevent this association by differentiating PW from sports, and the entertainment industry can prevent it by stopping their aggressive marketing of PW to children. C1 Massachusetts Gen Hosp, Dept Child & Adolescent Psychiat, Boston, MA 02114 USA. Harvard Med Sch, McLean Massachusets Gen Hosp Child & Adolescent P, Boston, MA USA. McLean Hosp, Masschussetts Gen Hosp, Boston, MA USA. RP Waxmonsky, J (reprint author), Massachusetts Gen Hosp, Dept Child & Adolescent Psychiat, WAC 725,55 Fruit St, Boston, MA 02114 USA. NR 9 TC 2 Z9 2 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD SUM PY 2001 VL 25 IS 2 BP 125 EP 131 DI 10.1176/appi.ap.25.2.125 PG 7 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 436AX UT WOS:000168915300013 ER PT J AU Mullins, ME Will, M Mehta, A Novelline, RA AF Mullins, ME Will, M Mehta, A Novelline, RA TI Evaluating medical students on radiology clerkships in a filmless environment: Use of an electronic test prepared from PACS and digital teaching collection images SO ACADEMIC RADIOLOGY LA English DT Article DE computers, teaching aid; education; images, display; picture archiving and communication system (PACS) ID COMPUTER-ASSISTED-INSTRUCTION; CLINICAL COMPETENCE EXAMINATION; MULTIPLE-CHOICE QUESTIONS; FILE; WRITTEN AB Rationale and Objectives. The competency of medical students in radiology clerkships is traditionally evaluated with film images, projected slides of photographed films, or printed reproductions of films. As radiology departments switch to filmless imaging, it seemed appropriate to determine the feasibility of an electronic evaluation prepared directly from digital images. Materials and Methods. The image-based portion of a multiple-choice final examination was prepared as a PowerPoint presentation that included images downloaded from the departmental picture archiving and communication system (PACS) or digital teaching collections. The images were downloaded as bitmap files, imported to Adobe Photoshop for image editing, converted to tagged image file format, and finally imported to PowerPoint, where they were combined with text to create 50 questions. A liquid crystal diode projector displayed the questions, with a timer set to advance them automatically. Results. The examination was easy and inexpensive to prepare (no photography costs). In an initial survey of 25 students, 17 (71%) of 24 students rated the resolution of images as excellent and five (21%) as good. No student gave an image a poor rating. Students preferred that images cover at least 40%-50% of the slides, and most approved of a blue background. An original allowance of 30 seconds per slide was reported to be too fast; the interval was increased to 45 seconds. Conclusion. An electronic final examination for medical students, prepared with images downloaded from PACS or digital teaching collections. is feasible, easy to prepare, and cost-effective, and it provides an excellent display of test images. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Novelline, RA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 17 TC 15 Z9 16 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JUN PY 2001 VL 8 IS 6 BP 514 EP 519 DI 10.1016/S1076-6332(03)80625-6 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 435ZK UT WOS:000168911900011 PM 11394546 ER PT J AU Ebersole, JL Cappelli, D Holt, SC AF Ebersole, JL Cappelli, D Holt, SC TI Periodontal diseases: to protect or not to protect is the question? SO ACTA ODONTOLOGICA SCANDINAVICA LA English DT Article; Proceedings Paper CT Conference on New Frontiers in Oral Immunological Diseases CY FEB 23-27, 2001 CL LILLEHAMMER, NORWAY DE antibody; antigens; biofilm; infection; inflammation; periodontitis ID EARLY-ONSET PERIODONTITIS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; PORPHYROMONAS-GINGIVALIS; VIRULENCE FACTORS; ANTIBODY; RESPONSES; FAMILIES; ADULT; IGG AB For decades, investigations have identified local and systemic humoral immune responses to microorganism comprising the supra- and subgingival biofilms in the oral cavity. Inflammation and tissue destruction in the periodontium are accompanied by alterations in the quantity, quality, and specificity of antibody. The conundrum in this scenario is the existence of a substantial plasma cell infiltrate at sites of periodontal lesions and a seemingly robust antibody response in the oral cavity and the serum, apparently coincident with progressing disease. Consequently, much effort has been expended to elucidate the critical characteristics of protective humoral responses and to develop strategies for enhancing these unique features. We and others have conducted studies attempting to distinguish disease susceptibility associated with: i) variations in response levels-significantly increased to some species with disease, minimal response to others; ii) functional comparisons of antibody-subclass differences, genetic regulation, and maturation of responses; iii) microbial and antigenic specificity of the antibody-focus on specific pathogens and identification of selected antigens as targets for immunoprotection; and, iv) kinetics of responses during disease and therapeutic interventions-linking immune changes with infection and as a measure of treatment success. This report summarizes varied research designs and results, to provide a profile of antibody in health, gingivitis, and periodontitis. These profiles may be used to provide a framework focusing on the humoral response to commensal microorganisms and likely pathogens, as they emerge in the biofilm-etiologic for or in response to disease processes. Models for antibody as a diagnostic adjunct and for predicting protective antibody responses are suggested. These concepts are likely relevant for considering vaccine approaches to periodontitis. C1 Univ Kentucky, Coll Dent, Ctr Oral Hlth Res, Chandler Med Ctr, Lexington, KY 40536 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Forsyth Inst, Boston, MA USA. RP Ebersole, JL (reprint author), Univ Kentucky, Coll Dent, Ctr Oral Hlth Res, Chandler Med Ctr, D544, Lexington, KY 40536 USA. NR 28 TC 29 Z9 29 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0001-6357 J9 ACTA ODONTOL SCAND JI Acta Odontol. Scand. PD JUN PY 2001 VL 59 IS 3 BP 161 EP 166 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 453TK UT WOS:000169932400009 PM 11501885 ER PT J AU Barron, HV Every, NR Parsons, LS Angeja, B Goldberg, RJ Gore, JM Chou, TM AF Barron, HV Every, NR Parsons, LS Angeja, B Goldberg, RJ Gore, JM Chou, TM CA Investigators Natl Registry Myocar TI The use of intra-aortic balloon counterpulsation in patients with cardiogenic shock complicating acute myocardial infarction: Data from the National Registry of Myocardial Infarction 2 SO AMERICAN HEART JOURNAL LA English DT Article ID GUSTO-I TRIAL; THROMBOLYTIC THERAPY; CORONARY-ARTERY; PLASMINOGEN-ACTIVATOR; REPERFUSION THERAPY; REVASCULARIZATION; STREPTOKINASE; LIMITATIONS; MORTALITY; FAILURE AB Background Cardiogenic shock complicating acute myocardial infarction (AMI) remains the leading cause of death in patients hospitalized with AMI. Although several studies have demonstrated the importance of establishing and maintaining a potent infarct-related artery, it remains unclear as to whether intra-aortic balloon counterpulsation (IABP) provides incremental benefit to reperfusion therapy. The purpose of this study was to determine whether IABP use is associated with lower in-hospital mortality rates in patients with AMI complicated by cardiogenic shock in a large AMI registry. Methods We evaluated patients participating in the National Registry of Myocardial Infarction 2 who had cardiogenic shock at initial examination or in whom cardiogenic shock developed during hospitalization (n = 23,180). Results The mean age of patients in the study was 72 years, 54% were men, and the majority were white. The overall morality rate in all patients who had cardiogenic shock or in whom cardiogenic shock developed was 70%. IABP was used in 7268 (31%) patients. IABP use was associated with a significant reduction in mortality rates in patients who received thrombolytic therapy (67% vs 49%) but was not associated with any benefit in patients treated with primary angioplasty (45% vs 47%). In a multivariate model, the use of IABP in conjunction with thrombolytic therapy decreased the odds of death by 18% (odds ratio, 0.82; 95% confidence interval, 0.72 to 0.93). Conclusions Patients with AMI complicated by cardiogenic shock may have substantial benefit from IABP when used in combination with thrombolytic therapy. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Genentech Inc, Dept Med Affairs, S San Francisco, CA 94080 USA. VA Puget Sound Healthcare Syst, NW HSR&D Field Program, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Univ Calif Los Angeles, Ventura Cty Med Ctr, Los Angeles, CA USA. Univ Massachusetts, Sch Med, Worcester, MA USA. RP Barron, HV (reprint author), 1 DNA Way, S San Francisco, CA 94080 USA. NR 21 TC 151 Z9 179 U1 2 U2 3 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 JUN PY 2001 VL 141 IS 6 BP 933 EP 939 DI 10.1067/mhj.2001.115295 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 438BH UT WOS:000169033500009 PM 11376306 ER PT J AU Wang, TJ Stafford, RS Ausiello, JC Chaisson, CE AF Wang, TJ Stafford, RS Ausiello, JC Chaisson, CE TI Randomized clinical trials and recent patterns in the use of statins SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; INFLUENCE MEDICAL-PRACTICE; MISSED OPPORTUNITIES; LOWERING MEDICATIONS; HEART-DISEASE; CHOLESTEROL; HYPERCHOLESTEROLEMIA; PRAVASTATIN; AWARENESS; TRENDS AB Background Three landmork trials involving 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) were published between 1994 and 1996 (the Scandinavian Simvastatin Survival Study [4S], the West of Scotland Coronary Prevention Study, and the Cholesterol and Recurrent Events trial). These trials provided evidence that lipid-lowering therapy decreases cardiovascular events, including mortality. Whether these recent data caused a shift toward statin use has not been evaluated. Methods Data from the Notional Ambulatory Medical Core Survey in 1980, 1981, 1985, and 1989 through 1998 were used. We analyzed 5053 visits by patients taking lipid-lowering medications to office-based physicians selected by stratified random sampling. The main outcome measure was use of specific lipid-lowering medications, including statins. Results In 1980 resins and niacin were the most commonly used lipid-lowering medications By 1985 rising use of fibrates caused reductions in niacin use and resin use. By 1989 statins replaced fibrates as the most heavily used medications. Statin use climbed continuously thereafter, accounting for 90% of visits by patients treated for hypercholesterolemia in 1998. In time series analyses, increases in overall statin use were temporally unrelated to the publication of clinical trials, although the 4S trial may have contributed to a shift from older statins to simvastatin. For patients receiving lipid-lowering therapy in 1993 to 1998, statin use was significantly more likely for female patients, white patients, and patients visiting cardiologists. Conclusions Although the market for lipid-lowering medications is dominated by statins, the rise in statins predated the recent clinical trials supporting their use. C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Stafford, RS (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. OI Chaisson, Christine/0000-0002-3207-9257 FU NHLBI NIH HHS [HL03548] NR 40 TC 25 Z9 28 U1 0 U2 2 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 JUN PY 2001 VL 141 IS 6 BP 957 EP 963 DI 10.1067/mhj.2001.115587 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 438BH UT WOS:000169033500013 PM 11376310 ER PT J AU Lu, L Walker, WA AF Lu, L Walker, WA TI Pathologic and physiologic interactions of bacteria with the gastrointestinal epithelium SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Experimental Biology 2000 Meeting CY APR 14-18, 2000 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nutr Sci DE epithelial-microbial crosstalk; type III secretion; probiotics; intestinal epithelium; Salmonella enterica typhimurium; Escherichia coli; Shigella flexneri ID ENTEROPATHOGENIC ESCHERICHIA-COLI; HOST-CELL; MAMMALIAN-CELLS; SMALL-INTESTINE; LACTOBACILLUS; SALMONELLA; PATHOGENS; INVASION; ADHESION; RECEPTOR AB Communication between microorganisms and the gastrointestinal epithelium, ie, bacterial-epithelial "crosstalk", is examined. Because most basic research on the molecular interaction of bacteria with the gut epithelium relates to pathogen enterocyte interaction, crosstalk with pathologic bacterial is considered in detail. Through their interactions with the intestinal epithelium, pathogens can modify epithelium function to enhance their penetration across the epithelial barrier and to exploit mucosal host defenses for their own benefit. Three representative pathogens are used to illustrate the various adaptive techniques used to colonize and penetrate the mucosal barrier. Salmonella enterica typhimurium interacts with the physiologic receptor for epidermal growth factor to co-opt the receptor's signal transduction mechanisms. Enteropathic Escherichia coli secretes a receptor (type III secretion) into the microvillus surface of enterocytes that disrupts the microvillus and alters its actin structure to form a dome-like anchoring site. Shigella flexneri is used to illustrate how pathogens use the follicular epithelial cell (M cell), the physiologic conduit for antigens to reach gut associated-lymphoid tissues, for penetration of the epithelial barrier. Shigella organisms attached to M cells use their endocytotic properties to enter the cell. Once inside the cell, the organism lyses the endocytic vacuole and co-opts actin and myosin to form a propelling tail for further penetration of the epithelium through the basolateral surface. Probiotics can protect the intestine by competing with pathogens for attachment, strengthening tight junctions between enterocytes, and enhancing the mucosal immune response to pathogens. However, additional molecular studies are needed to define more precisely the mechanism of probiotic-epithelial crosstalk. C1 Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Walker, WA (reprint author), Massachusetts Gen Hosp, Mucosal Immunol Lab, 114 16th St 1143503, Charlestown, MA 02129 USA. NR 53 TC 88 Z9 95 U1 1 U2 13 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 JUN PY 2001 VL 73 IS 6 BP 1124S EP 1130S PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 435JP UT WOS:000168878600026 PM 11393190 ER PT J AU Zembowicz, A McCusker, M Chiarelli, C Dei Tos, AP Granter, SR Calonje, E McKee, PH AF Zembowicz, A McCusker, M Chiarelli, C Dei Tos, AP Granter, SR Calonje, E McKee, PH TI Morphological analysis of nevoid melanoma - A study of 20 cases with a review of the literature SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE melanoma; minimal deviation melanoma; nevoid melanoma; nevus; small cell melanoma ID MINIMAL DEVIATION MELANOMA; MALIGNANT-MELANOMA; DIAGNOSIS; FEATURES; NEVUS AB Nevoid melanoma is a rare variant of melanoma characterized by deceptive morphologic features reminiscent of a benign melanocytic nevus. Twenty (13 nodular, 7 verrucous) nevoid melanomas were reviewed with the goal of identifying the predominant architectural patterns, cytologic features, and prognostic indicators. Although at scanning magnification, many lesions showed a strong resemblance to banal compound or dermal nevi, careful inspection in all cases demonstrated subtle pleomorphism and impaired maturation with depth, invariably accompanied by multiple dermal mitoses. Four tumors recurred and three metastasized, with subsequent death of the patients. Follow-up information for a period of at least 3 years was available in eight cases. In this group, mortality was 37.5%, the metastasis rate was 37.5%, and the local recurrence rate was 75%, with an average tumor thickness of 2.5 mm. We conclude that nevoid melanoma may be distinguished from a benign melanocytic nevus by a high index of suspicion, a careful analysis of architecture, and attention to cytologic features. Our data and a review of the literature do not support the notion that nevoid melanoma has a better prognosis than ordinary melanoma. C1 Brigham & Womens Hosp, Dept Pathol, Div Dermatopathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Dermatopathol Unit, Boston, MA 02114 USA. San Martino Hosp, Dept Pathol, Belluno, Italy. Reg Hosp, Dept Pathol, Treviso, Italy. St Thomas Hosp, St Johns Inst Dermatol, Dept Dermatopathol, London, England. RP McKee, PH (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Dermatopathol, 75 Francis St, Boston, MA 02115 USA. OI DEI TOS, ANGELO/0000-0002-1228-8940 NR 26 TC 50 Z9 51 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD JUN PY 2001 VL 23 IS 3 BP 167 EP 175 DI 10.1097/00000372-200106000-00001 PG 9 WC Dermatology SC Dermatology GA 438BY UT WOS:000169034900001 PM 11391094 ER PT J AU Granter, SR Weilbaecher, KN Quigley, C Fletcher, CDM Fisher, DE AF Granter, SR Weilbaecher, KN Quigley, C Fletcher, CDM Fisher, DE TI Microphthalmia transcription factor - Not a sensitive or specific marker for the diagnosis of desmoplastic melanoma and spindle cell (non-desmoplastic) melanoma SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE D5; melanoma; melanocytes; microphthalmia; Mitf; nevus; transcription factor ID MALIGNANT-MELANOMA; NEUROTROPIC MELANOMA; GENE-PRODUCT; DIFFERENTIATION; MELANOCYTES; EXPRESSION; TYROSINASE; ACTIVATION; MI AB Microphthalmia transcription factor (Mitf), a melanocytic nuclear protein critical for the embryonic development and postnatal viability of melanocytes, is a master lineage regulator and modulates extracellular signals. Recently, Mitf expression was shown to be both a sensitive and specific marker of epithelioid melanoma. Because loss of specific melanocytic markers in melanomas with spindle cell morphology is more common compared with those tumors with epithelioid morphology, we investigated the sensitivity of D5, an anti-Mitf antibody, for diagnosis in this diagnostically problematic subset of melanomas. Twenty of 21 (95%) spindle cell and desmoplastic melanomas examined were reactive for S-100 protein. Only 4 of 21 (19%) spindle cell and desmoplastic melanomas were reactive for HMB-45. Six of 21 tumors (29%) were reactive for D5, including one case that was non-reactive for S-100 and HMB-45. Melan-A reactivity was seen in 2 of 13 cases (15%) studied. Eight of 24 (33%) non-melanocytic spindle cell tumors were reactive for D5, including 4 of 6 dermatofibromas, 1 of 6 schwannomas, 1 of 2 leiomyomas, and 2 of 6 leiomyosarcomas. Although D5 was shown in a previous study to be a highly sensitive and specific marker for epithelioid melanomas, the results of this study show it is not a sensitive or specific marker of spindle cell and desmoplastic melanomas. Nevertheless, we believe that diffuse positive staining for D5 when taken in clinical, histologic and immunohistochemical context may be diagnostically useful in selected eases of melanoma. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Granter, SR (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 22 TC 54 Z9 54 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD JUN PY 2001 VL 23 IS 3 BP 185 EP 189 DI 10.1097/00000372-200106000-00004 PG 5 WC Dermatology SC Dermatology GA 438BY UT WOS:000169034900004 PM 11391097 ER PT J AU Bullman, TA Kang, HK AF Bullman, TA Kang, HK TI Seven year mortality follow-up of US Gulf war veterans. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 US Dept Vet Affairs, Washington, DC 20036 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN 1 PY 2001 VL 153 IS 11 SU S MA 443 BP S128 EP S128 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 437RB UT WOS:000169006400431 ER PT J AU Camargo, CA Clark, S Perry, M AF Camargo, CA Clark, S Perry, M TI Descriptive study of the American College of Epidemiology membership. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN 1 PY 2001 VL 153 IS 11 SU S MA 759 BP S207 EP S207 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 437RB UT WOS:000169006400738 ER PT J AU Camargo, CA Roberts, J Clark, S AF Camargo, CA Roberts, J Clark, S TI US Emergency Department visits for COPD exacerbations between 1992-1998. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 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 JUN 1 PY 2001 VL 153 IS 11 SU S MA 252 BP S80 EP S80 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 437RB UT WOS:000169006400245 ER PT J AU Feldman, M Cryer, B Mallat, D Go, MF AF Feldman, M Cryer, B Mallat, D Go, MF TI Role of Helicobacter pylori infection in gastroduodenal injury and gastric prostaglandin synthesis during long term/low dose aspirin therapy: A prospective placebo-controlled, double-blind randomized trial SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NEUTROPHIL-DEPENDENT PROCESS; MUCOSAL INJURY; HEALTHY HUMANS; DISEASE; CYCLOOXYGENASE-1; ULCERATION; ULCERS; NSAIDS AB OBJECTIVES: Whether gastric infection with Helicobacter pylori increases the risk of gastric mucosal injury during long term/low dose aspirin therapy is unknown. We examined whether H, pylori infection enhances upper GI mucosal damage, assessed endoscopically, in volunteers given low dose aspirin. We studied 61 healthy men and women, 29 with and 32 without active H. pylori infection. METHODS: We treated volunteers for 45 days with a placebo or aspirin (either 81 mg every day or 325 mg every 3 days). Gastroduodenal mucosal damage was then assessed by endoscopy, as was gastric histology and ex vivo gastric mucosal prostaglandin E, and F,, synthesis rates. RESULTS: Erosive disease from low dose aspirin (erosions and/or ulcers) occurred in 50% of H. pylori-infected volunteers and in 16% of their noninfected counterparts (p = 0.02). Aspirin caused a significantly higher average mucosal injury score in the gastric antrum in H, pylori-infected participants than in noninfected subjects (p = 0.03), and two H. pylori-infected subjects developed antral gastric ulcers. Subjects with H. pylori gastritis treated with the placebo had nearly 50% higher gastric mucosal prostaglandin (E-2 plus F-2 alpha) synthesis rates than their noninfected counterparts (108 +/- 6 ng/g/min versus 75 +/- 6 ng/g/min, p < 0.001). Aspirin reduced mucosal prostaglandin synthesis to similar levels in infected and noninfected participants. CONCLUSIONS: Long term/low dose aspirin therapy led to more gastric mucosal damage when H. pylori gastritis was present than when it was absent, despite similar degrees of gastric mucosal prostaglandin depletion. (C) 2001 by Am. Cell. of Gastroenterology. C1 Dept Vet Affairs Med Ctr, Dallas, TX USA. Dept Vet Affairs Med Ctr, Houston, TX USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75230 USA. Baylor Coll Med, Dept Internal Med, Houston, TX 77030 USA. RP Feldman, M (reprint author), Vet Adm Med Ctr, 111,4500 S Lancaster Rd, Dallas, TX 75216 USA. NR 27 TC 43 Z9 46 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUN PY 2001 VL 96 IS 6 BP 1751 EP 1757 DI 10.1016/S0002-9270(01)02491-1 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 440XB UT WOS:000169201000013 PM 11419825 ER PT J AU Serby, M Samuels, SC AF Serby, M Samuels, SC TI Diagnostic criteria for dementia with Lewy bodies reconsidered SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID BODY DISEASE; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; CLINICAL-FEATURES; SENILE DEMENTIA; INTERNATIONAL WORKSHOP; HALLUCINATIONS; VARIANT; SENSITIVITY; PATHOLOGY AB The validity of the consensus criteria for dementia with Lewy bodies (DLB) has been questioned. The authors, therefore, performed analyses of 242 published cases with clinicopathological correlation of DLB. The prevalence of specific consensus criteria in 69 patients reported on 41, the Newcastle and Nottingham groups in England (Group N) were compared with their prevalence in papers from all other investigators (Group O). Analysis of the entire sample (Groups N and O combined) revealed 64% with parkinsonism, 66%, with co-occurring parkinsonism and dementia, 39% with visual hallucinations (VH), and 30% with cognitive fluctuations (CF). Group N had significantly, more CF and co-occurring parkinsonism and dementia. Dopaminergic drugs were associated with the presence of VH. Although selection factors may, have contributed to investigator differences, parkinsonism and co-occurrence will) dementia appear to be the most consistent diagnostic criteria for DLB. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Bronx Vet Affairs Med Ctr, Bronx, NY USA. RP Serby, M (reprint author), Mt Sinai Med Ctr, Box 1230,1 Gustave L Levy Pl, New York, NY 10029 USA. NR 37 TC 9 Z9 9 U1 0 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD SUM PY 2001 VL 9 IS 3 BP 212 EP 216 DI 10.1176/appi.ajgp.9.3.212 PG 5 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 461PH UT WOS:000170372300003 PM 11481128 ER PT J AU Reichenberger, E Tiziani, V Watanabe, S Park, L Ueki, Y Santanna, C Baur, ST Shiang, R Grange, DK Beighton, P Gardner, J Hamersma, H Sellars, S Ramesar, R Lidral, AC Sommer, A do Amaral, CMR Gorlin, RJ Mulliken, JB Olsen, BR AF Reichenberger, E Tiziani, V Watanabe, S Park, L Ueki, Y Santanna, C Baur, ST Shiang, R Grange, DK Beighton, P Gardner, J Hamersma, H Sellars, S Ramesar, R Lidral, AC Sommer, A do Amaral, CMR Gorlin, RJ Mulliken, JB Olsen, BR TI Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the transmembrane protein ANK SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID CHROMOSOME 5P; GENE; MICROSATELLITES; REGION; MOUSE; MAPS AB Craniometaphyseal dysplasia (CMD) is a rare skeletal disorder characterized by progressive thickening and increased mineral density of craniofacial bones and abnormally developed metaphyses in long bones. Linkage studies mapped the locus for the autosomal dominant form of CMD to an similar to5-cM interval on chromosome 5p, which is defined by recombinations between loci D5S810 and D5S1954. Mutational analysis of positional candidate genes was performed, and we describe herein three different mutations, in five different families and in isolated cases, in ANK, a multipass transmembrane protein involved in the transport of intracellular pyrophosphate into extracellular matrix. The mutations are two in-frame deletions and one in-frame insertion caused by a splicing defect. All mutations cluster within seven amino acids in one of the six possible cytosolic domains of ANK. These results suggest that the mutated protein has a dominant negative effect on the function of ANK, since reduced levels of pyrophosphate in bone matrix are known to increase mineralization. C1 Harvard Sch Dent Med, Forsyth Inst, Harvard Forsyth Dept Oral Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Cell Biol, Boston, MA USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Genet, Boston, MA USA. Harvard Univ, Sch Med, Childrens Hosp, Div Plast Surg, Boston, MA USA. Univ Fed Sao Paulo, EPM, Campinas, SP, Brazil. Inst Cirurg Plast Craniofacial SOBRAPAR, Campinas, SP, Brazil. Showa Univ, Sch Med, Dept Plast & Reconstruct Surg, Tokyo 142, Japan. Virginia Commonwealth Univ, Med Coll Virginia, Dept Human Genet, Richmond, VA 23298 USA. St Louis Univ, Sch Med, Cardinal Glennon Childrens Hosp, Div Med Genet, St Louis, MO 63104 USA. Univ Cape Town, Sch Med, Dept Human Genet, ZA-7925 Cape Town, South Africa. Ohio State Univ, Coll Dent, Dept Orthodont, Columbus, OH 43210 USA. Childrens Hosp, Dept Genet, Columbus, OH 43205 USA. Univ Minnesota, Sch Dent, Dept Oral Biol & Genet, Minneapolis, MN 55455 USA. RP Reichenberger, E (reprint author), Harvard Sch Dent Med, Forsyth Inst, Harvard Forsyth Dept Oral Biol, 140 The Fenway, Boston, MA 02115 USA. RI Ramesar, Raj/I-6941-2015 OI Ramesar, Raj/0000-0001-5688-1634 FU NIAMS NIH HHS [AR36819, AR36820, R01 AR036819, R01 AR036820, R37 AR036819]; NIDCR NIH HHS [R01 DE014667, R01 DE014667-01, R01 DE014667-02, R01 DE014667-03, R01 DE014667-04] NR 16 TC 107 Z9 113 U1 0 U2 2 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 JUN PY 2001 VL 68 IS 6 BP 1321 EP 1326 DI 10.1086/320612 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 439DB UT WOS:000169094600002 PM 11326338 ER PT J AU Patterson, JA Ezra, E Gregor, ZJ AF Patterson, JA Ezra, E Gregor, ZJ TI Acute full-thickness macular hole after uncomplicated phacoemulsification cataract surgery SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID YAG LASER CAPSULOTOMY; COMPLICATIONS; EXTRACTION AB PURPOSE: To report the occurrence of a full thickness macular hole in the early postoperative period after uncomplicated phacoemulsification cataract surgery. METHODS: Retrospective analysis of a consecutive series of eyes referred for treatment of a full thickness macular hole after uncomplicated phacoemulsification cataract surgery. RESULTS: Zn a 4-year period, five eyes with acute full-thickness macular hole after uncomplicated phacoemulsification cataract surgery were examined. Metamorphopsia and vision loss had occurred 2 to 8 (mean, 4.4) days after phacoemulsification. AU eyes had attained normal corrected vision on day 1 postoperatively. A stage 2 full-thickness macular hole was present in four of the five, and a stage 3 full thickness macular hole in one of the five eyes with acuities of 20/60-20/120 (median, 20/80), All five eyes had successful closure with early primary full-thickness macular hole surgery with visual improvement to 20/20-20/60 (median, 20/40), CONCLUSION: Full-thickness macular hole may occur rarely during the early postoperative period after uncomplicated phacoemulsification, and early diagnosis and full-thickness macular hole surgery carries a favorable prognosis, The mechanisms underlying macular hole formation in these eyes are unclear. (Am J Ophthalmol 2001;131:799-800, (C) 2001 by Elsevier Science Inc. All rights reserved.). C1 Moorfields Eye Hosp, Vitroretinal Unit, London, England. RP Ezra, E (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. NR 5 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUN PY 2001 VL 131 IS 6 BP 799 EP 800 DI 10.1016/S0002-9394(00)00906-5 PG 2 WC Ophthalmology SC Ophthalmology GA 436YC UT WOS:000168962600021 PM 11384582 ER PT J AU Akiba, Y Furukawa, O Guth, PH Engel, E Nastaskin, I Kaunitz, JD AF Akiba, Y Furukawa, O Guth, PH Engel, E Nastaskin, I Kaunitz, JD TI Acute adaptive cellular base uptake in rat duodenal epithelium SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE intracellular pH; bicarbonate secretion; mucosal defense; mucus secretion; mucosal blood flow ID BICARBONATE SECRETION; MUCOSAL PERMEABILITY; ALKALINE SECRETION; LUMINAL ACID; BLOOD-FLOW; HYDROCHLORIC-ACID; PH; INJURY; CYTOPROTECTION; DIFFUSION AB We studied the role of duodenal cellular ion transport in epithelial defense mechanisms in response to rapid shifts of luminal pH. We used in vivo microscopy to measure duodenal epithelial cell intracellular pH (pH(i)), mucus gel thickness, blood flow, and HCO3- secretion in anesthetized rats with or without the Na+/H+ exchange inhibitor 5-(N,N-dimethyl)-amiloride (DMA) or the anion transport inhibitor DIDS. During acid perfusion pH(i) decreased, whereas mucus gel thickness and blood flow increased, with pH(i) increasing to over baseline (overshoot) and blood flow and gel thickness returning to basal levels during subsequent neutral solution perfusion. During a second brief acid challenge, pH(i) decrease was lessened (adaptation). These are best explained by augmented cellular HCO3- uptake in response to perfused acid. DIDS, but not DMA, abolished the overshoot and pH(i) adaptation and decreased acid-enhanced HCO3- secretion. In perfused duodenum, effluent total CO2 output was not increased by acid perfusion, despite a massive increase of titratable alkalinity, consistent with substantial acid back diffusion and modest CO2 back diffusion during acid perfusions. Rapid shifts of luminal pH increased duodenal epithelial buffering power, which protected the cells from perfused acid, presumably by activation of Na+-HCO3- cotransport. This adaptation may be a novel, important, and early duodenal protective mechanism against rapid physiological shifts of luminal acidity. C1 Univ Calif Los Angeles, Coll Letters & Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90024 USA. CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. RP Akiba, Y (reprint author), W Los Angeles Vet Affairs Med Ctr, Bldg 114,Rm 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [R01-DK-54221] NR 30 TC 24 Z9 25 U1 0 U2 0 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 JUN PY 2001 VL 280 IS 6 BP G1083 EP G1092 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 432DJ UT WOS:000168676700006 PM 11352800 ER PT J AU Iwakiri, D Podolsky, DK AF Iwakiri, D Podolsky, DK TI A silencer inhibitor confers specific expression of intestinal trefoil factor in gobletlike cell lines SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE intestinal goblet cells; transcriptional regulation; antisilencing ID SUCRASE-ISOMALTASE GENE; EPITHELIAL-CELLS; SPASMOLYTIC POLYPEPTIDE; ANTISILENCER ELEMENT; BINDING-PROTEINS; TRANSGENIC MICE; VIMENTIN GENE; IDENTIFICATION; PROMOTER; PEPTIDE AB Intestinal trefoil factor (ITF) is selectively expressed in intestinal goblet cells. Previous studies identified cis-regulatory elements in the proximal promoter of ITF, but these were insufficient to recapitulate the exquisite tissue- and cell-specific expression of native ITF in vivo. Preliminary studies suggested that goblet cell-specific expression of murine ITF requires elements far upstream that include a silencer element that effectively prevents ITF expression in non-goblet cells. Transient transfection studies using native or mutant ITF 5'-flanking sequences identified a region that restores expression in goblet cells. This element, designated goblet cell silencer inhibitor (GCSI) element, enables human and murine goblet cell-like cell lines to override the silencing effect of more proximal elements. The GCSI has no intrinsic enhancer activity and regulates expression only when the silencer element is present. Ligation of GCSI and silencer elements to sucrase-isomaltase conferred goblet cell-specific expression. Goblet cells but not non-goblet cells possess a nuclear protein that binds to the GCSI regulatory element (GCSI binding protein; GCSI-BP). Both transient transfection and gel mobility shift assay studies localize the GCSI and GCSI-BP to -2216 to -2204. We conclude that goblet cell-specific transcription of ITF in vivo depends on a regulatory element designated GCSI. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 32 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-43351, DK-46906] NR 43 TC 21 Z9 21 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUN PY 2001 VL 280 IS 6 BP G1114 EP G1123 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 432DJ UT WOS:000168676700010 PM 11352804 ER PT J AU Vaquero, E Gukovsky, I Zaninovic, V Gukovskaya, AS Pandol, SJ AF Vaquero, E Gukovsky, I Zaninovic, V Gukovskaya, AS Pandol, SJ TI Localized pancreatic NF-kappa B activation and inflammatory response in taurocholate-induced pancreatitis SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE acute pancreatitis; nuclear factor-kappa B; activator protein-1; cytokines; chemokines; inducible nitric oxide synthase ID TUMOR-NECROSIS-FACTOR; GENE-EXPRESSION; ACINAR-CELLS; CHEMOKINE EXPRESSION; THERAPEUTIC ERCP; RAT PANCREAS; FACTOR-ALPHA; AP-1; CYTOKINES; CERULEIN AB Transcription factor nuclear factor-kappaB (NF-kappaB) is activated in cerulein pancreatitis and mediates cytokine expression. The role of transcription factor activation in other models of pancreatitis has not been established. Here we report upregulation of NF-kappaB and inflammatory molecules, and their correlation with local pancreatic injury, in a model of severe pancreatitis. Rats received intraductal infusion of taurocholate or saline, and the pancreatic head and tail were analyzed separately. NF-kappaB and activator protein-1 (AP-1) activation were assessed by gel shift assay, and mRNA expression of interleukin-6, tumor necrosis factor-alpha, KC, monocyte chemoattractant protein-1, and inducible nitric oxide synthase was assessed by semiquantitative RT-PCR. Morphological damage and trypsin activation were much greater in the pancreatic head than tail, in parallel with a stronger activation of NF-kappaB and cytokine mRNA. Saline infusion mildly affected these parameters. AP-1 was strongly activated in both pancreatic segments after either taurocholate or saline infusion. NF-kappaB inhibition with N-acetylcysteine ameliorated the local inflammatory response. Correlation between localized NF-kappaB activation, cytokine upregulation, and tissue damage suggests a key role for NF-kappaB in the development of the inflammatory response of acute pancreatitis. