FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Bogdanov, A Matuszewski, L Bremer, C Petrovsky, A Weissleder, R AF Bogdanov, Alexei, Jr. Matuszewski, Lars Bremer, Christoph Petrovsky, Alexander Weissleder, Ralph TI Oligomerization of Paramagnetic Substrates Result in Signal Amplification and can be Used for MR Imaging of Molecular Targets SO MOLECULAR IMAGING LA English DT Article DE Magnetic resonance imaging; signal amplification; oxidoreductases; peroxidase; DOTA; gadolinium AB Magnetic resonance imaging (MRI) has evolved into a sophisticated, noninvasive imaging modality capable of high-resolution anatomical and functional characterization of transgenic animals. To expand the capabilities MRI, we have developed a novel MR signal amplification (MRamp) strategy based on enzyme-mediated polymerization of paramagnetic substrates into oligomers of higher magnetic relaxivity. The substrates consist of chelated gadolinium covalently bound to phenols, which then serve as electron donors during enzymatic hydrogen peroxide reduction by peroxidase. The converted monomers undergo rapid condensation into paramagnetic oligomers leading to a threefold increase in atomic relaxivity (R-1/Gd). The observed relaxivity changes are largely due to an increase in the rotational correlation time tau(r) of the lanthanide. Three applications of the developed system are demonstrated: (1) imaging of nanomolar amounts of an oxidoreductase (peroxidase); (2) detection of a model ligand using an enzyme-linked immunoadsorbent assay format; and (3) imaging of E-selectin on the surface of endothelial cells probed for with an anti-E-selectin-peroxidase conjugate. The development of "enzyme sensing'' probes is expected to have utility for a number of applications including in vivo detection of specific molecular targets. One particular advantage of the MRamp technique is that the same paramagnetic substrate can be potentially used to identify different molecular targets by attaching enzymes to various antibodies or other target-seeking molecules. C1 [Bogdanov, Alexei, Jr.; Matuszewski, Lars; Bremer, Christoph; Petrovsky, Alexander; Weissleder, Ralph] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bogdanov, A (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, CNY-5 Rm 5420,Bldg 149,13th St, Charlestown, MA 02129 USA. EM abogdanov@helix.mgh.harvard.edu FU Deutsche Forschungsgemeinschaft; Russian Department of Education Presidential Award; [1P50CA86355-01]; [5RO1 CA74424-01] FX The authors are grateful to Drs. Hanns-Joachim Weinmann and Bernt Raduechel (Schering) for providing GlyMetDOTA, tri tBu ester. The authors acknowledge the help of Jeanne-Marie Kiely for providing H18/7antibody fragment, Kay Case for the assistance with endothelial cell culture, and Dr. Michael Gimbrone, Jr. for the useful discussions (Vascular Research Division, Department of Pathology, Brigham and Women's Hospital). We acknowledge the input made by Dr. John Chen who contributed preliminary NMRD data analysis and made useful comments. This work has been supported in part by 1P50CA86355-01 (RW) and 5RO1 CA74424-01 (AB). CB was supported by a grant from Deutsche Forschungsgemeinschaft. AP was supported by the Russian Department of Education Presidential Award. NR 38 TC 100 Z9 103 U1 1 U2 11 PU B C DECKER INC PI HAMILTON PA 69 JOHN STREET SOUTH, STE 310, HAMILTON, ONTARIO L8N 2B9, CANADA SN 1535-3508 EI 1536-0121 J9 MOL IMAGING JI Mol. Imaging PD JAN PY 2002 VL 1 IS 1 BP 16 EP 23 DI 10.1162/153535002753395671 PG 8 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA V38CE UT WOS:000209320700002 PM 12920857 ER PT J AU Malynn, BA Shaw, AC Young, F Stewart, V Alt, FW AF Malynn, BA Shaw, AC Young, F Stewart, V Alt, FW TI Truncated immunoglobulin D mu causes incomplete developmental progression of RAG-deficient pro-B cells SO MOLECULAR IMMUNOLOGY LA English DT Article DE B lymphocyte; lymphocyte development; transgene; D mu protein ID SURROGATE LIGHT-CHAIN; HEAVY-CHAIN; GENE REARRANGEMENT; ALLELIC EXCLUSION; CROSS-LINKING; BONE-MARROW; LYMPHOCYTE DIFFERENTIATION; TYROSINE PHOSPHORYLATION; RAG-1-DEFICIENT MICE; ACTIVATED RAS AB Early stages of B cell development are dependent on the expression of a pre-B cell receptor (BCR), composed of a V heavy chain (HC) in association with surrogate light chain (SLC) proteins and the signaling molecules, Igalpha and Igbeta. During the formation of the variable region of the mu chain by somatic gene rearrangement, a truncated form of the L protein (called D L) is sometimes produced by the rearrangement of a D-H segment to a J(H) segment using one of three reading frames (designated rf2). When a Dmu protein is formed, subsequent B cell development is blocked by down-regulation of further HC rearrangements, so that a full-length muHC cannot be formed. In this study, we demonstrate that in recombinase activating gene (RAG)-2-deficient B220(+) CD43(+) pro-B cells in which B lymphopoiesis has been arrested at fraction C, transgenic expression of Dmu promoted partial developmental progression to fraction C', but was unable to mediate the pro-B to pre-B cell transition to fraction D effected by full-length muHC protein. These data suggest that the intracellular signaling pathways engaged by the Dmu pre-BCR are insufficient to facilitate the expansion and/or survival of pre-B cells, and are distinct from those engaged by the pre-BCR-containing full-length muHC. (C) 2002 Published by Elsevier Science Ltd. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Malynn, BA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. FU NCI NIH HHS [CA-61009]; NIAID NIH HHS [AI-01532, AI-20047] NR 47 TC 13 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 2002 VL 38 IS 7 BP 547 EP 556 DI 10.1016/S0161-5890(01)00085-2 PG 10 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 511EN UT WOS:000173251800006 PM 11750656 ER PT J AU Sotiropoulou, G Kono, M Anisowicz, A Stenman, G Tsuji, S Sager, R AF Sotiropoulou, G Kono, M Anisowicz, A Stenman, G Tsuji, S Sager, R TI Identification and functional characterization of a human GalNAc alpha 2,6-sialyltransferase with altered expression in breast cancer SO MOLECULAR MEDICINE LA English DT Article ID BETA-GALACTOSIDE ALPHA-2,6-SIALYLTRANSFERASE; POLYMERASE CHAIN-REACTION; DEVELOPMENTALLY-REGULATED MEMBER; SIALYLTRANSFERASE GENE FAMILY; MAMMARY EPITHELIAL-CELLS; SURFACE SIALIC-ACID; MOLECULAR-CLONING; LINKED OLIGOSACCHARIDES; TUMOR-CELLS; MOUSE-BRAIN AB Background: We sought to identify genes with altered expression during human breast cancer progression by applying mRNA comparisons of normal and tumor mammary cell lines with increasingly malignant phenotypes. The gene encoding a new sialyltransferase (STM) was found to be down-regulated in tumor cells. Abnormal expression and enzymatic activities of sialyltransferases in tumor cells result in the formation of tumor-associated carbohydrate antigens that can be used for the better understanding of the disease process and are applied for tumor diagnosis and immunotherapy. Altered glycosylation patterns of the MUC1 mucin, in particular, is a target antigen for immunotherapy of breast and other cancers. Materials and Methods: Total RNAs from multiple normal mammary epithelial cell strains and tumor cell lines were compared by differential display and the differential expression of selected cDNAs was confirmed by Northern analyses. Recombinant STM was expressed in COS-7 cells. The substrate and linkage specificity of STM was examined using various oligosaccharides and O-glycosylated proteins as acceptor substrates. The chromosomal localization of the SIATL1 gene was assigned by somatic cell hybrid analysis. Results: A human sialyltransferase gene was identified by differential display as being down-regulated in breast tumor cell lines as compared to normal mammary epithelial cell strains, and the corresponding full-length cDNA (stm) was cloned. The encoded protein of 374 amino acid residues contained the L- and S-sialylmotifs, two catalytic regions conserved in all functional sialyltransferases. Recombinant STM is an active GalNAc alpha2,6-sialyltransferase with Galbeta1,3 GalNAc-O-Ser/Thr and (+/-Neu5Acalpha2,3) Galbeta1,3GalNAc-O-Ser/Thr acceptor specificity. The SIATL1 gene, encoding STM, was mapped to the long arm of human chromosome 17 at q23-qter, a region that is non-randomly deleted in human breast cancers. However, Southern analyses indicated that SIATL1 is usually not grossly rearranged in breast tumors. Northern analyses showed that the gene was widely expressed in normal human tissues, as well as in normal breast and prostate epithelial cell lines, but significantly down-regulated or absent in corresponding tumor cell lines. Conclusions: Our findings suggest that aberrant expression of STM sialyltransferase in tumors could be a feature of the malignant phenotype. In breast cancers, the MUC1 mucin is overexpressed and contains shorter O-glycans as compared to the normal mucin. Because STM catalyzes the synthesis of O-glycans, cloning and characterization of its substrate specificity will contribute to the understanding of the molecular mechanisms underlying the aberrant glycosylation patterns of O-glycans and the formation of mucin-related antigens in human breast cancers. C1 Univ Patras, Dept Pharm, Sch Hlth Sci, Patras 26500, Greece. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Genet, Boston, MA 02115 USA. RIKEN, Inst Phys & Chem Res, Frontier Res Program, Lab Mol Glycobiol, Wako, Saitama 35101, Japan. Univ Gothenburg, Dept Pathol, Canc Genet Lab, Gothenburg, Sweden. RP Sotiropoulou, G (reprint author), Univ Patras, Dept Pharm, Sch Hlth Sci, Patras 26500, Greece. FU NCI NIH HHS [CA61253] NR 72 TC 12 Z9 12 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD JAN PY 2002 VL 8 IS 1 BP 42 EP 55 PG 14 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 546UN UT WOS:000175293400006 PM 11984005 ER PT J AU Sklar, P Gabriel, SB McInnis, MG Bennett, P Lim, YM Tsan, G Schaffner, S Kirov, G Jones, I Owen, M Craddock, N DePaulo, JR Lander, ES AF Sklar, P Gabriel, SB McInnis, MG Bennett, P Lim, YM Tsan, G Schaffner, S Kirov, G Jones, I Owen, M Craddock, N DePaulo, JR Lander, ES TI Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus SO MOLECULAR PSYCHIATRY LA English DT Article DE genomic; single-nucleotide polymorphism; SNP; linkage; transmission disequilibrium test; susceptibility loci ID TRYPTOPHAN-HYDROXYLASE GENE; MANIC-DEPRESSIVE ILLNESS; NEUROTROPHIC FACTOR BDNF; SINGLE-NUCLEOTIDE POLYMORPHISMS; UNIPOLAR AFFECTIVE-DISORDER; MAJOR AFFECTIVE-DISORDER; DNA DIAGNOSTIC METHOD; MOOD DISORDERS; LINKAGE DISEQUILIBRIUM; TYROSINE-HYDROXYLASE AB Identification of the genetic bases for bipolar disorder remains a challenge for the understanding of this disease. Association between 76 candidate genes and bipolar disorder was tested by genotyping 90 single-nucleotide polymorphisms (SNPs) in these genes in 136 parent-proband trios. In this preliminary analysis, SNPs in two genes, brain-derived neurotrophic factor (BDNF) and the alpha subunit of the voltage-dependent calcium channel were associated with bipolar disorder at the P<0.05 level. In view of the large number of hypotheses tested, the two nominally positive associations were then tested in independent populations of bipolar patients and only BDNF remains a potential risk gene. In the replication samples, excess transmission of the valine allele of amino acid fib of BDNF was observed in the direction of the original result in an additional sample of 334 parent-proband trios (T!U=108187, P=0.066). Resequencing of 29 kb surrounding the BDNF gene identified 44 additional SNPs. Genotyping eight common SNPs identified three additional markers transmitted to bipolar probands at the P<0.05 level. Strong LD was observed across this region and all adjacent pairwise haplotypes showed excess transmission to the bipolar proband. Analysis of these haplotypes using TRANSMIT revealed a global P value of 0.03. A single haplotype was identified that is shared by both the original dataset and the replication sample that is uniquely marked by both the rare A allele of the original SNP and a novel allele 11.5 kb 3'. Therefore, this study of 76 candidate genes has identified BDNF as a potential risk allele that will require additional study to confirm. C1 MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. Univ Wales Coll Cardiff, Coll Med, Dept Psychol Med, Cardiff CF1 3NS, S Glam, Wales. Univ Birmingham, Queen Elizabeth Hosp, Div Neurosci, Birmingham B15 2TH, W Midlands, England. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. RP Sklar, P (reprint author), MIT, Whitehead Inst, Ctr Genome Res, 1 Kendall Sq,Bldg 300, Cambridge, MA 02139 USA. RI Jones, Ian/B-4925-2009; turton, miranda/F-4682-2011; McInnis, Melvin/F-6963-2012; Schaffner, Stephen/D-1189-2011 OI McInnis, Melvin/0000-0002-0375-6247; NR 76 TC 417 Z9 432 U1 1 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2002 VL 7 IS 6 BP 579 EP 593 DI 10.1038/sj.mp.4001058 PG 15 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 577TT UT WOS:000177078500011 PM 12140781 ER PT J AU Frazer, A Benmansour, S AF Frazer, A Benmansour, S TI Delayed pharmacological effects of antidepressants SO MOLECULAR PSYCHIATRY LA English DT Article DE selective serotonin reuptake inhibitors; selective norepinephrine reuptake inhibitors; serotonin transporter; norepinephrine transporter ID NOREPINEPHRINE UPTAKE SITES; MAJOR DEPRESSIVE DISORDER; H-3 NISOXETINE; 5-HT UPTAKE; RAT; FLUOXETINE; BINDING; SEROTONIN; TRANSPORTER; BRAIN AB Although antidepressants may not be primary mood stabilizers, they are efficacious in the prophylaxis of recurrent depressive illnesses, as well as in the treatment of acute episodes. Pharmacological effects that may contribute to the prophylactic effects of these drugs are not understood. Studies have been carried out in which antidepressants have been given to laboratory animals, such as rats, for periods of up to 3-4 weeks. Data obtained in such studies are thought to be important for their beneficial effects in depressive episodes, but also may be relevant to their prophylactic effects. Results are presented showing that when selective inhibitors of serotonin or norepinephrine uptake are given for such time periods, they still produce selective effects on serotonergic or noradrenergic parameters. For example, long-term administration of selective norepinephrine reuptake inhibitors causes a down-regulation of beta(1) adrenoceptors. Selective serotonin reuptake inhibitors do not produce this effect. Longterm administration of selective serotonin reuptake inhibitors causes down-regulation of the serotonin transporter, but not the norepinephrine transporter. In contrast, selective norepinephrine reuptake inhibitors down-regulate the norepinephrine transporter but not the serotonin transporter. Substantial loss of serotonin transporter binding sites takes 15 days to occur and is accompanied by a marked reduction of serotonin transporter function in vivo. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78229 USA. Audie L Murphy Mem Hosp, S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Frazer, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, 7703 Floyd Curl Dr,Mail Code 7764, San Antonio, TX 78229 USA. NR 38 TC 53 Z9 56 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2002 VL 7 SU 1 BP S23 EP S28 DI 10.1038/sj.mp.4001015 PG 6 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 539XT UT WOS:000174898700004 PM 11986992 ER PT J AU Kemper, TL Bauman, ML AF Kemper, TL Bauman, ML TI Neuropathology of infantile autism SO MOLECULAR PSYCHIATRY LA English DT Article; Proceedings Paper CT Meeting on Microbiology Immunology and Toxicology of Autism and Other Neurodevelopmental Disorders CY FEB 11-14, 2001 CL COLD SPRING HARBOR, NEW YORK C1 Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Childrens Neurol Serv, Cambridge, MA 02138 USA. RP Kemper, TL (reprint author), Boston Univ, Sch Med, Dept Anat & Neurobiol, 715 Albany St,W701, Boston, MA 02118 USA. NR 10 TC 54 Z9 54 U1 3 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2002 VL 7 SU 2 BP S12 EP S13 DI 10.1038/sj.mp.4001165 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 579AZ UT WOS:000177154400006 PM 12142934 ER PT J AU Shefner, JM Cudkowicz, ME Brown, RH AF Shefner, JM Cudkowicz, ME Brown, RH TI Comparison of incremental with multipoint mune methods in transgenic ALS mice SO MUSCLE & NERVE LA English DT Article DE amyotrophic lateral sclerosis; incremental MUNE; motor unit number estimation; multipoint MUNE; MUNE ID AMYOTROPHIC-LATERAL-SCLEROSIS; POINT STIMULATION; MOTOR UNITS; NUMBER; REPRODUCIBILITY; DEGENERATION; FALS AB Several methods of motor unit number estimation (MUNE) are in current use. Uncertainty still exists about which is preferable and how results obtained from one Method compare to another. We studied changes with MUNE over time in the SOD1(G93A) transgenic mouse model of amyotrophic lateral sclerosis (ALS), using both incremental and multipoint methods. This mouse model of motor neuron degeneration is highly consistent, with a monotonic decline in motor neuron number starting at approximately 60 days of life. Five mice were studied four times each, starting at day 60 of life and approximately every 20 days thereafter, using both methods. Results were quite comparable for both methods, with the incremental method yielding slightly higher estimates of motor unit size, and hence smaller MUNEs. Correlations between the two methods were 0.71 for single motor unit action potential (SMUAP) amplitude and 0.95 for MUNE. In this model, therefore, both MUNE methods yield similar estimates and are equally effective at documenting progression of a lower motor neuron disorder. (C) 2002 John Wiley & Sons, Inc. C1 Upstate Med Univ, Dept Neurol, Syracuse, NY 13210 USA. Massachusetts Gen Hosp, Neurol Clin Trial Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cecil B Day Lab Neuromuscular Res, Boston, MA 02114 USA. RP Shefner, JM (reprint author), Upstate Med Univ, Dept Neurol, 750 E Adams St, Syracuse, NY 13210 USA. NR 16 TC 40 Z9 43 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD JAN PY 2002 VL 25 IS 1 BP 39 EP 42 DI 10.1002/mus.10000 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 505RC UT WOS:000172928500007 PM 11754183 ER PT J AU Proctor, ME Klein, BS Jones, JM Davis, JP AF Proctor, ME Klein, BS Jones, JM Davis, JP TI Cluster of pulmonary blastomycosis in a rural community: Evidence for multiple high-risk environmental foci following a sustained period of diminished precipitation SO MYCOPATHOLOGIA LA English DT Article DE Blastomyces dermatitidis; cluster investigation; fungal infection; pulmonary disease ID WISCONSIN; DERMATITIDIS; IMMUNITY; EPIDEMIC; OUTBREAK; SOIL AB Much of our understanding of the epidemiologic features of infection with Blastomyces dermatitidis has come from cluster and outbreak investigations which have established the association of human disease with recreational pursuits and the presence of infectious microfoci in areas of moist soil