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90073 USA. RP Vaquero, E (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Bldg 258,Rm 331,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIAAA NIH HHS [P50-AA-11999] NR 52 TC 100 Z9 109 U1 0 U2 4 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 JUN PY 2001 VL 280 IS 6 BP G1197 EP G1208 PG 12 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 432DJ UT WOS:000168676700019 PM 11352813 ER PT J AU Stojiljkovic, MP Zhang, DA Lopes, HF Lee, CG Goodfriend, TL Egan, BM AF Stojiljkovic, MP Zhang, DA Lopes, HF Lee, CG Goodfriend, TL Egan, BM TI Hemodynamic effects of lipids in humans SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE hypertension; nonesterified fatty acids; blood pressure ID SMOOTH-MUSCLE CELLS; PLASMA FATTY-ACIDS; OBESITY HYPERTENSION; OLEIC-ACID; UNITED-STATES; UTAH FAMILIES; RISK FACTOR; INSULIN; SENSITIVITY; MECHANISM AB Evidence suggests lipid abnormalities may contribute to elevated blood pressure, increased vascular resistance, and reduced arterial compliance among insulin-resistant subjects. In a study of 11 normal volunteers undergoing 4-h-long infusions of Intralipid and heparin to raise plasma nonesterified fatty acids (NEFAs), we observed increases of blood pressure. In contrast, blood pressure did not change in these same volunteers during a 4-h infusion of saline and heparin. To better characterize the hemodynamic responses to Intralipid and heparin, another group of 21 individuals, including both lean and obese volunteers, was studied after 3 wk on a controlled diet with 180 mmol sodium/day. Two and four hours after starting the infusions, plasma NEFAs increased by 134 and 111% in those receiving Intralipid and heparin, P< 0.01, whereas plasma NEFAs did not change in the first group of normal volunteers who received saline and heparin. The hemodynamic changes in lean and obese subjects in the second study were similar, and the results were combined. The infusion of Intralipid and heparin induced a significant increase in systolic (13.5 +/- 2.1 mmHg) and diastolic (8.0 +/- 1.5 mmHg) blood pressure as well as heart rate (9.4 +/- 1.4 beats/min). Small and large artery compliance decreased, and systemic vascular resistance rose. These data raise the possibility that lipid abnormalities associated with insulin resistance contribute to the elevated blood pressure and heart rate as well as the reduced vascular compliance observed in subjects with the cardiovascular risk factor cluster. C1 Med Univ S Carolina, Dept Pharmacol, Div Clin Pharmacol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Mil Med Acad, Dept Pharmacol & Toxicol, YU-11030 Belgrade, Yugoslavia. Univ Sao Paulo, Fac Med, Hosp Clin, Heart Inst,InCor,Unidade Hipertensao, BR-05403 Sao Paulo, Brazil. Univ Wisconsin, William S Middleton Mem Vet Hosp, Dept Med, Madison, WI 53705 USA. Univ Wisconsin, William S Middleton Mem Vet Hosp, Dept Pharmacol, Madison, WI 53705 USA. RP Egan, BM (reprint author), Med Univ S Carolina, Dept Pharmacol, Div Clin Pharmacol, 96 Jonathan Lucas St,CSB 826H, Charleston, SC 29425 USA. FU NCRR NIH HHS [RR-01070]; NHLBI NIH HHS [R01-HL58794, P01-HL55782] NR 41 TC 42 Z9 45 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD JUN PY 2001 VL 280 IS 6 BP R1674 EP R1679 PG 6 WC Physiology SC Physiology GA 432DK UT WOS:000168676800011 PM 11353670 ER PT J AU Zuk, A Bonventre, JV Matlin, KS AF Zuk, A Bonventre, JV Matlin, KS TI Expression of fibronectin splice variants in the postischemic rat kidney SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE alternative splicing; extracellular matrix; renal injury; regeneration; acute renal failure ID GROWTH-FACTOR-BETA; ACUTE-RENAL-FAILURE; MESSENGER-RNA PRECURSOR; EMBRYONIC FIBRONECTINS; EXTRACELLULAR-MATRIX; PROXIMAL TUBULE; TRANSFORMING GROWTH-FACTOR-BETA-1; DIFFERENTIAL EXPRESSION; CULTURED FIBROBLASTS; ISOFORM DISTRIBUTION AB Using an in vivo rat model of unilateral renal ischemia, we previously showed that the expression and distribution of fibronectin (FN), a major glycoprotein of plasma and the extracellular matrix, dramatically changes in response to ischemia-reperfusion. In the distal nephron in particular, FN accumulates in tubular lumens, where it may contribute to obstruction. In the present study, we examine whether the tubular FN is the plasma or cellular form, each of which is produced by alternative splicing of a single gene transcript. We demonstrate that FN in tubular lumens does not contain the extra type III A (EIIIA) and/or the extra type III B (EIIIB) region, both of which are unique to cellular FN. It does, however, contain the V95 region, which in the rat is a component of FNs in both plasma and the extracellular matrix. Expression of FN containing EIIIA increases dramatically in the renal interstitium after ischemic injury and continues to be produced at high levels 6 wk later. V95-containing FN also increases in the interstitial space, albeit more slowly and at lower levels than FN containing EIIIA; it also persists 6 wk later. FN containing the EIIIB region is not expressed in the injured kidney. The presence of V95 but not the EIIIA or EIIIB regions of FN in tubular lumens identifies the origin of FN in this location as the plasma; tubular FN is ultimately voided in the urine. The data indicate that both plasma and cellular FNs containing the V95 and/or EIIIA regions may contribute to the pathogenesis of acute renal failure and to the repair of the injured kidney. C1 Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Med Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Zuk, A (reprint author), Beth Israel Deaconess Med Ctr, Dept Surg, Bldg DA-880,330 Brookline Ave, Boston, MA 02215 USA. EM azuk@caregroup.harvard.edu FU NIDDK NIH HHS [DK-34854, R37-DK-39773, R01-DK-46768] NR 76 TC 32 Z9 32 U1 1 U2 1 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 JUN PY 2001 VL 280 IS 6 BP F1037 EP F1053 PG 17 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 432DL UT WOS:000168676900012 PM 11352844 ER PT J AU Manoach, DS Halpern, EF Kramer, TS Chang, YC Goff, DC Rauch, SL Kennedy, DN Gollub, RL AF Manoach, DS Halpern, EF Kramer, TS Chang, YC Goff, DC Rauch, SL Kennedy, DN Gollub, RL TI Test-retest reliability of a functional MRI working memory paradigm in normal and schizophrenic subjects SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PREFRONTAL CORTEX; ACTIVATION AB Objective: Repeated functional magnetic resonance imaging (fMRI) studies of schizophrenic subjects may identify brain activity changes in response to interventions. To interpret the findings, however, it is crucial to know the test-retest reliability of the measures used. Method: The authors scanned seven normal subjects and seven schizophrenic subjects on two occasions during performance of a working memory task. They quantified the reliability of task performance and brain activation. Results: In both groups, task performance was reliable, and all a priori regions were activated in group-averaged test and retest data. In individual schizophrenic subjects, however, indices of cognitive activation were not reliable across sessions. Normal subjects showed reasonable reliability of activation. Conclusions: Even given reliable task performance, stable clinical status, and a stable pattern of group-averaged activation, individual subjects showed unreliable brain activation. This suggests that repeated fMRI studies of schizophrenia should control for sources of variation, both artifactual and intrinsic. C1 Beth Israel Deaconess Med Ctr, Behav Neurol Unit, Dept Neurol, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Practices Evaluat Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Morphometr Anal, Boston, MA 02114 USA. RP Manoach, DS (reprint author), Beth Israel Deaconess Med Ctr, Behav Neurol Unit, Dept Neurol, 330 Brookline Ave, Boston, MA 02215 USA. RI Kennedy, David/H-3627-2012; OI Gollub, Randy L./0000-0002-9434-4044 FU PHS HHS [PA-00275, PA-11229] NR 8 TC 128 Z9 129 U1 0 U2 8 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 2001 VL 158 IS 6 BP 955 EP 958 DI 10.1176/appi.ajp.158.987.955 PG 4 WC Psychiatry SC Psychiatry GA 440KV UT WOS:000169175200022 PM 11384907 ER PT J AU Shenker, Y Skatrud, JB AF Shenker, Y Skatrud, JB TI Adrenal insufficiency in critically ill patients SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID ADRENOCORTICOTROPIN; METAANALYSIS; ILLNESS; SEPSIS C1 William S Middleton Mem Vet Hosp, Endocrinol Sect, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Med, Madison, WI USA. RP Shenker, Y (reprint author), William S Middleton Mem Vet Hosp, Endocrinol Sect, 2500 Overlook Terrace, Madison, WI 53705 USA. NR 25 TC 43 Z9 44 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUN PY 2001 VL 163 IS 7 BP 1520 EP 1523 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 443JE UT WOS:000169337400006 PM 11401866 ER PT J AU Lilly, CM Nakamura, H Belostotsky, OI Haley, KJ Garcia-Zepeda, EA Luster, AD Israel, E AF Lilly, CM Nakamura, H Belostotsky, OI Haley, KJ Garcia-Zepeda, EA Luster, AD Israel, E TI Eotaxin expression after segmental allergen challenge in subjects with atopic asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID GUINEA-PIG MODEL; BRONCHOALVEOLAR LAVAGE; CHEMOKINE EOTAXIN; AIRWAY HYPERRESPONSIVENESS; EOSINOPHIL CHEMOATTRACTANT; TISSUE EOSINOPHILIA; EPITHELIAL-CELLS; CELLULAR SOURCE; MESSENGER-RNA; RECEPTOR CCR3 AB Expression of pulmonary eotaxin protein and mRNA was determined in six subjects with atopic asthma and five nonatopic normal subjects. Levels of eotaxin expression and eosinophil mobilization were compared before and after segmental allergen challenge in subjects with atopic asthma. In the absence of allergen challenge, we found significantly higher levels of eotaxin in the bronchoalveolar lavage (BAL) fluid of subjects with asthma than in that of normal subjects (25 +/- 3 versus 15 +/- 2 pg/ml, p < 0.05). BAL eotaxin levels increased after segmental allergen challenge in all six subjects with atopic asthma tested, with a mean increase from 22 +/- 4 to 53 +/- 10 pg/ml (p = 0.013). Segmental allergen challenge was associated with a significant increase in the percentage of BAL macrophages and eosinophils that were immunopositive for eotaxin. Eotaxin mRNA was detectable by northern analysis in BAL cells exclusively from allergen-challenged segments. Allergen-induced increases in eotaxin levels were strongly associated with increases in BAL eosinophil recovery (r(2) = 0.88, p = 0.0036). Segmental allergen challenge also increased eotaxin expression in airway epithelial and endothelial cells obtained by endobronchial biopsy. These findings demonstrate, for the first time, that the airways of subjects with allergic asthma respond to allergen by increasing eotaxin expression. The tissue loci of eotaxin expression, the levels of eotaxin recovered in BAL fluid, and the association of eotaxin levels with eosinophil mobilization suggest either that eotaxin plays a mechanistic role in allergen-induced airway eosinophilia or that it serves as a biomarker for the causal mechanisms. C1 Brigham & Womens Hosp, Dept Med, Combined Program Pulm & Crit Care Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA USA. RP Lilly, CM (reprint author), Brigham & Womens Hosp, Dept Med, Combined Program Pulm & Crit Care Med, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL 03283]; NIAID NIH HHS [AI-40618] NR 35 TC 85 Z9 97 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUN PY 2001 VL 163 IS 7 BP 1669 EP 1675 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 443JE UT WOS:000169337400032 PM 11401892 ER PT J AU Smith, JJ Berlin, L AF Smith, JJ Berlin, L TI Malpractice issues in radiology - Picture archiving and communication systems (PACS) and the loss of patient examination records SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID LIABILITY C1 Rush N Shore Med Ctr, Dept Radiol, Skokie, IL 60076 USA. Rush Med Coll, Dept Radiol, Skokie, IL 60076 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Berlin, L (reprint author), Rush Med Coll, Dept Radiol, 9600 Gross Point Rd, Skokie, IL 60076 USA. NR 9 TC 7 Z9 8 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 JUN PY 2001 VL 176 IS 6 BP 1381 EP 1384 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436HF UT WOS:000168929900006 PM 11373196 ER PT J AU Chao, S Mullins, ME Slanetz, PJ AF Chao, S Mullins, ME Slanetz, PJ TI Radiologic-pathologic conferences of the Massachusetts General Hospital - Posterior mediastinal pheochromocytoma SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 Massachusetts Gen Hosp, Dept Radiol, Div Breast Imaging, ACC 219, Boston, MA 02115 USA. RP Slanetz, PJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Breast Imaging, ACC 219, 32 Fruit St, Boston, MA 02115 USA. NR 5 TC 2 Z9 2 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 JUN PY 2001 VL 176 IS 6 BP 1408 EP 1408 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436HF UT WOS:000168929900011 PM 11373201 ER PT J AU Greene, AK Hodin, RA AF Greene, AK Hodin, RA TI Laparoscopic splenectomy for massive splenomegaly using a Lahey bag SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE laparoscopy; splenectomy; splenomegaly; Lahey bag ID EXPERIENCE AB Background: Although the recent development of hand-assisted laparoscopic surgery (HALS) has made the laparoscopic retraction of large spleens feasible, the laparoscopic removal of massively enlarged spleens (> 1,000 g) remains a significant problem because these spleens do not fit into endoscopic bags. Consequently, in order to remove massive spleens either a large abdominal incision or morcellation of the spleen outside of an endoscopy bag is required. Methods: Two patients, with spleens weighing 2.510 g and 1.720 g, under-went laparoscopic splenectomy using a hand port to ensure safe retraction. The massive spleen was placed into a Lahey bag that was inserted into the abdomen through the hand port site. While in the Lahey bag, the spleen was removed piecemeal through the hand port site. Results: Both operations were completed laparoscopically without complications. The patients were discharged on postoperative day 2 and experienced minimal morbidity. Conclusions: The Lahey bag facilitates laparoscopic splenectomy for massive splenomegaly as even the most massive spleens will fit into a Lahey bag. A massive spleen may be removed piecemeal from the Lahey bag through the small hand port incision without risking a large abdominal incision, splenosis, or the insertion of a morcellator. (C) 2001 Excerpta Medica, Inc. All rights reserved. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. RP Hodin, RA (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,Gray 5 04, Boston, MA 02114 USA. NR 10 TC 23 Z9 24 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD JUN PY 2001 VL 181 IS 6 BP 543 EP 546 DI 10.1016/S0002-9610(01)00632-8 PG 4 WC Surgery SC Surgery GA 463WF UT WOS:000170499700014 PM 11513782 ER PT J AU de Leval, L Harris, NL Longtine, J Ferry, JA Duncan, LM AF de Leval, L Harris, NL Longtine, J Ferry, JA Duncan, LM TI Cutaneous B-cell lymphomas of follicular and marginal zone types - Use of Bcl-6, CD10, Bcl-2, and CD21 in differential diagnosis and classification SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE skin; lymphoma; MALT; follicular; CD21; Bcl-6; CD10; Bcl-2; immunohistochemistry; immunophenotype ID EUROPEAN-AMERICAN CLASSIFICATION; PROTEIN EXPRESSION; LYMPHOPROLIFERATIVE DISORDERS; PARAFFIN SECTIONS; TISSUE; SKIN; NEOPLASMS; PROPOSAL AB Cutaneous follicular lymphomas (FLs) and cutaneous B-cell lymphomas of extranodal marginal zone (MZL)/mucosal-associated lymphoid tissue (MALT) type may have morphologic overlap, despite the fact that they are thought to be of distinct derivation (germinal center vs. postgerminal center). The problem is compounded by the reported absence of bcl-2 expression by many cutaneous FLs, leading to speculation that cutaneous FL may be unrelated to nodal FL. The authors analyzed the expression of the germinal center-associated antigens bcl-6 and CD10 and of bcl-2 in 18 cutaneous B-cell lymphomas (10 FLs and eight MZLs), in relationship to CD21+ follicular structures, to clarify the relationship of nodal to cutaneous FLs and to explore the value of these antigens in differential diagnosis. The authors studied 10 cutaneous FLs (seven primary and three secondary) and eight MZLs (six primary and two secondary). The FLs (found in six men and four women age 45-75 years) involved the trunk (n = 3) and scalp, face and neck(n = 7). The MZLs (found in five women and three men age 34-81 years) involved the trunk (n = 4), face and neck (n = 2), and arm (n = 2). Immunostaining for CD21, bcl-6, CD10, and bcl-2 allowed the delineation of compartments within the tumors and yielded distinct patterns of staining in FL and MZL. In both follicular and interfollicular/diffuse areas of FL the neoplastic cells were bcl-6+ (10 of 10), often CD10+ (seven of 10, four of seven primary), and bcl-2+ (nine of 10, six of seven primary). Only three of seven cases tone of five primary) had bcl-2 rearrangement detectable by polymerase chain reaction. In the MZLs, the neoplastic B-cells were bcl-6-, CD10-, and bcl-2+ (eight of eight). Three patterns of CD21+ follicles were identified in MZL: reactive germinal centers, uniformly bcl-6+, CD10+, and bcl-2- (five of eight MZLs); colonized follicles, both bcl-6-, bcl-2+, and L26+ cells, and bcl-6+ and bcl-2- cells (five of eight MZLs); and expanded/colonized follicular dendritic cell meshworks, bcl-6- and bcl-2+ B cells with rare residual bcl-6+ and bcl-2- cells (four of eight MZLs). The authors conclude that cutaneous FLs express bcl-6 uniformly, usually express CD10 and bcl-2, and have a follicular pattern similar to nodal FL and consistent with a germinal center origin. The immunophenotype of cutaneous FL is distinct from that of cutaneous MZL, which is negative for bcl-6 and CD10. Colonized follicles in MZL, identified by CD21+ follicular dendritic cell meshworks, contained numerous bcl-6- and bcl-2+ B cells, and were readily distinguished from neoplastic follicles in FL. Conversely, CD21- interfollicular and diffuse areas in FLs contained bcl-6+ and CD10+ cells, which were not seen in diffuse areas of MZLs. Thus, the combination of bcl-2, bcl-6, and CD21 staining is useful for the distinction of cutaneous MZL from cutaneous FL. C1 Massachusetts Gen Hosp, Dept Pathol, Dermatopathol Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Duncan, LM (reprint author), Massachusetts Gen Hosp, Dept Pathol, Dermatopathol Unit, Warren 827,55 Fruit St, Boston, MA 02114 USA. RI Duncan, Lyn/E-9878-2013 NR 32 TC 71 Z9 71 U1 0 U2 2 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 JUN PY 2001 VL 25 IS 6 BP 732 EP 741 DI 10.1097/00000478-200106000-00004 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 436FN UT WOS:000168926000004 PM 11395550 ER PT J AU Maisto, SA Conigliaro, J McNeil, M Kraemer, K Kelley, ME AF Maisto, SA Conigliaro, J McNeil, M Kraemer, K Kelley, ME TI The relationship between eligibility criteria for participation in alcohol brief intervention trials and other alcohol and health-related variables SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; PRIMARY-CARE; PROBLEM DRINKERS; DRINKING; CONSUMPTION; AUDIT AB In clinical trials of brief interventions,for alcohol use, indiriduals typically are defined as eligible for tbe research through meeting quantity frequency (QF) of alcohol consumption criteria, alcohol-related problems criteria, or both. The purpose of this study was to evaluate preintervention and posttreatment differences among three groups of research participants eligible for participation in a brief intervention clinical trial by meeting the AUDIT total score criterion only, the QF criterion only, or both. The participants were 301 men and women 21 years of age or older who presented for medical treatment at one of twelve primary care clinics and were screened for participation in Me clinical trial. Participants completed an assessment protocol at preintervention and 1, 3, 6, 9, and 12 months postintervention. The analyses showed statistical differences among the three subgroups on three outcome dimensions of alcohol consumption, related consequences and behaviors, and medical complications; for both consumption and complications, the AUDIT + QF participants showed greater severity than participants in either of the other two groups. For consequences, AUDIT + QF participants scored higher than the QF participants on one variable constituting this dimension. The overall subgroup differences were maintained at six months in the consumption and consequences data. The implications of these findings for sensitivity of brief intervention trial design, the discovery of patient moderators of intervention effectiveness, and clinical practice are discussed. C1 Syracuse Univ, Dept Psychol, Syracuse, NY 13244 USA. Syracuse Univ, Div Gen Internal Med, Syracuse, NY 13244 USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Pittsburgh, PA USA. RP Maisto, SA (reprint author), Syracuse Univ, Dept Psychol, 430 Huntington Hall, Syracuse, NY 13244 USA. FU NIAAA NIH HHS [AA 00235, AA 10291] NR 32 TC 4 Z9 4 U1 1 U2 2 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD SUM PY 2001 VL 10 IS 3 BP 218 EP 231 PG 14 WC Substance Abuse SC Substance Abuse GA 474VL UT WOS:000171127500002 PM 11579620 ER PT J AU Monterosso, JR Flannery, BA Pettinati, HM Oslin, DW Rukstalis, M O'Brien, CP Volpicelli, JR AF Monterosso, JR Flannery, BA Pettinati, HM Oslin, DW Rukstalis, M O'Brien, CP Volpicelli, JR TI Predicting treatment response to naltrexone: The influence of craving and family history SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article; Proceedings Paper CT 153rd Annual Meeting of the American-Psychiatric-Association CY MAY 13-18, 2000 CL CHICAGO, ILLINOIS SP Amer Psychiat Assoc ID COMPULSIVE DRINKING SCALE; PLACEBO-CONTROLLED TRIAL; ALCOHOL DEPENDENCE; THERAPY; RISK AB Naltrexone has repeated ly been shown to reduce drinking in alcohol-dependent patients. Previous clinical research suggests that naltrexone may be more effective at reducing drinking among patients with high levels of alcohol craving at the beginning of treatment. In addition, laboratory studies suggest that naltrexone may be more, efficacious among patients with a high familial loading of alcohol problems. We explored both of these possibilities in the context of the first 12-week phase of a double blind, placebo-controlled naltrexone trial. A total of 121 patients were randomized to receive 100 mg/day naltrexone and 62 patients were randomized to receive placebo. Both naltrexone and placebo were given in conjunction with a psychosocial intervention designed to be integrated with the use of pharmacotherapy. This intervention was administered by nurse practitioners. Overall, patients randomized to naltrexone reported drinking fire or more drinks on fewer days than did placebo controls (p =. 04). Interactions were observed between medication group assignment and both craving level prior to randomization (p = .02) and family loading of alcohol problems (p = .05). In both cases, the interaction was in the predicted direction. These data suggest that patients with high levels of alcohol craving or a strong family history of alcoholism are more likely to benefit from naltrexone treatment. C1 Univ Penn, Dept Psychiat, Ctr Study Addict, Philadelphia, PA 19118 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Volpicelli, JR (reprint author), Univ Penn, Dept Psychiat, Ctr Study Addict, 40 W Evergreen Ave,Suite 106, Philadelphia, PA 19118 USA. FU NIAAA NIH HHS [R01AA-07517] NR 27 TC 132 Z9 136 U1 3 U2 5 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD SUM PY 2001 VL 10 IS 3 BP 258 EP 268 PG 11 WC Substance Abuse SC Substance Abuse GA 474VL UT WOS:000171127500006 PM 11579624 ER PT J AU Hirakura, Y Kagan, BL AF Hirakura, Y Kagan, BL TI Pore formation by beta-2-microglobulin: a mechanism for the pathogenesis of dialysis associated amyloidosis SO AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS LA English DT Article DE beta-2-microglobulin; dialysis amyloidosis; pore formation ID SERUM BETA(2)-MICROGLOBULIN; BETA-PROTEIN; CONGO RED; CHANNELS; HEMODIALYSIS; MEMBRANES; BLOCKADE; TOXIN AB Beta-2 microglobulin (beta 2M, molecular weight 10,000) is a 99 residue immune system protein which is part of the MHC Class I complex whose role is to present antigens to T cells. beta 2M serum levels rise dramatically in renal failure, and a syndrome called " dialysis associated amyloidosis " occurs with time in a majority of hemodialysis patients who exhibit beta 2M amyloid deposits in joints, bone and other organs(1). beta 2M can also induce Ca++ efflux from calvariae, collagenase production, and bone resportion(2-1). We report here that beta 2M formed relatively nonselective, long-lived, voltage independent ion channels in planar phospholipid bilayer membranes at physiologically relevant concentrations. The channels were inhibited by Congo red and blocked by zinc suggesting that they exist in an aggregated beta sheet stale as is common with other amyloid fibril forming peptides. Multiple single channel conductances were seen suggesting that various oligomers of beta 2M may be capable of forming channel structures. We suggest that beta 2M channel formation may account for some of the pathophysiologic effects seen in dialysis associated amyloidosis. These findings lend further weight to the "channel hypothesis" of amyloid pathogenesis. C1 Univ Calif Los Angeles, Inst Neuropsychiat, Dept Psychiat, Sch Med,Brain Res Inst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Mental Retardat Res Ctr, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Kagan, BL (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, Dept Psychiat, Sch Med,Brain Res Inst, 760 Westwood Plaza, Los Angeles, CA 90024 USA. FU NIMH NIH HHS [MH 01174] NR 31 TC 56 Z9 58 U1 0 U2 1 PU PARTHENON PUBLISHING GROUP PI CARNFORTH LANCASHIRE PA CASTERTON HALL, CARNFORTH LANCASHIRE LA6 2LA, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-J. Protein Fold. Disord. PD JUN PY 2001 VL 8 IS 2 BP 94 EP 100 DI 10.3109/13506120109007350 PG 7 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 439KT UT WOS:000169116600003 PM 11409039 ER PT J AU Lydon, AM Doyle, M Donnelly, MB AF Lydon, AM Doyle, M Donnelly, MB TI Ventilator-patient dyssynchrony induced by change in ventilation mode SO ANAESTHESIA AND INTENSIVE CARE LA English DT Article DE lung : work of breathing, patient ventilator synchrony ID INTERMITTENT MECHANICAL VENTILATION; PRESSURE SUPPORT; PERFUSION DISTRIBUTIONS; FLOW DYSSYNCHRONY; OUTPUT; WORK AB Patient-ventilator interactions may be coordinated (synchronous) or uncoordinated (dyssynchronous). Ventilator-patient dyssynchrony increases the work of breathing by imposing a respiratory muscle workload. Respiratory centre output responds to feedback from respiratory muscle loading. Mismatching of respiratory centre output and mechanical assistance results in dyssynchrony. We describe a case of severe patient-ventilator dyssynchrony and hypothesize that dyssynchrony was induced by a change in mode of ventilation from pressure-cycled to volume-cycled ventilation due to both ventilator settings and by the patient's own respiratory centre adaptation to mechanical ventilation. The causes, management and clinical implications of dyssynchrony are discussed. C1 Natl Childrens Hosp, Adelaide & Meath Hosp, Dept Anaesthesia & Intens Care Med, Dublin, Ireland. RP Lydon, AM (reprint author), Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care Med, 55 Fruit St, Boston, MA 02114 USA. NR 14 TC 1 Z9 1 U1 0 U2 0 PU AUSTRALIAN SOC ANAESTHETISTS PI EDGECLIFF PA P O BOX 600, EDGECLIFF, NSW 2021, AUSTRALIA SN 0310-057X J9 ANAESTH INTENS CARE JI Anaesth. Intensive Care PD JUN PY 2001 VL 29 IS 3 BP 273 EP 275 PG 3 WC Anesthesiology; Critical Care Medicine SC Anesthesiology; General & Internal Medicine GA 445UC UT WOS:000169476100009 PM 11439799 ER PT J AU Fitzsimons, MG Peterfreund, RA Raines, DE AF Fitzsimons, MG Peterfreund, RA Raines, DE TI Aprotinin administration and pulmonary thromboembolism during orthotopic liver transplantation: Report of two cases SO ANESTHESIA AND ANALGESIA LA English DT Article ID BLOOD-LOSS; TRANSFUSION REQUIREMENTS; MEDIATED FIBRINOLYSIS; SURVIVAL C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Fitzsimons, MG (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. NR 20 TC 33 Z9 34 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUN PY 2001 VL 92 IS 6 BP 1418 EP 1421 PG 4 WC Anesthesiology SC Anesthesiology GA 434WP UT WOS:000168839100012 PM 11375816 ER PT J AU Martinez-Ruiz, R Montero-Huerta, P Hromi, J Head, CA AF Martinez-Ruiz, R Montero-Huerta, P Hromi, J Head, CA TI Inhaled nitric oxide improves survival rates during hypoxia in a sickle cell (SAD) mouse model SO ANESTHESIOLOGY LA English DT Article ID OXYGEN-AFFINITY; PULMONARY VASOCONSTRICTION; S-NITROSOHEMOGLOBIN; BLOOD-FLOW; HEMOGLOBIN; DISEASE; VASOOCCLUSION; INHIBITION; GELATION; ANEMIA AB Background: The hallmark of sickle cell disease (SCD) is erythrocyte sickling during deoxygenation of the abnormal hemoglobin S (HbS), When HbS is deoxygenated, it aggregates into polymers, resulting in distortion of the erythrocyte structure, producing microvascular thrombosis and ischemia, The transgenic SAD mouse produces three types of human hemoglobin: S, Antilles, and D-Punjab (HbSAD) and provides an animal model for SCD. We studied the effects of nitric oxide (NO) breathing at various doses and time regimens in the presence of severe hypoxia (6% oxygen) using the SAD mouse model, Methods: Age- and sex-matched control and SAD mice were exposed to 6% oxygen breathing in an environmental chamber and assessed for survival up to 1 h. Animals received different inhaled NO concentrations before and/or during hypoxia, Blood was obtained to evaluate the oxyhemoglobin dissociation curve and measure methemoglobinemia. Results: Pretreatment by breathing NO at 20 ppm by volume in air for 30 min, and continuing to breathe 20 ppm NO during hypoxia resulted in improvement in survival rates in the SAD mouse (75%, n = 8) as compared with control SAD mice (11%, n = 9;P < 0.001), Pretreatment alone or breathing lower doses of NO were not protective, Changes in HbSAD oxygen affinity were not detected with NO breathing, and methemoglobin levels were low in ah surviving mice. Conclusions: Breathing NO produced a rapid, protective effect to severe hypoxic stress in SAD mice, There appears to be a required loading period between NO breathing and its beneficial effect during hypoxic stress, possibly because of the total amount of NO delivered to SAD hemoglobin, blood cell components, and endothelium. NO breathing may be beneficial as a therapeutic intervention in SCD. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Head, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL 42397] NR 36 TC 26 Z9 27 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUN PY 2001 VL 94 IS 6 BP 1113 EP 1118 DI 10.1097/00000542-200106000-00028 PG 6 WC Anesthesiology SC Anesthesiology GA 439VF UT WOS:000169137700024 PM 11465605 ER PT J AU West, SG Stoney, CM Hughes, JW Matacin, M Emmons, KM AF West, SG Stoney, CM Hughes, JW Matacin, M Emmons, KM TI Oral contraceptive use is associated with increased cardiovascular reactivity in nonsmokers SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article ID CIGARETTE-SMOKING; BLOOD-PRESSURE; MENSTRUAL-CYCLE; YOUNG-WOMEN; PSYCHOLOGICAL STRESS; RISK-FACTORS; LIPOPROTEIN; RESPONSES; DISEASE; SMOKERS AB Women who smoke and take oral contraceptives (OCs) have significantly increased risk of cardiovascular disease, but the exact mechanisms for the increased risk are not known. Cardiovascular reactivity to psychological stress may be one mechanism for the enhanced risk, but the small number of studies examining whether OC users who smoke have greater reactivity have produced mixed results. ne purpose of this study was to examine the effect of chronic cigarette smoking, acute nicotine administration, and OC use on cardiovascular and lipid reactivity. Sixty healthy women, half of whom had been using OCs for at least the previous 6 months, participated in the study. Approximately two thirds were smokers and were randomized to be tested after either a 12-hr nicotine deprivation or administration of nicotine gum. One third were nonsmokers. Heart rate, blood pressure, and lipid measures were taken at rest, during a videotaped speech task and during recovery from the task. Results indicated that, among OC nonusers, there was no effect of smoking status or nicotine administration on cardiovascular reactivity. However, among OC users, nonsmokers had significantly greater heart rate and diastolic blood pressure reactivity to stress. These data show that acute nicotine administration, in the form of nicotine gum, has no effect on cardiovascular or lipid stress reactivity in women. However OC use among nonsmoking women is associated with greater cardiovascular reactivity to stress. C1 Penn State Univ, University Pk, PA 16802 USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Hartford, W Hartford, CT 06117 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. RP Stoney, CM (reprint author), Ohio State Univ, 210 Townshed Hall,1885 Neil Ave, Columbus, OH 43210 USA. FU NHLBI NIH HHS [HL44847, HL48363] NR 52 TC 9 Z9 10 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD SUM PY 2001 VL 23 IS 3 BP 149 EP 157 DI 10.1207/S15324796ABM2303_2 PG 9 WC Psychology, Multidisciplinary SC Psychology GA 457DE UT WOS:000170121200002 PM 11495215 ER PT J AU Spaite, DW Maio, R Garrison, HG Desmond, JS Gregor, MA Stiell, IG Cayten, CG Chew, JL MacKenzie, EJ Miller, DR O'Malley, PJ AF Spaite, DW Maio, R Garrison, HG Desmond, JS Gregor, MA Stiell, IG Cayten, CG Chew, JL MacKenzie, EJ Miller, DR O'Malley, PJ TI Emergency Medical Services Outcomes Project (EMSOP) II: Developing the foundation and conceptual models for out-of-hospital outcomes research SO ANNALS OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Academic-Emergency-Medicine CY MAY 23-25, 2000 CL SAN FRANCISCO, CALIFORNIA SP Soc Acad Emergency Med ID ADVANCED LIFE-SUPPORT; HEALTH-CARE; SYSTEMS; TRAUMA; FUTURE AB Development of methodologically acceptable outcomes models for emergency medical services (EMS) is long overdue. In this article, the Emergency Medical Services Outcomes Project proposes a conceptual framework that will provide a foundation for future EMS outcomes research. The "Episode of Care Model" and the "Out-of-Hospital Unit of Service Model" are presented. The Episode of Care Model is useful in conditions in which interventions and outcomes, especially survival and major physiologic dysfunction, are linked in a time-dependent manner. Conditions such as severe trauma, anaphylaxis, airway obstruction, respiratory arrest, and nontraumatic cardiac arrest are amenable to this methodology. The Out-of-Hospital Unit of Service Model is essentially a subunit of the Episode of Care Model. it is valuable for evaluating conditions that have minimal-to-moderate therapeutic time dependency. This model should be used when studying outcomes limited to the out-of-hospital interval. An example of this is pain management for injuries sustained in motor vehicle crashes. These models can be applied to a wide spectrum of conditions and interventions. With the scrutiny of health care expenditures ever increasing, the identification of clinical interventions that objectively improve patient outcome takes on growing importance. Therefore, the development, dissemination, and use of meaningful methodologies for EMS outcomes research is key to the future of EMS system development and maintenance. C1 Univ Arizona, Coll Med, Div Emergency Med, Arizona Emergency Med Res Ctr, Tucson, AZ USA. Univ Michigan, Med Ctr, Dept Emergency Med, Ann Arbor, MI 48109 USA. E Carolina Univ, Brody Sch Med, Dept Emergency Med, Greenville, NC 27834 USA. Univ Ottawa, Div Emergency Med, Ottawa, ON, Canada. Univ Ottawa, Loeb Hlth Res Inst, Ottawa, ON, Canada. New York Med Coll, Inst Trauma & Emergency Care, Valhalla, NY 10595 USA. EMSSTAR Grp, Annapolis, MD USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. Hlth Span Transportat Serv, St Paul, MN USA. Allina Hlth Syst, St Paul, MN USA. Massachusetts Gen Hosp, Pediat Emergency Serv, Boston, MA 02114 USA. Massachusetts Dept Publ Hlth, Emergency Med Serv Children, Boston, MA USA. RP Spaite, DW (reprint author), Arizona Hlth Sci Ctr, Div Emergency Med, POB 245057, Tucson, AZ 85724 USA. OI Spaite, Daniel/0000-0003-2601-6476; Stiell, Ian/0000-0002-2583-6408 NR 45 TC 39 Z9 39 U1 0 U2 0 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 JUN PY 2001 VL 37 IS 6 BP 657 EP 663 DI 10.1067/mem.2001.115215 PG 7 WC Emergency Medicine SC Emergency Medicine GA 438UE UT WOS:000169072000015 PM 11385338 ER PT J AU Grabowski, TJ Cho, HS Vonsattel, JPG Rebeck, GW Greenberg, SM AF Grabowski, TJ Cho, HS Vonsattel, JPG Rebeck, GW Greenberg, SM TI Novel amyloid precursor protein mutation in an Iowa family with dementia and severe cerebral amyloid angiopathy SO ANNALS OF NEUROLOGY LA English DT Article ID CYSTATIN-C MUTATION; DUTCH-TYPE MUTANT; BETA-PROTEIN; ALZHEIMERS-DISEASE; A-BETA; INTRACEREBRAL HEMORRHAGE; ENDOTHELIAL-CELLS; SENILE PLAQUES; GENE-MUTATIONS; BRAIN AB Several mutations in the amyloid precursor protein (APP) gene have been found to associate with pathologic deposition of the beta -amyloid peptide (A beta) in neuritic plaques or in the walls of cerebral vessels. We report a mutation at a novel site in APP in a three-generation Iowa family with autosomal dominant dementia beginning in the sixth or seventh decade of life. The proband and an affected brother had progressive aphasic dementia, leukoencephalopathy, and occipital calcifications. Neuropathological examination of the proband revealed severe cerebral amyloid angiopathy, widespread neurofibrillary tangles, and unusually extensive distribution of A beta 40 in plaques. The affected brothers shared a missense mutation in APP, resulting in substitution of asparagine for aspartic acid at position 694. This site corresponds to residue 23 of A beta, thus differing from familiar Alzheimer's disease mutations, which occur outside the A beta sequence. Restriction enzyme analysis of DNA from 94 unrelated patients with sporadic cerebral amyloid angiopathy-related hemorrhage found no other instances of this mutation. These results suggest a novel site within A beta that may promote its deposition and toxicity. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Iowa, Coll Med, Dept Neurol, Iowa City, IA 52242 USA. Univ Iowa, Coll Med, Dept Radiol, Iowa City, IA 52242 USA. Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Wang ACC 836, Boston, MA 02114 USA. FU NIA NIH HHS [AG00725] NR 55 TC 286 Z9 289 U1 1 U2 14 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 JUN PY 2001 VL 49 IS 6 BP 697 EP 705 DI 10.1002/ana.1009 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 439BR UT WOS:000169091400004 PM 11409420 ER PT J AU Hyman, BT Smith, C Buldyrev, I Whelan, C Brown, H Tang, MX Mayeux, R AF Hyman, BT Smith, C Buldyrev, I Whelan, C Brown, H Tang, MX Mayeux, R TI Autoantibodies to amyloid-beta and Alzheimer's disease SO ANNALS OF NEUROLOGY LA English DT Article ID MODEL; IMMUNIZATION; PATHOLOGY; MOUSE AB Immunization against amyloid-beta has been suggested as a possible preventive or therapeutic treatment for Alzheimer's disease. We hypothesized that some individuals may have autoantibodies to amyloid-beta and that this may be protective. We analyzed the plasma of 365 individuals, drawn from a larger longitudinal epidemiological study, for the presence of antibodies to amyloid-beta, There were detectable but very low levels of anti-amyloid-beta antibodies in just over 50% of all samples and modest levels in under 5% of all samples. However, neither the presence nor the level of anti-amyloid-beta antibodies correlated with the likelihood of developing dementia or with plasma levels of amyloid-beta peptide. These data suggest that low levels of anti-amyloid-beta autoantibodies are frequent in the elderly population but do not confer protection against developing dementia. C1 Columbia Univ, Coll Phys & Surg, Gertrude H Sergievsky Ctr, Taub Inst Res Alzheimers Dis & Aging Brain,Dept N, New York, NY 10025 USA. Columbia Univ, Coll Phys & Surg, Gertrude H Sergievsky Ctr, Taub Inst Res Alzheimers Dis & Aging Brain,Dept P, New York, NY 10025 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Alzheimer Dis Res Unit, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Alzheimer Dis Res Unit, 114 16t St,Rm 2009, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG05134, AG07232, AG08702] NR 6 TC 106 Z9 113 U1 1 U2 4 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 JUN PY 2001 VL 49 IS 6 BP 808 EP 810 DI 10.1002/ana.1061 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 439BR UT WOS:000169091400020 PM 11409436 ER PT J AU Busaba, NY Ishoo, E Kieff, D AF Busaba, NY Ishoo, E Kieff, D TI Open Zenker's diverticulectomy using stapling techniques SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Broncho-Esophagological-Association CY MAY 15-16, 2000 CL ORLANDO, FLORIDA SP Amer Broncho Esophagol Assoc DE pharyngotomy; stapler; Zenker's diverticulum AB This is a prospective review of patients who underwent Zenker's diverticulectomy, closure of the pharyngotomy with nonabsorbable staples, and cricopharyngeal myotomy through an open neck approach over a period of 2 years. The study group consisted of 9 men with a mean age of 67 years. The diagnosis of Zenker's diverticulum was based on a barium swallow esophagram. The mean operative time was 1.5 hours, with a mean estimated blood loss of 25 mL. Barium swallow esophagrams performed on the first postoperative day showed no pharyngeal fistulas. Oral feeding was started after the esophagram. One patient was discharged on postoperative day 1, 1 was discharged on postoperative day 3, and the remaining 7 were discharged on postoperative day 2. All patients were able to take oral feeding by postoperative day 1. There were no operative complications in this series. We conclude that stapling with nonabsorbable staples is a relatively safe and effective method for closing pharyngeal defects after Zenker's diverticulectomy. The technique leads to shortening of the operative time and hospital stay, and allows early resumption of oral feeding. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Vet Adm Hlth Care Syst, Div Otolaryngol, Boston, MA USA. Boston Med Ctr, Dept Otolaryngol Head & Neck Surg, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Busaba, NY (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. NR 6 TC 10 Z9 10 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JUN PY 2001 VL 110 IS 6 BP 498 EP 501 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 441PK UT WOS:000169238600002 PM 11407839 ER PT J AU Ganchi, PA Wilhelmi, BJ Fujita, K Lee, WPA AF Ganchi, PA Wilhelmi, BJ Fujita, K Lee, WPA TI Ruptured pseudoaneurysm complicating an infected radial artery catheter: Case report and review of the literature SO ANNALS OF PLASTIC SURGERY LA English DT Review ID CRITICALLY ILL PATIENTS; CANNULATION; RISK; ENDARTERITIS; MANAGEMENT; GUIDELINES; PREVENTION; ANEURYSMS; THERAPY; SEPSIS AB The authors present the 16th case of a pseudoaneurysm forming at the site of an infected radial artery catheter and only the third case that presented with rupture and hemorrhage requiring emergent operative repair. Radial artery catheters are quite safe, and most infections can be treated effectively with line removal and intravenous antibiotics. However, two factors correlate strongly with the subsequent development of pseudoaneurysms. Infection with Staphylococcus aureus was seen in 15 of 16 cases, and persistent signs of infection lasting more than 48 hours after the institution of antibiotic therapy and line removal were seen in 16 of 16 cases. Therefore, patients with S. aureus radial artery line infections with persistence of infection more than 48 hours after the induction of treatment are at high risk and should be observed closely for signs of pseudoaneurysm formation. Once a pseudoaneurysm has formed, surgical repair is required. Most recommend ligating the artery if there is pulsatile backbleeding from the distal stump and Alien's test shows good perfusion of the hand by the ulnar artery. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Harvard Plast Surg Program, Dept Plast Surg, Boston, MA 02114 USA. RP Lee, WPA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Harvard Plast Surg Program, Dept Plast Surg, 15 Parkman St, Boston, MA 02114 USA. NR 36 TC 21 Z9 21 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 JUN PY 2001 VL 46 IS 6 BP 647 EP 650 DI 10.1097/00000637-200106000-00015 PG 4 WC Surgery SC Surgery GA 440MC UT WOS:000169178200016 PM 11405368 ER PT J AU Gonzalez, GM Tijerina, R Najvar, LK Bocanegra, R Luther, M Rinaldi, MG Graybill, JR AF Gonzalez, GM Tijerina, R Najvar, LK Bocanegra, R Luther, M Rinaldi, MG Graybill, JR TI Correlation between antifungal susceptibilities of Coccidioides immitis in vitro and antifungal treatment with caspofungin in a mouse model SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID L-743,872; CILOFUNGIN; CANDIDIASIS; SYNTHASE; INVITRO; AGENT AB Caspofungin (Merck Pharmaceuticals) was tested in vitro against 25 clinical isolates of Coccidoides immitis. In vitro susceptibility testing was performed in accordance with the National Committee for Clinical Laboratory Standards document M38-P guidelines. Two C. immitis isolates for which the caspofungin MICs were different were selected for determination of the minimum effective concentration (MEC), and these same strains mere used for animal studies. Survival and tissue burdens of the spleens, livers, and lungs were used as antifungal response markers. Mice infected,vith strain 98-449 (48-h MIG, 8 mug/ml; 48-h MEG, 0.125 mug/ml) showed 100% survival to day 50 when treated with caspofungin at greater than or equal to1 mg/kg. Nice infected with strain 98-571 (48-h MIG, 64 mug/ml; 48-h MEC,0.125 mug/ml) displayed greater than or equal to 80% survival when the treatment was caspofungin at greater than or equal to5 mg/kg. Treatment with caspofungin at 0.5, 1, 5, or 10 mg/kg was effective in reducing the tissue fungal burdens of mice infected with either isolate. When tissue fungal burden study results were compared between strains, caspofungin showed no statistically significant difference in efficacy in the organs of the mice treated with both strains. A better in vitro-in vivo correlation was noted when we used the MEC instead of the MIC as the endpoint for antifungal susceptibility testing. Caspofungin may have a role in the treatment of coccidioidomycosis. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis 7881, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. Univ Autonoma Nuevo Leon, Fac Med, Dept Microbiol, Monterrey, Nuevo Leon, Mexico. RP Gonzalez, GM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis 7881, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 18 TC 62 Z9 63 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 2001 VL 45 IS 6 BP 1854 EP 1859 DI 10.1128/AAC.45.6.1854-1859.2001 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 434YD UT WOS:000168842700037 PM 11353637 ER PT J AU Kollmann, C Tremblay, C Giguel, F Chou, TC Hirsch, MS AF Kollmann, C Tremblay, C Giguel, F Chou, TC Hirsch, MS TI In vitro anti-HIV-1 synergy between non-nucleoside reverse transcriptase inhibitors nevirapine and efavirenz SO ANTIVIRAL THERAPY LA English DT Article ID SINGLE-DOSE PHARMACOKINETICS; ZIDOVUDINE; LAMIVUDINE; INDINAVIR; INFECTION; THERAPY; ADULTS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Program Virol, Boston, MA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Hirsch, MS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Chou, Ting-Chao/B-4111-2009 OI Chou, Ting-Chao/0000-0002-3340-1594 NR 12 TC 7 Z9 7 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 JUN PY 2001 VL 6 IS 2 BP 143 EP 144 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 452DU UT WOS:000169842500008 PM 11491419 ER PT J AU Hafeli, UO Roberts, WK Pauer, GJ Kraeft, SK Macklis, RM AF Hafeli, UO Roberts, WK Pauer, GJ Kraeft, SK Macklis, RM TI Stability of biodegradable radioactive rhenium (Re-186 and Re-188) microspheres after neutron-activation SO APPLIED RADIATION AND ISOTOPES LA English DT Article DE microspheres; biodegradable; rhenium radioisotopes; Re-186; Re-188; neutron activation; poly(lactic acid); brachytherapy; radiopharmaceutical ID Y-90 MICROSPHERES; HEPATOCELLULAR-CARCINOMA; RADIATION SYNOVECTOMY; GLASS MICROSPHERES; GAMMA-IRRADIATION; POLY(LACTIC ACID); MOLECULAR-WEIGHT; DRUG-RELEASE; THERAPY; RADIOEMBOLIZATION AB Our objective was to determine if microspheres made from the biodegradable polymer poly(lactic acid) that contained rhenium could withstand the conditions of direct neutron activation necessary to produce therapeutic amounts of radioactive rhenium. The radiation damage of the polymer produced by gamma -doses of up to 1.05 MGy from Re-186 and Re-188 was examined by scanning electron microscopy and size exclusion chromatography. At a thermal neutron flux of 1.5 x 10(13) n/cm(2)/s the microspheres melted after 3 h in the nuclear reactor, but suffered little damage after 1 h of radiation and released less than 5% of the radioactivity during incubation in buffer at 37 degreesC. The radioactive microspheres produced in this manner have a specific activity too low for radioembolization for treatment of liver tumors, but could be injected directly into tumors or applied topically to the wound bed of partially resected tumors. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Cleveland Clin Fdn, Dept Radiat Oncol, Cleveland, OH 44195 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cleveland Clin Fdn, Dept Radiat Oncol, Desk T28,9500 Euclid Ave, Cleveland, OH 44195 USA. EM hafeliu@ccf.org RI Hafeli, Urs/B-4097-2012; OI Hafeli, Urs/0000-0003-0671-4509 NR 52 TC 27 Z9 27 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0969-8043 J9 APPL RADIAT ISOTOPES JI Appl. Radiat. Isot. PD JUN PY 2001 VL 54 IS 6 BP 869 EP 879 DI 10.1016/S0969-8043(00)00313-4 PG 11 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 415XL UT WOS:000167748800001 PM 11300399 ER PT J AU Raugi, G Berg, D Berkley, J Oppenheimer, P AF Raugi, G Berg, D Berkley, J Oppenheimer, P TI Virtual reality-based skin surgical simulation: Creating fast finite-element models from medical images SO ARCHIVES OF DERMATOLOGY LA English DT Meeting Abstract C1 Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Dermatol, Human Interface Technol Lab, Seattle, WA USA. Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUN PY 2001 VL 137 IS 6 MA 8 BP 811 EP 811 PG 1 WC Dermatology SC Dermatology GA 442EP UT WOS:000169272500028 ER PT J AU Soares, CD Almeida, OP Joffe, H Cohen, LS AF Soares, CD Almeida, OP Joffe, H Cohen, LS TI Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women - A double-blind, randomized, placebo-controlled trial SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID HORMONE REPLACEMENT THERAPY; ESTROGEN REPLACEMENT; POSTPARTUM DEPRESSION; MENOPAUSE; SYMPTOMS; IMPLANTS; UTILITY; MATRIX; SYSTEM; MOOD AB Background: Results of previous studies suggest that estrogen improves somatic and mild depressive symptoms experienced by perimenopausal women. This study investigated the efficacy of 17 beta -estradiol for the treatment of clinically significant depressive disorders in endocrinologically confirmed perimenopausal women. Methods: Perimenopausal women (aged 40-55 years, with irregular menstrual periods and serum concentrations of follicle-stimulating hormone >25 IU/L), met ring criteria for major depressive disorder, dysthymic disorder, or minor depressive disorder, according to DSM-IV, were randomized to receive transdermal patches of 17 beta -estradiol (100 mug) or placebo in a 12-week, double-blind, placebo-controlled study. A 4-week washout period followed the 12-week treatment phase. Outcome measures were the Montgomcry-Asberg Depression Rating Scale and Blatt-Kupperman Menopausal Index scorers. Results: Fifty women were enrolled in the study; 26 met DSM-IV criteria for major depressive disorder, 11 for dysthymic disorder, and 13 for minor depressive disorder. Remission of depression was observed in 17 (68%) women treated with 17 beta -estradiol compared with 5 (20%) in the placebo group (P = .001). Subjects responded similarly to estradiol treatment, regardless of DSM-IV diagnosis. Patients treated with estradiol sustained antidepressant benefit of treatment after the 4-week washout period, although somatic complaints increased in frequency and intensity. Treatment was well tolerated and adverse events were rare in both groups. Conclusion: Transdermal estradiol replacement is an effective treatment of depression for perimenopausal women. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Sao Paulo, Brazil. Univ Western Australia, Dept Psychiat & Behav Sci, Perth, WA 6009, Australia. RP Soares, CD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Perinatal & Reprod Psychiat Clin Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. RI Almeida, Osvaldo/A-4925-2008 NR 43 TC 371 Z9 397 U1 3 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUN PY 2001 VL 58 IS 6 BP 529 EP 534 PG 6 WC Psychiatry SC Psychiatry GA 439UT UT WOS:000169136500001 PM 11386980 ER PT J AU Amatuzzi, MG Northrop, C Liberman, MC Thornton, A Halpin, C Herrmann, B Pinto, LE Saenz, A Carranza, A Eavey, RD AF Amatuzzi, MG Northrop, C Liberman, MC Thornton, A Halpin, C Herrmann, B Pinto, LE Saenz, A Carranza, A Eavey, RD TI Selective inner hair cell loss in premature infants and cochlea pathological patterns from neonatal intensive care unit autopsies SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID HEARING-LOSS; HIGH-RISK; DEGENERATION; CARBOPLATIN AB Background: Deafness and handicapping sensorineural hearing impairment occur frequently in neonatal intensive care unit survivors for unknown reasons. Patients and Methods: Hearing was tested early and repeatedly in neonatal intensive care unit patients with an auditory brainstem response (ABR) screener. The temporal bones of 15 nonsurvivors (30 ears) were fixed promptly (average, 5 hours) after death for histological evaluation. Results: Among these patients, 12 failed the ABR screen bilaterally, 1 passed unilaterally, and 2 passed bilaterally. Cochlear histopathologic conditions that could contribute to hearing loss included bilateral selective outer hair cell loss in 2 patients, bilateral selective inner hair cell loss in 3 tall premature), and a combination of both outer and inner hair cell loss in 2. Other hair cell abnormalities were noted; the 2 infants who had passed the ABR screen demonstrated normal histological features. Neuronal counts were normal. Conclusions: Auditory brainstem response failure among these neonatal intensive care unit infants who died was extremely common in part owing to an unexpected histological alteration, selective inner hair cell loss among premature newborns, that should be detectable uniquely by the ABR testing method. Additional histological patterns suggest more than one cause for neonatal intensive care unit hearing loss. Hair cell loss patterns seem frequently compatible with in utero damage. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. Harvard Univ, Dept Otol & Laryngol, Boston, MA USA. Univ Autonoma Ctr Amer, Escuela Nacl Ciencias Med, Hosp Nacl Ninos, San Jose, Costa Rica. Univ Sao Paulo, Dept Otorhinolaryngol, Sao Paulo, Brazil. RP Eavey, RD (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [P30 DC005209, R01 DC00188] NR 27 TC 54 Z9 63 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JUN PY 2001 VL 127 IS 6 BP 629 EP 636 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 440KB UT WOS:000169173500001 PM 11405860 ER PT J AU Schwartz, S Patrick, DL Yueh, B AF Schwartz, S Patrick, DL Yueh, B TI Quality-of-life outcomes in the evaluation of head and neck cancer treatments SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; INTRAORAL TUMOR SURGERY; ADVANCED STAGE-III; LARYNGEAL-CANCER; ORAL-CANCER; PHARYNGEAL-CANCER; HEALTH-STATUS; RADIATION-THERAPY; FUNCTIONAL STATUS; WASHINGTON HEAD AB Objectives: To review the published literature to evaluate the design, use of terminology, and interpretation of results in studies using quality-of-life (QOL) instruments to measure differences between head and neck cancer treatments at a point in time or to report changes over time in one or more treatment groups. Data Source: MEDLINE search for subject headings "head and neck neoplasms" las a main topic) and "quality of life" or "health status" restricted to English-language sources and a 10-year period from 1989 to 1999. Study Selection: Four hundred forty-five abstracts were reviewed to find articles using an instrument to compare head and neck cancer therapy groups with a QOL outcome (13.7% included). Data Extraction: Two readers reviewed each article to determine how terminology was used, if a scientific study design was used, and if differences or changes in scores were clinically interpreted. Results: Sixty-one articles were reviewed. Forty different instruments were used. Terminology was used inconsistently in 21 (34.4%) of the 61 articles. A scientific study design was used in only 11 (18.0%) of the 61 articles (P < .001). A clinical interpretation of results was given in 16 (26.2%) of the 61 articles (P<.001). Conclusions: While QOL outcomes show promise for assisting with treatment decisions in head and neck cancer therapy, few studies using instruments to measure QOL outcomes are hypothesis driven and clinical interpretations of results are not commonly provided. We recommend that future studies identify the construct to be measured, specify comparator groups and hypotheses a priori, and provide clinical interpretations of results. C1 Univ Washington, Med Ctr, Sch Med, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA USA. RP Schwartz, S (reprint author), Univ Washington, Med Ctr, Sch Med, Dept Otolaryngol Head & Neck Surg, 1959 NE Pacific St,Box 356515, Seattle, WA 98195 USA. OI Yueh, Bevan/0000-0003-1380-1053 FU NIDCD NIH HHS [DC00018] NR 70 TC 22 Z9 23 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JUN PY 2001 VL 127 IS 6 BP 673 EP 678 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 440KB UT WOS:000169173500007 PM 11405866 ER PT J AU Ehde, DM Smith, DG Czerniecki, JM Campbell, KM Malchow, DM Robinson, RLR AF Ehde, DM Smith, DG Czerniecki, JM Campbell, KM Malchow, DM Robinson, RLR TI Back pain as a secondary disability in persons with lower limb amputations SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE amputation; back pain; health surveys; leg; pain measurement; rehabilitation ID SEVERITY AB Objective: To evaluate the frequency, duration, intensity, and interference of back pain in a sample of persons with lower limb amputations. Design: Retrospective, cross-sectional survey. Setting: Community-based survey from clinical databases. Participants: Participants who were 6 or more months post-lower limb amputation (n = 255). Intervention: An amputation pain survey that included several standardized pain measures. Main Outcome Measures: Frequency, duration, intensity, and interference of back pain. Results: Of the participants who completed the survey (return rate, 56%), 52% reported experiencing persistent, bothersome back pain. Of these, 43% reported average back pain intensity in the mild range (1-4 on 0-10 rating scale) and 25% reported pain of moderate intensity (5-6 on 0-10 scale). Most respondents with back pain rated the interference of their pain on function as none to minimal. However, nearly 25% of those with back pain described it as frequent, of severe intensity (greater than or equal to7 on 0-10 scale), and as severely interfering with daily activities including social, recreational, family, and work activities. Conclusions: Back pain may be surprisingly common in persons with lower limb amputations, and, for some who experience it, may greatly interfere with function. (C) 2001 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98104 USA. Univ Washington, Dept Orthopaed Surg, Seattle, WA 98104 USA. Univ Washington, Dept Nursing, Seattle, WA 98104 USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. VA Ctr Amputat Prosthet & Limb Loss Prevent, Seattle, WA USA. RP Ehde, DM (reprint author), Univ Washington, Sch Med, Dept Rehabil Med, 325 9th Ave,Box 359740, Seattle, WA 98104 USA. FU NICHD NIH HHS [P01 HD/NS33988] NR 7 TC 61 Z9 63 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUN PY 2001 VL 82 IS 6 BP 731 EP 734 DI 10.1053/apmr.2001.21962 PG 4 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 439KK UT WOS:000169115900003 PM 11387575 ER PT J AU Morris, DM Uswatte, G Crago, JE Cook, EW Taub, E AF Morris, DM Uswatte, G Crago, JE Cook, EW Taub, E TI The reliability of the wolf motor function test for assessing upper extremity function after stroke SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE brain injuries; cerebrovascular accident; rehabilitation ID INDUCED MOVEMENT THERAPY; RECOVERY AB Objective: To examine the reliability of the Wolf Motor Function Test (WMFT) for assessing upper extremity motor function in adults with hemiplegia. Design: Interrater and test-retest reliability. Setting: A clinical research laboratory at a university medical center. Patients: A sample of convenience of 24 subjects with chronic hemiplegia (onset > 1yr), showing moderate motor impairment. Intervention: The WMFT includes 15 functional tasks. Performances were timed and rated by using a 6-poinr functional ability scale. The WMFT was administered to subjects twice with a 2-week interval between administrations. All test sessions were videotaped for scoring at a later time by blinded and trained experienced therapists. Main Outcome Measure: Interrater reliability was examined by using intraclass correlation coefficients and internal consistency by using Cronbach's alpha. Results: Interrater reliability was .97 or greater for performance time and .88 or greater for functional ability. Internal consistency for test 1 was .92 for performance time and .92 for functional ability; for test 2, it was .86 for performance time and .92 for functional ability. Test-retest reliability was .90 for performance time and .95 for functional ability. Absolute Scores for subjects were stable over the 2 test administrations. Conclusion: The WMFT is an instrument with high interrater reliability, internal consistency, test-retest reliability, and adequate stability. (C) 2001 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 Univ Alabama, Div Phys Therapy, Birmingham, AL 35294 USA. Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. Univ Alabama, Dept Phys Therapy, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Phys Med & Rehabil Serv, Birmingham, AL USA. RP Morris, DM (reprint author), Univ Alabama, Div Phys Therapy, Bishop Bldg,Rm 102,900 19th St S, Birmingham, AL 35294 USA. RI Uswatte, Gitendra/C-4913-2009 NR 23 TC 244 Z9 259 U1 0 U2 9 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUN PY 2001 VL 82 IS 6 BP 750 EP 755 DI 10.1053/apmr.2001.23183 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 439KK UT WOS:000169115900006 PM 11387578 ER PT J AU Escalante, A Lichtenstein, MJ Hazuda, HP AF Escalante, A Lichtenstein, MJ Hazuda, HP TI Walking velocity in aged persons: Its association with lower extremity joint range of motion SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE hip; knee; joint range of motion; walking velocity; diabetes mellitus; Mexican Americans ID MEXICAN-AMERICANS; FLEXION RANGE; PAIN MAP; MOBILITY; DETERMINANTS; HIP; QUESTIONNAIRE; OBESITY AB Objective. To measure the association between walking velocity and hip and knee flexion range, ethnic background, anthropometrics, comorbid pathologies, and coimpairments, in a sample of community-dwelling aged persons. Methods. To reach our objective, we used data from the San Antonio Longitudinal Study of Aging (SALSA), a population-based cohort of Mexican American and European American persons aged 64 to 79. By fitting hierarchical regression models, we measured the variance in the walking velocity over 50 feet explained by hip and knee flexion range, adjusting for the combined influence of demographic and anthropometric variables, coexistent pathologic conditions, impairments, and the examiners who conducted the assessments. Results. The average walking velocity among the 702 subjects for whom data were available was 73.6 meters per minute (range 20 to 121). Bivariate analyses revealed significant associations between walking velocity and age, sex, ethnic back-round, height, weight, presence of arthritis, diabetes mellitus, stroke, upper leg pain, peripheral vascular disease, left ventricular hypertrophy, and forced expiratory volume at 1 second. The correlation (r) between walking velocity and flexion range of the hip and knee were 0.40 and 0.35, respectively (P less than or equal to 0.001 for each). Multivariate hierarchical models adjusting for demographic and anthropometric characteristics of the subjects, and examiner variation, revealed that hip and knee flexion range explained 6% of the variance in walking velocity. Adjusting for the presence of comorbid conditions and coimpairments reduced the variance attributable to hip and knee flexion range only slightly, to 5%. Conclusion. Hip and knee flexion range contribute significantly to walking velocity in the SALSA cohort of community-dwelling aged persons. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Clin Epidemiol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Clin Immunol & Rheumatol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriatr & Gerontol, San Antonio, TX 78284 USA. S Texas Vet Hlth Syst, Audie Murphy Div, Geriatr Res & Educ Ctr, GRECC 182, San Antonio, TX USA. RP Hazuda, HP (reprint author), 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NCRR NIH HHS [M01-RR-01346]; NIA NIH HHS [1-RO1-AG10444] NR 37 TC 19 Z9 19 U1 0 U2 4 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 JUN PY 2001 VL 45 IS 3 BP 287 EP 294 DI 10.1002/1529-0131(200106)45:3<287::AID-ART262>3.0.CO;2-1 PG 8 WC Rheumatology SC Rheumatology GA 487JT UT WOS:000171872500013 PM 11409671 ER PT J AU Zaitchik, D Solomon, GEA AF Zaitchik, D Solomon, GEA TI Putting semantics back into the semantic representation of living things SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material ID CHILDRENS AB The authors' model reduces the literature on conceptual representation to a single node: "encyclopedic knowledge." The structure of conceptual knowledge is riot so trivial. By ignoring the phenomena central to reasoning about living things, the authors base their dismissal of semantic systems oil inadequate descriptive ground, A better descriptive account is available in the conceptual development literature. Neuropsychologists could import the insights and tasks front cognitive development to improve their studies. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Zaitchik, D (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI PORT CHESTER PA 110 MIDLAND AVE, PORT CHESTER, NY 10573-9863 USA SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD JUN PY 2001 VL 24 IS 3 BP 496 EP + PG 8 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 475GZ UT WOS:000171155500057 ER PT J AU James, MF Manchanda, N Gonzalez-Agosti, C Hartwig, JH Ramesh, V AF James, MF Manchanda, N Gonzalez-Agosti, C Hartwig, JH Ramesh, V TI The neurofibromatosis 2 protein product merlin selectively binds F-actin but not G-actin, and stabilizes the filaments through a lateral association SO BIOCHEMICAL JOURNAL LA English DT Article DE actin cytoskeleton; ezrin/radixin/moesin family; merlin; neurofibromatosis 2 ID EXCHANGER REGULATORY FACTOR; TRANSMEMBRANE CONDUCTANCE REGULATOR; CELL EXTENSION ACTIVITY; NHE-RF; EZRIN/RADIXIN/MOESIN PROTEINS; BETA(2)-ADRENERGIC RECEPTOR; CAPPING PROTEIN; TERMINAL DOMAIN; ERM PROTEINS; EZRIN AB The neurofibromatosis 2 protein product merlin, named for its relatedness to the ezrin, radixin and moesin (ERM) family of proteins, is a tumour suppressor whose absence results in the occurrence of multiple tumours of the nervous system, particularly schwannomas and meningiomas. Merlin's similarity to ERMs suggests that it might share functions, acting as a link between cytoskeletal components and the cell membrane. The N-terminus of merlin has strong sequence identity to the N-terminal actin-binding region of ezrin; here we describe in detail the merlin-actin interaction. Employing standard actin co-sedimentation assays, we have determined that merlin isoform 2 binds F-actin with an apparent binding constant of 3.6 muM and a stoichiometry of 1 mol of merlin per 11.5 mol of actin in filaments at saturation. Further, solid-phase binding assays reveal that merlin isoforms 1 and 2 bind actin filaments differentially, suggesting that the intramolecular interactions in isoform 1 might hinder its ability to bind actin. However, merlin does not bind G-actin. Studies of actin filament dynamics show that merlin slows filament disassembly with no influence on the assembly rate, indicating that merlin binds along actin filament lengths. This conclusion is supported by electron microscopy, which demonstrates that merlin binds periodically along cytoskeletal actin filaments. Comparison of these findings with those reported for ERM proteins reveal a distinct role for merlin in actin filament dynamics. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Longwood Med Res Ctr, Div Expt Med, Boston, MA 02115 USA. RP Ramesh, V (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL56949]; NINDS NIH HHS [F32-NS10699, NS24279] NR 47 TC 51 Z9 53 U1 0 U2 4 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUN 1 PY 2001 VL 356 BP 377 EP 385 DI 10.1042/0264-6021:3560377 PN 2 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 442QE UT WOS:000169295800010 PM 11368764 ER PT J AU Saghir, AN Tuxworth, WJ Hagedorn, CH McDermott, PJ AF Saghir, AN Tuxworth, WJ Hagedorn, CH McDermott, PJ TI Modifications of eukaryotic initiation factor 4F (elF4F) in adult cardiocytes by adenoviral gene transfer: differential effects on elF4F activity and total protein synthesis rates SO BIOCHEMICAL JOURNAL LA English DT Article DE adenovirus; hypertrophy; translation ID CAP-DEPENDENT TRANSLATION; FACTOR 4E; PRESSURE-OVERLOAD; VOLUME OVERLOAD; PHOSPHORYLATION SITES; 4E-BINDING PROTEIN-1; SIGNALING PATHWAYS; FELINE CARDIOCYTES; COMPLEX-FORMATION; MAMMALIAN-CELLS AB In adult feline cardiocytes, increases in eukaryotic initiation factor 4F (eIF4F) activity are correlated with accelerated rates of total protein synthesis produced in response to increased load. Adenoviral gene transfer was employed to increase either eIF4F complex formation or the phosphorylation of eIF4E on Ser-209. To simulate load, cardiocytes were electrically stimulated to contract (2 Hz, 5 ms pulses). Non-stimulated cardiocytes were used as controls. Adenovirus-mediated overexpression of wildtype eIF4E increased the total eIF4E pool by 120-140% above endogenous levels after 24h and produced a corresponding increase in eIF4F content. However, it did not accelerate total protein synthesis rates in-quiescent cardiocytes; neither did it potentiate the increase produced by contraction. To modify the affinity of eIF4F, cardiocytes were infected with a mutant (eIF4E/W56F) with a decreased binding affinity for the mRNA cap. Overexpression of eIF4E/W56F increased the quantity of eIF4F but the rate of total protein synthesis was decreased in quiescent and contracting cardiocytes. Overexpression of a mutant that blocked eIF4E phosphorylation (eIF4E/S209A) increased the quantity of eIF4F without any significant effect on total protein synthesis rates in quiescent or contracting cardiocytes. Overexpression of the eIF4E kinase Mnk-1 increased eIF4E phosphorylation without a corresponding increase in eIF4F complex formation or in the rate of total protein synthesis. We conclude the following: (1) eIF4F assembly is increased by raising eIF4E levels via adenoviral gene transfer; (2) the cap binding affinity of eIF4F is a rate-limiting determinant for total protein synthesis rates; and (3) increases in the quantity of eIF4F alone or in eIF4E phosphorylation are not sufficient to accelerate total protein synthesis rates. C1 Gazes Cardiac Res Inst, Charleston, SC 29403 USA. Dept Med, Charleston, SC 29403 USA. Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. Emory Univ, Sch Med, Winship Canc Ctr, Dept Med, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Winship Canc Ctr, Genet Program, Atlanta, GA 30322 USA. RP McDermott, PJ (reprint author), Gazes Cardiac Res Inst, Strom Thurmond Biomed Res Bldg,Room 303,114 Dough, Charleston, SC 29403 USA. FU NHLBI NIH HHS [P01 HL-48788] NR 50 TC 37 Z9 37 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUN 1 PY 2001 VL 356 BP 557 EP 566 DI 10.1042/0264-6021:3560557 PN 2 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 442QE UT WOS:000169295800031 PM 11368785 ER PT J AU Herak-Kramberger, CM Breton, S Brown, D Kraus, O Sabolic, I AF Herak-Kramberger, CM Breton, S Brown, D Kraus, O Sabolic, I TI Distribution of the vacuolar H(+)ATPase along the rat and human male reproductive tract SO BIOLOGY OF REPRODUCTION LA English DT Article DE epididymis; male reproductive tract; penis; prostate; seminal vesicles; sperm maturation; testis; vas deferens ID CARBONIC-ANHYDRASE; DUCTULI-EFFERENTES; PROSTATIC FLUID; SPERM MOTILITY; H+-ATPASE; EPIDIDYMIS; PH; ACIDIFICATION; TESTIS; CELLS AB Luminal acidification in parts of the male reproductive tract generates an appropriate pH environment in which spermatozoa mature and are stored. The cellular mechanisms of proton (H+) secretion in the epididymis and the proximal vas deferens involve the activity of an apical vacuolar H(+)ATPase in specialized cell types, as well as an apical Na+/H+ exchanger in some tubule segments. In this study we used Western blotting and immunocytochemistry to localize the H(+)ATPase in various segments of the male reproductive tract in rat and man as a first step toward a more complete understanding of luminal acidification processes in this complex system of tissues. Immunoblotting of isolated total cell membranes indicated a variable amount of H(+)ATPase in various segments of the rat reproductive tract. In addition to its known expression in distinct cell types in the epididymis and vas deferens, the H(+)ATPase was also localized at the epical pole and in the cytoplasm of epithelial cells in the efferent duct (nonciliated cells), the ampulla of the vas deferens and the ventral prostate (scattered individual cells), the dorsal and lateral prostate, the ampullary gland, the coagulating gland, and all epithelial cells of the prostatic and penile urethra. Both apical and basolateral localization of the protein were found in epithelial cells of the prostatic ducts in the lateral prostate and in periurethral tissue. Only cytoplasmic, mostly perinuclear localization of the H(+)ATPase was found in all epithelial cells of the seminal vesicles and in most cells of the ventral prostate and coagulating gland. No staining was detected in the seminiferous tubules, rete testis, and bulbourethral gland. In human tissue, H(+)ATPase-rich cells were detected in the epididymis, prostate, and prostatic urethra. We conclude that the vacuolar H(+)ATPase is highly expressed in epithelial cells of most segments of the male reproductive tract in rat and man, where it may be involved in H+ secretion and/or intracellular processing of the material endocytosed from the luminal fluid or destined to be secreted by exocytosis. C1 Inst Med Res & Occupat Hlth, Unit Mol Toxicol, HR-10001 Zagreb, Croatia. Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. Clin Hosp Sisters Mercy, Urol Clin, Zagreb 10000, Croatia. RP Sabolic, I (reprint author), Inst Med Res & Occupat Hlth, Unit Mol Toxicol, Ksaverska Cesta 2,POB 291, HR-10001 Zagreb, Croatia. FU NIDDK NIH HHS [DK38452] NR 39 TC 49 Z9 50 U1 1 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUN PY 2001 VL 64 IS 6 BP 1699 EP 1707 DI 10.1095/biolreprod64.6.1699 PG 9 WC Reproductive Biology SC Reproductive Biology GA 437JH UT WOS:000168988200017 PM 11369598 ER PT J AU Ibrahim, JG Chen, MH Sinha, D AF Ibrahim, JG Chen, MH Sinha, D TI Bayesian semiparametric models for survival data with a cure fraction SO BIOMETRICS LA English DT Article DE cure rate model; Gibbs sampling; historical data; latent variables; piecewise exponential; posterior distribution; semiparametric model; smoothing parameter AB We propose methods for Bayesian inference for a new class of semiparametric survival models with a cure fraction. Specifically we propose a semiparametric cure rate model with a smoothing parameter that controls the degree of parametricity in the right tail of the survival distribution. We show that such a parameter is crucial for these kinds of models and can have an impact on the posterior estimates. Several novel properties of the proposed model are derived. In addition, we propose a class of improper noninformative priors based on this model and examine the properties of the implied posterior. Also, a class of informative priors based on historical data is proposed and its theoretical properties are investigated. A case study involving a melanoma clinical trial is discussed in detail to demonstrate the proposed methodology. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Worcester Polytech Inst, Dept Math Sci, Worcester, MA 01609 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. RP Ibrahim, JG (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 74015, R29-CA 69222, CA 70101] NR 4 TC 40 Z9 41 U1 0 U2 2 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2001 VL 57 IS 2 BP 383 EP 388 DI 10.1111/j.0006-341X.2001.00383.x PG 6 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 437QY UT WOS:000169006100009 PM 11414560 ER PT J AU Altaye, M Donner, A Klar, N AF Altaye, M Donner, A Klar, N TI Inference procedures for assessing interobserver agreement among multiple raters SO BIOMETRICS LA English DT Article DE confidence interval; interobserver agreement; multiple rater; sample size; type I error ID KAPPA AB We propose a new procedure for constructing inferences about a measure of interobserver agreement in studies involving a binary outcome and multiple raters. The proposed procedure, based on a chi-square goodness-of-fit test as applied to the correlated binomial model (Bahadur, 1961, in Studies in Item Analysis and Prediction, 158-176), is an extension of the goodness-of-fit procedure developed by Donner and Eliasziw (1992, Statistics in Medicine 11, 1511-1519) for the case of two raters. The new procedure is shown to provide confidence-interval coverage levels that are close to nominal over a wide range of parameter combinations. The procedure also provides a sample-size formula that may be used to determine the required number of subjects and raters for such studies. C1 Childrens Hosp Kings Daughters, Ctr Pediat Res, Eastern Virginia Med Sch, Norfolk, VA 23510 USA. Univ Western Ontario, Dept Epidemiol & Biostat, London, ON N6A 5C1, Canada. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Altaye, M (reprint author), Childrens Hosp Kings Daughters, Ctr Pediat Res, Eastern Virginia Med Sch, Norfolk, VA 23510 USA. EM altayem@chkd.com RI Altaye, Mekibib/N-5274-2015 NR 14 TC 19 Z9 19 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD JUN PY 2001 VL 57 IS 2 BP 584 EP 588 DI 10.1111/j.0006-341X.2001.00584.x PG 5 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 437QY UT WOS:000169006100037 PM 11414588 ER PT J AU Ibrahim, JG Chen, MH Lipsitz, SR AF Ibrahim, JG Chen, MH Lipsitz, SR TI Missing responses in generalised linear mixed models when the missing data mechanism is nonignorable SO BIOMETRIKA LA English DT Article DE EM algorithm; Gibbs sampling; maximum likelihood estimation; missing data mechanism; Monte Carlo EM; random effects model ID LONGITUDINAL DATA; EM ALGORITHM; INCOMPLETE DATA; DROP-OUT; NONRESPONSE; REGRESSION AB We propose a method for estimating parameters in the generalised linear mixed model with nonignorable missing response data and with nonmonotone patterns of missing data in the response variable. We develop a Monte Carlo EM algorithm for estimating the parameters in the model via the Gibbs sampler. For the normal random effects model, we derive a novel analytical form for the E- and M-steps, which is facilitated by integrating out the random effects. This form leads to a computationally feasible and extremely efficient Monte Carlo EM algorithm for computing maximum likelihood estimates and standard errors. In addition, we propose a very general joint multinomial model for the missing data indicators, which can be specified via a sequence of one-dimensional conditional distributions. This multinomial model allows for an arbitrary correlation structure between the missing data indicators, and has the potential of reducing the number of nuisance parameters. Real datasets from the International Breast Cancer Study Group and an environmental study involving dyspnoea in cotton workers are presented to illustrate the proposed methods. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Worcester Polytech Inst, Dept Math Sci, Worcester, MA 01609 USA. Med Univ S Carolina, Dept Biostat & Epidemiol, Charleston, SC 29425 USA. RP Ibrahim, JG (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. NR 31 TC 109 Z9 113 U1 0 U2 16 PU BIOMETRIKA TRUST PI LONDON PA UNIV COLLEGE LONDON GOWER ST-BIOMETRIKA OFFICE, LONDON, ENGLAND WC1E 6BT SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD JUN PY 2001 VL 88 IS 2 BP 551 EP 564 DI 10.1093/biomet/88.2.551 PG 14 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 447KW UT WOS:000169573400019 ER PT J AU Manz, MG Traver, D Miyamoto, T Weissman, IL Akashi, K AF Manz, MG Traver, D Miyamoto, T Weissman, IL Akashi, K TI Dendritic cell potentials of early lymphoid and myeloid progenitors SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; MOUSE BONE-MARROW; TUMOR-NECROSIS-FACTOR; TRANSCRIPTION FACTOR PU.1; RESCUES T-LYMPHOPOIESIS; IN-VIVO; B-CELLS; PRECURSOR CELLS; DEFICIENT MICE; CD8 EXPRESSION AB It has been proposed that there are at least 2 classes of dendritic cells (DCs), CD8 alpha (+) DCs derived from the lymphoid lineage and CD8 alpha (-) DCs derived from the myeloid lineage. Here, the abilities of lymphoid- and myeloid-restricted progenitors to generate DCs are compared, and their overall contributions to the DC compartment are evaluated. It has previously been shown that primitive myeloid-committed progenitors (common myeloid progenitors [CMPs]) are efficient precursors of both CD8 alpha (+) and CD8 alpha (-) DCs in vivo. Here it is shown that the earliest lymphoid-committed progenitors (common lymphoid progenitors [CLPs]) and CMPs and their progeny granulocyte-macrophage progenitors (GMPs) can give rise to functional DCs in vitro and in vivo. CLPs are more efficient in generating DCs than their T-lineage descendants, the early thymocyte progenitors and pro-T cells, and CMPs are more efficient DC precursors than the descendant GMPs, whereas pro-B cells and megakaryocyte-erythrocyte progenitors are incapable of generating DCs, Thus, DC developmental potential is preserved during T- but not B-lymphoid differentiation from CLP and during granulocyte-macrophage but not megakaryocyte-erythrocyte development from CMP In vivo reconstitution experiments show that CLPs and CMPs can reconstitute CD8 alpha (+) and CD8 alpha (-) DCs with similar efficiency on a per cell basis, However, CMPs are 10-fold more numerous than CLPs, suggesting that at steady state, CLPs provide only a minority of splenic DCs and approximately half the DCs in thymus, whereas most DCs, including CD8 alpha (+) and CD8 alpha (-) subtypes, are of myeloid origin. (Blood, 2001;97:3333-3341) (C) 2001 by The American Society of Hematology. C1 Stanford Univ, Sch Med, Beckman Ctr B261, Dept Pathol & Dev Biol, Stanford, CA 94305 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA. RP Manz, MG (reprint author), Stanford Univ, Sch Med, Beckman Ctr B261, Dept Pathol & Dev Biol, 279 Campus Dr, Stanford, CA 94305 USA. RI Manz, Markus/C-7588-2011 FU NCI NIH HHS [CA-42551]; NIAID NIH HHS [5T32-AI-07290] NR 57 TC 257 Z9 265 U1 0 U2 5 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 JUN 1 PY 2001 VL 97 IS 11 BP 3333 EP 3341 DI 10.1182/blood.V97.11.3333 PG 9 WC Hematology SC Hematology GA 436GJ UT WOS:000168927900004 PM 11369621 ER PT J AU Han, JH Choi, SJ Kurihara, N Koide, M Oba, Y Roodman, GD AF Han, JH Choi, SJ Kurihara, N Koide, M Oba, Y Roodman, GD TI Macrophage inflammatory protein-1 alpha is an osteoclastogenic factor in myeloma that is independent of receptor activator of nuclear factor kappa B ligand SO BLOOD LA English DT Article ID HUMAN-BONE-MARROW; GIANT-CELL TUMORS; MULTIPLE-MYELOMA; PARATHYROID-HORMONE; IN-VIVO; OSTEOPROTEGERIN LIGAND; STROMAL CELLS; INTERLEUKIN-6; EXPRESSION; RESORPTION AB A complementary DNA expression library derived from marrow samples from myeloma patients was recently screened and human macrophage inflammatory protein-1 alpha (hMIP-1 alpha) was identified as an osteoclastogenic factor expressed in these samples. hMIP-1 alpha enhanced osteoclast (OCL) formation in human marrow cultures and by highly purified OCL precursors in a dose-dependent manner (5-200 pg/mL), Furthermore, hMIP-1 alpha enhanced OCL formation induced by human interleukin-6 (IL-6), which is produced by marrow stromal cells when they interact with myeloma cells. hMIP-1 alpha also enhanced OCL formation induced by parathyroid hormone-related protein (PTHrP) and receptor activator of nuclear factor KB ligand (RANKL), factors also implicated in myeloma bone disease. Time-course studies revealed that the hMIP-1 alpha acted during the last 2 weeks of the 3-week culture period. Reverse transcription-polymerase chain reaction analysis showed that the chemokine receptors for hMIP-1 alpha (CCR1 and CCR5) were expressed by human bone marrow and highly purified early OCL precursors. Furthermore, hMIP-1 alpha did not increase expression of RANKL, These data demonstrate that hMIP-1 alpha is an osteoclastogenic factor that appears to act directly on human OCL progenitors and acts at the later stages of OCL differentiation. These data further suggest that in patients with myeloma, MIP-la produced by myeloma cells, in combination with RANKL and IL-6 that are produced by marrow; stromal cells in response to myeloma cells, enhances OCL formation through their combined effects on Od precursors. (Blood. 2001; 97:3349-3353). C1 Audie L Murphy Mem Vet Adm Hosp, Res Serv 151, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Adm Hosp, Gen Clin Res Ctr, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med Hematol, San Antonio, TX USA. RP Roodman, GD (reprint author), Audie L Murphy Mem Vet Adm Hosp, Res Serv 151, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. RI Han, J/G-4671-2010 FU NCI NIH HHS [CA40035] NR 33 TC 207 Z9 215 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 2001 VL 97 IS 11 BP 3349 EP 3353 DI 10.1182/blood.V97.11.3349 PG 5 WC Hematology SC Hematology GA 436GJ UT WOS:000168927900006 PM 11369623 ER PT J AU Deng, M Daley, GQ AF Deng, M Daley, GQ TI Expression of interferon consensus sequence binding protein induces potent immunity against BCR/ABL-induced leukemia SO BLOOD LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; COMPLETE CYTOGENETIC REMISSION; REGULATORY FACTOR FAMILY; BCR-ABL; TRANSCRIPTION FACTOR; LYMPHOCYTES-B; CML PATIENTS; ALPHA; GAMMA AB Mice deficient in the interferon consensus sequence binding protein (ICSBP) develop a disease resembling chronic myeloid leukemia (CML), which in humans is caused by the BCR/ABL oncoprotein. Interferon-alpha (IFN-alpha) induces ICSBP expression and is an effective therapy for CML, This study examined whether enforced expression of ICSBP might antagonize BCR/ABL-induced leukemia; results demonstrated that ICSBP-modified cells generated a protective CD8(+) cytotoxic T-cell response against BCR/ABL-transformed BaF3 cells in a murine leukemia model. ICSBP expression represents a novel means of stimulating a host immune response to BCR/ABL(+) leukemia cells and a potential strategy for immunotherapy of CML. (Blood, 2001;97:3491-3497) (C) 2001 by The American Society of Hematology. C1 Whitehead Inst, Cambridge, MA 02142 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA USA. RP Daley, GQ (reprint author), Whitehead Inst, 9 Cambridge Ctr, Cambridge, MA 02142 USA. FU NCI NIH HHS [CA86991, CA76418] NR 45 TC 43 Z9 43 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 JUN 1 PY 2001 VL 97 IS 11 BP 3491 EP 3497 DI 10.1182/blood.V97.11.3491 PG 7 WC Hematology SC Hematology GA 436GJ UT WOS:000168927900025 PM 11369642 ER PT J AU Baer, MR Stewart, GC Dodge, RK Leget, G Sule, N Mrozek, K Schiffer, CA Powel, BL Kolitz, JE Moore, JO Stone, RM Davey, FR Carrol, AJ Larson, RA Bloomfield, CD AF Baer, MR Stewart, GC Dodge, RK Leget, G Sule, N Mrozek, K Schiffer, CA Powel, BL Kolitz, JE Moore, JO Stone, RM Davey, FR Carrol, AJ Larson, RA Bloomfield, CD TI High frequency of immunophenotype changes in acute myeloid leukemia at relapse: implications for residual disease detection (Cancer and Leukemia Group B Study 8361) SO BLOOD LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; MULTIPARAMETER FLOW-CYTOMETRY; ACUTE MYELOBLASTIC-LEUKEMIA; P-GLYCOPROTEIN EXPRESSION; COLONY-STIMULATING FACTOR; 1ST RELAPSE; PROTEIN MRP; PHASE-I; DIAGNOSIS; CANCER AB Multiparameter flow cytometry (MFC) has the potential to allow for sensitive and specific monitoring of residual disease (RD) in acute myeloid leukemia (AML). The use of MFC for RD monitoring assumes that AML cells identified by their immunophenotype at diagnosis can be detected during remission and at relapse. AML cells from 136 patients were immunophenotyped by MFC at diagnosis and at first relapse using 9 panels of 3 monoclonal antibodies. Immunophenotype changes occurred in 124 patients (91%); they consisted of gains or losses of discrete leukemia cell populations resolved by MFC (42 patients) and gains or losses of antigens on leukemia cell populations present at both time points (108 patients). Antigen expression defining unusual phenotypes changed frequently: CD13, CD33, and CD34, absent at diagnosis in 3, 33, and 47 cases, respectively, were gained at relapse in 2 (67%), 15 (45%), and 17 (36%); CD56, CD19, and CD14, present at diagnosis in 5, 16, and 20 cases, were lost at relapse in 2 (40%), 6 (38%), and 8 (40%). Leukemia cell gates created in pretreatment samples using each 3-antibody panel allowed identification of relapse AML cells in only 68% to 91% of cases, but use of 8 3-antibody panels, which included antibodies to a total of 16 antigens, allowed identification of relapse AML cells in all cases. Thus, the immunophenotype of AML cells is markedly unstable; nevertheless, despite this instability, MFC has the potential to identify RD in AML if multiple antibody panels are used at all time points. C1 Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. CALGB, Ctr Stat, Durham, NC USA. Southeastern Canc Ctr, Lumberton, NC USA. Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. Wayne State Univ, Sch Med, Detroit, MI USA. Wake Forest Univ, Sch Med, Winston Salem, NC USA. N Shore Univ Hosp, Manhasset, NY USA. Duke Univ, Med Ctr, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. SUNY Upstate Med Univ, Syracuse, NY USA. Univ Alabama Birmingham, Birmingham, AL USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. RP Roswell Pk Canc Inst, Dept Med, Elm & Carlton St, Buffalo, NY 14263 USA. EM maria.baer@roswellpark.org RI Mrozek, Krzysztof/A-3142-2008; OI Larson, Richard/0000-0001-9168-3203 FU NCI NIH HHS [CA03927, CA02599, CA31946, CA32291, CA33601, CA35279, CA41287, CA47559, CA47577, CA77658] NR 43 TC 113 Z9 118 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JUN 1 PY 2001 VL 97 IS 11 BP 3574 EP 3580 DI 10.1182/blood.V97.11.3574 PG 7 WC Hematology SC Hematology GA 436GJ UT WOS:000168927900036 PM 11369653 ER PT J AU Buhler, L Goepfert, C Kitamura, H Basker, M Gojo, S Alwayn, IPJ Chang, Q Downs, JD Tsai, H Wise, R Sachs, DH Cooper, DKC Robson, SC Sackstein, R AF Buhler, L Goepfert, C Kitamura, H Basker, M Gojo, S Alwayn, IPJ Chang, Q Downs, JD Tsai, H Wise, R Sachs, DH Cooper, DKC Robson, SC Sackstein, R TI Porcine hematopoietic cell xenotransplantation in nonhuman primates is complicated by thrombotic microangiopathy SO BONE MARROW TRANSPLANTATION LA English DT Article DE thrombotic thrombocytopenic purpura; bone marrow transplantation; von Willebrand factor; mixed chimerism; pig-to-primate ID BONE-MARROW TRANSPLANTATION; FACTOR-CLEAVING PROTEASE; HEMOLYTIC-UREMIC SYNDROME; THROMBOCYTOPENIC PURPURA; PLASMA-EXCHANGE; TOLERANCE INDUCTION; ANTI-GAL-ALPHA-1-3GAL ANTIBODY; FACTOR-VIII; IN-VITRO; BABOONS AB Thrombotic microangiopathy (TM) is a serious complication of bone marrow transplantation (BMT) that resembles thrombotic thrombocytopenic purpura (TTP). In attempting to achieve hematopoietic cell chimerism in the pig-to-baboon model, we have observed TM following infusion of high doses (>10(10) cells/kg) of porcine peripheral blood mobilized progenitor cells (PBPC) into baboons. We performed investigations to analyze the pathobiology of this TM and to test therapeutic interventions to ameliorate it. PBPC were obtained by leukapheresis of cytokine-stimulated swine. The initial observations were made in two baboons that underwent a non-myeloablative regimen (NMR) prior to PBPC transplantation (TX) (group 1). We then studied three experimental groups. Group 2 (n = 2) received NMR without PBPC TX. Group 3 (n = 2) received PBPC TX alone. Group 4 (n = 6) received NMR + PBPC TX combined with prostacyclin, low-dose heparin, methylprednisolone. and cyclosporine was replaced by anti-CD40L mAb in five cases. Baboons in groups I and 3 developed severe thrombocytopenia (<10000/mm(3)), intravascular hemolysis with schistocytosis (>10/high powered field (hpf)), increase in plasma lactate dehydrogenase (LDH) (2500-9000 U/l), transient neurologic changes, renal insufficiency, and purpura. Autopsy on two baboons confirmed extensive platelet thrombi in the microcirculation, and, similar to clinical BMT-associated TM/TTP, no unusually large vWF multimers or changes in vWF protease activity were observed in the plasma of baboons with TM. In group 2, self-limited thrombocytopenia occurred for 10-15 days following NMR. Group 4 baboons developed thrombocytopenia (<20000/mm(3)) rarely requiring platelet transfusion, minimal schistocytosis (<3/hpf), minor increase in LDH (<1000 U/l), with no clinical sequelae. We conclude that high-dose porcine PBPC infusion into baboons induces a microangiopathic state with VWF biochemical parameters resembling clinical BMT-associated TM/TTP and that administration of antithrombotic and anti-inflammatory agents ran ameliorate this complication. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. BioTransplant Inc, Charlestown, MA USA. Montefiore Med Ctr, Albert Einstein Coll Med, Div Hematol, Bronx, NY 10467 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Hematol, Boston, MA 02115 USA. RP Sackstein, R (reprint author), Harvard Inst Med, 77 Ave Louis Pasteur,Room 671, Boston, MA 02115 USA. FU NIAID NIH HHS [5P01 AI39755] NR 44 TC 23 Z9 23 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JUN PY 2001 VL 27 IS 12 BP 1227 EP 1236 DI 10.1038/sj.bmt.1703067 PG 10 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 452RU UT WOS:000169873200002 PM 11548840 ER PT J AU Pecora, AL Lazarus, HM Stadtmauer, EA Winter, J Van Vliet, A Berry, D Gray, R Jennis, A Goldberg, S Cooper, BW Preti, R AF Pecora, AL Lazarus, HM Stadtmauer, EA Winter, J Van Vliet, A Berry, D Gray, R Jennis, A Goldberg, S Cooper, BW Preti, R TI Effect of induction chemotherapy and tandem cycles of high-dose chemotherapy on outcomes in autologous stem cell transplant for metastatic breast cancer SO BONE MARROW TRANSPLANTATION LA English DT Article DE tandem high-dose chemotherapy; breast cancer ID BONE-MARROW TRANSPLANTATION; PROGRESSION-FREE SURVIVAL; COLONY-STIMULATING FACTOR; HEMATOPOIETIC SUPPORT; NO IMPROVEMENT; FOLLOW-UP; PHASE-II; THERAPY; CARBOPLATIN; RESCUE AB We assessed the effect standard-dose induction chemotherapy and tandem cycles of high-dose chemotherapy (HDC) have on outcomes in metastatic breast cancer, One hundred and one women with metastatic breast cancer were enrolled in two non-randomized phase II studies, The first group of 64 patients (induction group) received four cycles of docetaxel 75 mg/m(2) and doxorubicin 50 mg/m(2). The next 37 patients did not receive induction (no induction group). Both groups received two (tandem) cycles of HDC, Blood-derived stem cells were collected after the first HDC cycle, processed using CD34(-) cell selection and then reinfused after the second HDC cycle. Outcomes were compared between the two groups and also to patients participating in the Philadelphia (inter-group) randomized metastatic breast cancer transplant trial (PBT-01), Intent-to-treat analysis revealed no significant differences in complete response rates (37.5% vs 27%; P = 0.20), overall response (75% vs 71%), median progression free survival (PFS) (11.9 vs 8 months; P = 0.24) and overall survival (OS) (>36 vs 25 months; P = 0.16), in the induction vs no induction groups, respectively. Adjusting for differences in known baseline characteristics, induction group patients were found to have significantly longer PFS (P = 0.002), OS (P = 0.01) and more frequent conversion from a partial to complete response (58% vs less than or equal to 13%, P less than or equal to 0.0002) when compared with PBT-01 patients, Induction chemotherapy administered prior to tandem cycles of HDC does not appear to adversely affect outcomes in metastatic breast cancer patients, Outcomes in our induction group also compare favorably with those observed in PBT-01 and warrant further clinical investigation. C1 Hackensack Univ, Med Ctr, Hackensack, NJ USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Ctr, Boston, MA USA. Progenitor Cell Therapy LLC, Hackensack, NJ USA. RP Pecora, AL (reprint author), Div Hematol Oncol, 20 Prospect St, Hackensack, NJ 07601 USA. NR 42 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JUN PY 2001 VL 27 IS 12 BP 1245 EP 1253 DI 10.1038/sj.bmt.1703066 PG 9 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 452RU UT WOS:000169873200004 PM 11548842 ER PT J AU Foster, D Strong, R Morgan, WW AF Foster, D Strong, R Morgan, WW TI A tetracycline-repressible transactivator approach suggests a shorter half-life for tyrosine hydroxylase mRNA SO BRAIN RESEARCH PROTOCOLS LA English DT Article DE tyrosine hydroxylase; mRNA stability; post-transcriptional regulation; tyrosine hydroxylase gene; catecholamines ID PROTEIN-KINASE-A; PYRIMIDINE-RICH SEQUENCE; MESSENGER-RNA STABILITY; 3'-UNTRANSLATED REGION; GENE-EXPRESSION; ONGOING RNA; PC12 CELLS; ACTIVATION; BINDING; PHOSPHORYLATION AB Long-term increases in catecholamine release result in elevated levels of the mRNA for tyrosine hydroxylase (TH), the rate-limiting enzyme in the biosynthesis of these compounds. This increase is due, in part, to increased transcription. However, recent evidence suggests that increased stability of TH mRNA may also play a role. One of the problems in studying the stability of the TH message is the limitation of current methods for assessing transcript half-life. in this study the regulation of the expression of the rat TH gene was placed under the control of a tetracycline (Tet)-repressible transactivator (tTA). In the absence of doxycycline (Dox), an analogue of Tet, TH mRNA was synthesized. However, when Dox was present, transcription of TH message was essentially totally suppressed, and the resulting degradation of the TH mRNA provided an index of the half-life of this message. With this approach the computed half-life of TH mRNA was significantly shorter than that determined following actinomycin D administration. This effect was not due to some unique feature of the chimeric gene used to synthesize TH mRNA or to an untoward effect of the Tet analogue used to suppress TH transcription. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA. RP Morgan, WW (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, Mail Code 7762,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NIA NIH HHS [AG14674]; NIDDK NIH HHS [DK52543] NR 35 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1385-299X J9 BRAIN RES PROTOC JI Brain Res. Protoc. PD JUN PY 2001 VL 7 IS 2 BP 137 EP 146 DI 10.1016/S1385-299X(01)00056-3 PG 10 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 437YL UT WOS:000169026900007 PM 11356380 ER PT J AU Kern, H Kuring, A Redlich, U Dopfmer, UR Sims, NM Spies, CD Kox, WJ AF Kern, H Kuring, A Redlich, U Dopfmer, UR Sims, NM Spies, CD Kox, WJ TI Downward movement of syringe pumps reduces syringe output SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE equipment; syringe pumps ID INFUSION-PUMP; HEMODYNAMIC STABILITY; EPINEPHRINE INFUSION; FLOW-RATE; OPERATION AB We studied how lowering a syringe pump and changing the outflow pressure could affect syringe pump output. We experimentally reduced the height of three different syringe pump systems by 80 cm (adult setting) or 130 cm (neonatal setting), as can happen clinically, using five flow rates. We measured the rime of backward flow, no flow and the total time without flow. An exponential negative correlation was present between infusion rate and time without flow (r(2)=0.809 to 0.972, P <0.01). Minimum flow rates of 4.4 and 2.6 mi h(-1) respectively were calculated to give 60 and 120 s without infusion. The compliance of the different syringe pumps and their infusion systems was linearly correlated with the effective time without infusion (r(2)=0.863, P <0.05). We conclude that the height of the syringe pumps should not be changed during transportation. If vertical movement of the syringe pump is necessary, the drugs should be diluted so that the flow rate is at least 5 mi h(-1). C1 Univ Hosp Charite, Dept Anaesthesia & Intens Care Med, D-10117 Berlin, Germany. Univ Jena, Dept Biomed Engn, D-6900 Jena, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners Healthcare Biomed Engn, Boston, MA USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA USA. RP Kern, H (reprint author), Univ Hosp Charite, Dept Anaesthesia & Intens Care Med, Schumannstr 20-21, D-10117 Berlin, Germany. NR 9 TC 23 Z9 27 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD JUN PY 2001 VL 86 IS 6 BP 828 EP 831 DI 10.1093/bja/86.6.828 PG 4 WC Anesthesiology SC Anesthesiology GA 439WV UT WOS:000169141300015 PM 11573591 ER PT J AU Ma, JY Qiu, JH Hirt, L Dalkara, T Moskowitz, MA AF Ma, JY Qiu, JH Hirt, L Dalkara, T Moskowitz, MA TI Synergistic protective effect of caspase inhibitors and bFGF against brain injury induced by transient focal ischaemia SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE growth factors; bFGF; caspase inhibitors; neuroprotection; focal cerebral ischaemia ID FIBROBLAST-GROWTH-FACTOR; POSSIBLE NEUROPROTECTIVE MECHANISM; NEURONAL CELL-DEATH; CEREBRAL-ISCHEMIA; BCL-X; THERAPEUTIC WINDOW; APOPTOSIS; BAX; EXPRESSION; SURVIVAL AB 1 We tested the hypothesis that combined use of trophic factors and caspase inhibitors increases brain resistance to ischaemia in mice. 2 Intracerebroventricular administration of bFGF (> 10 ng) 30 min after MCA occlusion decreased infarct size and neurological deficit in a dose-dependent manner following 2 h ischemia and reperfusion (20 h). 3 Combined administration of the subthreshold doses of bFGF (3 ng) and caspase inhibitors (z-VAD.FMK, 27 ng or z-DEVD.FMK, 80 mg) reduced infarct volume by 60%, and reduced neurological deficit. 4 Treatment with a subthreshold dose of bFGF (3 ng) extended the therapeutic window for z-DEVD.FMK (480 ng) from 1 to 3 h after reperfusion. 5 Caspase-3 activity in the ischaemic brain was increased 30 min and 2 h after reperfusion but, was significantly reduced in bFGF-treated animals by 29 and 16%, respectively. Caspase-3 activity was not reduced by a direct bFGF effect because addition of bFGF (10 nM-2 muM) did not decrease recombinant caspase-3 activity, in vitro. 6 Our data show that combining caspase inhibitors and bFGF lengthens the treatment window for the second treatment, plus lowers the dosage requirements for neuroprotection. These findings are important because low doses of caspase inhibitors or bFGF reduce the possibility of side effects plus extend the short treatment window for ischaemic stroke. C1 Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Serv Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Hacettepe Univ Hosp, Dept Neurol, Ankara, Turkey. RP Moskowitz, MA (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 6403, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011; Hirt, Lorenz/G-3553-2010 OI Hirt, Lorenz/0000-0002-2921-5000 FU NINDS NIH HHS [F32 NS010828, NS10828, NS374141-02, P01 NS010828, P50 NS010828] NR 36 TC 32 Z9 32 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JUN PY 2001 VL 133 IS 3 BP 345 EP 350 DI 10.1038/sj.bjp.0704075 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 437WR UT WOS:000169022800004 PM 11375250 ER PT J AU Tondo, L Baldessarini, RJ Floris, G AF Tondo, L Baldessarini, RJ Floris, G TI Long-term clinical effectiveness of lithium maintenance treatment in types I and II bipolar disorders SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 1st European Stanley Foundation Symposium on Bipolar Disorder CY SEP 24-25, 1998 CL ROYAL SOC, LONDON, ENGLAND SP Stanley Fdn HO ROYAL SOC ID RECURRENT AFFECTIVE-ILLNESS; MANIC-DEPRESSIVE ILLNESS; FOLLOW-UP; SUICIDAL-BEHAVIOR; MOOD STABILIZERS; PROPHYLAXIS; DISCONTINUATION; SEQUENCE; CARBAMAZEPINE; RESPONSES AB Background The effectiveness of lithium is being questioned increasingly and requires clarification. Aims To assess the effectiveness of lithium treatment in depression and mania, syndromal types I and II, with predominantly mixed or psychotic episodes or rapid cycling, during treatment resumed following discontinuation, and across three decades. Method The longitudinal course of 360 patients with bipolar disorder compliant with lithium treatment for at least I year and without comorbidity for substance use disorder was reviewed. Results Risk of single-episode recurrences, a common index of treatment failure. was similar to that in other reports. Both episode frequency and 'time ill' improved more in type than type I cases. Reduced morbidity during treatment was similar in patients with mixed or psychotic episodes, or rapid cycling. and in less complex cases. Retreatment yielded minor decrements in response, and there was no tendency for lesser responses in more recent years. Conclusions Based on overall affective morbidity, long-term lithium treatment in compliant patients without comorbid substance use disorder. though imperfect, remains effective, even in subgroups of supposedly poor prognosis. C1 Univ Cagliari, Dept Psychol, Sardinia, Italy. Harvard Univ, Sch Med, McLean Hosp, Dept Psychiat, Boston, MA USA. Ctr Lucio Bini, I-09128 Cagliari, Italy. Massachusetts Gen Hosp, McLean Div, Int Consortium Bipolar Disorders Res Bipolar & Ps, Belmont, MA USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. RP Tondo, L (reprint author), Ctr Lucio Bini, 28 Via Cavalcanti, I-09128 Cagliari, Italy. NR 66 TC 17 Z9 17 U1 1 U2 5 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD JUN PY 2001 VL 178 SU 41 BP S184 EP S190 DI 10.1192/bjp.178.41.s184 PG 7 WC Psychiatry SC Psychiatry GA 443QD UT WOS:000169351100013 ER PT J AU Kraus, MD Fleming, MD Vonderheide, RH AF Kraus, MD Fleming, MD Vonderheide, RH TI The spleen as a diagnostic specimen - A review of 10 years' experience at two tertiary care institutions SO CANCER LA English DT Article DE spleen; splenomegaly; primary splenic lymphoma; diagnostic splenectomy ID FINE-NEEDLE ASPIRATION; SPLENIC MARGINAL ZONE; NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMAS; MALIGNANT-LYMPHOMAS; CLINICAL-FEATURES; SPLENECTOMY; BIOPSY; CLASSIFICATION; DISEASES AB BACKGROUND. Few studies have examined the yield of the diagnostic splenectomy, and the relevance of these studies to the management of patients with unexplained splenomegaly or a splenic mass are limited by low number of cases, the use of selection criteria, and the lack of modern terminology and modern ancillary studies. The current study correlates clinical intent with preoperative clinical and radiologic studies and histologic findings in an assessment of the diagnostic yield of splenectomy. METHODS. The medical charts, laboratory data, radiologic studies, and pertinent preoperative biopsies on all patients who underwent splenectomy between the years 1986 and 1995 were reviewed, and the clinical intent behind the procedure was correlated with histologic findings. RESULTS. One hundred twenty-two of the 1280 patients underwent splenectomy for diagnosis, and in 116 patients a specific disease was identified histologically that explained the splenomegaly/splenic mass; malignancy was the most common cause of unexplained splenomegaly or splenic mass, though benign neoplasms and reactive disorders were documented in 25% of the cases. Primary splenic lymphomas were most commonly of large cell B-cell type. CONCLUSIONS, In the setting of splenomegaly or splenic mass, splenectomy has a high diagnostic yield and usually discloses a malignancy. The clinical category of "primary splenic lymphoma" is biologically heterogeneous, and the diagnosis is usually an intermediate grade (not low grade) lymphoma. The range of conditions associated with splenic masses were quite commonly associated with diseases that are amenable to fine-needle aspiration (FNA) diagnosis, whereas those disorders associated only with splenomegaly included a large fraction of diseases for which FNA may yield either incomplete or misleading results. Cancer 2001;91:2001-9. (C) 2001 American Cancer Society. C1 Barnes Jewish Hosp, Dept Pathol, St Louis, MO 63110 USA. St Louis Childrens Hosp, St Louis, MO 63178 USA. Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Med Oncol, Boston, MA 02115 USA. RP Kraus, MD (reprint author), Washington Univ, Sch Med, Dept Pathol, Box 8118,660 S Euclid Ave, St Louis, MO 63110 USA. NR 49 TC 71 Z9 75 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 2001 VL 91 IS 11 BP 2001 EP 2009 DI 10.1002/1097-0142(20010601)91:11<2001::AID-CNCR1225>3.0.CO;2-3 PG 9 WC Oncology SC Oncology GA 436LX UT WOS:000168938300006 PM 11391578 ER PT J AU Loehrer, PJ Jiroutek, M Aisner, S Aisner, J Green, M Thomas, CR Livingston, R Johnson, DH AF Loehrer, PJ Jiroutek, M Aisner, S Aisner, J Green, M Thomas, CR Livingston, R Johnson, DH TI Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma - An intergroup trial SO CANCER LA English DT Article DE etoposide; ifosfamide; cisplatin; thymic carcinoma; thymoma ID INVASIVE THYMOMA; RECURRENT THYMOMA; RADIATION-THERAPY; CYCLOPHOSPHAMIDE; CHEMOTHERAPY; DOXORUBICIN; EXPRESSION; P53 AB BACKGROUND, Patients with thymic tumors (thymoma and thymic carcinoma) are known to respond to a variety of chemotherapeutic agents, including single-agent ifosfamide and cisplatin with etoposide. The purpose of this trial was to evaluate the response rate, progression free survival, overall survival, and toxicity of combined etoposide, ifosfamide, and cisplatin MP) in patients with advanced thymoma and thymic carcinoma. METHODS. From July 1995 through February 1997, 34 patients with advanced thymoma or thymic carcinoma were entered on trial to receive etoposide (75 mg/m(2) on Days 1-4) ifosfamide (1.2 g/m(2) on Days 1-4), and cisplatin (20 mg/m(2) on Days 1-4). Cycles were repeated every 3 weeks for four total cycles. RESULTS. Among 28 evaluable patients (pathology review excluded 6 patients), there were no complete responses and 9 partial responses (complete and partial responses combined, 32%; 95% confidence interval, 16-52%). The median follow-up was 43 months (range, 12.8-52.3 months), the median duration of response was 11.9 months (range, < 1-26 months), and the median overall survival was 31.6 months. Based on Kaplan-Meier estimates, the 1-year and 2-year survival rates were 89% and 70%, respectively. The toxicity was predominantly myelosuppression. CONCLUSIONS, The VIP regimen has moderate activity in patients with advanced thymic malignancies. However, with limited follow-up, the results of this trial appear to be inferior to other chemotherapy regimens reported in large Phase II trials performed in patients with this disease. Cancer 2001;91:2010-5. (C) 2001 American Cancer Society. C1 Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA. Walther Canc Inst, Indianapolis, IN USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Canc Inst New Jersey, New Brunswick, NJ USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Radiat Oncol, Charleston, SC 29425 USA. Univ Washington, Dept Med, Seattle, WA USA. Vanderbilt Univ, Dept Oncol, Nashville, TN USA. RP Loehrer, PJ (reprint author), Indiana Canc Pavil,535 Barnhill Dr,Room 473, Indianapolis, IN 46202 USA. RI Johnson, David/A-7437-2009 FU NCI NIH HHS [CA23318, CA 21115, CA38926, CA49883, CA49959, CA66636] NR 24 TC 115 Z9 123 U1 0 U2 5 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 2001 VL 91 IS 11 BP 2010 EP 2015 DI 10.1002/1097-0142(20010601)91:11<2010::AID-CNCR1226>3.0.CO;2-2 PG 6 WC Oncology SC Oncology GA 436LX UT WOS:000168938300007 PM 11391579 ER PT J AU Blagosklonny, MV Pardee, AB AF Blagosklonny, MV Pardee, AB TI Exploiting cancer cell cycling for selective protection of normal cells SO CANCER RESEARCH LA English DT Review ID ANTICANCER DRUG TARGETS; TYROSINE KINASE INHIBITOR; DNA-DAMAGE; PROTEIN-KINASE; PHASE-II; PROSTATE-CANCER; MAMMALIAN-CELLS; CDK INHIBITORS; GROWTH-FACTORS; G(2) ARREST AB Chemotherapy of cancer is limited by its toxicity to normal cells. On the basis of discoveries in signal transduction and cell cycle regulation, novel mechanism-based therapeutics are being developed. Although these cell cycle modulators were designed to target cancer cells, some of them can also be applied for a different purpose, i.e., to protect normal cells against the lethality of chemotherapy. Loss of sensitivity of cancer cells to cell cycle inhibitors can be exploited for selective protection of normal cells that retain this response. Indeed, inhibition of redundant or overactivated pathways (e.g., growth factor-activated pathways) or stimulation of absent pathways in cancer cells (e.g, p53, Rb, and p16) may not arrest cycling of cancer cells. But growth arrest of normal cells will then permit selective killing of cancer cells by cycle-dependent chemotherapy. C1 NCI, Med Branch, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Blagosklonny, MV (reprint author), NCI, Med Branch, NIH, Bldg 10,Room 12 N 226, Bethesda, MD 20892 USA. NR 99 TC 127 Z9 141 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 JUN 1 PY 2001 VL 61 IS 11 BP 4301 EP 4305 PG 5 WC Oncology SC Oncology GA 438KA UT WOS:000169051100002 PM 11389048 ER PT J AU Soukos, NS Hamblin, MR Keel, S Fabian, RL Deutsch, TF Hasan, T AF Soukos, NS Hamblin, MR Keel, S Fabian, RL Deutsch, TF Hasan, T TI Epidermal growth factor receptor-targeted immunophotodiagnosis and photoimmunotherapy of oral precancer in vivo SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; HAMSTER BUCCAL POUCH; MONOCLONAL-ANTIBODIES; NUDE-MICE; SOLID TUMORS; CARCINOEMBRYONIC ANTIGEN; DIFFERENTIAL EXPRESSION; OVARIAN-CANCER; HUMAN HEAD; PHASE-I AB Immunophotodiagnosis uses a fluorescence-labeled monoclonal antibody (MAb) that recognizes a tumor-associated antigen to image the fluorescence emitted from the fluorophore-bound MAb that has localized in the tissue, It may be used to diagnose malignant or precancerous lesions, to delineate the margins for tumor resection, or as a feedback mechanism to assess response to treatment. In oral precancer, the epidermal growth factor receptor (EGFR) is overexpressed and could be used as a marker for early detection or as a target for therapy, The goal of this study was to test an anti-EGFR MAb (C225) coupled to either the near-infrared fluorescent dye N,N ' -di-carboxypentyl -indodicarbocyanine-5,5 ' -disulfonic acid for detection or a photochemically active dye (chlorin(e6)) for therapy of early premalignancy in the hamster cheek pouch carcinogenesis model, fluorescence levels in the carcinogen-treated tissue correlated with the histological stage of the lesions when the C225-N,N ' -di-carboxypentyl-indodicarbocyanine-5,5 '- acid conjugate was used but did not do so with the irrelevant conjugates. Discrete areas of clinically normal mucosa with high fluorescence (hot spots) were subsequently shown by histology to contain dysplastic areas. The best contrast between normal and carcinogen-treated cheek pouches vias found at 4-8 days after injection, To test the potential of immunophotodiagnosis as a feedback modality for therapeutic intervention, experiments were conducted with the same MAb conjugated to chlorin(e6) followed by illumination to reduce expression of the EGFR by a photodynamic effect. Subsequent immunophotodiagnosis showed that this treatment led to a significant reduction in fluorescence in the carcinogen-treated cheek pouch compared with nonilluminated areas, This difference between illuminated and dark areas was not seen in the normal cheek pouch, Taken together, the results demonstrate the potential for development of immunophotodiagnosis as a diagnostic fool and as a method of monitoring response to therapy and that the EGFR may be an appropriate target in head and neck cancer. C1 Massachusetts Gen Hosp, Dept Dermatol, Wellman Labs Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. RP Hasan, T (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Wellman Labs Photomed, 50 Blossom St WEL224, Boston, MA 02114 USA. EM hasan@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NCI NIH HHS [R01 CA083882]; NIAMS NIH HHS [R01 AR040352, R01 AR40352] NR 45 TC 87 Z9 95 U1 0 U2 13 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2001 VL 61 IS 11 BP 4490 EP 4496 PG 7 WC Oncology SC Oncology GA 438KA UT WOS:000169051100034 PM 11389080 ER PT J AU Bashore, TM Bates, ER Kern, MJ Berger, PB Laskey, WK Clark, DA O'Laughlin, MP Cusma, JT Oesterle, S Dehmer, GJ Popma, JJ AF Bashore, TM Bates, ER Kern, MJ Berger, PB Laskey, WK Clark, DA O'Laughlin, MP Cusma, JT Oesterle, S Dehmer, GJ Popma, JJ TI American College of Cardiology/Society for Cardiac Angiography and Interventions clinical expert consensus document on cardiac catheterization laboratory standards: Summary of a report of the American College of Cardiology task force on clinical expert consensus documents SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article C1 Duke Univ, Med Ctr, Cardiac Catheterizat Lab, Durham, NC 27710 USA. Univ Michigan, Ann Arbor, MI 48109 USA. St Louis Univ Hosp, St Louis, MO USA. Mayo Clin, Rochester, MN USA. Univ Maryland, Baltimore, MD 21201 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ N Carolina, Chapel Hill, NC USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bashore, TM (reprint author), Duke Univ, Med Ctr, Cardiac Catheterizat Lab, Box 3012, Durham, NC 27710 USA. NR 4 TC 4 Z9 4 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 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JUN PY 2001 VL 53 IS 2 BP 281 EP 286 DI 10.1002/ccd.1166 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 437TX UT WOS:000169010600026 PM 11387622 ER PT J AU Morita, Y Maravei, DV Bergeron, L Wang, S Perez, G Tsutsumi, O Taketani, Y Asano, M Horai, R Korsmeyer, SJ Iwakura, Y Yuan, J Tilly, JL AF Morita, Y Maravei, DV Bergeron, L Wang, S Perez, G Tsutsumi, O Taketani, Y Asano, M Horai, R Korsmeyer, SJ Iwakura, Y Yuan, J Tilly, JL TI Caspase-2 deficiency prevents programmed germ cell death resulting from cytokine insufficiency but not meiotic defects caused by loss of ataxia telangiectasia-mutated (Atm) gene function SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE apoptosis; cell death; oocyte; ovary; caspase; ATM; Bax ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; OOCYTE APOPTOSIS; MICE DEFICIENT; GONADAL-DYSGENESIS; PROPHASE-I; MOUSE; BAX; BCL-2; CHEMOTHERAPY; CHROMOSOMES AB It is well established that programmed cell death claims up to two-thirds of the oocytes produced during gametogenesis in the developing fetal ovaries, However, the mechanisms underlying prenatal germ cell loss in females remain poorly understood, Herein we report that caspase-11 null female mice are born with a reduced number of oocyte-containing primordial follicles, This phenotype is likely due to failed cytokine processing known to occur in caspase-11 mutants since neonatal female mice lacking both interleukin (IL)-1 alpha and IL-1 beta also exhibit a reduced endowment of primordial follicles, In addition, germ cell death in wild-type fetal ovaries cultured ex vivo is suppressed by either cytokine, likely via ligand activation of type 1 IL-1 receptors expressed in fetal germ cells, Normal oocyte endowment can be restored in caspase-11 null female mice by simultaneous inactivation of the gene encoding the cell death executioner enzyme, caspase-2, However, caspase-2 deficiency cannot overcome gametogenic failure resulting from meiotic recombination defects in ataxia telangiectasia-mutated (Atm) null female mice, Thus, genetically distinct mechanisms exist for developmental deletion of oocytes via programmed cell death, one of which probably functions as a meiotic quality-control checkpoint that cannot be overridden. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Univ Tokyo, Fac Med, Dept Obstet & Gynecol, Tokyo 1138655, Japan. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Univ Tokyo, Inst Med Sci, Ctr Expt Med, Tokyo 1088639, Japan. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, VBK137C-GYN,55 Fruit St, Boston, MA 02114 USA. RI Iwakura, Yoichiro/E-5457-2011 OI Iwakura, Yoichiro/0000-0002-9934-5775 FU NIA NIH HHS [R01-AG12279, R01-AG12859]; NIEHS NIH HHS [R01-ES08430] NR 61 TC 48 Z9 51 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD JUN PY 2001 VL 8 IS 6 BP 614 EP 620 DI 10.1038/sj.cdd.4400845 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 439NK UT WOS:000169123100010 PM 11536012 ER PT J AU Goldstein, JM Seidman, LJ Horton, NJ Makris, N Kennedy, DN Caviness, VS Faraone, SV Tsuang, MT AF Goldstein, JM Seidman, LJ Horton, NJ Makris, N Kennedy, DN Caviness, VS Faraone, SV Tsuang, MT TI Normal sexual dimorphism of the adult human brain assessed by in vivo magnetic resonance imaging SO CEREBRAL CORTEX LA English DT Article ID GAMMA-AMINOBUTYRIC-ACID; RECEPTOR MESSENGER-RNA; HUMAN TEMPORAL CORTEX; HUMAN CEREBRAL-CORTEX; ESTROGEN-RECEPTORS; GENDER DIFFERENCES; MORPHOMETRIC ANALYSIS; INSITU HYBRIDIZATION; ANTERIOR COMMISSURE; HUMAN HYPOTHALAMUS AB The etiology and consistency of findings on normal sexual dimorphisms of the adult human brain are unresolved. In this study, we present a comprehensive evaluation of normal sexual dimorphisms of cortical and subcortical brain regions, using in vivo magnetic resonance imaging, in a community sample of 48 normal adults. The men and women were similar in age, education, ethnicity, socioeconomic status, general intelligence and handedness. Forty-five brain regions were assessed based on T-1-weighted three-dimensional images acquired from a 1.5 T magnet. Sexual dimorphisms of adult brain volumes were more evident in the cortex, with women having larger volumes, relative to cerebrum size, particularly in frontal and medial paralimbic cortices. Men had larger volumes, relative to cerebrum size, in frontomedial cortex, the amygdala and hypothalamus. A permutation test showed that, compared to other brain areas assessed in this study, there was greater sexual dimorphism among brain areas that are homologous with those identified in animal studies showing greater levels of sex steroid receptors during critical periods of brain development. These findings have implications for developmental studies that would directly test hypotheses about mechanisms relating sex steroid hormones to sexual dimorphisms in humans. C1 Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Brockton W Roxbury Vet Affairs Med Ctr, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Radiol Sci, Ctr Morphometr Anal,Massachusetts Gen Hosp, Boston, MA 02129 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Massachusetts Mental Hlth Ctr, Harvard Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. RP Goldstein, JM (reprint author), Massachusetts Mental Hlth Ctr, Harvard Inst Psychiat Epidemiol & Genet, 74 Fenwood Rd, Boston, MA 02115 USA. RI Horton, Nicholas/A-2493-2008; Kennedy, David/H-3627-2012; OI Horton, Nicholas/0000-0003-3332-4311; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH46318, K21 MH00976, R01 MH43518] NR 78 TC 486 Z9 496 U1 7 U2 54 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JUN PY 2001 VL 11 IS 6 BP 490 EP 497 DI 10.1093/cercor/11.6.490 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 434XD UT WOS:000168840400002 PM 11375910 ER PT J AU Littner, M Szymusiak, RS AF Littner, M Szymusiak, RS TI To sleep deeply, perchance to wake refreshed SO CHEST LA English DT Editorial Material ID SCALE; APNEA; PERFORMANCE; NARCOLEPSY C1 Univ Calif Los Angeles, Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda, CA 91343 USA. RP Littner, M (reprint author), Univ Calif Los Angeles, Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, 16111 Plummer St, Sepulveda, CA 91343 USA. NR 12 TC 0 Z9 0 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 JUN PY 2001 VL 119 IS 6 BP 1633 EP 1634 DI 10.1378/chest.119.6.1633 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 441NB UT WOS:000169235500005 PM 11399683 ER PT J AU Harris, LN Yang, L Liotcheva, V Pauli, S Iglehart, JD Colvin, OM Hsieh, TS AF Harris, LN Yang, L Liotcheva, V Pauli, S Iglehart, JD Colvin, OM Hsieh, TS TI Induction of topoisomerase II activity after ErbB2 activation is associated with a differential response to breast cancer chemotherapy SO CLINICAL CANCER RESEARCH LA English DT Article ID DNA TOPOISOMERASE; CELL LINES; OVEREXPRESSION; EXPRESSION; SENSITIVITY; DOXORUBICIN; HER-2/NEU; CARCINOMA; REPAIR; GROWTH AB ErbB2 (HER-2) gene amplification and overexpression have been shown to predict a better outcome,vith doxorubicin-based chemotherapy as opposed to alkylator-based chemotherapy in early stage breast cancer, To understand the mechanism of differential response to these two regimens, we have evaluated the effect of signaling through the ErbB2 receptor on downstream enzymes that may affect drug response, using two different models, The first system employs breast cancer cells that have high levels of endogenous ErbB2 by gene amplification (BT-474 and SKBR3 cells). The second system allows us to isolate the effect of ErbB2 receptor-mediated intracellular signaling using an epidermal growth factor receptor-ErbB2 chimeric receptor activated by epidermal growth factor. Our experiments show that the cytotoxicity of doxorubicin is inhibited in ErbB2+ breast cancer cells by the anti-ErbB2 antibody, Herceptin. This is accompanied by a decrease in topoisomerase (topo) II alpha protein and activity, suggesting that this is the mechanism of change in doxorubicin response, In addition, a 10-100-fold (1-2 log) decrease in the LD,, of doxorubicin is seen after ErbB2 activation using the chimeric receptor model. Furthermore, we see a 100-fold decrease in the LD,, of etoposide, another topo II inhibitor. This increase in doxorubicin sensitivity is associated with a 4.5-fold increase in the amount of topo II alpha protein and an increase in topo II activity as measured by DNA decatenating and unknotting activities, as well as cleavable complex formation, In contradistinction to doxorubicin, we have observed an increased resistance to cyclophosphamide chemotherapy after chimeric receptor activation, We propose that the differential benefit seen with doxorubicin- versus alkylator-based chemotherapy in ErbB2+ breast cancer is due, in some cases, to ErbB2-mediated topo II alpha activation, These data also suggest hypotheses for the optimal sequencing of Herceptin and chemotherapy agents in ErbB2+ breast cancer. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Ctr Comprehens Canc, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Harris, LN (reprint author), Dana Farber Canc Inst, Room 1210,44 Binney St, Boston, MA 02115 USA. RI Wu, Wan-lin /G-8937-2012; Hsieh, Tao-shih/G-9305-2012 NR 34 TC 63 Z9 70 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 JUN PY 2001 VL 7 IS 6 BP 1497 EP 1504 PG 8 WC Oncology SC Oncology GA 442XQ UT WOS:000169310600003 PM 11410482 ER PT J AU Shapiro, GI Supko, JG Patterson, A Lynch, C Lucca, J Zacarola, PF Muzikansky, A Wright, JJ Lynch, TJ Rollins, BJ AF Shapiro, GI Supko, JG Patterson, A Lynch, C Lucca, J Zacarola, PF Muzikansky, A Wright, JJ Lynch, TJ Rollins, BJ TI A phase II trial of the cyclin-dependent kinase inhibitor flavopiridol in patients with previously untreated stage IV non-small cell lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID BREAST-CARCINOMA CELLS; NONSMALL CELL; TUMOR SUPPRESSION; DOWN-REGULATION; SOLID TUMORS; APOPTOSIS; INACTIVATION; ARREST; P16(INK4A); PROTEIN AB Purpose: Flavopiridol is a patent cyclin-dependent kinase inhibitor with preclinical activity against non-small cell lung cancer (NSCLC), inhibiting tumor growth in vitro and in vivo by cytostatic and cytotoxic mechanisms. A Phase IT trial was conducted to determine the activity and toxicity of flavopiridol in untreated patients with metastatic NSCLC, Experimental Design: A total of 20 patients were treated with a 72-h continuous infusion of flavopiridol every 14 days at a dose of 50 mg/m(2)/day and a concentration of 0.1-0.2 mg/ml, Dose escalation to 60 mg/m(2)/day was permitted if no significant toxicity occurred. Response was initially assessed after every two infusions; patients treated longer than 8 weeks were then assessed after every four infusions. Plasma levels of flavopiridol were measured daily during the first two infusions to determine steady-state concentrations. Results: This study was designed to evaluate a total of 45 patients in two stages. However, because no objective responses were seen in the first 20 patients, the early-stopping rule was invoked, and patient accrual was halted. In four patients who received eight infusions, progression was documented at 15, 20, 40, and 65 weeks, respectively, The most common toxicities included grade 1 or 2 diarrhea in 11 patients, asthenia in 10 patients, and venous thromboses in 7 patients. The mean +/- SD steady-state concentration of drug during the first infusion was 200 +/- 89.9 nM, sufficient for cytostatic effects in irt vitro models, Conclusions: At the current doses and schedule, flavopiridol does not have cytotoxic activity in NSCLC, although protracted periods of disease stability were observed with an acceptable degree of toxicity. C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NCI, Div Canc Treatment & Diagnost, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Shapiro, GI (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Mayer 422B,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [U01 CA62490-07] NR 65 TC 127 Z9 134 U1 0 U2 0 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 JUN PY 2001 VL 7 IS 6 BP 1590 EP 1599 PG 10 WC Oncology SC Oncology GA 442XQ UT WOS:000169310600016 PM 11410495 ER PT J AU Dinovo, EC Renner, SW Mody, FV AF Dinovo, EC Renner, SW Mody, FV TI Use of CKMBmass for confirmation of the first or an isolated positive troponin I result. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Div Cardiol, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2001 VL 47 IS 6 SU S MA 689 BP A210 EP A210 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 437MX UT WOS:000168996400806 ER PT J AU Dinovo, EC Renner, SW Mody, FV AF Dinovo, EC Renner, SW Mody, FV TI Fast troponin I elimination in a subset of chest pain patients. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Div Cardiol, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2001 VL 47 IS 6 SU S MA 688 BP A210 EP A210 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 437MX UT WOS:000168996400805 ER PT J AU Howanitz, PJ Steindel, SJ Heard, NV AF Howanitz, PJ Steindel, SJ Heard, NV TI Use of critical values lists in 623 institutions. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 SUNY Brooklyn, Brooklyn, NY USA. Ctr Dis Control & Prevent, Atlanta, GA USA. W Los Angeles Vet Affairs Med Ctr, W Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2001 VL 47 IS 6 SU S MA 718 BP A219 EP A220 PN 2 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 437MX UT WOS:000168996400835 ER PT J AU Howanitz, PJ Renner, SW Walsh, MK AF Howanitz, PJ Renner, SW Walsh, MK TI Patient wristband errors are reduced with continuous monoring: A College of American Pathologist Q-Tracks study in 214 institutions. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. W Los Angeles Vet Affairs Med Ctr, W Los Angeles, CA USA. Coll Amer Pathologists, Northfield, MN USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2001 VL 47 IS 6 SU S MA 717 BP A219 EP A219 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 437MX UT WOS:000168996400834 ER PT J AU Peterson, KP Knudson, PE Chaiken, J Peterson, CM Finney, WF Yang, X Weinstock, RS AF Peterson, KP Knudson, PE Chaiken, J Peterson, CM Finney, WF Yang, X Weinstock, RS TI Clinical use of noninvasive tissue-modulated Raman spectroscopic measurement of blood glucose in whole blood. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 LighTouch Med, Syracuse, NY USA. Joslin Diabet Ctr, Syracuse, NY USA. LighTouch Med, Potomac, MD USA. RI Peterson, Karen/E-8084-2015 OI Peterson, Karen/0000-0001-6737-8698 NR 0 TC 1 Z9 1 U1 0 U2 4 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2001 VL 47 IS 6 SU S MA 538 BP A164 EP A165 PN 2 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 437MX UT WOS:000168996400655 ER PT J AU Wang, C Swerdloff, RS Iranmanesh, A Dobs, A Snyder, PJ Cunningham, G Matsumoto, AM Weber, T Berman, N AF Wang, C Swerdloff, RS Iranmanesh, A Dobs, A Snyder, PJ Cunningham, G Matsumoto, AM Weber, T Berman, N CA Testosterone Gel Study Grp TI Effects of transdermal testosterone gel on bone turnover markers and bone mineral density in hypogonadal men SO CLINICAL ENDOCRINOLOGY LA English DT Article ID CLINICAL RESEARCH-CENTER; AROMATASE DEFICIENCY; PARATHYROID-HORMONE; OSTEOPOROSIS; MASS; ANDROGENS; ESTROGEN; THERAPY; CELLS; PREVENTION AB OBJECTIVE Androgen replacement has been reported to increase bone mineral density (BMD) in hypogonadal men. We studied the effects of 6 months of treatment with a new transdermal testosterone (T) gel preparation on bone turnover markers and BMD. DESIGN This was a prospective, randomized, multicentre, parallel clinical trial where 227 hypogonadal men, mean age 51 years (range: 19-68 years) were studied in 16 academic and research institutions in the USA. Subjects were randomized to apply 1% T gel containing 50 or 100 mg T (delivering approximately 5-10 mg T/day) or two T patches (delivering 5 mg T/day) transdermally for 90 days. At day 91, depending on the serum T concentration, the T gel dose was adjusted upward or downward to 75 mg T/day until day 180. No dose adjustment occurred in the T patch group. MEASUREMENTS Serum T, free T and oestradiol, bone turnover markers and BMD were measured on days 0, 30, 90 and 180 before and after treatment. RESULTS Application of T gel 100 mg/day resulted in serum T concentrations 1.4 and 1.9-fold higher than in the T gel 50 mg/day and the T patch groups, respectively, Proportional increases occurred in serum oestradiol. Urine N-telopeptide/creatinine ratio, a marker for bone resorption, decreased significantly (P = 0.0019) only in the T gel 100 mg/day group, Serum bone osteoblastic activity markers (osteocalcin, procollagen and skeletal alkaline phosphatase) increased significantly during the first 90 days of treatment without intergroup differences but declined to baseline thereafter. BMD increased significantly both in the hip (+1.1 +/- 0.3%) and spine (+2.2 +/- 0.5%) only in the T gel 100 mg/day group (P = 0.0001). CONCLUSIONS Transdermal testosterone gel application for 6 months decreased bone resorption markers and increased osteoblastic activity markers for a short period, which resulted in a small but significant increase in BMD. Ongoing long-term studies should answer whether the observed increases in BMD are sustained or continue to be dependent on the dose of testosterone administered. C1 Harbor UCLA Med Ctr, Gen Clin Res Ctr, Div Endocrinol, Dept Med, Torrance, CA 90509 USA. Harbor UCLA Med Ctr, Div Endocrinol, Dept Pediat, Torrance, CA 90509 USA. Res & Educ Inst, Torrance, CA USA. VA Med Ctr, Salem, VA USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Duke Univ, Med Ctr, Durham, NC USA. RP Wang, C (reprint author), Harbor UCLA Med Ctr, Gen Clin Res Ctr, Div Endocrinol, Dept Med, 1000 W Carson St, Torrance, CA 90509 USA. NR 42 TC 79 Z9 81 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD JUN PY 2001 VL 54 IS 6 BP 739 EP 750 DI 10.1046/j.1365-2265.2001.01271.x PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 453BM UT WOS:000169896900007 PM 11422108 ER PT J AU Lewandrowski, K AF Lewandrowski, K TI Point-of-care testing - Preface SO CLINICS IN LABORATORY MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Clin Labs, Boston, MA 02114 USA. RP Lewandrowski, K (reprint author), Massachusetts Gen Hosp, Clin Labs, 55 Fruit St,GRB 5 Chem, 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 JUN PY 2001 VL 21 IS 2 BP XI EP XIII PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 445DA UT WOS:000169441800001 ER PT J AU Lee-Lewandrowski, E Lewandrowski, K AF Lee-Lewandrowski, E Lewandrowski, K TI Point-of-care testing - An overview and a look to the future SO CLINICS IN LABORATORY MEDICINE LA English DT Article ID BLOOD-GLUCOSE; COST-ANALYSIS AB Point-of-care testing is an emerging specialty in laboratory medicine and has attracted considerable interest in the medical literature. This article presents a general overview of point-of-care testing including its history, menu, clinical utility, aspects of analytical performance, regulatory issues, and management in the hospital setting. Some perspectives concerning the possible future of point-of-care testing are also presented in view of current issues in the hospital and clinical laboratory. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lewandrowski, K (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fuit St,GRB 5, Boston, MA 02114 USA. NR 20 TC 8 Z9 8 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD JUN PY 2001 VL 21 IS 2 BP 217 EP + PG 24 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 445DA UT WOS:000169441800002 PM 11396080 ER PT J AU Lee-Lewandrowski, E Lewandrowski, K AF Lee-Lewandrowski, E Lewandrowski, K TI Regulatory compliance for point-of-care testing - A perspective from the United States (Circa 2000) SO CLINICS IN LABORATORY MEDICINE LA English DT Article AB Regulatory guidelines concerning point-of-care testing have had a major impact on the development and evolution of these technologies. Beginning with mandates under CLIA '88, hospital accreditation organizations have developed guidelines for the management of point-of-care testing to ensure quality testing. Over the past decade, most hospitals have learned to manage these new technologies as part of the laboratory quality assurance program. Issues concerning regulatory compliance continue to influence the development and use of point-of-care technologies providing opportunity for continuous quality improvement and improved patient care. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lewandrowski, K (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,GRB 5 Chem, Boston, MA 02114 USA. NR 6 TC 3 Z9 3 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 JUN PY 2001 VL 21 IS 2 BP 241 EP + PG 14 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 445DA UT WOS:000169441800003 PM 11396081 ER PT J AU Van Cott, EM AF Van Cott, EM TI Coagulation point-of-care testing SO CLINICS IN LABORATORY MEDICINE LA English DT Article ID PATHOLOGISTS CONFERENCE XXXI; ORAL ANTICOAGULANT-THERAPY; PATIENT SELF-MANAGEMENT; VON-WILLEBRAND-DISEASE; PROTHROMBIN TIME; WARFARIN THERAPY; CONTROLLED TRIAL; CARDIAC-SURGERY; HEPARIN; MONITOR AB A growing number of point-of-care devices are becoming available for prothrombin time, activated partial thromboplastin time, and activated clotting time, the most commonly performed coagulation tests. Various clinical studies have been performed using point-of-care devices, in some cases to assess whether these devices are sufficiently accurate for clinical purposes. This article discusses coagulation point-of-care methodologies and clinical studies investigating the potential uses of these technologies. C1 Massachusetts Gen Hosp, Div Lab Med, Coagulat Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Van Cott, EM (reprint author), Massachusetts Gen Hosp, Div Lab Med, Coagulat Lab, Fruit St,Gray Jackson 235, Boston, MA 02114 USA. NR 34 TC 4 Z9 4 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 JUN PY 2001 VL 21 IS 2 BP 337 EP + PG 15 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 445DA UT WOS:000169441800009 PM 11396087 ER PT J AU Yang, JM AF Yang, JM TI Toxicology and drugs of abuse testing at the point of care SO CLINICS IN LABORATORY MEDICINE LA English DT Article ID IMMUNOASSAYS AB Point-of-care methods have been developed for the detection of abused drugs in urine. This article identifies substances, illicit and Licit, that are targeted by testing for reasons of medical care, drugs policy, or law enforcement. The advantages and disadvantages of point-of-care testing, and clinical interpretation of test results, are discussed. Point-of-care breath alcohol analysis and its use as an alternative to laboratory blood measurement are also included. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Yang, JM (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 9 TC 4 Z9 4 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD JUN PY 2001 VL 21 IS 2 BP 363 EP + PG 14 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 445DA UT WOS:000169441800011 PM 11396089 ER PT J AU Lee-Lewandrowski, E Lewandrowski, K AF Lee-Lewandrowski, E Lewandrowski, K TI Selected topics in point-of-care testing - Urinalysis, pregnancy testing, microbiology, fecal occult blood, and other tests SO CLINICS IN LABORATORY MEDICINE LA English DT Article AB This article reviews a number of point-of-care testing technologies. Some of these tests (e.g., urinalysis, pregnancy testing, and occult blood testing) are among the more commonly performed point-of-care tests in the hospital and outpatient settings. The clinical use of these tests in the point-of-care setting is reviewed along with the authors' experience concerning the management of these manual point-of-care technologies. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lewandrowski, K (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,GRB 5, Boston, MA 02114 USA. NR 8 TC 1 Z9 1 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 JUN PY 2001 VL 21 IS 2 BP 389 EP + PG 17 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 445DA UT WOS:000169441800013 PM 11396091 ER PT J AU Safren, SA Hollander, G Hart, TA Heimberg, RG AF Safren, SA Hollander, G Hart, TA Heimberg, RG TI Cognitive-behavioral therapy with lesbian, gay, and bisexual youth SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID SEXUAL ORIENTATION; LIFE EVENTS; COMMUNITY SETTINGS; RISK-FACTORS; SUICIDE; STRESS; ADOLESCENTS; DEPRESSION; CHILDHOOD; HOPELESSNESS AB The purpose of the present paper is to sensitize cognitive-behavior therapists to issues that are faced by many lesbian, gay, and bisexual youth. Little information is available to cognitive-behavioral therapists about same-sex sexual attractions in lesbian, gay, and bisexual youth, or how to incorporate these concerns into one functional analysis and treatment plan. However lesbian, gay, and bisexual youth may be at risk for a variety of clinical problems amenable to cognitive-behavioral therapy. We provide necessary information for the incorporation of issues concerning same-sex sexuality into one's case formulations when working with lesbian, gay, and bisexual youth, illustrated by case examples and clinical vignettes. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Fenway Community Hlth, Boston, MA USA. Univ Wisconsin, Sch Med, Madison, WI 53706 USA. Temple Univ, Philadelphia, PA 19122 USA. RP Safren, SA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, WACC-815,15 Parkman St, Boston, MA 02114 USA. OI Hart, Trevor/0000-0001-5107-7452 NR 59 TC 12 Z9 12 U1 0 U2 3 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD SUM PY 2001 VL 8 IS 3 BP 215 EP 223 DI 10.1016/S1077-7229(01)80056-0 PG 9 WC Psychology, Clinical SC Psychology GA 473UY UT WOS:000171067500001 ER PT J AU Franko, DL AF Franko, DL TI Rethinking prevention efforts in eating disorders SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID DIETING-INDUCED DISORDERS; BULIMIA-NERVOSA; PROGRAM; ATTITUDES; SMOKING; DISTURBANCES; POPULATION; BEHAVIORS; CHILDREN; ALCOHOL AB The prevention of eating disorders has been a complicated and elusive goal for researchers. Using an innovative design, the Body Logic Program (Varnado-Sullivan et al., 2001) was found to successfully reduce fear of fatness and decrease intentions to diet in a study of adolescent girls. Previous researchers have recommended separating universal (primary) and indicated (secondary) prevention. However, the authors found that this was not easily accomplished. When at-risk girls were identified and invited to participate in an intensive program, only I (of 55) elected to do so. Future prevention efforts will need to examine innovative approaches to reach these at-risk girls, including the use of incentives for participation, a focus on advocacy and action, the involvement of parents, and an integration of eating disorders prevention with other adolescent health concerns. C1 Harvard Univ, Sch Med, Eating Disorders Ctr, Boston, MA 02114 USA. Univ Massachusetts, Dartmouth, MA USA. RP Franko, DL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Eating Disorders Ctr, WACC 725,15 Parkman St, Boston, MA 02114 USA. NR 38 TC 11 Z9 11 U1 1 U2 1 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD SUM PY 2001 VL 8 IS 3 BP 265 EP 270 DI 10.1016/S1077-7229(01)80063-8 PG 6 WC Psychology, Clinical SC Psychology GA 473UY UT WOS:000171067500008 ER PT J AU McNally, RJ Otto, MW Hornig, CD Deckersbach, T AF McNally, RJ Otto, MW Hornig, CD Deckersbach, T TI Cognitive bias in panic disorder: A process dissociation approach to automaticity SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE panic disorder, cognitive bias; process dissociation; automaticity ID ANXIETY SENSITIVITY; MEMORY BIAS; THREAT AB We applied a variant of Jacoby's (1991) process dissociation procedure to parse the relative contributions of automatic and controlled processes to word-stem completion performance involving threatening, positive, and neutral material in patients with panic disorder and healthy control participants. Contrary to prediction, processing of threatening (relative to nonthreatening) information in panic disorder was not disproportionately influenced by automatic processing. We found limited evidence, however, that panic patients exhibit a baseline bias for completing sterns relevant to threat relative to nonthreat stems, perhaps indicating a proneness to engage in self-generated priming of threat material. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP McNally, RJ (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. NR 23 TC 7 Z9 8 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD JUN PY 2001 VL 25 IS 3 BP 335 EP 347 DI 10.1023/A:1010740617762 PG 13 WC Psychology, Clinical SC Psychology GA 415GE UT WOS:000167711900008 ER PT J AU Coney, P Washenik, K Langley, RGB DiGiovanna, JJ Harrison, DD AF Coney, P Washenik, K Langley, RGB DiGiovanna, JJ Harrison, DD TI Weight change and adverse event incidence with a low-dose oral contraceptive: two randomized, placebo-controlled trials SO CONTRACEPTION LA English DT Article DE low-dose oral contraceptives; weight side effects; levonorgestrel; ethinyl estradiol; placebo-controlled ID 100 MU-G; ETHINYL ESTRADIOL; LEVONORGESTREL; DISCONTINUATION; ADOLESCENT; COMBINATION; MISUSE; CYCLE; USERS; GAIN AB Changes in body weight and the incidence of estrogen-related side effects with low-dose oral contraceptives (OCs) containing 20 mug ethinyl estradiol (EE) have not been demonstrated in placebo-controlled trials. Two placebo-controlled, randomized trials demonstrated the efficacy of a low-dose OC for the treatment of acne in healthy females (n = 704, greater than or equal to 14 years old) with regular menstrual cycles and moderate facial acne. Patients were randomized to receive 20 mug EE/100 mug levonorgestrel (LNG) or placebo for six cycles. Body weight was measured at baseline and during Cycles 1, 3, and 6. The occurrence of adverse events was recorded at each visit. Mean changes in weight from baseline were similar with 20 mug EE/100 mug LNG [0.72 kg +/- 2.64 (SD; n = 349)] and placebo [0.56 kg +/- 2.64 (SD; n = 355; p > 0.05)] for the last measured weight of each patient. Rates of headache, nausea, weight gain, and breast pain, side effects commonly attributed to OCs, were also similar between groups (p > 0.05). No serious, unexpected, drug-related adverse events occurred during the study. The low-dose OC containing 20 mug EE/100 mug LNG is safe, well tolerated, and does not cause weight gain. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Wyeth Ayerst Labs, St Davids, PA 19087 USA. So Illinois Univ, Sch Med, Dept Obstet & Gynecol, Springfield, IL 62794 USA. NYU, Med Ctr, Dept Dermatol, New York, NY 10016 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brown Univ, Sch Med, Dept Dermatol, Providence, RI 02912 USA. Rhode Isl Hosp, Providence, RI USA. RP Harrison, DD (reprint author), Wyeth Ayerst Labs, St Davids, PA 19087 USA. NR 26 TC 65 Z9 66 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0010-7824 J9 CONTRACEPTION JI Contraception PD JUN PY 2001 VL 63 IS 6 BP 297 EP 302 DI 10.1016/S0010-7824(01)00208-6 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 461RX UT WOS:000170378200002 PM 11672550 ER PT J AU Moy, CS Albert, DM Diener-West, M McCaffrey, LD Scully, RE Willson, JKV AF Moy, CS Albert, DM Diener-West, M McCaffrey, LD Scully, RE Willson, JKV CA Collaborative Ocular Melanoma Stud COMS Mortality Coding Comm TI Cause-specific mortality coding: Methods in the Collaborative Ocular Melanoma Study COMS report no. 14 SO CONTROLLED CLINICAL TRIALS LA English DT Article DE mortality coding; cause-specific mortality; disease-specific mortality; all-cause mortality; postmortem diagnosis; death certificate; choroidal melanoma; clinical trial ID DEATH CERTIFICATE; AUTOPSY; ACCURACY; CANCER; DIAGNOSES; STATISTICS; SURVIVAL AB Ascertainment of cause of death is often sought in clinical trials in which mortality is an outcome of interest. Standardized methods of coding all-cause and disease-specific mortality were developed and evaluated in the Collaborative Ocular Melanoma Study randomized trial of pre-enucleation radiation of large choroidal melanoma. All available clinical and pathologic materials documenting events prior to each reported death were reviewed systematically by a Mortality Coding Committee (MCC) to determine whether melanoma metastasis or local recurrence was present at the time of death. A level of certainty was assigned based on availability of local or central review of pathology materials. The outcome of the mortality coding protocol was evaluated both by assessing agreement between the judgment of the MCC and the presumed cause of death reported by the clinical center and, for a subset of patients, by assessing agreement between the MCC classification and the cause of death reported on the death certificate. As of July 31, 1997 (the cutoff date for the initial mortality report), 435 (95%) of 457 deceased patient files had been reviewed. The MCC classified 269 patients (62%) as dead with melanoma metastasis, 22 (5%) as dead with another malignant tumor, and 92 (21%) as dead with a malignant tumor of uncertain origin. Thirty-eight patients (9%) died with no evidence of malignancy; in 14 cases (3%), the presence or absence of malignancy could not be established due to lack of clinical information. Fair agreement (kappa = 0.34) was observed between the determinations of the MCC based on detailed review of materials and the cause of death reported on the death certificate, but death certificates alone underestimated the proportion of deaths due to metastatic choroidal melanoma. Detailed mortality coding identified difficulties associated with accurate reporting of cause-specific mortality in patients with choroidal melanoma. (C) Elsevier Science Inc. 2001. C1 Johns Hopkins Univ, Baltimore, MD USA. Univ Wisconsin, Madison, WI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Moy, CS (reprint author), COMS Coordinating Ctr, 550 N Broadway,9th Floor, Baltimore, MD 21205 USA. FU NEI NIH HHS [EY06269, EY06288, EY06282, EY06839, EY06899, EY06259, EY06284, EY06275, EY06253, EY06844, EY06258, EY06264, EY06270, EY06848, EY06858, EY06287, EY06260, EY06268, EY06283, EY06289, EY06274, EY06257, EY06266, EY06843, EY06280, EY06265, EY06291, EY06276, EY06279] NR 38 TC 19 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD JUN PY 2001 VL 22 IS 3 BP 248 EP 262 DI 10.1016/S0197-2456(01)00113-1 PG 15 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 435PW UT WOS:000168890700005 PM 11384789 ER PT J AU Brenner, BE Chavda, KK Karakurum, MB Karras, DJ Camargo, CA AF Brenner, BE Chavda, KK Karakurum, MB Karras, DJ Camargo, CA CA MARC Invest TI Circadian differences among 4,096 emergency department patients with acute asthma SO CRITICAL CARE MEDICINE LA English DT Article DE asthma; diurnal; circadian; nocturnal; bronchospasm ID NOCTURNAL ASTHMA; INFLAMMATION; EPINEPHRINE; PERCEPTION; HISTAMINE; CORTISOL; SYMPTOMS; DYSPNEA AB Introduction: In patients with asthma, airways narrow during the night, The clinical implications of a nocturnal presentation of patients with acute asthma to the emergency department (ED) are uncertain. Objective: Our objective was to determine whether patients with asthma who had ED visits during the night (midnight to 7:59 am) vs, other times were more severe, responded less well to ED therapy, and had worse clinical outcomes. Design and Setting: We performed a cohort study, as part of the Multicenter Airway Research Collaboration (n = 77 sites). ED patients with acute asthma, ages 2-54 yrs, underwent a structured interview in the ED. Chart review of missed/refusal patients created a truly consecutive case series. Measurements and Main Results: Among 1,602 children, 19% presented at night. Nighttime patients were more likely to be younger, male, and have a shorter duration of symptoms; there were no other clinical differences noted, Among 2,494 adults, 20% presented at night, and they were more likely to be female and to have a history of steroid use for asthma, Nighttime adults also had a shorter duration of symptoms and slightly lower peak flows (mean, 45% vs, 49% of predicted; p = .006) and were more likely to receive steroids, They were more likely to be intubated (2.0% vs, 0.2%; p < .001), but, overall, they were equally likely to be admitted or relapse after ED discharge. In contrast to objective measures of acute asthma severity, both nighttime children and adults were significantly less likely to report their asthma symptoms as severe. Conclusion: Except for endotracheal intubation (in adults only), circadian differences minimally affect ED presentation, therapy, or the outcomes of acute asthma, Nighttime asthmatics may be relatively insensitive to the symptoms of severe asthma. C1 Brooklyn Hosp Ctr, Dept Emergency Med, Brooklyn, NY USA. Brooklyn Hosp Ctr, Dept Pediat, Brooklyn, NY USA. Temple Univ, Sch Med, Div Emergency Med, Philadelphia, PA 19122 USA. Harvard Univ, Sch Med, Dept Emergency Med, Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, Boston, MA USA. RP Brenner, BE (reprint author), Univ Arkansas Med Sci, Dept Emergency Med, 4301 W Markham St, Little Rock, AR 72205 USA. FU NHLBI NIH HHS [HL-03533, HL-63253] NR 31 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 2001 VL 29 IS 6 BP 1124 EP 1129 DI 10.1097/00003246-200106000-00005 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 442BY UT WOS:000169266400004 PM 11414269 ER PT J AU Rogers, PL Jacob, H Rashwan, AS Pinsky, MR AF Rogers, PL Jacob, H Rashwan, AS Pinsky, MR TI Quantifying learning in medical students during a critical care medicine elective: A comparison of three evaluation instruments SO CRITICAL CARE MEDICINE LA English DT Article DE education, medical; students, medical; critical care; teaching; educational measurement; clinical clerkships; intensive care unit; clinical competence ID STRUCTURED CLINICAL EXAMINATION; PERFORMANCE; COMPETENCE; SKILLS AB Objective: To compare three different evaluative instruments and determine which is able to measure different aspects of medical student learning. Design: Student learning was evaluated by using written examinations, objective structured clinical examination, and patient simulator that used two clinical scenarios before and after a structured critical care elective, by using a crossover design. Participation: Twenty-four 4th-yr students enrolled in the critical care medicine elective. Interventions: All students took a multiple-choice written examination; evaluated a live simulated critically in patient, requested data from a nurse, and intervened as appropriate at different stations (objective structured clinical examination); and evaluated the computer-controlled patient simulator and intervened as appropriate. Measurements and Main Results: Students' knowledge was assessed by using a multiple-choice examination containing the same data incorporated into the other examinations. Student performance on the objective structured clinical examination was evaluated at five stations. Both objective structured clinical examination and simulator tests were videotaped for subsequent scores of responses, quality of responses, and response time. The videotapes were reviewed for specific behaviors by faculty masked to time of examination. Students were expected to perform the following: a) assess airway, breathing, and circulation; b) prepare a mannequin for intubation; c) provide appropriate ventilator settings; d) manage hypotension; and e) request, interpret, and provide appropriate intervention for pulmonary artery catheter data. Students were expected to perform identical behaviors during the simulator examination; however, the entire examination was performed on the whole-body computer-controlled mannequin. The primary outcome measure was the difference in examination scores before and after the rotation. The mean preelective scores were 77 +/- 16%, 47 +/- 15%, and 41 +/- 14% for the written examination, objective structured clinical examination, and simulator, respectively, compared with 89 +/- 11%, 76 +/- 12%, and 62 +/- 15% after the elective (p < .0001). Prerotation scores for the written examination were significantly higher than the objective structured clinical examination or the simulator; postrotation scores were highest for the written examination and lowest for the simulator. Conclusion: Written examinations measure acquisition of knowledge but fail to predict if students can apply knowledge to problem solving, whereas both the objective structured clinical examination and the computer-controlled patient simulator can be used as effective performance evaluation tools. C1 Univ Pittsburgh, Med Ctr, Dept Anesthesiol, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Dept Crit Care Med, Pittsburgh, PA USA. RP Rogers, PL (reprint author), VA Pittsburgh Healthcare Syst, Crit Care Serv 124U, Univ Dr, Pittsburgh, PA 15240 USA. NR 14 TC 27 Z9 28 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 2001 VL 29 IS 6 BP 1268 EP 1273 DI 10.1097/00003246-200106000-00039 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 442BY UT WOS:000169266400028 PM 11395619 ER PT J AU Bernards, A Hariharan, IK AF Bernards, A Hariharan, IK TI Of flies and men - studying human disease in Drosophila SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID DOUBLE-STRANDED-RNA; SAETHRE-CHOTZEN SYNDROME; P-ELEMENT INSERTIONS; GENETIC INTERFERENCE; MUTATIONS; MELANOGASTER; GENOME; SUPPRESSION; HOMOLOG; P53 AB During the past year, the Drosophila genome has been sequenced. More than 60% of genes implicated in human disease have Drosophila orthologues. Developments in RNA-mediated interference and homologous recombination have made 'reverse genetics' feasible in Drosophila. Conventional Drosophila genetics is being used increasingly to place human disease genes of unknown function in the context of functional pathways. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Bernards, A (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 FU NEI NIH HHS [EY11632]; NIGMS NIH HHS [GM61672]; NINDS NIH HHS [NS36084] NR 49 TC 32 Z9 35 U1 2 U2 10 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD JUN PY 2001 VL 11 IS 3 BP 274 EP 278 DI 10.1016/S0959-437X(00)00190-8 PG 5 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 437TW UT WOS:000169010500007 PM 11377963 ER PT J AU Nunez, R Ackermann, M Saeki, Y Chiocca, A Fraefel, C AF Nunez, R Ackermann, M Saeki, Y Chiocca, A Fraefel, C TI Flow cytometric assessment of transduction efficiency and cytotoxicity of herpes simplex virus type 1-based amplicon vectors SO CYTOMETRY LA English DT Article DE HSV-1 amplicon vectors; flow cytometry; transduction efficiency; cytotoxicity ID GREEN-FLUORESCENT PROTEIN; LONG UNIQUE REGION; HEMATOPOIETIC-CELLS; ESCHERICHIA-COLI; DNA-SEQUENCES; GENE-TRANSFER; NEURAL CELLS; EXPRESSION; MARKER; IDENTIFICATION AB Background: In this study, we compared herpes simplex virus type 1 (HSV-1) amplicon vector stocks prepared by transient cotransfection with two different BAG-cloned packaging-defective HSV-1 helper genomes, fHSV Delta pac Delta 27 and fHSV Delta pac, with respect to transduction efficiency and cytotoxicity. Both fHSV Delta pac Delta 27 and fHSV Delta pac are packaging defective because the pac signals have been deleted; fHSV Delta pac Delta 27 contains an additional deletion in the HSV-1 ICP27 gene, which increases the safety of the system. Methods: HSV-1 amplicon pHSVGFP under the control of the HSV-1 immediate-early (IE) 4/5 promotor was packaged into virus pat-tides by transient cotransfection with either fHSV Delta pac Delta 27 or fHSV Delta pac DNA. Cultures were infected with the two different vector stocks and examined under the fluorescence microscope and analyzed by flow cytometry over a 5-day period to assess transduction efficiency and cytotoxicity. Results: Both vector stocks, pHSVGFP{fHSV Delta pac Delta 27} and pHSVGFP{fHSV Delta pac}, efficiently transduced the target cells. Interestingly, the highest mean fluorescence intensities were measured at 1 day after infection, whereas the number of GFP-fluorcscent cells reached a peak at day 3 after infection. At day 3 after infection, a slight increase in the number of dead cells was observed in those cultures transduced with high doses of vector stock. Between days 3 and 4 after infection, the number of dead cells increased dramatically in all the cultures, transduced and nontransduced. Only the cultures infected with a high dose of pHSVGFP{fHSV Delta pac} displayed a significant further increase in the number of dead cells between days 4 and 5 postinfection. Conclusions: Flow cytometry allowed comparison of transduction efficiency and cytotoxicity mediated by the two different amplicon vector stocks. Cultures infected with pHSVGFP{fHSV Delta pac Delta 27} were more viable than those infected with pHSVGFP{fHSV Delta pac}(P < 0.05). The practical implications of this study are at the level of vector design. Flow cytometry has proven a fast and reliable approach to assess the quality of potential gene transfer vectors prior to their use in (pre) clinical trials. Cytometry 44:93-99, 2001. (C) 2001 Wiley-Liss, Inc. C1 Univ Zurich, Inst Virol, Zurich, Switzerland. Osaka Univ, Grad Sch Med, Div Gene Therapy Sci, Osaka, Japan. Massachusetts Gen Hosp, Serv Neurol, Mol Nerooncol Labs, Charlestown, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Nunez, R (reprint author), Mem Sloan Kettering Canc Ctr, Program Immunol, Box 98,1275 York Ave, New York, NY 10021 USA. NR 27 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 0196-4763 J9 CYTOMETRY JI Cytometry PD JUN 1 PY 2001 VL 44 IS 2 BP 93 EP 99 DI 10.1002/1097-0320(20010601)44:2<93::AID-CYTO1086>3.0.CO;2-G PG 7 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 438JD UT WOS:000169049100001 PM 11378858 ER PT J AU Klein, RS Rubin, JB Gibson, HD DeHaan, EN Alvarez-Hernandez, X Segal, RA Luster, AD AF Klein, RS Rubin, JB Gibson, HD DeHaan, EN Alvarez-Hernandez, X Segal, RA Luster, AD TI SDF-1 alpha induces chemotaxis and enhances Sonic hedgehog-induced proliferation of cerebellar granule cells SO DEVELOPMENT LA English DT Article DE chemokine; SDF-1 alpha; Sonic hedgehog; granule cell; cerebellum; mouse ID PROTEIN-KINASE-A; CHEMOKINE RECEPTOR CXCR4; RAT NERVOUS-SYSTEM; I IGF-I; NEURONAL DEVELOPMENT; EXPRESSION; GROWTH; MICE; CHEMOATTRACTANT; FACTOR-1-ALPHA AB The chemokine SDF-1 alpha (CXC12) and its receptor CXCR4 have been shown to play a role in the development of normal cerebellar cytoarchitecture. We report here that SDF-1 alpha both induces chemotactic responses in granule precursor cells and enhances granule cell proliferative responses to Sonic hedgehog. Chemotactic and proliferative responses to SDF-1 alpha are greater in granule cells obtained from cerebella of animals in the first postnatal week, coinciding with the observed in vivo peak in cerebellar CXCR4 expression. SDF-1 alpha activation of neuronal CXCR4 differs from activation of CXCR4 in leukocytes in that SDF-1 alpha -induced calcium flux is activity dependent, requiring predepolarization with KCI or pretreatment with glutamate. However, as is the case in leukocytes, neuronal responses to SDF-1 alpha are all abolished by pretreatment of granule cells with pertussis toxin, suggesting they occur through G(alphai) activation. In conclusion, SDF-1 alpha plays a role in two important processes of granule cell maturation - proliferation and migration assisting in the achievement of appropriate cell number and position in the cerebellar cortex. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Dept Pathol, Southborough, MA 01772 USA. RP Klein, RS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. FU NIAID NIH HHS [AI46999]; NICHD NIH HHS [HD 01393]; NIDA NIH HHS [DA00522]; NINDS NIH HHS [NS 37757] NR 71 TC 226 Z9 230 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 JUN PY 2001 VL 128 IS 11 BP 1971 EP 1981 PG 11 WC Developmental Biology SC Developmental Biology GA 442NF UT WOS:000169291300005 PM 11493520 ER PT J AU Serluca, FC Fishman, MC AF Serluca, FC Fishman, MC TI Pre-pattern in the pronephric kidney field of zebrafish SO DEVELOPMENT LA English DT Article DE pronephros; kidney field; glomerulus; cell fate; regulative development; zebrafish ID WILMS-TUMOR GENE; XENOPUS-LAEVIS; EXPRESSION; HEART; DUCT; LINEAGE; SYSTEM; CELLS; DIFFERENTIATION; SPECIFICATION AB Vertebrate embryos use a series of transient kidneys to regulate fluid balance, osmolarity and metabolic waste during development. The first kidney to form in the embryo is the pronephros. This kidney is composed of several cell types with very different functions and is organized into discrete segments: glomerulus, tubules and nephric duct. The site of origin of these cells is poorly understood, as are their lineage relationships. We have defined regions of the intermediate mesoderm as candidates for the pronephric field by expression patterns of the Wilms' Tumor suppressor gene (wt1), single-minded 1 (sim1) and pax2.1, All of these potential kidney markers are expressed in a stripe of intermediate mesoderm, with distinct, overlapping antero-posterior borders. We labeled small groups of cells in this area by laser uncaging of a fluorescent dextran, and then tracked their fates. We found that there was a bounded contiguous region of the intermediate mesoderm that provides pronephric progenitors. As is true for other organ fields, the pronephric field regulates after focal destruction, such that a normal pronephros forms after laser-mediated removal of the wt1 domain, The progenitors for podocytes, tubular cells and duct are restricted to subdomains within the pronephric field. The most anterior cells in the pronephric field give rise to podocytes, This corresponds to the wt1-expressing region. The next more posterior cells contribute to the tubule, and express both wt1 and pax2.1. The most posterior cells contribute to the nephric duct, and these express pax2.1 and sim1, but not wt1. Thus, there is a field for the pronephric kidney with classical attributes of defined border, pre-pattern and regulation. The pattern of the fate map reflects particular combinations of transcription factors. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dev Biol Lab, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02129 USA. RP Fishman, MC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02129 USA. FU NHLBI NIH HHS [R01HL63206, R01HL49579]; NIDDK NIH HHS [R01DK55383] NR 50 TC 92 Z9 96 U1 0 U2 6 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 JUN PY 2001 VL 128 IS 12 BP 2233 EP 2241 PG 9 WC Developmental Biology SC Developmental Biology GA 450XN UT WOS:000169770300006 PM 11493543 ER PT J AU Zhao, T He, CF Su, M West, CA Swanson, SJ Young, AJ Mentzer, SJ AF Zhao, T He, CF Su, M West, CA Swanson, SJ Young, AJ Mentzer, SJ TI Cell adhesion molecule expression in the sheep thymus SO DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY LA English DT Article DE monoclonal antibodies; cell adhesion molecules; thymus gland; sheep ID LUNG MICROVASCULAR ENDOTHELIUM; BETA T-CELLS; LYMPHOCYTES-T; GAMMA-DELTA; ALPHA-BETA; COUNTER-RECEPTORS; MEMBRANE MOLECULE; POSTNATAL THYMUS; EPITHELIAL-CELLS; ANTIGEN-3 LFA-3 AB Cell adhesion molecules are potential regulating factors in both prethymic and intrathymic T cell development. An experimental challenge has been the development of a large animal model that facilitates in vivo studies of both intrathymic development and lymphocyte migration. To extend earlier studies of thymic development. we have developed a panel of monoclonal antibodies (mAb) to a variety of sheep cell adhesion molecules. Immunohistochemistry was used to define mAb reactivity and flow cytometry was used to quantify expression of cell adhesion molecules within the thymus. To facilitate Row cytometry definition of cortical thymocytes. mAbs were developed to the sheep CD1 antigen. Dual parameter Row cytometry provided a phenotypic characterization of cell adhesion molecule expression on both CD1(+) and CD1(-) sheep thymocyte populations. These studies: demonstrated significantly enhanced cortical thymocyte expression of three cell adhesion molecules: beta1 integrin (CD29), ICAM-2 and LFA-3. The beta1 integrin cell adhesion molecule was also expressed at higher levels on CD1(+) thymocytes in post-natal lambs as compared to adult sheep. These studies of thymocyte membrane molecule expression should facilitate future investigations of sheep intrathymic development and T lymphocyte immigration. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Harvard Surg Res Labs, Dana Farber Canc Inst,Lab Immunophysiol, Boston, MA 02115 USA. RP Mentzer, SJ (reprint author), Harvard Univ, Sch Med, Harvard Surg Res Labs, Dana Farber Canc Inst,Lab Immunophysiol, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL47078] NR 58 TC 3 Z9 3 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-305X J9 DEV COMP IMMUNOL JI Dev. Comp. Immunol. PD JUN-JUL PY 2001 VL 25 IS 5-6 BP 519 EP 530 DI 10.1016/S0145-305X(01)00006-4 PG 12 WC Immunology; Zoology SC Immunology; Zoology GA 441XF UT WOS:000169254300016 PM 11356231 ER PT J AU Babb, SG Barnett, J Doedens, AL Cobb, N Liu, Q Sorkin, BC Yelick, PC Raymond, PA Marrs, JA AF Babb, SG Barnett, J Doedens, AL Cobb, N Liu, Q Sorkin, BC Yelick, PC Raymond, PA Marrs, JA TI Zebrafish E-cadherin: Expression during early embryogenesis and regulation during brain development SO DEVELOPMENTAL DYNAMICS LA English DT Article DE cadherin; zebrafish; Danio rerio; neurogenesis; midbrain; hindbrain; wnt1; pax2.1; cyclops ID CELL-ADHESION MOLECULES; CENTRAL-NERVOUS-SYSTEM; EMBRYONIC HISTOGENESIS; INT-1 PROTOONCOGENE; XENOPUS-EMBRYOS; MOUSE-BRAIN; MIDBRAIN; MORPHOGENESIS; HINDBRAIN; MUTANT AB Zebrafish E-cadherin (cdh1) cell adhesion molecule cDNAs were cloned. We investigated spatial and temporal expression of cdh1 during early embryogenesis. Expression was observed in blastomeres, the anterior mesoderm during gastrulation, and developing epithelial structures. In the developing nervous system, cdh1 was detected at the pharyngula stage (24 hpf) in the midbrain-hindbrain boundary (MHB), Developmental. regulation of MHB formation involves wnt1 and pax2.1. wnt1 expression preceded cdh1 expression during MHB formation, and cdh1 expression in the MHD was dependent on normal development of this structure. (C) 2001 Wiley-Liss, Inc. C1 Indiana Univ, Med Ctr, Dept Med, Indianapolis, IN 46202 USA. Univ Michigan, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA. Forsyth Inst, Boston, MA USA. RP Marrs, JA (reprint author), Indiana Univ, Med Ctr, Dept Med, Fesler Hall 115,1120 South Dr, Indianapolis, IN 46202 USA. RI Clendenon, Sherry/F-7651-2010; OI Clendenon, Sherry/0000-0002-3353-0919; Raymond, Pamela/0000-0003-1083-5530 FU NEI NIH HHS [EY04318, EY06892, EY11365] NR 36 TC 33 Z9 34 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JUN PY 2001 VL 221 IS 2 BP 231 EP 237 DI 10.1002/dvdy.1132 PG 7 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 435YV UT WOS:000168910500009 PM 11376490 ER PT J AU Kampman, KM Volpicelli, JR Mulvaney, F Alterman, AI Cornish, J Gariti, P Cnaan, A Poole, S Muller, E Acosta, T Luce, D O'Brien, C AF Kampman, KM Volpicelli, JR Mulvaney, F Alterman, AI Cornish, J Gariti, P Cnaan, A Poole, S Muller, E Acosta, T Luce, D O'Brien, C TI Effectiveness of propranolol for cocaine dependence treatment may depend on cocaine withdrawal symptom severity SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE cocaine withdrawal; propranolol; pharmacotherapy; double-blind; beta-blocker ID ABSTINENCE SYMPTOMATOLOGY; MEMORY STORAGE; DESIPRAMINE; ANXIETY; ABUSE; INVOLVEMENT; ACTIVATION; ATTRITION AB Propranolol may reduce symptoms of autonomic arousal associated with early cocaine abstinence and improve treatment outcome. This trial was an 8-week, double-blind, placebo-controlled trial of propranolol in 108 cocaine dependent subjects. The primary outcome measure was quantitative urinary benzoylecgonine levels. Secondary outcome measures included treatment retention, addiction severity index results, cocaine craving, mood and anxiety symptoms, cocaine withdrawal symptoms. and adverse events. Propranolol treated subjects had lower cocaine withdrawal symptom severity but otherwise did not differ from placebo treated subjects in any outcome measure. However, in a secondary, exploratory analysis, subjects with more severe cocaine withdrawal symptoms responded better to propranolol in comparison to placebo. In these subjects, propranolol treatment was associated with better treatment retention and lower urinary benzoylecgonine levels as compared with the placebo treatment. Propranolol may be useful only for the treatment of cocaine dependent patients with severe cocaine withdrawal symptoms. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Kampman, KM (reprint author), Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [K20 DA00238, Y01 DA30012] NR 43 TC 85 Z9 86 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUN 1 PY 2001 VL 63 IS 1 BP 69 EP 78 DI 10.1016/S0376-8716(00)00193-9 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 428VE UT WOS:000168481700006 PM 11297832 ER PT J AU Neary, JT Lenz, G Kang, Y Rodnight, R Avruch, J AF Neary, JT Lenz, G Kang, Y Rodnight, R Avruch, J TI Role of mitogen-activated protein kinase cascades in P2Y receptor-mediated trophic activation of astroglial cells SO DRUG DEVELOPMENT RESEARCH LA English DT Article; Proceedings Paper CT 1st International Workshop on Nucleotides and their Receptors in the Immune System CY SEP 08-10, 2000 CL FERRARA, ITALY DE extracellular ATP; gliosis; signal transduction; purinergic receptors; mitogenesis; brain injury; protein kinases; astrocytes ID FIBROBLAST GROWTH-FACTORS; SMOOTH-MUSCLE CELLS; EXTRACELLULAR ATP; PURINERGIC RECEPTORS; DNA-SYNTHESIS; INDUCED PROLIFERATION; NUCLEOTIDE RECEPTORS; REACTIVE ASTROCYTES; P-2 PURINOCEPTORS; CYCLE ARREST AB The trophic actions of extracellular nucleotides and nucleosides on astroglial cells in the central nervous system may be important in development as well as injury and repair. Here we summarize recent findings on the signal transduction mechanisms and gene expression that mediate the trophic effects of extracellular ATP on astrocyte cultures, with a particular emphasis on mitogenesis. Activation of ATP/P2Y receptors leads to the stimulation of mitogen-activated protein kinase (MAPK) cascades, which play a crucial role in cellular proliferation, differentiation, and survival. Inhibition of ERK and p38, members of two distinct MAPK cascades, interferes with the ability of extracellular ATP to stimulate astrocyte proliferation, thereby indicating their importance in mitogenic signaling by P2Y receptors. Signaling from P2Y receptors to ERK involves phospholipase D and a calcium-independent protein kinase C isoform, PKC; this pathway is independent of the phosphatidylinositol-phospholipase C / calcium pathway which is also coupled to P2Y receptors. Pharmacological studies suggest that astrocytes may express an as-yet uncloned P2Y receptor that recruits a novel MEK activator in the ERK cascade. Extracellular ATP can also potentiate fibroblast growth factor (FGF)-2-induced proliferation, and studies on interactions between ATP and FGF-2 signaling pathways have revealed that although ATP does not activate cRaf-1, the first protein kinase in the ERK cascade, it can reduce cRaf-1 activation by FGF-2. As intermediate levels of Raf activity stimulate the cell cycle, the partial inhibition of FGF-incluced Raf activity by ATP may contribute to the enhancing effect of ATP on FGF-2-induced astrocyte proliferation. Activation of P2Y receptors also leads to nuclear signaling, and the use of DNA arrays has shown that treatment of astrocytes with extracellular ATP results in the up- and downregulation of a number of genes; studies to determine which of these genes are regulated by MAPKs are now in progress. Elucidation of the components of MAPK pathways linked to P2Y receptors and subsequent changes in gene expression may provide targets for a new avenue of drug development aimed at the management of astrogliosis which occurs in many types of neurological disorders and neurodegeneration. Published 2001 Wiley-Liss, Inc. C1 VA Med Ctr, Res Serv 151, Miami, FL 33125 USA. Univ Miami, Sch Med, Dept Pathol, Miami, FL USA. Univ Miami, Sch Med, Dept Biochem, Miami, FL USA. Univ Fed Rio Do Sul, Dept Biofis, Porto Alegre, RS, Brazil. Univ Fed Rio Do Sul, Dept Quim, Porto Alegre, RS, Brazil. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Diabet Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Neary, JT (reprint author), VA Med Ctr, Res Serv 151, 1201 NW 16th St, Miami, FL 33125 USA. RI Lenz, Guido/A-7618-2008 NR 53 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 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD JUN-JUL PY 2001 VL 53 IS 2-3 BP 158 EP 165 DI 10.1002/ddr.1183 PG 8 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 484PJ UT WOS:000171698500015 ER PT J AU Hawighorst, T Velasco, P Streit, M Hong, YK Kyriakides, TR Brown, LF Bornstein, P Detmar, M AF Hawighorst, T Velasco, P Streit, M Hong, YK Kyriakides, TR Brown, LF Bornstein, P Detmar, M TI Thrombospondin-2 plays a protective role in multistep carcinogenesis: a novel host anti-tumor defense mechanism SO EMBO JOURNAL LA English DT Article DE angiogenesis; cancer; skin; thrombospondin-2 ID ENDOTHELIAL GROWTH-FACTOR; MOUSE SKIN CARCINOGENESIS; KERATIN GENE-EXPRESSION; TRANSGENIC MICE; ANGIOGENESIS INHIBITOR; MALIGNANT PROGRESSION; ENDOGENOUS INHIBITOR; CANCER; CELLS; PROTEIN AB The angiogenic switch during tumorigenesis is thought to be induced by a change in the balance of pro-angiogenic and anti-angiogenic factors. To elucidate the biological role of the endogenous angiogenesis inhibitor thrombospondin-2 (TSP-2) during multistep carcinogenesis, we subjected TSP-2-deficient and wildtype mice to a chemical skin carcinogenesis regimen. Surprisingly, TSP-2 expression was strongly upregulated in the mesenchymal stroma of wild-type mice throughout the consecutive stages of tumorigenesis whereas the angiogenesis factor, vascular endothelial growth factor, was induced predominantly in tumor cells. TSP-2 deficiency dramatically enhanced susceptibility to skin carcinogenesis and resulted in accelerated and increased tumor formation. The angiogenic switch occurred in early stages of pre-malignant tumor formation, and tumor angiogenesis was significantly enhanced in TSP-2-deficient mice. While TSP-2 deficiency did not affect tumor differentiation or proliferation, tumor cell apoptosis was significantly reduced. These results reveal upregulation of an endogenous angiogenesis inhibitor during multistep tumorigenesis and identify enhanced stromal TSP-2 expression as a novel host anti-tumor defense mechanism. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Dermatol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Washington, Dept Biochem, Seattle, WA 98195 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Detmar, M (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA69184, CA86410, R01 CA069184, R01 CA086410]; NHLBI NIH HHS [HL18645, P01 HL018645]; NIAMS NIH HHS [AR45418, R01 AR045418] NR 53 TC 103 Z9 107 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 1 PY 2001 VL 20 IS 11 BP 2631 EP 2640 DI 10.1093/emboj/20.11.2631 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 441LL UT WOS:000169231800003 PM 11387198 ER PT J AU Gupta, N Nodzenski, E Khodarev, NN Yu, JQ Khorasani, L Beckett, MA Kufe, DW Weichselbaum, RR AF Gupta, N Nodzenski, E Khodarev, NN Yu, JQ Khorasani, L Beckett, MA Kufe, DW Weichselbaum, RR TI Angiostatin effects on endothelial cells mediated by ceramide and RhoA SO EMBO REPORTS LA English DT Article ID FOCAL ADHESION KINASE; BOTULINUM C3 EXOENZYME; GROWTH-FACTOR; INDUCED APOPTOSIS; ACTIVATION; PHOSPHORYLATION; SPHINGOMYELINASE; CYTOSKELETON; ANGIOGENESIS; EXPRESSION AB Angiostatin is a cleavage product of plasminogen that has anti-angiogenic properties. We investigated whether the effects of angiostatin on endothelial cells are mediated by ceramide, a lipid implicated in endothelial cell signaling. Our results demonstrate that angiostatin produces a transient increase in ceramide that correlates with actin stress fiber reorganization, detachment and death. DNA array expression analysis performed on ceramide-treated human endothelial cells demonstrated induction of certain genes involved in cytoskeleton organization. Specifically, we report that treatment with angiostatin or ceramide results in the activation of RhoA, an important effector of cytoskeletal structure. We also show that treatment of endothelial cells with the antioxidant N-acetylcysteine abrogates morphological changes and cytotoxic effects of treatment with angiostatin or ceramide. These findings support a model in which angiostatin induces a transient rise in ceramide, RhoA activation and free radical production. C1 Univ Chicago, Dept Surg, Chicago, IL 60637 USA. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. Dana Farber Canc Inst, Div Canc Pharmacol, Boston, MA 02115 USA. RP Weichselbaum, RR (reprint author), Univ Chicago, Dept Surg, MC 9006,5758 S Maryland Ave, Chicago, IL 60637 USA. NR 34 TC 27 Z9 29 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD JUN PY 2001 VL 2 IS 6 BP 536 EP 540 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 444ZQ UT WOS:000169432700016 PM 11415988 ER PT J AU MacLaughlin, DT Teixeira, J Donahoe, PK AF MacLaughlin, DT Teixeira, J Donahoe, PK TI Perspective: Reproductive tract development - New discoveries and future directions SO ENDOCRINOLOGY LA English DT Article ID MULLERIAN-INHIBITING SUBSTANCE; ADRENAL HYPOPLASIA CONGENITA; II RECEPTOR; GONADAL DEVELOPMENT; GENE-EXPRESSION; STEROID 5-ALPHA-REDUCTASE; SEX DETERMINATION; HORMONE-RECEPTOR; MOLECULAR-BASIS; MOUSE C1 Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. RP Donahoe, PK (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs, Warren 10, Boston, MA 02114 USA. EM pdonahoe@partners.org NR 61 TC 17 Z9 18 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 2001 VL 142 IS 6 BP 2167 EP 2172 DI 10.1210/en.142.6.2167 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 435VP UT WOS:000168903100003 PM 11356658 ER PT J AU Seminara, SB Crowley, WF AF Seminara, SB Crowley, WF TI Perspective: The importance of genetic defects in humans in elucidating the complexities of the hypothalamic-pituitary-gonadal axis SO ENDOCRINOLOGY LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; FOLLICLE-STIMULATING-HORMONE; LINKED KALLMANN-SYNDROME; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; LUTEINIZING-HORMONE; RECEPTOR GENE; BETA-SUBUNIT; INACTIVATING MUTATION; ADRENAL HYPOPLASIA; DEFICIENCY C1 Massachusetts Gen Hosp, Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Sci Ctr, Bartlett Hall,Extenst 5, Boston, MA 02114 USA. FU NICHD NIH HHS [P30 HD028138, R01 HD015788, U54 HD029164, U54 HD028138] NR 46 TC 21 Z9 23 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 JUN PY 2001 VL 142 IS 6 BP 2173 EP 2177 DI 10.1210/en.142.6.2173 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 435VP UT WOS:000168903100004 PM 11356659 ER PT J AU Matikainen, T Perez, GI Zheng, TS Kluzak, TR Rueda, BR Flavell, RA Tilly, JL AF Matikainen, T Perez, GI Zheng, TS Kluzak, TR Rueda, BR Flavell, RA Tilly, JL TI Caspase-3 gene knockout defines cell lineage specificity for programmed cell death signaling in the ovary SO ENDOCRINOLOGY LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; GRANULOSA-CELLS; FAMILY MEMBERS; OOCYTE APOPTOSIS; CYTOCHROME-C; FOLLICULAR ATRESIA; CORPUS-LUTEUM; MOUSE OVARY; RAT OVARY; IN-VIVO AB Previous studies have proposed the involvement of caspase-3, a downstream executioner enzyme common to many paradigms of programmed cell death (PCD), in mediating the apoptosis of both germ and somatic cells in the ovary. Herein we used caspase-3 gene knockout mice to directly test for the functional requirement of this protease in oocyte and/or granulosa cell demise. Using both in vivo and in vitro approaches, we determined that oocyte death initiated as a result of either developmental cues or pathological insults was unaffected by the absence of caspase-3. However, granulosa cells of degenerating antral follicles in both mouse and human ovaries showed a strong immunoreaction using an antibody raised against the cleaved (activated) form of caspase-3. Furthermore, caspase-3 mutant female mice possessed aberrant atretic follicles containing granulosa cells that failed to be eliminated by apoptosis, as confirmed by TUNEL (terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick end labeling) analysis of DNA cleavage and 4 ' ,6-diamidino-2-phenylindole staining of nuclear morphology (pyknosis). These in vivo results were supported by findings from in vitro cultures of wild-type and caspase-3-deficient antral follicles or isolated granulosa cells. Contrasting the serum starvation-induced occurrence of apoptosis in wild-type granulosa cells, caspasc-3-null granulosa cells deprived of hormonal support were TUNEL-negative, showed attenuated chromatin condensation by 4 ' ,6-diamidino-2-phenylindole staining and exhibited delayed internucleosomal DNA cleavage. Such ex vivo findings underscore the existence of a cell autonomous (granulosa cell intrinsic) defect in apoptosis execution resulting from caspase-3 deficiency. We conclude that caspase-3 is functionally required for granulosa cell apoptosis during follicular atresia, but that the enzyme is dispensable for germ cell apoptosis in the female. C1 Massachusetts Gen Hosp, Harvard Med Sch, Vincent Ctr Reprod Biol, Dept Obstet & Gynecol, Boston, MA 02114 USA. Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06510 USA. Univ Kansas, Sch Med, Dept Obstet & Gynecol, Wichita, KS 67214 USA. Wesley Med Ctr, Wichita, KS 67214 USA. RP Tilly, JL (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Vincent Ctr Reprod Biol, Dept Obstet & Gynecol, VBK137C-GYN,55 Fruit St, Boston, MA 02114 USA. FU NIA NIH HHS [R01-AG-12279]; NICHD NIH HHS [R01-HD-34226] NR 55 TC 121 Z9 129 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 2001 VL 142 IS 6 BP 2468 EP 2480 DI 10.1210/en.142.6.2468 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 435VP UT WOS:000168903100041 PM 11356696 ER PT J AU Chen, X Zhang, SL Pang, L Filep, JG Tang, SS Ingelfinger, JR Chan, JSD AF Chen, X Zhang, SL Pang, L Filep, JG Tang, SS Ingelfinger, JR Chan, JSD TI Characterization of a putative insulin-responsive element and its binding protein(s) in rat angiotensinogen gene promoter: Regulation by glucose and insulin SO ENDOCRINOLOGY LA English DT Article ID PROXIMAL TUBULAR CELLS; OPOSSUM KIDNEY-CELLS; MESSENGER-RNA; EXPRESSION; RENIN; IDENTIFICATION; ISOPROTERENOL; SYSTEM; FKHR; SEQUENCES AB We previously demonstrated that high glucose activates angiotensinogen (ANG) expression and that insulin inhibits this activation. The present studies aim to investigate whether insulin regulates ANG gene expression in kidney proximal tubular cells at the transcription level via interaction of the putative insulin-response element (IRE) with its binding protein(s) in the 5 ' -flanking region of the ANG gene. Fusion genes containing various lengths of the 5 ' -flanking region of the rat ANG gene fused to a human GH (hGH) gene as reporter were constructed and transiently introduced into rat immortalized renal proximal tubular cells (IRPTCs). The expression of the fusion genes was monitored by the amount of immunoreactive hGH secreted into the medium as assayed by a specific RIA for hGH. Insulin inhibited the expression of pOGH (rANG N-1498/+ 18), pOGH (rANG N-1120/+18) and pOGH (rANG N-882/+18) but not pOGH (rANG N-854/+18), pOGH (rANG N-820/+18), pOGH (rANG N-688/+18) and pOGH (rANG N-53/+18) in high-glucose (i.e. 25 mM) medium. Site-directed mutagenesis of nucleotides N-874 to N-867 (5 ' CCC GCC CT 3 ') in the 5 ' -flanking region of the rat ANG gene abolished the response to insulin. Insulin also inhibited the expression of the fusion gene containing the DNA fragment ANG N-882 to N-855 inserted upstream of the ANG gene promoter (N-53/+18), but had no effect on a mutant of N-882 to N-855. Gel mobility shift assays revealed that the labeled putative rat ANG-IRE motif (N-878 to N-864, 5 ' CCT TCC CGC CCT TCA 3 ') was bound to the nuclear proteins of IRPTCs. This binding was displaced by unlabeled ANG IRE and IRE of human glyceraldehyde phosphate dehydrogenase but not by mutants of ANG-IRE and IRE of the rat glucagon gene. Southwestern blotting analysis revealed that the labeled putative ANG-IRE motif bound to a major nuclear protein with an apparent molecular mass of 48 kDa. Finally, high glucose levels enhanced 48-kDa nuclear protein expression and induced an additional 70-kDa nuclear protein expression in IRPTCs, as revealed by Southwestern blotting. Insulin inhibited both 48- and 70-kDa nuclear proteins expression induced by high glucose levels. Its inhibitory effect was reversed by the presence of PD98059 tan inhibitor of mitogen-activated protein kinase, MAPK) but not by wortmannin tan inhibitor of phosphatidylinositol 3-kinase). These studies demonstrate that insulin action on ANG gene expression is at the transcriptional level. The molecular mechanism (s) Of insulin action is mediated, at least in part, via interaction of the functional IRE with unidentified 48- and 70- kDa nuclear proteins in the rat ANG gene and is MAPK dependent. C1 Univ Montreal, Hotel Dieu, Res Ctr, CHUM, Montreal, PQ H2W 1T8, Canada. Univ Montreal, Hop Maison Neuve Rosemont, Ctr Rech, Montreal, PQ H1T 2M4, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. RP Chan, JSD (reprint author), Univ Montreal, Hotel Dieu, Res Ctr, CHUM, Pavillon Masson,3850 St Urbain St, Montreal, PQ H2W 1T8, Canada. FU NHLBI NIH HHS [HL-48455]; NIDDK NIH HHS [DK-50836] NR 46 TC 21 Z9 22 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 JUN PY 2001 VL 142 IS 6 BP 2577 EP 2585 DI 10.1210/en.142.6.2577 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 435VP UT WOS:000168903100052 PM 11356707 ER PT J AU Ross, DS AF Ross, DS TI Assessment of thyroid function and disease - Preface SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Massachusetts Gen Hosp, Thyroid Univ ACC720, Boston, MA 02114 USA. RP Ross, DS (reprint author), Massachusetts Gen Hosp, Thyroid Univ ACC720, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD JUN PY 2001 VL 30 IS 2 BP XI EP XII PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 446XJ UT WOS:000169539200001 ER PT J AU Ross, DS AF Ross, DS TI Serum thyroid-stimulating hormone measurement for assessment of thyroid function and disease SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID THYROTROPIN-SUPPRESSIVE THERAPY; L-THYROXINE TREATMENT; ENDOGENOUS SUBCLINICAL HYPERTHYROIDISM; BONE-MINERAL DENSITY; QUALITY-OF-LIFE; NONTHYROIDAL ILLNESS; CENTRAL HYPOTHYROIDISM; EXERCISE CAPACITY; 3RD GENERATION; CONCANAVALIN-A AB Third generation thyroid stimulating hormone (TSH) assays have emerged as the single most useful test of thyroid function, and are used widely and appropriately as a screening test. TSH measurement alone may be misleading in complicated patients and those undergoing treatment for thyroid dysfunction. Before obtaining thyroid function tests, clinicians need to consider whether the patient might have pituitary or hypothalamic disease or severe nonthyroidal illness, and whether assessment of the pituitary-thyroid axis reflects steady-state conditions. Subclinical hyperthyroidism is associated with adverse effects on the skeleton and the heart, and is best assessed by measurement of serum TsH with a third-generation assay. C1 Massachusetts Gen Hosp, Thyroid Unit ACC730, Thyroid Associates, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Ross, DS (reprint author), Massachusetts Gen Hosp, Thyroid Unit ACC730, Thyroid Associates, Boston, MA 02114 USA. NR 95 TC 61 Z9 70 U1 2 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD JUN PY 2001 VL 30 IS 2 BP 245 EP + DI 10.1016/S0889-8529(05)70186-9 PG 21 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 446XJ UT WOS:000169539200002 PM 11444162 ER PT J AU Nahas, Z Li, XB Chae, JH Oliver, NC Anderson, B Kapp, B George, MS AF Nahas, Ziad Li, Xingbao Chae, Jeong-Ho Oliver, Nicholas C. Anderson, Berry Kapp, Becky George, Mark S. TI What Does ECS Stand for? Repetitive Transcranial Magnetic Stimulation in Depression SO EPILEPSY & BEHAVIOR LA English DT Article DE transcranial magnetic stimulation; repetitive transcranial magnetic stimulation; mood; depression; frontal lobes; limbic AB Transcranial magnetic stimulation (TMS) refers to a technique in which electrodeless stimulation of neurons or muscle fibers is produced by a rapid oscillation in electrical and then magnetic energy (and consequently magnetic fields of the order of 1 T). In light of the growing knowledge of the distributed neuronal networks that are involved in various neuropsychiatric phenomena, TMS has been applied as a neurophysiological probe and a tool to modulate (and possibly regulate) dysfunctional brain regions. Dorsolateral prefrontal cortex (DLPFC) TMS affects local brain activity as well as more distal paralimbic regions involved in mood regulation. There is growing consensus that TMS has acute antidepressant effects, although little is known about the role played by a variety of stimulation parameters such as the intensity or frequency of stimulation and the total dose (number of stimuli and number of sessions/time). Studies of maintenance TMS for depression are underway. More experience and research are needed for TMS to become integrated into routine clinical practice as an antidepressant. (C) 2001 Academic Press C1 [Nahas, Ziad] Med Univ S Carolina, Brain Stimulat Lab, Inst Psychiat, Charleston, SC 29425 USA. [George, Mark S.] Med Univ S Carolina, Dept Radiol, Brain Stimulat Lab, Charleston, SC 29425 USA. [George, Mark S.] Med Univ S Carolina, Dept Neurol, Brain Stimulat Lab, Charleston, SC 29425 USA. [Li, Xingbao] Shandong Univ, Jinen, Shandong, Peoples R China. [Chae, Jeong-Ho] Catholic Univ Korea, Seoul, South Korea. [George, Mark S.] Ralph H Johnson Vet Hosp, Charleston, SC USA. RP Nahas, Z (reprint author), Med Univ S Carolina, Brain Stimulat Lab, Inst Psychiat, 67 President St,Room 502 N, Charleston, SC 29425 USA. EM nahasz@musc.edu FU NARSAD; Stanley Foundation; Borderline Research Foundation; NIMH and NINDS; MUSC Health Science Foundation FX The authors are grateful for financial support from NARSAD, the Stanley Foundation, the Borderline Research Foundation, NIMH and NINDS, and the MUSC Health Science Foundation. NR 62 TC 2 Z9 2 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 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD JUN PY 2001 VL 2 IS 3 SU S BP S21 EP S29 DI 10.1006/ebeh.2001.0212 PG 9 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA V21LF UT WOS:000208208400006 ER PT J AU Leaf, A AF Leaf, A TI The electrophysiological basis for the antiarrhythmic actions of polyunsaturated fatty acids SO EUROPEAN HEART JOURNAL SUPPLEMENTS LA English DT Article; Proceedings Paper CT Consensus Meeting on Clinical effect, Biological Background, and Research Priorities on n-3 Fatty Acids CY FEB 17-19, 2000 CL FLORENCE, ITALY SP Res Ctr Italian Natl Assoc Hosp Cardiol DE omega-3; n-3; omega-6; n-6; eicosapentaenoic acid; docosahexaenoic acid; arrhythmias; seizures ID RAT CARDIAC MYOCYTES; VENTRICULAR MYOCYTES; ALPHA-SUBUNIT; NA+ CHANNELS; LONG-CHAIN; CLASS-I; PREVENTION; ARRHYTHMIAS; CURRENTS; SODIUM AB Aims To determine whether n-3 polyunsaturated fatty acids (PUFAs) have cardiac antiarrhythmic effects. and, if so, to determine the basis(es) for such an effect. Methods and results First, tests were made of the ability of administering n-3 PUFAs to a reliable dog model to prevent ischaemia-induced sudden cardiac death. Infusion of an emulsion of fish oil free fatty acids just prior to coronary artery obstruction prevented ventricular fibrillation (VF) (P <0.005) in exercising, unanaesthetized dogs. Similar results were obtained with pure n-3 free docosahexaenoic, eicosapentaenoic or alpha-linolenic acids. PUFAs prevented induced fibrillation of cultured neonatal rat cardiomyocytes for all cardiotoxins tested. After fibrillation was induced, the arrhythmias were terminated by the PUFAs. The electrophysiological effects of low micromolar concentrations of PUFAs are to increase the depolarizing current required to elicit an action potential by about 50% and prolong the refractory period by about threefold. These effects result because the PUFAs, modulate the conductance of ion channels, primarily of Na+ and Ca2+, in cardiomyocytes from neonatal and adult rats, and the human myocardial Na+ channel with the alpha-subunit and the alpha+beta-subunits transiently expressed in HEK293t cells using whole cell patch-clamp. Conclusions These dietary PUFAs are shown to be potent, safe antiarrhythmic agents. More clinical trials, such as the GISSI-Prevenzione, are needed to extend these findings to humans. Potential, very large public health benefits may accrue from this new understanding. (C) 2001 The European Society of Cardiology. C1 Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Leaf, A (reprint author), Massachusetts Gen Hosp, Dept Med, E Bldg 149,13th St, Charlestown, MA 02129 USA. NR 26 TC 15 Z9 15 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1520-765X J9 EUR HEART J SUPPL JI Eur. Heart J. Suppl. PD JUN PY 2001 VL 3 IS D BP D98 EP D105 DI 10.1016/S1520-765X(01)90127-0 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 491JR UT WOS:000172105700017 ER PT J AU He, YL Kitada, N Yasuhara, M Hori, R AF He, YL Kitada, N Yasuhara, M Hori, R TI Quantitative estimation of renal clearance of N-acetylprocainamide in Rats with various experimental acute renal failure SO EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE dosage regimens; renal elimination; N-acetylprocainamide; N-1-methyinicotinamide; organic cation; renal failure ID EXPERIMENTAL PAPILLARY NECROSIS; BORDER MEMBRANE-VESICLES; CREATININE CLEARANCE; SERUM CREATININE; PROCAINAMIDE; TRANSPORT; DRUGS; N-1-METHYLNICOTINAMIDE; N1-METHYLNICOTINAMIDE; INSUFFICIENCY AB The dosage regimen of a drug eliminated predominantly through the kidney need to be adjusted for the patients with renal disease. The objective of the present study was to establish a quantitative approach to precisely predicting the renal clearances of basic drugs using N-1-methylnicotinamide (NMN). A variety of experimental acute renal failure (ARF) in rats were prepared and N-acetylprocainamide (NAPA) was used as a model drug. The renal clearances of NAPA were significantly decreased in rats with ARF, resulting in significantly increased plasma concentrations. Remarkable reduction in clearance ratios (CL,,,,,) was observed, indicating that the impairment in tubular and glomerular function did not proceed in a parallel manner. The renal clearance of NAPA (CLrNMN) was better predicted from the renal clearance of NMN (CLrNMN) than from GFR. A mathematical equation was also constructed to estimate the CLrNMN from the NMN plasma concentration. Therefore, the renal clearance of basic drugs excreted predominantly from the kidney can be easily and more accurately estimated based on the concentrations of endogenous NMN to provide a precise dosage regimen for patients with renal failure. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anaesthesia & Crit Care, Boston, MA 02114 USA. Takarazuka City Hosp Pharm, Takarazuka, Hyogo, Japan. Tokyo Med & Dent Univ, Hosp Pharm, Tokyo, Japan. Kinki Univ, Inst Pharmaceut Res & Technol, Kinki, Japan. RP He, YL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anaesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. NR 34 TC 3 Z9 3 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-0987 J9 EUR J PHARM SCI JI Eur. J. Pharm. Sci. PD JUN PY 2001 VL 13 IS 3 BP 303 EP 308 DI 10.1016/S0928-0987(01)00117-8 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 442RQ UT WOS:000169299100008 PM 11384853 ER PT J AU Poulaki, V Mitsiades, N Mastorakos, G Caspi, RR Chrousos, GP Bouzas, E AF Poulaki, V Mitsiades, N Mastorakos, G Caspi, RR Chrousos, GP Bouzas, E TI Fas/Fas Ligand-associated apoptosis in experimental autoimmune uveoretinitis in rodents: Role of proinflammatory corticotropin-releasing hormone SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE apoptosis; Fas Ligand; Fas; autoimmune uveoretinitis; corticotropin-releasing hormone ID HUMAN FETAL MEMBRANES; FAS LIGAND; RECEPTOR ANTAGONIST; MEDIATED APOPTOSIS; CD95 LIGAND; EXPRESSION; MECHANISM; CELLS; ANTALARMIN; UVEITIS AB We have previously shown that corticotropin-releasing hormone plays an important proinflammatory role in the induction of experimental autoimmune uveoretinitis. In this study, we examined the role of apoptosis in the destruction of the retina during experimental autoimmune uveoretinitis, and the role of corticotropin-releasing hormone as a local regulator of Fas and Fas Ligand expression in this condition. We evaluated apoptosis by the terminal deoxynucleotidyl transferase dUTP nick end labeling method and Fas and Fas Ligand presence by immunohistochemistry. We examined formalin-fixed, paraffin-embedded eye sections from female Lewis rats or B10.A mice immunized with the major pathogenetic epitope (R16 peptide) of the interphotoreceptor retinoid-binding protein. Female B10.A mice similarly immunized were treated with intraperitoneal injections of the rabbit anti-corticotropin-releasing hormone antibody TS-2 or nonimmune rabbit serum. The percentage of retinal cells undergoing apoptosis and the expression of Fas and Fas Ligand were increased in inflamed retinas in immunized Lewis rats and B10.A mice, compared to controls, Retinas from immunized B10.A mice treated with anti-corticotropin-releasing hormone antibody showed significantly lower apoptosis and Fas and Fas Ligand expression than placebo-treated animals. In conclusion, retinal cells in experimental autoimmune uveoretinitis undergo apoptosis associated with concurrent upregulation of Fas and Fas Ligand. The local presence of corticotropin-releasing hormone appears to be of pivotal importance in this process. C1 Evgenidion Hosp, Natl Canc Inst, Pathol Lab, Natl Inst Hlth, Athens, Greece. Evgenidion Hosp, Endocrine Unit, Athens, Greece. Red Cross Hosp, Natl Eye Inst, Immunol Lab, Natl Inst Hlth, Athens, Greece. Red Cross Hosp, Natl Inst Child Hlth & Human Dev, Pediat & Reprod Endocrinol Branch, Natl Inst Hlth, Athens, Greece. Red Cross Hosp, Dept Ophthalmol, Athens, Greece. RP Mitsiades, N (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Mayer Bldg,Room M557,44 Binney St, Boston, MA 02115 USA. OI Caspi, Rachel/0000-0002-7140-7671 NR 23 TC 17 Z9 17 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD JUN PY 2001 VL 72 IS 6 BP 623 EP 629 DI 10.1006/exer.2001.0992 PG 7 WC Ophthalmology SC Ophthalmology GA 442RK UT WOS:000169298600002 PM 11384150 ER PT J AU Poznansky, MC Olszak, IT Foxall, RB Piascik, A Adams, GB Evans, RH Cheng, T Scadden, DT AF Poznansky, MC Olszak, IT Foxall, RB Piascik, A Adams, GB Evans, RH Cheng, T Scadden, DT TI Tissue source dictates lineage outcome of human fetal CD34(+)CD38(-) cells SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; PROGENITOR CELLS; IN-VIVO; FUNCTIONAL-CHARACTERIZATION; MYELOID DIFFERENTIATION; BONE-MARROW; T-LINEAGE; B-LINEAGE; CULTURE; LIVER AB Objective. The translocation from fetal liver hematopoiesis to secondary organs occurs during the second trimester of human gestation. It has been hypothesized that stem cells migrate and acquire lineage potential based on cues specific to the adopted microenvironment, We evaluated primitive hematopoietic cell populations in the fetal human to determine if lineage restriction precedes or follows translocation to sites of hematopoietic activity including thymus, spleen, bone marrow, and liver. Methods. Sets of hematopoietic tissues from individual second-trimester human abortuses were used to compare and quantitate the lineage outcome of immunophenotypically primitive cells from each of the hematopoietic organs using ex vivo myeloid and lymphoid differentiation systems, Results, Despite uniformity in immunophenotype, functional capabilities were highly restricted by the tissue of origin and alteration in the ex vivo differentiation context did not lead to a change in differentiation outcome, Conclusion, Translocation of primitive cells from fetal liver to tissues of mature hematopoietic activity is associated with tissue-specific, quantitative changes in differentiation potential that are unresponsive to alternative differentiation environments. These data suggest that multipotentiality is lost prior to or upon stem-cell migration in the developing human. It is not persistent with residence in a secondary hematopoietic organ. (C) 2001 International Society for Experimental Hematology. published by Elsevier Science inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02129 USA. RP Scadden, DT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr, 149 13th St,Room 5212, Boston, MA 02129 USA. OI Foxall, Russell/0000-0001-9821-0708 NR 25 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUN PY 2001 VL 29 IS 6 BP 766 EP 774 DI 10.1016/S0301-472X(01)00643-9 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 440KR UT WOS:000169174900013 PM 11378272 ER PT J AU Natsume, A Mata, M Goss, J Huang, SH Wolfe, D Oligino, T Glorioso, J Fink, DJ AF Natsume, A Mata, M Goss, J Huang, SH Wolfe, D Oligino, T Glorioso, J Fink, DJ TI Bcl-2 and GDNF delivered by HSV-Mediated Gene Transfer Act additively to protect dopaminergic neurons from 6-OHDA-induced degeneration SO EXPERIMENTAL NEUROLOGY LA English DT Article DE gene therapy; herpes simplex; apoptosis; 6-hydroxydopamine; Parkinson ID SIGNAL-TRANSDUCTION PATHWAYS; RECEPTOR TYROSINE KINASE; NEUROTROPHIC FACTOR; SUBSTANTIA-NIGRA; PARKINSONS-DISEASE; RET RECEPTOR; PC12 CELLS; IN-VIVO; 6-HYDROXYDOPAMINE-INDUCED DEGENERATION; PROGRESSIVE DEGENERATION AB Previous studies have demonstrated that either the neurotrophin glial-derived neurotrophic factor (GDNF) or the antiapoptotic peptide Bcl-2 delivered into striatum by a viral vector protects dopaminergic neurons of the substantia nigra in vivo from degeneration induced by the administration of the neurotoxin g-hydroxydopamine (6-OHDA), In this study we used recombinant, replication-incompetent, genomic herpes simplex virus-based vectors to deliver the genes coding for Bcl-2 and GDNF into rat substantia nigra (SN) 1 week prior to 6-OHDA injection into the striatum. Vector-mediated expression of either Bcl-2 or GDNF alone each resulted in a doubling in cell survival as measured by retrograde labeling with fluorogold (FG) and a 50% increase in tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the lesioned SN compared to the unlesioned side. Gene transfer of Bcl-2 and GDNF were equivalent in this effect. Coadministration of the Bcl-2-expressing vector with the GDNF-expressing vector improved the survival of lesioned SN neurons as measured by FG labeling by 33% and by the expression of TH-IR by 15%. These results suggest that the two factors delivered together act in an additive fashion to improve DA cell survival in the face of 6-OHDA toxicity. (C) 2001 Academic Press. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA 15240 USA. RP Natsume, A (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. RI Natsume, Atsushi/I-7364-2014 OI Natsume, Atsushi/0000-0002-9113-0470 NR 51 TC 63 Z9 66 U1 0 U2 1 PU ACADEMIC PRESS INC 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 JUN PY 2001 VL 169 IS 2 BP 231 EP 238 DI 10.1006/exnr.2001.7671 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 440TF UT WOS:000169189800002 PM 11358438 ER PT J AU Miyama, S Takahashi, T Goto, T Bhide, PG Caviness, VS AF Miyama, S Takahashi, T Goto, T Bhide, PG Caviness, VS TI Continuity with ganglionic eminence modulates interkinetic nuclear migration in the neocortical pseudostratified ventricular epithelium SO EXPERIMENTAL NEUROLOGY LA English DT Article ID MOUSE CORPUS STRIATUM; MURINE CEREBRAL WALL; CELL-CYCLE KINETICS; DNA-DAMAGE; ZONE; CHECKPOINTS; BEHAVIOR; CORTEX; PATTERNS; MARKER AB Cells of the pseudostratified ventricular epithelium (PVE) undergo interkinetic nuclear migration whereby position of cell soma with nucleus is systematically dependent upon cell cycle phase. We examined if the interkinetic nuclear migration in the neopallial PVE is influenced by tissue continuity with the ganglionic eminence (GE) of the basal forebrain in explants from embryonic day 13 mice. We found that when continuity between the neopallial wall and the GE is intact, some neopallial PVE cells discontinue interkinetic nuclear migration following S-phase and upon entry into G2-phase, The somata and nuclei of those cells shift outward from the S-phase zone toward the subventricular and the intermediate zones, The outward migration of post-S-phase cells is observed only in the lateral region of the cerebral wall, which is closely adjacent to the GE, but not in the medial reson, and only when tissue continuity with GE is maintained. We suggest that the outward moving PVE cells seed the secondary proliferative population (SPP) and that exit of the SPP seeding cells occurs in GB-phase, The phenomenon recapitulates similar migratory behavior of neopallial PVE cells in vivo and appears to represent a "choice" between two opposing options available to post-S-phase cells of the PVE. The choice appears to be imposed by mechanisms dependent upon continuity with the GE. We conclude that GE, and/or other adjacent basal forebrain structures, modulates interkinetic nuclear migration in the neopallial PVE. (C) 2001 Academic Press. C1 Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Keio Univ, Sch Med, Dept Pediat, Tokyo, Japan. RP Bhide, PG (reprint author), Massachusetts Gen Hosp, Dept Neurol, 149,13th St, Charlestown, MA 02129 USA. OI Bhide, Pradeep/0000-0003-4236-9415 FU NINDS NIH HHS [NS 32657, NS12005] NR 33 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC 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 JUN PY 2001 VL 169 IS 2 BP 486 EP 495 DI 10.1006/exnr.2001.7676 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 440TF UT WOS:000169189800026 PM 11358462 ER PT J AU Mitsiades, N Poulaki, V Mitsiades, CS Anderson, KC AF Mitsiades, N Poulaki, V Mitsiades, CS Anderson, KC TI Induction of tumour cell apoptosis by matrix metalloproteinase inhibitors: new tricks from a (not so) old drug SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE apoptosis; doxorubicin; FasL; matrix metalloproteinase; MMPI; MMP-7 ID FAS LIGAND EXPRESSION; COLON-CARCINOMA CELLS; NECROSIS-FACTOR-ALPHA; HUMAN T-LYMPHOCYTES; TISSUE INHIBITOR; IN-VIVO; MEDIATED APOPTOSIS; DOWN-REGULATION; SOLUBLE FORM; TNF-ALPHA AB Matrix metalloproteinases (MMPs) regulate the turnover of extracellular matrix (ECM) components and play an important role in embryo development, morphogenesis and tissue remodelling, as well as in tumour invasion and metastasis. Synthetic MMP inhibitors (MMPIs) were designed to prevent tumour cell-induced changes in ECM and thereby achieve antitumour activity. Several MMPIs have entered clinical trials but the preliminary results did not meet the expectations. Recent evidence suggests that MMPs may have more diverse roles than originally believed, influencing angiogenesis, cytokine secretion, as well as tumour cell growth and survival. In particular, synthetic MMPls may directly induce apoptosis of cancer cells via their inhibitory effect on the shedding of Fas Ligand (FasL), a transmembrane member of the TNF superfamily that kills susceptible cells through its receptor, Fas. Several types of cancers have been shown to express FasL and to shed it from their surface as a soluble form, which is significantly less potent in promoting apoptosis. MMP-7 was recently reported to catalyse this process. Conversely, inhibition of Fast-shedding by a synthetic MMPI results in apoptosis of Fas-sensitive cancer cells. More importantly, DNA-damaging anticancer agents, such as adriamycin, kill cancer cells, at least in part, by upregulating Fast. By inhibiting the proteolytic cleavage of Fast, MMPIs can potentiate the killing effect of traditional chemotherapeutic drugs. These studies therefore demonstrate a direct link between DNA-damaging chemotherapeutic drugs, the apoptosis-inducing Fas/FasL system and the proteolytic activity of MMPs and have important therapeutic implications. For example, the proteolytic activity of MMP-7, which is broadly expressed in primary and especially metastatic human malignancies, may contribute to tumour resistance to cytotoxic agents; targeting and inactivating MMP-7 may, therefore, enhance the efficacy of conventional cancer chemotherapy. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Res Lab, Boston, MA USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Mayer Bldg,Room M557,44 Binney St, Boston, MA 02115 USA. EM Kenneth_Anderson@dfci.harvard.edu NR 86 TC 16 Z9 16 U1 0 U2 5 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD JUN PY 2001 VL 10 IS 6 BP 1075 EP 1084 DI 10.1517/13543784.10.6.1075 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 438XZ UT WOS:000169080700006 PM 11772236 ER PT J AU Claud, EC Walker, WA AF Claud, EC Walker, WA TI Hypothesis: inappropriate colonization of the premature intestine can cause neonatal necrotizing enterocolitis SO FASEB JOURNAL LA English DT Article DE necrotizing enterocolitis; prematurity; intestinal inflammation ID PLATELET-ACTIVATING-FACTOR; RAT SMALL-INTESTINE; ISCHEMIC BOWEL NECROSIS; BREAST-FED INFANTS; NF-KAPPA-B; BACTERIAL-COLONIZATION; EPITHELIAL-CELLS; HUMAN-MILK; SALMONELLA-TYPHIMURIUM; FACTOR ACETYLHYDROLASE AB Neonatal necrotizing enterocolitis (NEC) is a major cause of morbidity in preterm infants. We hypothesize that the intestinal injury in this disease is a consequence of synergy among three of the major risk factors for NEC: prematurity, enteral feeding, and bacterial colonization. Together these factors result in an exaggerated inflammatory response, leading to ischemic bowel necrosis. Human milk may decrease the incidence of NEC by decreasing pathogenic bacterial colonization, promoting growth of nonpathogenic flora, promoting maturation of the intestinal barrier, and ameliorating the proinflammatory response. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Combined Program Pediat Gastroenterol & N, Dev Gastroenterol Lab, Boston, MA USA. RP Walker, WA (reprint author), Massachusetts Gen Hosp, Dev Gastroenterol Lab, 149 13th St, Charlestown, MA 02129 USA. EM walker@helix.mgh.harvard.edu FU NICHD NIH HHS [R01-HD31852, R37-HD12437]; NIDDK NIH HHS [P01-DK33506] NR 60 TC 188 Z9 198 U1 0 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUN PY 2001 VL 15 IS 8 BP 1398 EP 1403 DI 10.1096/fj.00-0833hyp PG 6 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 442AF UT WOS:000169261200007 PM 11387237 ER PT J AU Leopold, JA Cap, A Scribner, AW Stanton, RC Loscalzo, J AF Leopold, JA Cap, A Scribner, AW Stanton, RC Loscalzo, J TI Glucose-6-phosphate dehydrogenase deficiency promotes endothelial oxidant stress and decreases endothelial nitric oxide bioavailability SO FASEB JOURNAL LA English DT Article DE glutathione; nitric oxide; reactive oxygen species ID SYNTHASE GENERATES SUPEROXIDE; OXIDATIVE STRESS; CELL-DEATH; TETRAHYDROBIOPTERIN; EXPRESSION; DEHYDROEPIANDROSTERONE; INTERLEUKIN-1-BETA; EPIANDROSTERONE; FIBROBLASTS; INHIBITION AB The vascular endothelium compensates for oxidant stress by increasing the activity of antioxidant enzymes such as glucose-6-phophate dehydrogenase (G6PD). G6PD provides reducing equivalents of NAPDH to maintain glutathione stores and modulates nitric oxide synthase (eNOS) activity. To determine whether deficient G6PD activity perturbs these responses, we treated bovine aortic endothelial cells with dehydroepiandrosterone or an antisense oligodeoxynucleotide to G6PD mRNA to decrease G6PD activity and expression. When exposed to hydrogen peroxide, reactive oxygen species (ROS) accumulation was increased in G6PD-deficient cells compared with those with normal activity. To determine the source of increased oxidant stress in G6PD-deficient cells, we used inhibitors of ROS generation, which suggested that eNOS was contributing to ROS production. Treatment with L-NMMA, an inhibitor of eNOS mediated-nitric oxide (NO) but not superoxide, production confirmed this observation; in contrast to L-NAME, L-NMMA promoted ROS generation in G6PD-deficient cells. In addition, deficient G6PD activity was associated with a decrease in endothelium-derived bioavailable NO in response to the agonists A23187 and bradykinin as demonstrated by decreased endothelial cGMP and nitrate/nitrite levels. Enhanced ROS accumulation and decreased NO bioavailability may represent one mechanism by which G6PD deficiency contributes to vascular oxidant stress and endothelial dysfunction. 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 02115 USA. RP Leopold, JA (reprint author), Boston Univ, Sch Med, Whitaker Cardiovasc Inst, CABR-507,715 Albany St, Boston, MA 02118 USA. EM jane.leopold@bmc.org NR 28 TC 75 Z9 78 U1 1 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUN PY 2001 VL 15 IS 8 BP 1771 EP + DI 10.1096/fj.00-0893fje PG 25 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 442AF UT WOS:000169261200023 PM 11481225 ER PT J AU Pahlavani, MA Mele, JF Richardson, A AF Pahlavani, MA Mele, JF Richardson, A TI Effect of overexpression of human Cu/Zn-SOD on activation-induced lymphocyte proliferation and apoptosis SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE transgenic mice; Cu/Zn-SOD; mitogenesis; apoptosis; free radicals ID SUPEROXIDE-DISMUTASE ACTIVITY; PREMATURE THYMIC INVOLUTION; TRANSGENIC MICE; T-CELLS; OXIDATIVE STRESS; DOWNS-SYNDROME; FREE-RADICALS; ELEVATED LEVEL; IMMUNE-SYSTEM; GROWTH-FACTOR AB The process of lymphocyte proliferation and apoptosis is known to be linked to oxidative stress. In the present study, we have used a new transgenic mouse model to investigate the effect of human Cu/Zn superoxide dismutase (Cu/Zn-SOD) overexpression on activation-induced lymphocytes proliferation and apoptosis. Cu/Zn-SOD activity was 3.5-fold higher in the spleen of the transgenic mice overexpressing Cu/Zn-SOD (Tg-Cu/Zn-SOD) compared to the wild-type littermates. Proliferative response of lymphocytes to lipopolysaccharide (LPS), Concanavalin A (Con A), and anti-CD3 was measured by [H-3]-thymidine incorporation. Activation-induced apoptosis was determined by incubating the T cells with anti-CD3 (primary stimulus) for 72 h, followed by restimulation with Con A (secondary stimulus) for various times. Apoptosis was assessed by measuring DNA fragmentation using a spectrofluorimetric assay and monitoring the expression of the specific apoptotic markers Fas/CD95 receptor and Fas/CD95 ligand (Fas-L) using flow cytometry. There was no significant difference in proliferative response of lymphocytes to LPS, Con A, or anti-CD3 in transgenic mice overexpressing human Cu/Zn superoxide dismutase (Tg-Cu/Zn-SOD) compared to wild-type littermates. In addition, no significant difference was observed in lymphocyte populations and subsets between Tg-Cu/Zn-SOD mice and wild-type littermates. However, splenic T cells from Tg-Cu/Zn-SOD mice exhibited a significantly (p < .05) higher level of activation-induced DNA fragmentation than T cells from wild-type littermates. The increase in DNA fragmentation was paralleled with an increase in the proportion of T cells expressing Fas and Fas-L molecules. The possible consequences of Cu/Zn-SOD overproduction on activation-induced apoptosis are discussed. (C) 2001 Elsevier Science Inc. C1 Audie L Murphy Mem Vet Hosp, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. RP Pahlavani, MA (reprint author), Audie Murphy VA Hosp, GRECC, 182,7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NIA NIH HHS [AG00677, AG14088, AG13319] NR 69 TC 8 Z9 9 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JUN 1 PY 2001 VL 30 IS 11 BP 1319 EP 1327 DI 10.1016/S0891-5849(01)00529-9 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 440LZ UT WOS:000169177900013 PM 11368930 ER PT J AU Podolsky, DK AF Podolsky, DK TI Comment from the editors - Editorial transition SO GASTROENTEROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2001 VL 120 IS 7 BP 1577 EP 1578 DI 10.1053/gast.2001.25122 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 437QA UT WOS:000169004000005 PM 11375939 ER PT J AU Schnell, TG Sontag, SJ Chejfec, G Aranha, G Metz, A O'Connell, S Seidel, UJ Sonnenberg, A AF Schnell, TG Sontag, SJ Chejfec, G Aranha, G Metz, A O'Connell, S Seidel, UJ Sonnenberg, A TI Long-term nonsurgical management of Barrett's esophagus with high-grade dysplasia SO GASTROENTEROLOGY LA English DT Article ID ADENOCARCINOMA; ESOPHAGECTOMY; PROTOCOL; CANCER AB (Background & Aims) under bar: Surgical resection of the esophagus is frequently recommended for Barrett's high-grade dysplasia (HGD) without cancer, (Methods) under bar: During a 20-year period, patients were diagnosed and observed through an organized surveillance program at the Hines Veterans Affairs Hospital. The program was supported by Hines VA and organized and managed by 2 endoscopists using preestablished endoscopic criteria. (Results) under bar: Barrett's esophagus was diagnosed in 1099 patients, and 36,251 esophageal mucosal specimens were reviewed. Seventy-nine of 1099 patients (7.2%) initially had HGD (34 prevalent) or subsequently developed HGD (45 incident) without evidence of cancer, Of the 75 HGD patients who remained without detectable cancer after the 1 year of intensive searching, 12 developed cancer (16%) during a mean 7.3-year surveillance period: 11 of the 12 who were compliant were considered cured with surgical or ablation therapy. Cancer did not develop in the remaining 63 HGD patients during the surveillance period. (Conclusions) under bar: HGD without cancer in Barrett's esophagus follows a relatively benign course in the majority of patients. In the patients who eventually progress to cancer during regular surveillance, surgical resection is curative. Surveillance endoscopies with biopsy is a valid and safe follow-up strategy for Barrett's patients who have HGD without cancer. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Med, Hines, IL 60141 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Pathol, Hines, IL 60141 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Med, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. Dept Vet Affairs, Dept Med, Albuquerque, NM USA. RP Schnell, TG (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Med, Bldg 1,Room B321,151B3, Hines, IL 60141 USA. NR 19 TC 379 Z9 382 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2001 VL 120 IS 7 BP 1607 EP 1619 DI 10.1053/gast.2001.25065 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 437QA UT WOS:000169004000010 PM 11375943 ER PT J AU Farrell, JJ Friedman, LS AF Farrell, JJ Friedman, LS TI Gastrointestinal disorders in the elderly - Preface SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastroenterol Unit, Boston, MA 02114 USA. RP Farrell, JJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastroenterol Unit, 55 Fruit St, Boston, MA 02114 USA. NR 1 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 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD JUN PY 2001 VL 30 IS 2 BP XIII EP XIV PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 447UQ UT WOS:000169591200001 ER PT J AU Hazzard, WR AF Hazzard, WR TI Demographic peristalsis - Implications of the age wave for gastroenterologists SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article ID NATURAL DEATH; COMPRESSION; MORBIDITY AB With the advent of the twenty-first century, a new phenomenon in human history emerged, one is expected to dominate the social, economic, health, and health care agenda of the United States and the world. This so-called "age wave" represents an unprecedented demographic trend that will make the oldest cohorts, especially those older than 75, 85, and 100 years old, the fastest growing segment of the population for at least the next 50 years. C1 Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Hazzard, WR (reprint author), Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, S-182-GEC,1660 S Columbian Way, Seattle, WA 98108 USA. NR 11 TC 5 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD JUN PY 2001 VL 30 IS 2 BP 297 EP + DI 10.1016/S0889-8553(05)70183-7 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 447UQ UT WOS:000169591200002 PM 11432293 ER PT J AU Farrell, AJ Friedman, LS AF Farrell, AJ Friedman, LS TI Gastrointestinal bleeding in the elderly SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Review ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ENDOSCOPIC VARICEAL SCLEROTHERAPY; BENIGN ESOPHAGEAL STRICTURE; MITRAL-VALVE-PROLAPSE; PEPTIC-ULCER; OXYGEN DESATURATION; SUPPLEMENTAL OXYGEN; BACTERIAL-ENDOCARDITIS; ESTROGEN-PROGESTERONE; RISK-FACTORS AB Among patients with acute gastrointestinal bleeding, older age is associated with an increased rate of comorbidity, greater medication use, and atypical clinical presentations. The aging of the population makes the evaluation and management of gastrointestinal bleeding in the elderly a special and increasingly common clinical challenge. The unique features and common causes of upper and lower gastrointestinal bleeding in the elderly are reviewed. Important management issues considered include hemodynamic resuscitation; anticoagulation; and medical, surgical, and endoscopic therapy. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Friedman, LS (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Blake 456D,55 Fruit St, Boston, MA 02114 USA. EM friedman.lawrence@mgh.harvard.edu NR 162 TC 23 Z9 23 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8553 EI 1558-1942 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD JUN PY 2001 VL 30 IS 2 BP 377 EP + PG 32 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 447UQ UT WOS:000169591200006 ER PT J AU Farrell, RJ Farrell, TT Morrin, MM AF Farrell, RJ Farrell, TT Morrin, MM TI Diverticular disease in the elderly SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article ID ACUTE COLONIC DIVERTICULITIS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; LAPAROSCOPIC SURGERY; COLORECTAL ADENOMAS; NATURAL-HISTORY; SIGMOID COLON; MANAGEMENT; COLONOSCOPY; HEMORRHAGE; DIAGNOSIS AB Diverticular disease is of special significance in the elderly and presents almost exclusively in patients over 40 years of age. The incidence and severity of diverticular disease increases with age. Elderly patients often present with complicated diverticular disease, and because of their advanced age, poor ability to provide a history, and muted symptoms and signs, the diagnosis is particularly difficult to make. Consequently, great demands are placed on the physician to diagnose and treat diverticular disease in the elderly. in the past, advanced age made conservative therapy the standard of care for most patients; however, recent endoscopic, radiologic, and surgical advances have helped define more definitive therapies for patients with complicated diverticular disease. C1 Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Farrell, RJ (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gastroenterol, Dana 501,330 Brookline Ave, Boston, MA 02115 USA. NR 82 TC 39 Z9 40 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD JUN PY 2001 VL 30 IS 2 BP 475 EP + DI 10.1016/S0889-8553(05)70191-6 PG 24 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 447UQ UT WOS:000169591200010 PM 11432301 ER PT J AU Brandwein, SL Farrell, JJ Centeno, BA Brugge, WR AF Brandwein, SL Farrell, JJ Centeno, BA Brugge, WR TI Detection and tumor staging of malignancy in cystic, intraductal, and solid tumors of the pancreas by EUS SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY; PAPILLARY MUCINOUS NEOPLASMS; DIFFERENTIAL-DIAGNOSIS; COMPUTED-TOMOGRAPHY; ULTRASONOGRAPHY; ULTRASOUND; CANCER; SYSTEM; BIOPSY AB Background: EUS can provide detailed imaging of pancreatic malignancies and direct fine needle aspiration (FNA) of pancreatic masses,The ability of EUS to detect and stage malignancy in cystic and intraductal lesions has not been investigated. Our aim was to determine the sensitivity and specificity of EUS imaging and FNA in detecting and staging of malignancy in solid, cystic, and intraductal lesions of the pancreas. Methods: The records of 96 patients (46 solid, 26 cystic, 24 intraductal lesions) who underwent EUS followed by surgical exploration over a 3-year period were reviewed, The accuracy of EUS for detecting and staging malignancy was calculated based on the results of surgery and histology. Results: EUS-guided FNA provided evidence of malignancy in solid, cystic, and ductal lesions with sensitivities of 59.5%, 50%, and 60%, respectively. The accuracy of staging by EUS was significantly less for intraductal lesions (47%), compared with cystic (100%) and solid lesions (85%) (p < 0.05). Conclusions: EUS can be used to detect malignancy in cystic and intraductal tumors of the pancreas. C1 Massachusetts Gen Hosp, Dept Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, Dept Med Serv, GI Unit, Blake 452C,55 Fruit St, Boston, MA 02114 USA. NR 25 TC 126 Z9 130 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JUN PY 2001 VL 53 IS 7 BP 722 EP 727 DI 10.1067/mge.2001.114783 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 438UZ UT WOS:000169073800006 PM 11375578 ER PT J AU Maher, EA Furnari, FB Bachoo, RM Rowitch, DH Louis, DM Cavenee, WK DePinho, RA AF Maher, EA Furnari, FB Bachoo, RM Rowitch, DH Louis, DM Cavenee, WK DePinho, RA TI Malignant glioma: genetics and biology of a grave matter SO GENES & DEVELOPMENT LA English DT Review ID EPIDERMAL GROWTH-FACTOR; TUMOR-SUPPRESSOR GENE; HUMAN GLIOBLASTOMA CELLS; CENTRAL-NERVOUS-SYSTEM; HUMAN-BRAIN-TUMORS; NEURAL STEM-CELLS; OLIGODENDROCYTE PROGENITOR CELLS; FACTOR-ALPHA-RECEPTOR; CONFERS ENHANCED TUMORIGENICITY; HIGH-GRADE GLIOMAS C1 Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92037 USA. Univ Calif San Diego, Dept Med, Ctr Genet Mol, La Jolla, CA 92037 USA. Univ Calif San Diego, Ctr Canc, La Jolla, CA 92037 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. NR 218 TC 763 Z9 796 U1 7 U2 59 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUN 1 PY 2001 VL 15 IS 11 BP 1311 EP 1333 DI 10.1101/gad.891601 PG 23 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 440AR UT WOS:000169151400001 PM 11390353 ER PT J AU Smith, MR AF Smith, MR TI Complementary and alternative therapies for advanced prostate cancer SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID BONE-MINERAL DENSITY; HOT FLASHES; PC-SPES; BREAST-CANCER; DICHLOROMETHYLENE-DIPHOSPHONATE; ANDROGEN DEPRIVATION; CLODRONATE TREATMENT; CIMICIFUGA-RACEMOSA; MEGESTROL-ACETATE; MULTIPLE-MYELOMA AB This article reviews complementary and alternative therapies for advanced prostate cancer. This is not a comprehensive survey of nontraditional therapies for prostate cancer. Rather, this review focuses on alternative and complementary therapies with published studies to evaluate efficacy and safety. Three areas are addressed: alternative forms of hormonal therapy, management of side effects of hormonal therapy, and management of skeletal complications. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, Cox 640,100 Blossom St, Boston, MA 02114 USA. FU NCRR NIH HHS [5M01RR1066-20] NR 73 TC 11 Z9 11 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD JUN PY 2001 VL 15 IS 3 BP 559 EP + DI 10.1016/S0889-8588(05)70232-X PG 14 WC Oncology; Hematology SC Oncology; Hematology GA 467RR UT WOS:000170718000011 PM 11525297 ER PT J AU Bastepe, M Pincus, JE Sugimoto, T Tojo, K Kanatani, M Azuma, Y Kruse, K Rosenbloom, AL Koshiyama, H Juppner, H AF Bastepe, M Pincus, JE Sugimoto, T Tojo, K Kanatani, M Azuma, Y Kruse, K Rosenbloom, AL Koshiyama, H Juppner, H TI Positional dissociation between the genetic mutation responsible for pseudohypoparathyroidism type Ib and the associated methylation defect at exon A/B: evidence for a long-range regulatory element within the imprinted GNAS1 locus SO HUMAN MOLECULAR GENETICS LA English DT Article ID GS-ALPHA GENE; PARATHYROID-HORMONE; HEREDITARY OSTEODYSTROPHY; CHROMOSOME 20Q13.3; PROTEIN; ANTISENSE; REGION; IDENTIFICATION; TRANSCRIPTS; NEURONATIN AB Pseudohypoparathyroidism type Ib (PHP-Ib) is a paternally imprinted disorder which maps to a region on chromosome 20q13.3 that comprises GNAS1 at its telomeric boundary. Exon AIS of this gene was recently shown to display a loss of methylation in several PHP-Ib patients. In nine unrelated PHP-Ib kindreds, in whom haplotype analysis and mode of inheritance provided no evidence against linkage to this chromosomal region, we confirmed lack of exon A/B methylation for affected individuals, while unaffected carriers showed no epigenetic abnormality at this locus. However, affected individuals in one kindred (Y2) displayed additional methylation defects involving exons NESP55, AS and XL, and unaffected carriers in this family showed an abnormal methylation at exon NESP55, but not at other exons, Taken together, current evidence thus suggests that distinct mutations within or close to GNAS1 can lead to PHP-Ib and the associated epigenetic changes. To further delineate the telomeric boundary of the PHP-Ib locus, the previously reported kindred F, in which patient F-V/51 is recombinant within GNAS1, was investigated with several new markers and direct nucleotide sequence analysis. These studies revealed that F-V/51 remains recombinant at a single nucleotide polymorphism (SNP) located 1.2 kb upstream of XL, No heterozygous mutation was identified between exon XL and an SNP similar to8 kb upstream of NESP55, where this affected individual becomes linked, suggesting that the genetic defect responsible for parathyroid hormone resistance in kindred F, and probably other PHP-Ib patients, is located greater than or equal to 56 kb centromeric of the abnormally methylated exon A/B, A region upstream of the known coding exons of GNAS1 is therefore predicted to exert, presumably through imprinting of exon A/B, long-range effects on G(s)alpha expression. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. MassGen Hosp Children, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Kobe Univ, Sch Med, Dept Med, Div 3, Kobe, Hyogo 657, Japan. Tokyo Jikei Univ, Sch Med, Dept Internal Med, Div Endocrinol & Metab, Tokyo, Japan. Kyoto Natl Hosp, Dept Internal Med, Kyoto, Japan. Univ Klinikum Lubeck, Klin Kinder & Jugendmed, Lubeck, Germany. Univ Florida, Dept Pediat, Div Endocrinol, Gainesville, FL 32610 USA. Hyogo Prefectural Amagasaki Hosp, Dept Internal Med, Div Endocrinol & Metab, Amagasaki, Hyogo, Japan. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RI Koshiyama, Hiroyuki/H-3877-2011 FU PHS HHS [R01 46718-06] NR 35 TC 90 Z9 92 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN 1 PY 2001 VL 10 IS 12 BP 1231 EP 1241 DI 10.1093/hmg/10.12.1231 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 444LG UT WOS:000169400500001 PM 11406605 ER PT J AU Ntziachristos, V Hielscher, AH Yodh, AG Chance, B AF Ntziachristos, V Hielscher, AH Yodh, AG Chance, B TI Diffuse optical tomography of highly heterogeneous media SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE artifacts; correction; diffuse media; diffuse optical tomography; reconstruction ID MAGNETIC-RESONANCE; MAMMOGRAPHY; TISSUE AB We investigate the performance of diffuse optical tomography to image highly heterogeneous media, such as breast tissue, as a function of background heterogeneity, To model the background heterogeneity, we have employed the functional information derived from Gadolinium-enhanced magnetic resonance images of the breast. We demonstrate that overall image quality and quantification accuracy worsens as the background heterogeneity increases. Furthermore we confirm the appearance of characteristic artifacts at the boundaries that scale with background heterogeneity. These artifacts are very similar to the ones seen in clinical examinations and can be misinterpreted as actual objects if not accounted for. To eliminate the artifacts and improve the overall image reconstruction, we apply a data-correction algorithm that yields superior reconstruction results and is virtually independent of the degree of the background heterogeneity. C1 Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. Univ Penn, Dept Biochem Biophys, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. SUNY Hlth Sci Ctr, Dept Pathol, Brooklyn, NY 11201 USA. Univ Penn, Dept Phys & Astron, Philadelphia, PA 19104 USA. Univ Penn, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. RP Ntziachristos, V (reprint author), Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. FU NCI NIH HHS [R0I CA60182] NR 18 TC 42 Z9 43 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD JUN PY 2001 VL 20 IS 6 BP 470 EP 478 DI 10.1109/42.929613 PG 9 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 445HW UT WOS:000169452900002 PM 11437107 ER PT J AU Baden, LR Maguire, JH AF Baden, LR Maguire, JH TI Gastrointestinal infections in the immuncompromised host SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID BONE-MARROW TRANSPLANTATION; STEM-CELL TRANSPLANT; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDERS; RESISTANT ENTEROCOCCUS-FAECIUM; CHRONIC LYMPHOCYTIC-LEUKEMIA; HERPES-SIMPLEX VIRUS; KIDNEY-TRANSPLANT; IMMUNOCOMPROMISED PATIENTS; CYTOMEGALOVIRUS-INFECTION; RENAL-TRANSPLANTATION AB Gastrointestinal disease is a significant cause of morbidity and mortality in the immunocompromised patient. This article focuses on the infectious gastrointestinal complications associated with the treatment of malignant disease and with solid organ transplantation but not HIV. Gastrointestinal defenses and the various mechanisms by which they are impaired are reviewed. The major pathogens and malignancies of this patient population and an approach to their diagnosis, treatment, and prevention are discussed. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Div Infect Dis, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Baden, LR (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Div Infect Dis, PBB A4,75 Francis St, Boston, MA 02115 USA. NR 150 TC 8 Z9 9 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 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD JUN PY 2001 VL 15 IS 2 BP 639 EP + DI 10.1016/S0891-5520(05)70163-X PG 35 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 451RT UT WOS:000169815600016 PM 11447713 ER PT J AU Vivien, L Benoist, C Mathis, D AF Vivien, L Benoist, C Mathis, D TI T lymphocytes need IL-7 but not IL-4 or IL-6 to survive in vivo SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE cytokine; homeostasis; IL; signaling; survival; T cell ID RECEPTOR-DEFICIENT MICE; CELLS IN-VIVO; CLASS-II MOLECULES; MHC CLASS-I; INTERLEUKIN-7 RECEPTOR; NAIVE; PROLIFERATION; HOMEOSTASIS; EXPRESSION; LYMPHOPOIESIS AB The role of IL-4, -6 and -7 in the survival of T lymphocytes was studied in vivo. The decay of polyclonal populations of CD4(+) and CD8(+) T cells was monitored in thymectomized anti-cytokine receptor mab-treated and/or cytokine-deficient mice. The lack of IL-4 or -6 did not have any detectable effect on T cell survival, but IL-7 played an important role in the survival of the naive T cell compartment, especially of naive CD4(+) T cells. C1 ULP, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch, France. RP Benoist, C (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. NR 42 TC 86 Z9 86 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUN PY 2001 VL 13 IS 6 BP 763 EP 768 DI 10.1093/intimm/13.6.763 PG 6 WC Immunology SC Immunology GA 440PU UT WOS:000169184100006 PM 11369703 ER PT J AU Weissman, JS AF Weissman, JS TI Readmissions - are we asking too much? SO INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE LA English DT Editorial Material ID QUALITY C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. RP Weissman, JS (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. NR 7 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1353-4505 J9 INT J QUAL HEALTH C JI Int. J. Qual. Health Care PD JUN PY 2001 VL 13 IS 3 BP 183 EP 185 DI 10.1093/intqhc/13.3.183 PG 3 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 453JJ UT WOS:000169912500004 PM 11476142 ER PT J AU Gibbs, J Clark, K Khuri, S Henderson, W Hur, K Daley, J AF Gibbs, J Clark, K Khuri, S Henderson, W Hur, K Daley, J TI Validating risk-adjusted surgical outcomes: chart review of process of care SO INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE LA English DT Article DE chart review; outcomes; quality of care; surgery ID QUALITY; MORTALITY; RELIABILITY; SURGERY AB Objective. The primary purpose of this study was to validate risk-adjusted surgical outcomes as indicators of the quality) of surgical care at US Department of Veterans Affairs (VA) hospitals. The secondary purpose was to validate the risk-adjustment models for screening cases for quality review Design. We compared quality of care, determined by structured implicit chart review for patients from hospitals with higher and lower than expected operative mortality and morbidity (hospital-level tests) and between patients with high and low predicted risk of mortality and morbidity who died or developed complications (patient-level tests). Subjects. 739 general, peripheral vascular and orthopedic surgery cases sampled from the 44 VA hospitals participating in the National VA Surgical Risk Study. Main outcome measures. A global rating of quality of care based on chart review Results. Ratings of overall quality of care did not differ significantly between patients from hospitals with higher and lower than expected mortality and morbidity: On some of the secondary measures, patient care was rated higher for hospitals with lower than expected operative mortality At the patient level of analysis, those who died or developed complications and had a high predicted risk of mortality or morbidity were rated higher on quality of care than those with a low predicted risk of adverse outcome. Conclusions. The absence of a relationship between most of our measures of process of care and risk-adjusted outcomes may be due to an insensitivity of chart reviews to hospital-level differences in quality of care. Site visits to National VA Surgical Risk Study hospitals with high and low risk-adjusted mortality and morbidity) have detected differences on a number of dimensions of quality: The patient-level findings suggest that the risk-adjustment models are useful for screening adverse outcome cases for quality of care review. C1 Vet Affairs Edward Hines Jr Hosp, Cooperat Studies Program Coordinating Ctr 151K, Hines, IL 60141 USA. Northwestern Univ, Inst Hlth Serv Res & Policy Studies, Evanston, IL USA. Boston VA New England Hlth Care Syst, W Roxbury, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Partners Hlth Care Syst, Inst Hlth Policy, Boston, MA USA. RP Gibbs, J (reprint author), Vet Affairs Edward Hines Jr Hosp, Cooperat Studies Program Coordinating Ctr 151K, Hines, IL 60141 USA. NR 20 TC 29 Z9 29 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1353-4505 J9 INT J QUAL HEALTH C JI Int. J. Qual. Health Care PD JUN PY 2001 VL 13 IS 3 BP 187 EP 196 DI 10.1093/intqhc/13.3.187 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 453JJ UT WOS:000169912500005 PM 11476143 ER PT J AU Shunk, KA Atalar, E Lima, JAC AF Shunk, KA Atalar, E Lima, JAC TI Possibilities of transesophageal MRI for assessment of aortic disease: A review SO INTERNATIONAL JOURNAL OF CARDIAC IMAGING LA English DT Article DE aorta; atherosclerosis; echocardiography; MRI ID CORONARY-ARTERY DISEASE; THORACIC AORTA; HUMAN ATHEROSCLEROSIS; ISCHEMIC STROKE; PLAQUE; MARKER; COIL; ECHOCARDIOGRAPHY; PROSTATE AB The thoracic aortic wall is a common site of atherosclerotic plaque in humans. Tools for serial, non-invasive assessment of these plaques are of value for addressing gaps in our basic understanding of the biology of plaque rupture and its relationship to atherosclerotic disease progression as well as for monitoring response to anti-atherosclerotic interventions in therapeutic clinical trials. Common approaches to assessment of the wall of the thoracic aorta in vivo are limited. Here we discuss some of the challenges and limitations encountered by conventional techniques and review a novel approach, transesophageal MRI (TEMRI). Initial experiences in applying the TEMRI approach to assessment of aortic morphology and pathology are discussed. C1 Johns Hopkins Univ, Div Cardiol, Baltimore, MD USA. RP Shunk, KA (reprint author), San Francisco VA Med Ctr, Div Cardiol 111C, 4150 Clement St, San Francisco, CA 94121 USA. RI Atalar, Ergin/D-3184-2012 OI Atalar, Ergin/0000-0002-6874-6103 NR 27 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-9899 J9 INT J CARDIAC IMAG JI Int. J. Card. Imaging PD JUN PY 2001 VL 17 IS 3 BP 179 EP 185 DI 10.1023/A:1010667617641 PG 7 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 460BV UT WOS:000170286700003 PM 11587451 ER PT J AU Kawada, H Ito, T Pharr, PN Spyropoulos, DD Watson, DK Ogawa, M AF Kawada, H Ito, T Pharr, PN Spyropoulos, DD Watson, DK Ogawa, M TI Defective megakaryopoiesis and abnormal erythroid development in Fli-1 gene-targeted mice SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article DE Fli-1; megakaryocyte; hematopoiesis; c-mpl ID MURINE C-MPL; TRANSCRIPTION FACTOR; ETS FAMILY; RECEPTOR MPL; CELL-LINES; EXPRESSION; DIFFERENTIATION; PROMOTER; PROTEINS; BINDING AB Mouse embryos homozygous for a targeted disruption in the Fli-1 gene show hemorrhage into the neural tube and brain on embryonic day (E)11.0 and die shortly thereafter. Livers from the mutant embryos contain drastically reduced numbers of pronormoblasts, basophilic normoblasts, and colony-forming cells. To determine the nature of impaired hematopoiesis. we carried out cell culture studies of mutant embryonic stem (ES) cells and cells from the aorta-gonad-mesonephros (AGM) region of E10.0 mutant embryos. There was a striking reduction in the number of megakaryocytes in cultures of mutant AGM cells compared with cultures of AGM cells from wild-type or heterozygous embryos. Furthermore, Fli-1 mutant ES cells failed to produce megakaryocyte colonies and multilineage colonies containing megakaryocytes, Consistent with the observed defect in megakaryopoiesis. we also demonstrated the down-regulation of c-mpl in the AGM of mutant embryos. The percentages of pronormoblasts and basophilic normoblasts were significantly reduced in cultures of mutant AGM embryos, which contained primarily polychromatophilic and orthochromatic normoblasts. These results provide further evidence for the role of Fli-1 in the regulation of hematopoiesis and for c-mpl as a Fli-1 target gene. Int J Hematol. 2001,73:463-468. (C) 2001 The Japanese Society of Hematology. C1 Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Med, Lab Canc Genom, Hollings Canc Ctr, Charleston, SC 29425 USA. RP Ogawa, M (reprint author), Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. FU NCI NIH HHS [P01-CA78582]; NIDDK NIH HHS [R01-DK54197] NR 34 TC 55 Z9 57 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD JUN PY 2001 VL 73 IS 4 BP 463 EP 468 DI 10.1007/BF02994008 PG 6 WC Hematology SC Hematology GA 452GF UT WOS:000169849000008 PM 11503960 ER PT J AU Geller, DA Biederman, J Faraone, SV Bellordre, CA Kim, GS Hagermoser, L Cradock, K Frazier, J Coffey, BJ AF Geller, DA Biederman, J Faraone, SV Bellordre, CA Kim, GS Hagermoser, L Cradock, K Frazier, J Coffey, BJ TI Disentangling chronological age from age of onset in children and adolescents with obsessive-compulsive disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE obsessive-compulsive disorder; paediatric; developmental; age at onset; chronological age ID CLINICAL-FEATURES; FAMILY; COMORBIDITY; PHENOMENOLOGY; EPIDEMIOLOGY; SYMPTOMS; BEHAVIOR AB Although paediatric obsessive-compulsive disorder (OCD) is increasingly recognized as a putative developmental subtype of the disorder, it remains uncertain as to whether additional subtyping by age at onset in childhood or adolescence is warranted. Subjects included children and adolescents meeting DSM-III-R and DSM-IV criteria for OCD referred to a specialized OCD clinic. Ali youth were systematically evaluated with structured diagnostic interviews and clinical assessment by an OCD expert. Irrespective of current age, an earlier age at onset predicted increased risk for attention deficit hyperactivity disorder, simple phobia, agoraphobia and multiple anxiety disorders, in contrast, mood and psychotic disorders were associated with chronological age and were more prevalent in older subjects. Tourette's disorder showed associations with both chronological age and age at onset. Chronological age and age at onset predicted different patterns of comorbidity and dysfunction in children and adolescents with OCD. Considering the heterogeneity of OCD. age at onset may help identify meaningful developmental subtypes of the disorder beyond chronological age. C1 McLean Hosp, OCD Clin, Belmont, MA 02478 USA. McLean Hosp, Pediat Psychopharmacol Clin, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Geller, DA (reprint author), McLean Hosp, OCD Clin, 115 Mill St, Belmont, MA 02478 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K08 MH01481] NR 32 TC 44 Z9 44 U1 2 U2 6 PU CAMBRIDGE UNIV PRESS PI PORT CHESTER PA 110 MIDLAND AVE, PORT CHESTER, NY 10573-9863 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2001 VL 4 IS 2 BP 169 EP 178 PG 10 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 452HU UT WOS:000169852900010 PM 11466167 ER PT J AU Matthews, KA Abrams, B Crawford, S Miles, T Neer, R Powell, LH Wesley, D AF Matthews, KA Abrams, B Crawford, S Miles, T Neer, R Powell, LH Wesley, D TI Body mass index in mid-life women: relative influence of menopause, hormone use, and ethnicity SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE menopause; hormone replacement therapy; ethnicity; weight; obesity ID FAT DISTRIBUTION; REPLACEMENT THERAPY; OVARIAN-FUNCTION; PHYSICAL-ACTIVITY; BLOOD-PRESSURE; DOUBLE-BLIND; WEIGHT; HYSTERECTOMY; TRANSITION; MORTALITY AB OBJECTIVE: To assess the relative influence of menopausal status and hormone use on body mass index (BMI) among a multiethnic sample of mid-life women. DESIGN: Cross-sectional telephone survey conducted at seven sites where each site targeted an ethnic minority group and Caucasians as part of Study of Women's Health Across the Nation (SWAN). SUBJECTS: A total of 7181 Caucasians, 3949 African-Americans, 1660 Hispanics, 562 Chinese Americans, and 803 Japanese Americans between ages of 40 and 55 y residing in or near Boston, Chicago, Detroit, Los Angeles, Newark, Nj, Oakland, CA, and Pittsburgh, PA. MEASUREMENTS: Self-reported BMI based on weight in kg divided by height in m(2) menopausal status, physical inactivity, postmenopausal hormone use, ethnicity, and age in years. RESULTS: Compared to premenopausal women (covariate adjusted M = 27.3), women reporting a surgical menopause (M = 28.2) or being in the perimenopausal transition (M = 27.7 for early and 27.9 for late perimenopause) had higher BMI. Women reporting a natural menopause (M = 27.4) did not have a higher BMI than premenopausal women, after adjusting for chronological age and other covariates. Hormone use was associated with lower BMI (M = 26.5 vs 27.3). A comparison of effect sizes showed that menopausal status (F = 13.1), followed by chronological age (F = 24.0), were the least powerful predictors of BMI, whereas the more powerful predictors were physical activity level (F = 1377.1) and ethnicity (F = 400.5). CONCLUSIONS: The menopausal transition affects body mass index in mid-life, but the effect is small relative to other influences. Interventions to increase physical activity are highly recommended to prevent increases in adiposity common in mid-life. C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. New England Res Inst, Watertown, MA 02172 USA. Univ Texas, Hlth Sci Ctr, Dept Family Practice, San Antonio, TX 78285 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Rush Presbyterian St Lukes Med Ctr, Dept Prevent Med, Chicago, IL 60612 USA. RP Matthews, KA (reprint author), 3811 O Hara St, Pittsburgh, PA 15213 USA. OI Miles, Toni/0000-0003-0823-2319 FU NIA NIH HHS [AG12495, AG12505, AG12554, AG12531, AG12539, AG12546, AG12553]; NINR NIH HHS [NR 04061] NR 47 TC 67 Z9 69 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD JUN PY 2001 VL 25 IS 6 BP 863 EP 873 DI 10.1038/sj.ijo.0801618 PG 11 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 436CQ UT WOS:000168919300016 PM 11439301 ER PT J AU Stavreva, N Niemierko, A Stavrev, P Goitein, M AF Stavreva, N Niemierko, A Stavrev, P Goitein, M TI Modelling the dose-volume response of the spinal cord, based on the idea of damage to contiguous functional subunits SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article ID RADIATION; PROBABILITY; ARCHITECTURE; TOLERANCE; TISSUES AB Purpose: To investigate the response of the spinal cord of experimental animals to homogeneous irradiation, the main purpose being to propose a new version of the Critical Volume Normal Tissue Complication Probability (NTCP) model, incorporating spatial correlation between damaged functional subunits (FSU). Method: The standard Critical Volume NTCP model and its modified version, the Contiguous Damage model promoted here, are described in mathematical terms. Also, a fiber-like structure of the spinal cord is considered, which is a more complex structure than the standard Critical Volume NTCP model assumes. It is demonstrated that the Contiguous Damage model predicts different responses to two-segment irradiation and to single-segment irradiation to the same combined length as observed in experiments on rats, a result that cannot be described by the standard Critical Volume NTCP model. Results and conclusions : Both the Critical Volume model and the Contiguous Damage model, are fitted to two sets of canine spinal cord radiation data corresponding to two different fractionation regimes of irradiation. Whole-organ irradiation as well as partial irradiation to different lengths are considered, allowing the investigation of dose-volume effects. Formal goodness-of-fit investigation shows that both models fit the canine spinal cord data equally well. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Niemierko, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 32 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [CA 21239, CA 50628] NR 16 TC 12 Z9 12 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD JUN PY 2001 VL 77 IS 6 BP 695 EP 702 PG 8 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 441RR UT WOS:000169243700006 PM 11403709 ER PT J AU Chan, AW Ancukiewicz, M Carballo, N Montgomery, W Wang, CC AF Chan, AW Ancukiewicz, M Carballo, N Montgomery, W Wang, CC TI The role of postradiotherapy neck dissection in supraglottic carcinoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 18-23, 1997 CL ORLANDO, FLORIDA SP Amer Soc Therapeut Radiol & Oncol DE supraglottic carcinoma; radiotherapy; accelerated hyperfractionation; neck dissection; regional response ID SQUAMOUS-CELL CARCINOMA; THERAPY ONCOLOGY GROUP; LYMPH-NODE METASTASES; RADIATION-THERAPY; DEFINITIVE RADIOTHERAPY; PROGNOSTIC FACTORS; PHARYNX CARCINOMA; REGIONAL CONTROL; LOCAL-CONTROL; HEAD AB Purpose: To evaluate our policy of performing neck dissection based on regional response after definitive radiotherapy in patients with supraglottic carcinoma and to identify the prognostic factors in this group of patients. Methods and Materials: Between 1970 and 1995, 121 patients with node-positive squamous cell carcinoma of the supraglottic larynx were treated with definitive radiotherapy. Sixty-nine percent of patients presented with 1997 AJCC Stage IV disease. The N-stage distribution was N1, 49; N2, 62; and N3, 10. The median size of the lymph nodes was 3 cm (range, 0.5-8 cm). Forty-five patients received once-a-day treatment with a median total dose of 65 Gy (range, 58.0-70.8 Gy) in 1.8-2.0 Gy per fraction over 48 days, and 76 patients received split-course accelerated hyperfractionation with a median total dose of 67.2 Gy (range, 63.2-73.6 Gy) in 1.6 Gy twice a day over 43 days. Patients whose lymph nodes were not clinically detectable at 4-6 weeks after the completion of radiotherapy (complete response) were followed without any neck dissection. Patients with persistent neck adenopathy (partial response) underwent neck dissection whenever possible. Mean follow-up of the living patients was 6.5 years. Results: Regional response was related to the size of lymph nodes at presentation. Eighty-seven percent of patients with nodal size of 3 cm or less had a complete response, whereas 43% of patients with nodal size greater than 3 cm had a partial response. The rate of regional control at 3 years for all patients in the study was 66%. The 3-year ultimate regional control rate after salvage neck dissection was 75%. A relapse in both the primary and regional sites was the most common pattern of relapse, accounting for 39% of all the failures. Local failure was associated with subsequent regional relapse with a relative risk of 4.3. For patients with complete response in whom postradiotherapy neck dissection was withheld, the regional control rates were 75% and 86% for N1 and N2, respectively. The rate of isolated regional relapse in this group of patients was 7.5%. In multivariate analysis, significant favorable factors predictive for regional control were female gender, accelerated hyperfractionation, and complete response; whereas factors predictive for overall survival were Karnofsky Performance Scale score and regional response. The rate of Radiation Therapy Oncology Group (RTOG) Grade 2 or 3 neck fibrosis was 17% and 23% for patients with and without postradiotherapy neck dissection, respectively. Conclusion: Isolated regional relapse is not common in patients with supraglottic carcinoma when a complete response is achieved at 4-6 weeks after definitive radiotherapy and postradiotherapy neck dissection is not performed. Female gender, accelerated hyperfractionation, and complete response are favorable predictors of regional control. (C) 2001 Elsevier Science Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Chan, AW (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St,Cox 302, Boston, MA 02114 USA. NR 26 TC 38 Z9 38 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUN 1 PY 2001 VL 50 IS 2 BP 367 EP 375 DI 10.1016/S0360-3016(01)01468-7 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 433VG UT WOS:000168781000011 PM 11380223 ER PT J AU Bremer, C Kreft, G Roggan, A Filler, T Reimer, P AF Bremer, C Kreft, G Roggan, A Filler, T Reimer, P TI Ex vivo evaluation of novel miniaturized laser-induced interstitial thermotherapy applicators for effective small-volume tissue ablation SO INVESTIGATIVE RADIOLOGY LA English DT Article DE laser; thermotherapy; ablation; applicator design; magnetic resonance imaging ID PRELIMINARY CLINICAL-EXPERIENCE; BENIGN PROSTATIC HYPERPLASIA; INTERVENTIONAL MR; RADIOFREQUENCY ABLATION; LIVER METASTASES; TUMORS; THERMOMETRY; THERAPY; LITT; COAGULATION AB RATIONALE AND OBJECTIVES. For effective small-volume tissue ablation in clinical and experimental settings, smaller laser-induced interstitial thermotherapy (LITT) applicator designs are required. The aim of this study was to compare the ablation properties of recently developed ultrasmall and small to standard LITT applicators. METHODS. Laser-induced interstitial thermotherapy was performed on liver samples using ultrasmall, small, and standard LITT applicators. Thermotherapy was monitored by magnetic resonance imaging, and lesion sizes were measured for each image. True lesion sizes were then determined macroscopically and by histology, RESULTS. For continuous laser application over 5 minutes, maximum power settings were 5 W for the ultrasmall and small applicators and 10 W for the standard applicator. Given identical LITT settings, lesion volume measured by magnetic resonance imaging was significantly larger and histological tissue damage was more severe with the ultrasmall and small applicators than with the standard applicator, CONCLUSIONS, Small and ultrasmall LITT applicators can be used for effective tissue ablation of small target volumes in experimental and clinical applications. C1 Free Univ Berlin, Inst Med Phys & Laser Med, D-1000 Berlin, Germany. Univ Munster, Inst Clin Radiol, D-4400 Munster, Germany. Univ Munster, Inst Anat, D-4400 Munster, Germany. Stadt Klinikum Karlsruhe, Zent Inst Bildgebende Diagnost, Karlsruhe, Germany. RP Bremer, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Bldg 149,13th St 5407, Charlestown, MA 02129 USA. RI Filler, Timm/I-5779-2014 OI Filler, Timm/0000-0002-2922-5110 NR 33 TC 7 Z9 8 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 JUN PY 2001 VL 36 IS 6 BP 327 EP 334 DI 10.1097/00004424-200106000-00005 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 442WD UT WOS:000169307200005 PM 11410753 ER PT J AU Hequembourg, S Liberman, MC AF Hequembourg, S Liberman, MC TI Spiral ligament pathology: A major aspect of age-related cochlear degeneration in C57BL/6 mice SO JARO LA English DT Article DE cochlea; hearing; histopathology; aging ID HAIR CELL LOSS; LATERAL WALL; HEARING-LOSS; INNER-EAR; MOUSE; NERVE; FIBROCYTES; EXPRESSION; STRIA; CATS AB Data from systematic, light microscopic examination of cochlear histopathology in an age-graded series of C57BL/6 mice (1.5-15 months) were compared with threshold elevations (measured by auditory brain stem response) to elucidate the functionally important structural changes underlying age-related hearing loss in this inbred strain. In addition to quantifying the degree and extent of hail cell and neuronal loss, all structures of the cochlear duct were qualitatively evaluated and any degenerative changes were quantified. Hair cell and neuronal loss patterns suggested two degenerative processes. In the basal half of the cochlea, inner and outer hair cell loss proceeded fi om base to apex with increasing age, and loss of cochlear neurons Tvas consistent with degeneration occurring secondary to inner hair cell loss. In the apical half of the cochlea with advancing age, there was selective loss of outer hair cells which increased from the middle to the extreme apex. A similar gradient of ganglion cell loss was noted, characterized by widespread somatic aggregation and demyelination. In addition to these changes in hair cells and their innervation, there was widespread degeneration of fibrocytes in the spiral ligament, especially among the type IV cell class. The cell loss in the ligament preceded the loss of hair cells and/or neurons in both space and time suggesting that fibrocyte pathology may be a primary cause of the hearing loss and ultimate sensory cell degeneration in this mouse strain. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [P30 DC005209, R01 DC0188] NR 29 TC 157 Z9 162 U1 1 U2 8 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1525-3961 J9 JARO JI JARO PD JUN PY 2001 VL 2 IS 2 BP 118 EP 129 PG 12 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 445JE UT WOS:000169453700003 PM 11550522 ER PT J AU Meisenhelder, JB Chandler, EN AF Meisenhelder, JB Chandler, EN TI Frequency of prayer and functional health in Presbyterian pastors SO JOURNAL FOR THE SCIENTIFIC STUDY OF RELIGION LA English DT Article ID RELIGIOUS SERVICES; DEPRESSION; MORTALITY; OLDER; ATTENDANCE; DEATH; RISK AB The purpose of this correlational study was to examine the relationship of frequency of prayer to eight subcategories of physical and mental health. As part of the ongoing Presbyterian Panel, 1,412 active Presbyterian pastors drawn from a national, random sample were surveyed by mail regarding their frequency of prayer and self-perceptions of health outcomes. The results indicated a high level of functioning overall for all eight categories of physical and mental health. Predictably, frequency of prayer was extremely skewed towards high frequency. Despite a lack of variation in both health and prayer, high frequency of prayer was significantly related to higher scores in three health outcomes: vitality, general health, and mental health. These relationships remained significant in the analysis even after controlling for the influence of demographic variables, such as gender and age. Various explanations of the results are explored. C1 Massachusetts Gen Hosp, Inst Hlth Profess, Grad Nursing Program, Boston, MA 02114 USA. RP Meisenhelder, JB (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, Grad Nursing Program, 101 Merrimac St, Boston, MA 02114 USA. NR 30 TC 17 Z9 17 U1 1 U2 3 PU SOC SCIENTIFIC STUDY RELIGION PI PROVO PA BRIGHAM YOUNG UNIV, 875 SWKT, SOCIOLOGY DEPT, PROVO, UT 84602 USA SN 0021-8294 J9 J SCI STUD RELIG JI J. Sci. Stud. Relig. PD JUN PY 2001 VL 40 IS 2 BP 323 EP 329 DI 10.1111/0021-8294.00059 PG 7 WC Sociology; Religion SC Sociology; Religion GA 453YF UT WOS:000169945200014 ER PT J AU Beal, AC Ausiello, J Perrin, JM AF Beal, AC Ausiello, J Perrin, JM TI Social influences on health-risk behaviors among minority middle school students SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE parent influence; peer influence; social influence; tobacco; alcohol; sexual activity; drug use; health-risk behaviors; adolescents; minority ID COMPROMISING BEHAVIORS; ABUSE PREVENTION; UNITED-STATES; ADOLESCENTS; SMOKING; INITIATION; ALCOHOL; PROGRAM; IMPACT; YOUTH AB Purpose: To determine whether parent social influences are associated with health-risk behaviors more than peer social influences among young minority adolescents. Methods: We conducted a cross-sectional survey of seventh-grade students in a public urban magnet middle school using a survey instrument adapted from the Centers for Disease Control and Prevention Youth Risk Behavior Survey. The sample consisted of all seventh-grade students in the school, and the survey was part of a needs assessment for a school-based health education program. We measured four health-risk behaviors: use of (a) tobacco, (b) alcohol, (c) onset of sexual activity, and (d) marijuana use; and five social influences: (a) parent disapproval of health-risk behaviors, (b) parent modeling of health-risk behaviors, (c) parent monitoring of health-risks, (d) peer disapproval of health risks, and (e) peer modeling of health-risk behaviors. The analyses included measures of the prevalence of health-risk behaviors, bivariate analyses to evaluate relationships between health-risk behaviors and social influences, and regressions analyses to determine the independent associations of the social influences with the four health-risk behaviors. Results: Twenty percent of respondents reported using tobacco, over 50% used alcohol in the past year, 13.3% were sexually active, and 12% reported marijuana use. Parent influences were associated with differences in alcohol use, whereas peer influences were associated with differences in all measured health-risk behaviors: tobacco and alcohol use, sexual activity, and marijuana use. Regression analyses demonstrated that peer social influences were the only measures independently associated with abstinence from tobacco (p < .05), alcohol (p < .01), sexual activity (p < .05), and marijuana use (p < .05). In all analyses, peers emerged as the most consistent social influence on health-risk behavior. Conclusion: This study suggests peers and peer group behavior may be better predictors of adolescent health-risk behaviors than parental social influences among young adolescents. (C) Society for Adolescent Medicine, 2001. C1 Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Hlth Policy Res & Dev Unit, Boston, MA 02114 USA. RP Beal, AC (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Dept Pediat, 50 Staniford St,Suite 901, Boston, MA 02114 USA. NR 30 TC 114 Z9 118 U1 0 U2 26 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD JUN PY 2001 VL 28 IS 6 BP 474 EP 480 DI 10.1016/S1054-139X(01)00194-X PG 7 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 434JK UT WOS:000168811200006 PM 11377991 ER PT J AU Cherniack, EP Senzel, RS Pan, CX AF Cherniack, EP Senzel, RS Pan, CX TI Correlates of use of alternative medicine by the elderly in an urban population SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID UNITED-STATES; COMPLEMENTARY; PREVALENCE AB Objective: To investigate the prevalence and predictors of use of complementary and alternative medicine (CAM) by the elderly. Design: Cross-sectional survey examining patterns of use of complementary therapies in two urban multiethnic populations of older adults. Setting and Subjects: A convenience sample of 421 older participants were interviewed at two sites: a university geriatrics primary care practice and a veterans medical clinic, both in New York City. Subjects were excluded if they did not speak English or if they were moderately cognitively impaired. Measurement: Use of CAM within the previous year. Results: Fifty-eight percent (58%) of all subjects surveyed used some form of CAM, and close to 75% at the university practice alone. Use correlated most strongly with female gender (p < 0.0001), greater education (p = 0.0095), thyroid disease (p = 0.0190) and arthritis (p = 0.0251). There was no correlation with income, race, age, or self-perceived health status. Conclusions: CAM use is highly prevalent in older persons in this study, especially among females and those who are more highly educated. C1 Bronx Vet Affairs Med Ctr, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA. RP Cherniack, EP (reprint author), Bronx Vet Affairs Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. NR 8 TC 50 Z9 50 U1 1 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD JUN PY 2001 VL 7 IS 3 BP 277 EP 280 DI 10.1089/107555301300328160 PG 4 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 445ZN UT WOS:000169488600020 PM 11439850 ER PT J AU Hooper, DC AF Hooper, DC TI Global resistance emergence: Human experience SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JUN PY 2001 VL 47 SU 1 MA 12 BP 3 EP 3 PG 1 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 444DC UT WOS:000169382900003 ER PT J AU Andes, D AF Andes, D TI Pharmacokinetics and pharmacodynamics of the des F(6) quinolone SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Meeting Abstract C1 William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JUN PY 2001 VL 47 SU 1 MA 73 BP 9 EP 10 PG 2 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 444DC UT WOS:000169382900029 ER PT J AU Fairfield, WP Treat, M Rosenthal, DI Frontera, W Stanley, T Corcoran, C Costello, M Parlman, K Schoenfeld, D Klibanski, A Grinspoon, S AF Fairfield, WP Treat, M Rosenthal, DI Frontera, W Stanley, T Corcoran, C Costello, M Parlman, K Schoenfeld, D Klibanski, A Grinspoon, S TI Effects of testosterone and exercise on muscle leanness in eugonadal men with AIDS wasting SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE resistance exercise training; muscle attenuation; acquired immunodeficiency syndrome ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; SKELETAL-MUSCLE; COMPUTED-TOMOGRAPHY; INSULIN SENSITIVITY; BODY-COMPOSITION; DETERMINANTS; TRIALS; WOMEN; MASS AB Loss of lean body and muscle mass characterizes the acquired immunodeficiency syndrome (AIDS) wasting syndrome (AWS). Testosterone and exercise increase muscle mass in men with AWS, with unclear effects on muscle composition. We examined muscle composition in 54 eugonadal men with AWS who were randomized to 1) testosterone (200 mg im weekly) or placebo and simultaneously to 2) resistance training or no training in a 2 x 2 factorial design. At baseline and after 12 wk, we performed assessments of whole body composition by dual-energy X-ray absorptiometry and single-slice computed tomography for midthigh cross-sectional area and muscle composition. Leaner muscle has greater attenuation. Baseline muscle attenuation correlated inversely with whole body fat mass (r = -0.52, P = 0.0001). This relationship persisted in a model including age, body mass index, testosterone level, viral load, lean body mass, and thigh muscle cross-sectional area (P = 0.02). Testosterone (P = 0.03) and training (P = 0.03) increased muscle attenuation. These data demonstrate that thigh muscle attenuation by computed tomography varies inversely with whole body fat and increases with testosterone and training. Anabolic therapy in these patients increases muscle leanness. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR-01066]; NIDDK NIH HHS [F32-DK-09218, R01-DK-49302] NR 25 TC 48 Z9 50 U1 0 U2 2 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 JUN PY 2001 VL 90 IS 6 BP 2166 EP 2171 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 436WC UT WOS:000168958000020 PM 11356779 ER PT J AU Ramsdell, CD Mullen, TJ Sundby, GH Rostoft, S Sheynberg, N Aljuri, N Maa, M Mukkamala, R Sherman, D Toska, K Yelle, J Bloomfield, D Williams, GH Cohen, RJ AF Ramsdell, CD Mullen, TJ Sundby, GH Rostoft, S Sheynberg, N Aljuri, N Maa, M Mukkamala, R Sherman, D Toska, K Yelle, J Bloomfield, D Williams, GH Cohen, RJ TI Midodrine prevents orthostatic intolerance associated with simulated spaceflight SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE cardiovascular system; vasovagal syncope ID SHORT-DURATION SPACEFLIGHT; ARTERIAL-PRESSURE; VASOVAGAL SYNCOPE; HYPOTENSION; MECHANISMS; HUMANS AB Many astronauts after being weightless in space become hypotensive and presyncopal when they assume an upright position. This phenomenon, known as orthostatic intolerance, may interfere with astronaut function during reentry and after spaceflight and may limit the ability of an astronaut to exit a landed spacecraft unaided during an emergency. Orthostatic intolerance is more pronounced after long-term spaceflight and is a major concern with respect to the extended flights expected aboard the International Space Station and for interplanetary exploration class missions, such as a human mission to Mars. Fully effective countermeasures to this problem have not yet been developed. To test the hypothesis that alpha -adrenergic stimulation might provide an effective countermeasure, we conducted a 16-day head-down-tilt bedrest study (an analog of weightlessness) using normal human volunteers and administered the alpha (1)-agonist drug midodrine at the end of the bed-rest period. Midodrine was found to significantly ameliorate excessive decreases in blood pressure and presyncope during a provocative tilt test. We conclude that midodrine may be an effective countermeasure for the prevention of orthostatic intolerance following spaceflight. C1 MIT, Harvard MIT Div Hlth Sci & Technol, NASA Ctr Quantitat Cardiovasc Physiol, Cambridge, MA 02139 USA. Brigham & Womens Hosp, Div Endocrine Hypertens, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Royal Norwegian Air Force, Inst Aviat Med, N-0313 Oslo, Norway. Univ Oslo, Dept Physiol, N-0317 Oslo, Norway. NASA, Lyndon B Johnson Space Ctr, Cardiovasc Lab, Houston, TX 77058 USA. Columbia Univ, New York, NY 10032 USA. RP Cohen, RJ (reprint author), MIT, Harvard MIT Div Hlth Sci & Technol, NASA Ctr Quantitat Cardiovasc Physiol, 45 Carlton St,Rm E25-335A, Cambridge, MA 02139 USA. FU NCRR NIH HHS [RR-02635] NR 18 TC 30 Z9 32 U1 1 U2 3 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 JUN PY 2001 VL 90 IS 6 BP 2245 EP 2248 PG 4 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 436WC UT WOS:000168958000030 PM 11356789 ER EF