with high organic content. This report describes the clustering of eight cases of pulmonary blastomycosis without an apparent common source exposure which occurred during a 90 day period in a 96 square mile area (population 4,450) within Oconto County, Wisconsin. We conclude that multiple high-risk environmental foci may have existed following a sustained five-year period of diminished precipitation in the cluster area. A case-control study which included family and community controls concluded that multiple earth-disturbing activities engaged in by case-patients was statistically associated with illness. Lymphocyte-proliferation assays of whole blood samples detected previously unrecognized infection with B. dermatitidis among five of 32 family controls. C1 Wisconsin Dept Hlth & Family Serv, Div Publ Hlth, Bur Communicable Dis, Madison, WI 53701 USA. Univ Wisconsin, Sch Med, Dept Pediat, Madison, WI USA. Univ Wisconsin, Sch Med, Dept Med, Madison, WI USA. William S Middleton Mem Vet Adm Med Ctr, Clin & Res Serv, Madison, WI 53705 USA. RP Proctor, ME (reprint author), Wisconsin Dept Hlth & Family Serv, Div Publ Hlth, Bur Communicable Dis, Madison, WI 53701 USA. NR 29 TC 18 Z9 18 U1 2 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0301-486X J9 MYCOPATHOLOGIA JI Mycopathologia PY 2002 VL 153 IS 3 BP 113 EP 120 DI 10.1023/A:1014515230994 PG 8 WC Mycology SC Mycology GA 530KC UT WOS:000174356000001 PM 11998870 ER PT J AU Saunders-Pullman, R Ozelius, L Bressman, SB AF Saunders-Pullman, R Ozelius, L Bressman, SB TI Inherited myoclonus-dystonia SO MYOCLONUS AND PAROXYSMAL DYSKINESIAS SE ADVANCES IN NEUROLOGY LA English DT Article ID D2 DOPAMINE-RECEPTOR; MUSCULAR-DYSTROPHY 2D; EPSILON-SARCOGLYCAN; CHROMOSOME 7Q; MAJOR LOCUS; GENE; 7Q21-Q31; FAMILIES C1 Beth Israel Med Ctr, Dept Neurol, New York, NY 10003 USA. Massachusetts Gen Hosp, Dept Mol Neurogenet, Charlestown, MA USA. RP Saunders-Pullman, R (reprint author), Beth Israel Med Ctr, Dept Neurol, New York, NY 10003 USA. NR 40 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0091-3952 J9 ADV NEUROL JI Adv.Neurol. PY 2002 VL 89 BP 185 EP 191 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BV80M UT WOS:000180075900020 PM 11968443 ER PT J AU Sagot, I Klee, SK Pellman, D AF Sagot, I Klee, SK Pellman, D TI Yeast formins regulate cell polarity by controlling the assembly of actin cables SO NATURE CELL BIOLOGY LA English DT Article ID ALDRICH-SYNDROME PROTEIN; SACCHAROMYCES-CEREVISIAE; MITOTIC SPINDLE; ARP2/3 COMPLEX; BUDDING YEAST; MICROTUBULE ORIENTATION; CYTOSKELETAL CONTROL; BUD SITE; IN-VIVO; BNI1P AB Formins are conserved Rho-GTPase effectors that communicate Rho-GTPase signals to the cytoskeleton. We found that formins were required for the assembly of one of the three budding yeast actin structures: polarized arrays of actin cables. A dominant-active formin induced the assembly of actin cables. The activation and localization of the formin Bni1p required components of the polarisome complex. These findings potentially define the cellular function of formins in budding yeast and explain their involvement in the generation of cell polarity. A requirement for formins in constructing specific actin structures might be the basis for the diverse activities of formins in development. C1 Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Stuttgart, Inst Biochem, D-70569 Stuttgart, Germany. RP Sagot, I (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM61345] NR 48 TC 292 Z9 295 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD JAN PY 2002 VL 4 IS 1 BP 42 EP 50 DI 10.1038/nc719 PG 9 WC Cell Biology SC Cell Biology GA 513MC UT WOS:000173381500015 PM 11740491 ER PT J AU Armstrong, SA Staunton, JE Silverman, LB Pieters, R de Boer, ML Minden, MD Sallan, SE Lander, ES Golub, TR Korsmeyer, SJ AF Armstrong, SA Staunton, JE Silverman, LB Pieters, R de Boer, ML Minden, MD Sallan, SE Lander, ES Golub, TR Korsmeyer, SJ TI MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia SO NATURE GENETICS LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC-CELLS; CHROMOSOME-TRANSLOCATION; CLINICAL CHARACTERISTICS; DROSOPHILA-TRITHORAX; T(4-11)(Q21-Q23); FUSION; T(7-11)(P15-P15); REARRANGEMENTS AB Acute lymphoblastic leukemias carrying a chromosomal translocation involving the mixed-lineage leukemia gene (MLL, ALL1, HRX) have a particularly poor prognosis. Here we show that they have a characteristic, highly distinct gene expression profile that is consistent with an early hematopoietic progenitor expressing select multilineage markers and individual HOX genes. Clustering algorithms reveal that lymphoblastic leukemias with MLL translocations can clearly be separated from conventional acute lymphoblastic and acute myelogenous leukemias. We propose that they constitute a distinct disease, denoted here as MLL, and show that the differences in gene expression are robust enough to classify leukemias correctly as MLL, acute lymphoblastic leukemia or acute myelogenous leukemia. Establishing that MLL is a unique entity is critical, as it mandates the examination of selectively expressed genes for urgently needed molecular targets. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. MIT, Whitehead Inst Biomed Res, Ctr Genome Res, Cambridge, MA 02142 USA. Univ Rotterdam, Sophia Childrens Hosp, Div Pediat Hematol Oncol, Rotterdam, Netherlands. Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. RP Korsmeyer, SJ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 47 TC 1129 Z9 1160 U1 2 U2 12 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2002 VL 30 IS 1 BP 41 EP 47 DI 10.1038/ng765 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 508TL UT WOS:000173105600012 PM 11731795 ER PT J AU Anderson, MG Smith, RS Hawes, NL Zabaleta, A Chang, B Wiggs, JL John, SWM AF Anderson, MG Smith, RS Hawes, NL Zabaleta, A Chang, B Wiggs, JL John, SWM TI Mutations in genes encoding melanosomal proteins cause pigmentary glaucoma in DBA/2J mice SO NATURE GENETICS LA English DT Article ID BROWN LOCUS PROTEIN; OCULOCUTANEOUS ALBINISM; DISPERSION SYNDROME; MOUSE MUTATION; IRIS ATROPHY; TYROSINASE; MELANOCYTES; MELANOMA; TYRP1; GP75 AB Pigmentary glaucoma is a significant cause of human blindness. Abnormally liberated iris pigment and cell debris enter the ocular drainage structures, leading to increased intraocular pressure (IOP) and glaucoma(1-3). DBA/2J (D2) mice develop a form of pigmentary glaucoma involving iris pigment dispersion (IPD) and iris stromal atrophy (ISA)(4,5). Using high-resolution mapping techniques, sequencing and functional genetic tests, we show that IPD and ISA result from mutations in related genes encoding melanosomal proteins. IPD is caused by a premature stop codon mutation in the Gpnmb (Gpnmb(R150X)) gene, as proved by the occurrence of IPD only in D2 mice that are homozygous with respect to Gpnmb(R150X). otherwise, similar D2 mice that are not homozygous for Gpnmb(R150X) do not develop IPD. ISA is caused by the recessive Tyrp1(b) mutant allele and rescued by the transgenic introduction of wildtype Tyrp1. We hypothesize that IPD and ISA alter melanosomes, allowing toxic intermediates of pigment production to leak from melanosomes, causing iris disease and subsequent pigmentary glaucoma. This is supported by the rescue of IPD and ISA in D2 eyes with substantially decreased pigment production. These data indicate that pigment production and mutant melanosomal protein genes may contribute to human pigmentary glaucoma. The fact that hypopigmentation profoundly alleviates the D2 disease indicates that therapeutic strategies designed to decrease pigment production may be beneficial in human pigmentary glaucoma. C1 Howard Hughes Med Inst, Bar Harbor, ME 04609 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA. RP John, SWM (reprint author), Howard Hughes Med Inst, Bar Harbor, ME 04609 USA. RI Anderson, Michael/B-4580-2009 OI Anderson, Michael/0000-0001-5730-6105 FU NEI NIH HHS [F32 EY007015] NR 30 TC 231 Z9 240 U1 0 U2 6 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2002 VL 30 IS 1 BP 81 EP 85 DI 10.1038/ng794 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 508TL UT WOS:000173105600018 PM 11743578 ER PT J AU Shipp, MA Ross, KN Tamayo, P Weng, AP Kutok, JL Aguiar, RCT Gaasenbeek, M Angelo, M Reich, M Pinkus, GS Ray, TS Koval, MA Last, KW Norton, A Lister, TA Mesirov, J Neuberg, DS Lander, ES Aster, JC Golub, TR AF Shipp, MA Ross, KN Tamayo, P Weng, AP Kutok, JL Aguiar, RCT Gaasenbeek, M Angelo, M Reich, M Pinkus, GS Ray, TS Koval, MA Last, KW Norton, A Lister, TA Mesirov, J Neuberg, DS Lander, ES Aster, JC Golub, TR TI Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning SO NATURE MEDICINE LA English DT Article ID NON-HODGKINS-LYMPHOMA; NF-KAPPA-B; PROGNOSTIC-SIGNIFICANCE; SIGNAL-TRANSDUCTION; HEMATOPOIETIC-CELLS; THERAPEUTIC TARGET; APOPTOSIS; RECEPTOR; PROTEIN; DIFFERENTIATION AB Diffuse large B-cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is curable in less than 50% of patients. Prognostic models based on pre-treatment characteristics, such as the International Prognostic Index (IPI), are currently used to predict outcome in DLBCL. However, clinical outcome models identify neither the molecular basis of clinical heterogeneity, nor specific therapeutic targets. We analyzed the expression of 6,817 genes in diagnostic tumor specimens from DLBCL patients who received cyclophosphamide, adriamycin, vincristine and prednisone (CHOP)-based chemotherapy, and applied a supervised learning prediction method to identify cured versus fatal or refractory disease. The algorithm classified two categories of patients with very different five-year overall survival rates (70% versus 12%). The model also effectively delineated patients within specific IPI risk categories who were likely to be cured or to die of their disease. Genes implicated in DLBCL outcome included some that regulate responses to B-cell-receptor signaling, critical serine/threonine phosphorylation pathways and apoptosis. Our data indicate that supervised learning classification techniques can predict outcome in DLBCL and identify rational targets for intervention. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. MIT, Whitehead Inst Biomed Res, Ctr Genome Res, Cambridge, MA 02139 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA USA. St Bartholomews Hosp, Imperial Canc Res Fund, Med Oncol Unit, London, England. St Bartholomews Hosp, Pathol Unit, London, England. Univ W Indies, Dept Comp Sci Math & Phys, Bridgetown, Barbados. MIT, Dept Biol, Cambridge, MA USA. RP Shipp, MA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Weng, Andrew/I-5015-2014 NR 45 TC 1366 Z9 1429 U1 14 U2 78 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 JAN PY 2002 VL 8 IS 1 BP 68 EP 74 DI 10.1038/nm0102-68 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 507XQ UT WOS:000173056900033 PM 11786909 ER PT J AU Gusella, J MacDonald, M AF Gusella, J MacDonald, M TI No post-genetics era in human disease research SO NATURE REVIEWS GENETICS LA English DT Review ID NEURONAL INTRANUCLEAR INCLUSIONS; EXPANDED CAG REPEAT; KNOCK-IN MICE; HUNTINGTONS-DISEASE; MUTANT HUNTINGTIN; TRANSGENIC MICE; NEUROFIBROMATOSIS TYPE-2; NUCLEAR-LOCALIZATION; TERMINAL FRAGMENTS; STRIATAL NEURONS AB In the 1980s, linkage emerged as a route to discovering genetic defects, spurring the rise of genomics and making gene-based approaches available to previously Phenotype-orientated researchers. In the post-genomics era, genetics is fundamental to understanding disease at all stages of the pathogenic process. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. RP Gusella, J (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. NR 58 TC 19 Z9 20 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD JAN PY 2002 VL 3 IS 1 BP 72 EP 79 DI 10.1038/nrg706 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 511MG UT WOS:000173267200019 PM 11823793 ER PT J AU Melder, RJ Munn, LL Stoll, BR Marecos, EM Baxter, LT Weissleder, R Jain, RK AF Melder, RJ Munn, LL Stoll, BR Marecos, EM Baxter, LT Weissleder, R Jain, RK TI Systemic distribution and tumor localization of adoptively transferred lymphocytes in mice: Comparison with physiologically based pharmacokinetic model SO NEOPLASIA LA English DT Article DE lymphocyte; trafficking; pharmacokinetic; mathematical model; tumor ID POSITRON EMISSION TOMOGRAPHY; ADHESION MOLECULES; CELL-ADHESION; KILLER-CELLS; GENE-THERAPY; CANCER; EXPRESSION; IMMUNOTHERAPY; ENDOTHELIUM; ANGIOGENESIS AB The mechanisms by which tumors are able to evade cellular immune responses are still largely unknown. It Is likely, however, that the initial recruitment of lymphocytes to tumor vessels is limited by cell retention in normal tissue, which results in a low flux of these cells into the tumor vasculature. We grew MCaIV (mouse mammary carcinoma) tumors in the leg of SCID mice and injected In-111-oxine-labeled, primed T lymphocytes directed against the tumor intravenously. The systemic distribution of cells in normal organs was similar between mice injected with primed and control lymphocyte populations, except for a delayed clearance of primed lymphocytes from the lungs. Kinetics of lymphocyte localization to the tumor were Identical between the primed and control lymphocyte populations. Splenectomy before the injection of primed lymphocytes increased delivery of cells to the lungs and liver after I hour with no significant improvement in tumor localization. Within 24 to 168 hours after injection, localization of cells in the liver of splenectomized mice was higher than in the control group. However, no significant difference in tumor localization was observed between groups. A physiologically based compartmental model of lymphocyte distribution predicted the compartmental sequestration and identified model parameters critical for experimental planning and therapeutic optimization. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 7, Boston, MA 02114 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NCI NIH HHS [R01 CA086782, R01 CA86782, P01 CA080124, P01 CA80124]; NHLBI NIH HHS [R01 HL064240, R01 HL64240] NR 36 TC 12 Z9 12 U1 0 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD JAN-FEB PY 2002 VL 4 IS 1 BP 3 EP 8 DI 10.1038/sj.neo.7900209 PG 6 WC Oncology SC Oncology GA 513ZU UT WOS:000173412000002 PM 11922388 ER PT J AU Heckers, S AF Heckers, S TI Memory and hippocampus function in schizophrenia SO NERVENHEILKUNDE LA German DT Article DE episodic memory; recall; hippocampus ID EPISODIC MEMORY; RETRIEVAL AB The declarative memory for facts and for personal events is impaired in schizophrenia. Memory studies using neuroimaging methods have demonstrated that abnormalities in prefrontal cortex, thalamus, hippocampus, and cerebellum are the neural basis of these memory deficits. Impaired recruitment of the hippocampus during conscious recollection is a novel finding, that could explain some of the memory impairment in schizophrenia. Together with the evidence for structural abnormalities of the hippocampus in schizophrenia, this points to a major role of the hippocampus for the explanation of cognitive deficits and psychopathology in schizophrenia. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. RP Heckers, S (reprint author), Massachusetts Gen Hosp, Dept Psychiat, E CNY-9132,Bldg 149,13th St, Charlestown, MA 02129 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 NR 30 TC 0 Z9 0 U1 2 U2 2 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0722-1541 J9 NERVENHEILKUNDE JI Nervenheilkunde PY 2002 VL 21 IS 8 BP 400 EP + PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 607DA UT WOS:000178775000003 ER PT S AU Barton, JJS Cherkasova, MV Lindgren, K Goff, DC Intriligator, JM Manoach, DS AF Barton, JJS Cherkasova, MV Lindgren, K Goff, DC Intriligator, JM Manoach, DS BE Kaminski, HJ Leigh, RJ TI Antisaccades and task switching Studies of control processes in saccadic function in normal subjects and schizophrenic patients SO NEUROBIOLOGY OF EYE MOVEMENTS: FROM MOLECULES TO BEHAVIOR SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Neurobiology of Eye Movement - From Molecules to Behavior CY OCT 04-06, 2001 CL CASE WESTERN RESERVE UNIV, CLEVELAND, OHIO SP NY Acad Sci, Univ Hosp Cleveland, Evenor Armington Fund HO CASE WESTERN RESERVE UNIV DE antisaccades; task switching; executive; attention; latency; schizophrenia ID CARD SORTING TEST; EYE-MOVEMENT; PERFORMANCE; LESIONS; MEMORY; COSTS; SET AB Executive functions allow us to respond flexibly rather than stereotypically to the environment. We examined two such functions, task switching and inhibition in the antisaccade paradigm, in two studies. One study involved 18 normal subjects; the other, 21 schizophrenic patients and 16 age-matched controls. Subjects performed blocks of randomly mixed prosaccades and antisaccades. Repeated trials were preceded by the same type of trial (i.e., an antisaccade following an antisaccade), and switched trials were preceded by a trial of the opposite type. We measured accuracy rate and latency as indices of processing costs. Whereas schizophrenic patients had a threefold increase in error rate for antisaccades compared to normals, the effect of task switching on their accuracy did not differ from that in normal subjects. Moreover, the accuracy rate of trials combining antisaccade and task switching was equivalent to a multiplication of the accuracy rates from trials In which each was done alone. Schizophrenic latencies were disproportionately increased for antisaccades, but again they were no different from normal subjects in the effect of task switching. In both groups the effect of task switching on antisaccades was a paradoxical latency reduction. We conclude that the executive dysfunction in schizophrenia is not generalized but selective, sparing task switching from exogenous cues, in which the switch Is limited to a stimulus-response remapping. The accuracy data in both groups support independence of antisaccade and task-switching functions. The paradoxical task-switching benefit in antisaccadic latency effects challenges current models of task switching. It suggests either carryover inhibition by antisaccadic performance In the prior trial or facilitation of antisaccades by simultaneous performance of other cognitive operations. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurol, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Ophthalmol, Boston, MA 02215 USA. Boston Univ, Dept Bioengn, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Barton, JJS (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurol, KS-454,330 Brookline Ave, Boston, MA 02215 USA. RI Barton, Jason/A-6362-2012 FU NIMH NIH HHS [K23MH01829-01] NR 32 TC 19 Z9 19 U1 1 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-394-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 956 BP 250 EP 263 PG 14 WC Multidisciplinary Sciences; Ophthalmology SC Science & Technology - Other Topics; Ophthalmology GA BU36T UT WOS:000175781500022 PM 11960809 ER PT J AU Ahveninen, J Jaaskelainen, IP Kaakkola, S Tiitinen, H Pekkonen, E AF Ahveninen, J Jaaskelainen, IP Kaakkola, S Tiitinen, H Pekkonen, E TI Aging and cholinergic modulation of the transient magnetic 40-Hz auditory response SO NEUROIMAGE LA English DT Article DE 40-Hz response; acetylcholine; aging; Alzheimer's disease; auditory event-related potentials; electroencephalography; magnetoencephalography; memory; muscarinic receptors; scopolamine ID SYNAPTIC TRANSMISSION; NUCLEUS BASALIS; NERVOUS-SYSTEM; SCOPOLAMINE; DEMENTIA; MEMORY; CORTEX; FIELDS; POTENTIALS; ATTENTION AB Cholinergic blockade by scopolamine, a central muscarinic receptor antagonist, may produce transient memory impairment in healthy subjects, and it has been used as a neurochemical model of cognitive degeneration in aged individuals. To observe the muscarinic modulation of memory and cortical auditory processing, nine cognitively intact elderly subjects (59-80 years) were studied using neuropsychological tests and 122-channel magnetoencephalography (MEG) after an administration of scopolamine hydrobromide (0.3 mg, iv) or glycopyrrolate (0.2 mg, iv), a peripheral muscarinic antagonist. A double-blind randomized crossover design was used in two sessions separated by at least 1 week. Scopolamine, but not glycopyrrolate, produced a transient impairment of verbal memory performance in the elderly subjects. MEG indicated that tire auditory-evoked 40-Hz magnetic response was significantly larger after scopolamine than after glycopyrrolate administration. Furthermore, reanalysis of our earlier results in younger subjects (20-31 years), basically supporting the present MEG findings, tentatively suggests that the scopolamine effects on the 40-Hz response may be slightly pronounced with aging. In sum, the transient magnetic 40-Hz auditory response may be useful in studies on brain cholinergic deficits in elderly subjects. (C) 2002 Elsevier Science. C1 Univ Helsinki, Dept Psychol, Cognit Brain Res Unit, FIN-00014 Helsinki, Finland. Univ Helsinki, Dept Psychol, Appercept & Cort Dynam Res Team, FIN-00014 Helsinki, Finland. Univ Helsinki, Dept Neurol, FIN-00014 Helsinki, Finland. Univ Helsinki, Cent Hosp, Med Engn Ctr, Biomag Lab, Helsinki, Finland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA USA. RP Ahveninen, J (reprint author), Univ Helsinki, Dept Psychol, Cognit Brain Res Unit, POB 13, FIN-00014 Helsinki, Finland. RI Jaaskelainen, Iiro/C-7392-2012; OI Jaaskelainen, Iiro/0000-0001-6001-6950; Pekkonen, Eero/0000-0003-1621-8752 NR 28 TC 9 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN PY 2002 VL 15 IS 1 BP 153 EP 158 DI 10.1006/nimg.2001.0956 PG 6 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 509XJ UT WOS:000173174900015 PM 11771983 ER PT J AU Haueisen, J Tuch, DS Ramon, C Schimpf, PH Wedeen, VJ George, JS Belliveau, JW AF Haueisen, J Tuch, DS Ramon, C Schimpf, PH Wedeen, VJ George, JS Belliveau, JW TI The influence of brain tissue anisotropy on human EEG and MEG SO NEUROIMAGE LA English DT Article ID NEUROMAGNETIC FIELDS; CONDUCTIVITY CHANGES; MAGNETIC-FIELDS; INVERSE PROBLEM; HEAD; POTENTIALS; SIMULATION; MODELS; TORSO AB The influence of gray and white matter tissue anisotropy on the human electroencephalogram (EEG) and magnetoencephalogram (MEG) was examined with a high resolution finite element model of the head of an adult male subject. The conductivity tensor data for gray and white matter were estimated from magnetic resonance diffusion tensor imaging. Simulations were carried out with single dipoles or small extended sources in the cortical gray matter. The inclusion of anisotropic volume conduction in the brain was found to have a minor influence on the topology of EEG and MEG (and hence source localization). We found a major influence on the amplitude of EEG and MEG (and hence source strength estimation) due to the change in conductivity and the inclusion of anisotropy. We expect that inclusion of tissue anisotropy information will improve source estimation procedures. (C) 2002 Elsevier Science. C1 Univ Jena, Biomagnet Zentrum, Jena, Germany. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA USA. Univ Washington, Dept Elect Engn, Seattle, WA 98195 USA. Washington State Univ, Sch Elect Engn & Comp Sci, Spokane, WA USA. Los Alamos Natl Lab, Biophys Grp, Los Alamos, NM USA. RP Haueisen, J (reprint author), Univ Jena, Biomagnet Zentrum, Jena, Germany. RI Haueisen, Jens/B-7183-2011 OI Haueisen, Jens/0000-0003-3871-2890 NR 24 TC 137 Z9 143 U1 2 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN PY 2002 VL 15 IS 1 BP 159 EP 166 DI 10.1006/nimg.2001.0962 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 509XJ UT WOS:000173174900016 PM 11771984 ER PT J AU Kiechle, T Dedeoglu, A Kubilus, J Kowall, NW Beal, MF Friedlander, RM Hersch, SM Ferrante, RJ AF Kiechle, T Dedeoglu, A Kubilus, J Kowall, NW Beal, MF Friedlander, RM Hersch, SM Ferrante, RJ TI Cytochrome c and caspase-9 expression in Huntington's disease SO NEUROMOLECULAR MEDICINE LA English DT Article DE Huntington's; apoptosis; caspase; cytochrome c; immunocytochemistry; Western blot ID TRANSGENIC MOUSE MODEL; AMYOTROPHIC-LATERAL-SCLEROSIS; CELL-DEATH; NEURODEGENERATIVE DISEASES; ALZHEIMERS-DISEASE; APOPTOSIS; ACTIVATION; MITOCHONDRIA; PROTEASE; PATHOGENESIS AB There is increasing evidence implicating apoptosis-mediated cell death in the pathogenesis of neurodegenerative diseases. One important event in the apoptotic cascade is the release of cytochrome c by mitochondria into the cytoplasm, activating caspase-9, leading to the subsequent activation of downstream executioner caspases. In the present study, we examined the distribution of cytochrome c and caspase-9 in Huntington's disease (HD) patients and in a transgenic model of HD (R6/2 line). Neuronal cytochrome c immunoreactivity increased with neuropathological severity in HD patients. Concomitant with this finding, Western-blot analysis showed a shift in the distribution of cytochrome c from the mitochondrial to the cytosolic fraction with incremental cytosolic expression associated with greater striatal degeneration. Active caspase-9 immunoreactivity was present in both HD striatal neurons and in Western blots of severe-grade specimens. Similar findings were observed in the R6/2 mice. There was a temporal increase in expression and shift of cytochrome c from the mitochondrial to the cytosolic fraction from 4-13 wk of age. Activated caspase-9 and caspase 3 activities were present only at endstage disease. Although the present results provide evidence that key components of the intrinsic mitochondrial apoptotic pathway are activated in both HD patients and a transgene murine model of HD, these phenomena are prominent in only severe neuropathological grades in HD patients and HD mice, suggesting that apoptosis may play a greater role in neuronal death at endstage disease. C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY USA. Harvard Univ, Brigham & Womens Hosp, Dept Neurosurg, Neuroapoptosis, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat Dis, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Bedford VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bedford, MA USA. RP Ferrante, RJ (reprint author), Bedford VA Med Ctr, GRECC Unit, Bldg 18,200 Springs Rd, Bedford, MA 01730 USA. RI Kowall, Neil/G-6364-2012; Friedlander, Robert/A-2845-2016 OI Kowall, Neil/0000-0002-6624-0213; Friedlander, Robert/0000-0003-4423-9219 FU NCCIH NIH HHS [AT00613]; NIA NIH HHS [AG12992, AG13846]; NINDS NIH HHS [NS35255, NS37102] NR 45 TC 74 Z9 78 U1 2 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2002 VL 1 IS 3 BP 183 EP 195 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 608VH UT WOS:000178867500003 PM 12095160 ER PT J AU Verfaellie, M Schacter, DL Cook, SP AF Verfaellie, M Schacter, DL Cook, SP TI The effect of retrieval instructions on false recognition: exploring the nature of the gist memory impairment in amnesia SO NEUROPSYCHOLOGIA LA English DT Article DE amnesia; gist memory; false recognition ID HEALTHY OLDER ADULTS; FUZZY-TRACE THEORY; COGNITIVE NEUROSCIENCE; KORSAKOFF PATIENTS; TRUE RECOGNITION; RECALL; CATEGORIES; FAMILIARITY; SIMILARITY; ILLUSIONS AB In previous studies, we found that amnesic patients show reduced levels of false recognition in a converging semantic associates paradigm. This finding was interpreted as reflecting an impairment in amnesia in the ability to form, retain and/or retrieve a well-organized representation of the semantic 'gist' of studied items. To further explore the nature of amnesics' impairment in gist memory, the current study compared performance in two retrieval conditions. In a standard retrieval condition, participants were asked to endorse on a recognition test only items that had appeared on the study list. In a meaning retrieval condition, participants were asked to endorse any item that shared the meaning of studied items. Meaning retrieval instructions failed to eliminate the reduction in false recognition in amnesia. These results suggest that amnesics' impairment in gist memory is not attributable to a failure to access well-formed gist representations when given item-specific retrieval cues. Rather, it suggests that amnesic patients are impaired in their ability to encode, store, or maintain strong gist information. Published by Elsevier Science Ltd. C1 Boston VA Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02130 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Verfaellie, M (reprint author), Boston VA Healthcare Syst, Memory Disorders Res Ctr, 151A,150 S Huntington Ave, Boston, MA 02130 USA. OI Schacter, Daniel/0000-0002-2460-6061 FU NIA NIH HHS [AG08441]; NIMH NIH HHS [MH 57681]; NINDS NIH HHS [NS 26985] NR 48 TC 28 Z9 30 U1 3 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2002 VL 40 IS 13 BP 2360 EP 2368 AR PII S0028-3932(02)00074-X DI 10.1016/S0028-3932(02)00074-X PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 623RH UT WOS:000179716300015 PM 12417465 ER PT J AU Weber, R Draf, W Keerl, R Kahle, G Kind, M Schinzel, S Thomann, S Weber, A AF Weber, R Draf, W Keerl, R Kahle, G Kind, M Schinzel, S Thomann, S Weber, A TI Magnetic resonance imaging following fat obliteration of the frontal sinus SO NEURORADIOLOGY LA English DT Article DE frontal sinus surgery; osteoplastic flap operation; frontal sinus obliteration; fat transplantation; magnetic resonance imaging; frontal sinus mucocoele; half-life of transplanted fat ID SURGERY; SEQUENCE; TISSUE AB The paper describes the evaluation of magnetic resonance imaging (MRI) following osteoplastic flap procedure with fat obliteration. MRI scans performed in patients after surgery between 1st January 1986 and 31st December 1997 were evaluated. Outcome parameters were time-dependent changes in the distribution of adipose or connective tissue, development of necroses or oil cysts, recurrences, inflammatory complications, or mucococles. Eighty-six postoperative MRI scans from 51 operations were evaluated. In 19 cases between two and five MRI scans were available. Time between surgery and the last MRI scan was 24.1 months on average. We found five mucococles. The amount of adipose tissue depictable on the last scan was less than 20% in the majority of cases (53%) and more than 60% in only 18% of cases. Statistical tests and modelling showed a significant decrease of adipose tissue with time, with a median half-life of 15.4 months in a subgroup with at least two MRIs. MRI is at times the most valuable diagnostic tool after frontal sinus obliteration using adipose tissue. The method has sonic limitations with regard to detection of small (recurrences of) mucocoeles and differentiation between vital adipose tissue and fat necroses in the form of oil cysts. In difficult cases long-term MRI follow-up is necessary for definitive evaluation. C1 Fulda Hosp, Dept Otorhinolaryngol Head Neck & Facial Plast Su, Fulda, Germany. Marienhosp Stuttgart, Dept Otorhinolaryngol Head & Neck Surg, D-70199 Stuttgart, Germany. Hosp Fulda, Inst Radiol, Fulda, Germany. Hosp Fulda, Inst Pathol, Fulda, Germany. Hoechst Marion Roussell Germany, Dept Biometry, Bad Soden, Germany. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Inst Radiol, Boston, MA USA. RP Weber, R (reprint author), Fulda Hosp, Dept Otorhinolaryngol Head Neck & Facial Plast Su, Fulda, Germany. NR 25 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-3940 J9 NEURORADIOLOGY JI Neuroradiology PD JAN PY 2002 VL 44 IS 1 BP 52 EP 58 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 518AL UT WOS:000173643700010 PM 11942501 ER PT J AU McAllister, TW Arciniegas, D AF McAllister, TW Arciniegas, D TI Evaluation and treatment of postconcussive symptoms SO NEUROREHABILITATION LA English DT Review DE postconcussion syndrome; mild traumatic brain injury; postconcussive symptoms ID TRAUMATIC BRAIN INJURY; MINOR HEAD-INJURY; POSTTRAUMATIC-STRESS-DISORDER; MAGNETIC-RESONANCE SPECTROSCOPY; CORTICAL COGNITIVE FUNCTION; POST-CONCUSSION SYMPTOMS; POSITRON EMISSION TOMOGRAPHY; RANDOMIZED CONTROLLED TRIAL; WORKING-MEMORY PERFORMANCE; ROUTINE FOLLOW-UP AB Postconcussive symptoms such as headache, dizziness, irritability, and difficulties with memory and attention are reported frequently after traumatic brain injuries (TBI) of all severities. The etiology of these symptoms in individuals with mild TBI has been a subject of some controversy with theories ranging from neural damage to malingering. Furthermore, although the term postconcussive syndrome is commonly used clinically and in the scientific literature, it is not clear that postconcussive symptoms constitute a syndrome per se. Instead, it may be the case that the various symptoms that commonly co-occur after TBI are relatively independent consequences of a single neurological event. In other words, because the locations and severity of injury vary between individuals despite ostensibly similar injuries, it follows that there should be variations in symptom type and severity between individuals as well. This article reviews the sequelae and natural course of recovery from mild TBI, the evidence regarding both persistent postconcussive symptoms and the postconcussive syndrome, and outlines an approach to the assessment and treatment of individuals with these symptoms after TBI. C1 Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Dept Psychiat, Lebanon, NH 03756 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. RP Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Dept Psychiat, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM Thomas.W.McAllister@Dartmouth.edu RI Arciniegas, David/A-3792-2009 FU NINDS NIH HHS [R01 NS40472-01] NR 197 TC 67 Z9 68 U1 3 U2 13 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1053-8135 EI 1878-6448 J9 NEUROREHABILITATION JI Neurorehabilitation PY 2002 VL 17 IS 4 BP 265 EP 283 PG 19 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 636GA UT WOS:000180445200002 PM 12547976 ER PT J AU Hiott, DW Labbate, L AF Hiott, DW Labbate, L TI Anxiety disorders associated with traumatic brain injuries SO NEUROREHABILITATION LA English DT Article DE traumatic brain injury; obsessive compulsive disorder; posttraumatic stress disorder; panic disorder; generalized anxiety disorder ID OBSESSIVE-COMPULSIVE DISORDER; POSTTRAUMATIC-STRESS-DISORDER; HEAD-INJURY; PSYCHIATRIC-DISORDERS; PANIC DISORDER; CONSEQUENCES; INDIVIDUALS; DEPRESSION; TOMOGRAPHY; LESIONS AB Anxiety disorders are common in the general population and may be even more common in people with traumatic brain injuries. This article presents a review of the literature on anxiety disorders as a result of traumatic brain injury, specifically post-traumatic stress disorder, generalized anxiety disorder, obsessive compulsive disorder, and panic disorder. Our current understanding suggests that the increased frequency of anxiety disorders after TBI may reflect an overlap between brain regions vulnerable to traumatic brain injury, and the neural circuitry of these disorders. Issues regarding treatment are largely anecdotal, and much remains unsettled. More research is needed, both in terms of diagnosis and treatment. C1 Med Univ S Carolina, Dept Psychiat & Behav Sci, Ralph H Johnson VAMC, Charleston, SC 29425 USA. RP Hiott, DW (reprint author), Med Univ S Carolina, Dept Psychiat, 67 President St,5 South, Charleston, SC 29412 USA. NR 44 TC 43 Z9 45 U1 1 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1053-8135 J9 NEUROREHABILITATION JI Neurorehabilitation PY 2002 VL 17 IS 4 BP 345 EP 355 PG 11 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 636GA UT WOS:000180445200008 PM 12547982 ER PT J AU Sattin, A Senanayake, SS Pekary, AE AF Sattin, A Senanayake, SS Pekary, AE TI Lithium modulates expression of TRH receptors and TRH-related peptides in rat brain SO NEUROSCIENCE LA English DT Article DE bipolar disorder; mood stabilizers; nucleus accumbens; amygdala thyrotropin releasing hormone (TRH) ID THYROTROPIN-RELEASING-HORMONE; CENTRAL-NERVOUS-SYSTEM; SEIZURES INCREASE LEVELS; PITUITARY RECEPTORS; INHIBITING FACTOR; BIPOLAR DISORDER; DEPRESSION; GLUTAMATE; RADIOIMMUNOASSAY; PATHOPHYSIOLOGY AB Lithium is an established mood stabilizer and neuroprotective agent frequently used in the treatment of bipolar disorder and as an adjuvant in drug-resistant unipolar depression. The mechanisms underlying both the therapeutic efficacy of lithium and the exacerbation of symptoms following rapid withdrawal are not understood. From previous studies showing antidepressant and neuroprotective activities of thyrotropin releasing hormone (TRH) and TRH-related neuropeptides we hypothesized that lithium may have substantial effects on the expression and secretion of these peptides and/or their receptors in various rat brain regions involved in the regulation of mood. Chronic lithium effect on TRH receptor binding studies: The effect of 1 and 2 weeks of dietary lithium on [H-3]3-Me-His-TRH binding to plasma membranes of nucleus accumbens, amygdala and pituitary of young adult male Wistar and the endogenously 'depressed' Wistar Kyoto (WKY) rats was measured by the method of Burt and Taylor [Burt, D.R., Taylor, R.L., Endocrinology 106 (1980) 1416-1423]. Acute, chronic and withdrawal effect of lithium on TRH and TRH-like peptide levels in young, adult male Sprague-Dawley rats: Rats were divided into four lithium treatment groups. Control animals received a standard laboratory rodent chow. The acute group received a single i.p. injection of 1.5 milli-equivalents of LiCl 2 h prior to killing. The chronic and withdrawal groups received standard rodent chow containing 1.7 g/kg LiCl for 2 weeks. Withdrawal rats were returned to standard chow 48 h prior to killing while the chronic animals continued on the LiCl diet. TRH, TRH-Gly (pGlu-His-Pro-Gly, a TRH precursor), EEP (pGlu-Glu-Pro-NH2, a TRH-like peptide with antidepressant activity) and Ps4 (a prepro-TRH-derived TRH-enhancing decapeptide) immunoreactivity (IR) were measured in 13 brain regions. The remaining samples were pooled and fractionated by high-pressure liquid chromatography followed by EEP radioimmunoassay. Chronic lithium treatment increased [H-3]3Me-TRH binding in the nucleus accumbens and amygdala about two-fold in both Wistar and WKY rats but no change was observed in pituitary binding. The most widespread changes in TRH and TRH-related peptide levels were observed in the withdrawal group compared to the controls. The direction of change for the total IR was consistent for all TRH-IR and TRH-related peptide-IR within a given tissue. For example, withdrawal increased all peptide levels in the pyriform cortex and striatum but decreased these levels in the anterior cingulate and lateral cerebellum. Both acute injection and chronic treatment with LiCl decreased TRH and TRH-related peptide levels in the entorhinal cortex. Acute injection and withdrawal both increased EEP-IR in striatum by more than two-fold. The acute effects are most likely due to changes in the release of these peptides since 2 h is not sufficient time for alterations in peptide biosynthesis. Chronic treatment increased levels of pGlu-Phe-Pro-NH2 levels in hippocampus, pGlu-Leu-Pro-NH2, and peak '2' in septum by more than four-fold. The present results are consistent with a component role for TRH and related peptides in the mood-altering effects of lithium administration and withdrawal frequently observed during treatment for depression and bipolar disorder. Published by Elsevier Science Ltd on behalf of IBRO. C1 VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Psychiat Serv, 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 Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA 90024 USA. RP Pekary, AE (reprint author), W Los Angeles Vet Affairs Med Ctr, Bldg 114,Room 200,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 61 TC 10 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2002 VL 115 IS 1 BP 263 EP 273 AR PII S0306-4522(02)00373-1 DI 10.1016/S0306-4522(02)00373-1 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 615DX UT WOS:000179231500024 PM 12401339 ER PT J AU Frederickson, CJ Cuajungco, MP Labuda, CJ Suh, SW AF Frederickson, CJ Cuajungco, MP Labuda, CJ Suh, SW TI Nitric oxide causes apparent release of zinc from presynaptic boutons SO NEUROSCIENCE LA English DT Article DE hippocampus; zinc staining; vesicular zinc; synaptically released zinc ID HIPPOCAMPAL SLICES; GLUTAMATE; ENHANCEMENT; CULTURES; CHANNELS; BRAIN AB One of us showed preciously [Cuajungeo and Lees (1998) Brain Res. 799. 188-129] that nitric oxide injected into the cerebrum vivo causes zinc staining to appear in the somata of neurons and suggested that this staining of somata might be accompanied by a depletion (release) of zinc from axon terminals. In the present studs. we confirm earlier results and report that there is a dramatic loss (apparent release) of histologically reactive zinc from the boutons of zinc-containing axons induced by infusion of nitric oxide into the brain in vivo. Rats were anesthetized with halothane and a cannula was inserted into the hippocampus, Either nitric oxide donor (spermineNONOate, 100 mM/2 mul) or control (spermine. 100 mM/2 1) was infused into the hippocarripus or the cerebellar cortex. Two hours after infusion, methox 1-8-quinolyl)-para-toluenesulfonamide (TSQ) staining For zinc in the brains revealed that sperminenitric oxide, but not control (spermine only) produced tip to 95% depletion of zinc staining from the zinc-containing boutons. TSQ-positive e neurons were also conspicuous throughout injection sites, in both the cerebral cortex and in the cerebellar cortex,,A here the Purkinje neurons were especially vivid, despite the scarcity of zinc-containing axonal boutons. It is suggested that the TSQ-stainable zinc in somata might represent intracellular stores mobilized from within or permeating extracellular stores, (C) 2002 IBRO. Published by Elsevier Science Ltd, All rights reserved. C1 NeuroBioTex Inc, Galveston, TX 77550 USA. Univ Texas, Med Branch, Jennie Sealy Hosp 625, Ctr Biomed Engn, Galveston, TX 77555 USA. Univ Texas, Med Branch, Jennie Sealy Hosp 625, Dept Anat & Neurosci, Galveston, TX 77555 USA. Massachusetts Gen Hosp, Lab Oxidat Biol, Genet & Aging Unit, Charlestown, MA 02129 USA. RP Frederickson, CJ (reprint author), NeuroBioTex Inc, 101 Christopher Columbus Blvd, Galveston, TX 77550 USA. RI Cuajungco, Math/B-2647-2008 OI Cuajungco, Math/0000-0003-0749-9564 FU NINDS NIH HHS [NS 40701] NR 15 TC 48 Z9 50 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2002 VL 115 IS 2 BP 471 EP 474 AR PII S0306-4522(02)00399-8 DI 10.1016/S0306-4522(02)00399-8 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 617PT UT WOS:000179370600015 PM 12421613 ER PT J AU Zaidi, NF Berezovska, O Choi, EK Miller, JS Chan, H Lilliehook, C Hyman, BT Buxbaum, JD Wasco, W AF Zaidi, NF Berezovska, O Choi, EK Miller, JS Chan, H Lilliehook, C Hyman, BT Buxbaum, JD Wasco, W TI Biochemical and immunocytochemical characterization of calsenilin in mouse brain SO NEUROSCIENCE LA English DT Article DE calsenilin; interacting protein; presenilins; Alzheimer's disease ID FAMILIAL ALZHEIMERS-DISEASE; CALCIUM-BINDING PROTEIN; C-TERMINAL FRAGMENT; APOLIPOPROTEIN-E; PREFERENTIALLY INTERACTS; SIGNAL-TRANSDUCTION; MISSENSE MUTATIONS; GENE PRESENILIN-1; TYPE-4 ALLELE; BETA-CATENIN AB Mutations in the presenilin 1and 2 genes cause the majority of early onset familial forms of Alzheimer's disease. Here we describe the biochemical and immunohistochemical characterization of calsenilin, a novel calcium binding protein that we have previously shown to interact with presenilins 1 and 2. in mouse brain. The co-immunoprecipitation of endogenous calsenilin and presenilin 1 demonstrates that these proteins are physiologic binding partners, Although calsenilin has been predicted to be a soluble protein, we have found that the majority of it is tightly associated with the cytoplasmic face of intracellular membranes and that it can only be dissociated using harsh treatments such as urea. In addition. we have demonstrated that calsenilin is a developmentally regulated protein that is mainly present in the brain, where it localizes to both the hippocampus and cerebellum. Calsenilin staining co-localized with the somato-dendritic marker microtubule-associated protein-2 primarily in the granular cell layer of the cerebellum, indicating that calsenilin expression is primarily neuronal. In primary cultured neurons, calsenilin immunoreactivity was observed in cell bodies as well as in some neuronal processes. Co-localization experiments using specific axonal and dendritic markers indicate that these processes were mainly axonal in nature. although a smaller subset of dendrites also appears to contain calsenilin. In summary, we have established that calsenilin and presenilin 1 can interact at physiologic levels, and that calsenilin is a developmentally regulated protein that is expressed primarily in the cerebellum and hippocampus. Although calsenilin is a soluble protein, it is tightly associated with the membrane. Finally. the expression pattern of calsenilin. which is similar to that of the presenilin(s), suggests that the common locations of these two proteins provide an opportunity for physical interaction in vivo. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Alzheimers Res Unit, Charlestown, MA 02129 USA. Mt Sinai Med Ctr, Dept Psychiat, New York, NY 10029 USA. Mt Sinai Med Ctr, Dept Neurobiol, New York, NY 10029 USA. RP Wasco, W (reprint author), Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Unit, 114,16th St, Charlestown, MA 02129 USA. OI Buxbaum, Joseph/0000-0001-8898-8313 NR 69 TC 26 Z9 28 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2002 VL 114 IS 1 BP 247 EP 263 AR PII S0306-4522(02)00251-8 DI 10.1016/S0306-4522(02)00251-8 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 593UD UT WOS:000178011200023 PM 12207970 ER PT J AU Strecker, RE Nalwalk, J Dauphin, LJ Thakkar, MM Chen, Y Ramesh, V Hough, LB McCarley, RW AF Strecker, RE Nalwalk, J Dauphin, LJ Thakkar, MM Chen, Y Ramesh, V Hough, LB McCarley, RW TI Extracellular histamine levels in the feline preoptic/anterior hypothalamic area during natural sleep-wakefulness and prolonged wakefulness: An in vivo microdialysis study SO NEUROSCIENCE LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the Society-for-Neuroscience CY OCT 23-28, 1999 CL MIAMI BEACH, FLORIDA SP Soc Neurosci DE sleep deprivation; prolonged wakefulness; ventrolateral preoptic area; brain; REM sleep; hypothalamus ID WAKING DISCHARGE; AROUSAL MECHANISMS; CAT HYPOTHALAMUS; BASAL FOREBRAIN; PREOPTIC AREA; RAT-BRAIN; IN-VITRO; NEURONS; ACTIVATION; RECEPTOR AB In creased activity of the histaminergic neurons of the posterior hypothalamus has been implicated in the facilitation of behavioral wakefulness. Recent evidence of reciprocal projections between the sleep-active neurons of the preoptic/anterior hypothalamus and the histaminergic neurons of the tuberomammillary nucleus suggests that histaminergic innervation of the preoptic/anterior hypothalamic area may be of particular importance in the wakefulness-promoting properties of histamine. To test this possibility, we used microdialysis sample collection in the preoptic/ anterior hypothalamic area of cats during natural sleep-wakefulness cycles, 6 h of sleep deprivation induced by gentle handling/playing, and recovery sleep. Samples were analyzed by a sensitive radioenzymatic assay. Mean basal levels of histamine in microdialysate during periods of wakefulness (1.155 +/- 0.225 pg/mul) did not vary during the 6 It of sleep deprivation. However, during the different sleep states, dramatic changes were observed in the extracellular histamine levels of preoptic/anterior hypothalamic area: wakefulness > non-rapid eye movement sleep > rapid eye movement sleep. Levels of histamine during rapid eye movement sleep were lowest (0.245 +/- 0.032 pg/mul), being significantly lower than levels during non-rapid eye movement sleep (0.395 +/- 0.081 pg/mul) and being only 21% of wakefulness levels. This pattern of preoptic/anterior hypothalamic area extracellular histamine levels across the sleep-wakefulness cycle closely resembles the reported single unit activity of histaminergic neurons. However, the invariance of histamine levels during sleep deprivation suggests that changes in histamine level do not relay information about sleep drive to the sleep-promoting neurons of the preoptic/anterior hypothalamic area. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 VA Boston Healthcare Syst, Dept Psychiat, Brockton, MA 02301 USA. Harvard Univ, Sch Med, Brockton, MA 02301 USA. Albany Med Coll, Ctr Neuropharmacol & Neurosci, Albany, NY 12208 USA. RP Strecker, RE (reprint author), VA Boston Healthcare Syst, Dept Psychiat, 151C,940 Belmont St, Brockton, MA 02301 USA. RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NIDA NIH HHS [DA 03816]; NIMH NIH HHS [NIMH 01798, NIMH 39683] NR 54 TC 51 Z9 54 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2002 VL 113 IS 3 BP 663 EP 670 AR PII S0306-4522(02)00158-6 DI 10.1016/S0306-4522(02)00158-6 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 590VH UT WOS:000177844300019 PM 12150786 ER PT J AU Spittaels, K Van Den Haute, C Van Dorpe, J Terwel, D Vandezande, K Lasrado, R Bruynseels, K Irizarry, M Verhoye, M Van Lint, J Vandenheede, JR Ashton, D Mercken, M Loos, R Hyman, B Van Der Linden, A Geerts, H Van Leuven, F AF Spittaels, K Van Den Haute, C Van Dorpe, J Terwel, D Vandezande, K Lasrado, R Bruynseels, K Irizarry, M Verhoye, M Van Lint, J Vandenheede, JR Ashton, D Mercken, M Loos, R Hyman, B Van Der Linden, A Geerts, H Van Leuven, F TI Neonatal neuronal overexpression of glycogen synthase kinase-3 beta reduces brain size in transgenic mice SO NEUROSCIENCE LA English DT Article DE glycogen synthase kinase-3 beta; microtubule-associated protein 2; microcephaly; transgenic mice ID AMYLOID PRECURSOR PROTEIN; IN-VIVO; NEGATIVE REGULATOR; NEURITE RETRACTION; SIGNALING PATHWAY; KINASE 3-BETA; BETA-CATENIN; PHOSPHORYLATION; TAU; EXPRESSION AB Glycogen synthase kinase-3beta (GSK-3beta) is important in neurogenesis. Here we demonstrate that the kinase influenced post-natal maturation and differentiation of neurons in vivo in transgenic mice that overexpress a constitutively active GSK-3beta[S9A]. Magnetic resonance imaging revealed a reduced volume of the entire brain, concordant with a nearly 20% reduction in wet brain weight. The reduced volume was most prominent for the cerebral cortex, without however, disturbing the normal cortical layering. The resulting compacted architecture was further demonstrated by an increased neuronal density, by reduced size of neuronal cell bodies and of the somatodendritic compartment of pyramidal neurons in the cortex. No evidence for apoptosis was obtained. The marked overall reduction in the level of the microtubule-associated protein 2 in brain and in spinal cord, did not affect the ultrastructure of the microtubular cytoskeleton in the proximal apical dendrites. The overall reduction in size of the entire CNS induced by constitutive active GSK-3beta caused only very subtle changes in the psychomotoric ability of adult and ageing GSK-3beta transgenic mice. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Katholieke Univ Leuven, Dept Human Genet, Expt Genet Grp, B-3000 Louvain, Belgium. Massachusetts Gen Hosp East, Alzheimer Dis Res Unit, Charlestown, MA 02120 USA. Univ Antwerp, Dept Phys, Bioimaging Lab, B-2020 Antwerp, Belgium. Katholieke Univ Leuven, Dept Biochem, B-3000 Louvain, Belgium. Janssen Res Fdn, B-2340 Beerse, Belgium. Katholieke Univ Leuven, Dept Human Genet, Louvain, Belgium. RP Van Leuven, F (reprint author), Katholieke Univ Leuven, Dept Human Genet, Expt Genet Grp, Campus Gasthuisberg O&N 06, B-3000 Louvain, Belgium. NR 60 TC 61 Z9 64 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2002 VL 113 IS 4 BP 797 EP 808 AR PII S0306-4522(02)00236-1 DI 10.1016/S0306-4522(02)00236-1 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 592ZL UT WOS:000177966700007 PM 12182887 ER PT J AU Newhauser, WD Titt, U Dexheimer, D Yan, X Nill, S AF Newhauser, WD Titt, U Dexheimer, D Yan, X Nill, S TI Neutron shielding verification measurements and simulations for a 235-MeV proton therapy center SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT LA English DT Article; Proceedings Paper CT International Workshop on Neutron Field Spectrometry in Science, Technology and Radiation Protection (NEUSPEC 2000) CY JUN 04-08, 2000 CL PISA, ITALY DE neutron shielding; proton therapy; Monte Carlo simulations ID ENERGY AB The neutron shielding at the Massachusetts General Hospital's 235-MeV proton therapy facility was investigated with measurements, analytical calculations, and realistic three-dimensional Monte Carlo simulations. In 37 of 40 cases studied, the analytical calculations predicted higher neutron dose equivalent rates outside the shielding than the measured, typically by more than a factor of 10, and in some cases more than 100. Monte Carlo predictions of dose equivalent at three locations are, on average, 1.1 times the measured values. Except at one location, all of the analytical model predictions and Monte Carlo simulations overestimate neutron dose equivalent. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Bechtel Corp, San Francisco, CA USA. Harvard Cyclotron Univ, Cambridge, MA USA. Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany. RP Newhauser, WD (reprint author), Massachusetts Gen Hosp, 55 Fruit St,NPT-100, Boston, MA 02114 USA. NR 13 TC 25 Z9 25 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-9002 J9 NUCL INSTRUM METH A JI Nucl. Instrum. Methods Phys. Res. Sect. A-Accel. Spectrom. Dect. Assoc. Equip. PD JAN 1 PY 2002 VL 476 IS 1-2 BP 80 EP 84 AR PII S0168-9002(01)01400-0 DI 10.1016/S0168-9002(01)01400-0 PG 5 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Nuclear; Physics, Particles & Fields SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA 522FT UT WOS:000173885900014 ER PT J AU Yan, X Titt, U Koehler, AM Newhauser, WD AF Yan, X Titt, U Koehler, AM Newhauser, WD TI Measurement of neutron dose equivalent to proton therapy patients outside of the proton radiation field SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT LA English DT Article; Proceedings Paper CT International Workshop on Neutron Field Spectrometry in Science, Technology and Radiation Protection (NEUSPEC 2000) CY JUN 04-08, 2000 CL PISA, ITALY DE proton therapy; patient neutron exposures AB Measurements of neutron dose equivalent values and neutron spectral fluences close to but outside of the therapeutic proton radiation field are presented. The neutron spectral fluences were determined at five locations with Bonner sphere measurements and established by unfolding techniques. More than 50 additional neutron dose equivalent values were measured with LiI and BF3 thermal neutron detectors surrounded by a 25 cm polyethylene moderating sphere. For a large-field treatment, typical values of neutron dose equivalent per therapeutic proton absorbed dose, H/D, at 50 cm distance from isocenter, range from 1 mSv/Gy (at 0degrees with respect to the proton beam axis) to 5 mSv/Gy (at 90degrees). Experiments reveal that H/D varies significantly with the treatment technique, e.g., patient orientation, proton beam energy, and range-modulation. The relative uncertainty in H/D values is approximately 40% (one standard deviation). (C) 2002 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Cyclotron Lab, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Yan, X (reprint author), Harvard Univ, Cyclotron Lab, 44 Oxford St, Cambridge, MA 02138 USA. NR 10 TC 109 Z9 110 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-9002 J9 NUCL INSTRUM METH A JI Nucl. Instrum. Methods Phys. Res. Sect. A-Accel. Spectrom. Dect. Assoc. Equip. PD JAN 1 PY 2002 VL 476 IS 1-2 BP 429 EP 434 AR PII S0168-9002(01)01483-8 DI 10.1016/S0168-9002(01)01483-8 PG 6 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Nuclear; Physics, Particles & Fields SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA 522FT UT WOS:000173885900077 ER PT J AU Epner, DE Morrow, S Wilcox, M Houghton, JL AF Epner, DE Morrow, S Wilcox, M Houghton, JL TI Nutrient intake and nutritional indexes in adults with metastatic cancer on a phase I clinical trial of dietary methionine restriction SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID BRAIN-TUMOR XENOGRAFTS; METABOLIC DEFECT; ATHYMIC MICE; CULTURE; CELLS; 5-FLUOROURACIL; DEPENDENCE; STARVATION; SURVIVAL; SYNERGY AB Animal studies have shown that dietary methionine restriction selectively inhibits growth of a variety of human tumor xenografts but has relatively few deleterious effects on normal tissues. The objectives of the present study were to determine whether enteral methionine restriction is safe and tolerable in adults with metastatic cancer and whether it reduces plasma methionine levels. Eight patients with a variety of metastatic solid tumors were enrolled in a phase I clinical trial. A commercially available methionine free medical food served as the primary dietary protein source for all patients. Patients were prescribed diets containing 0.6-0.8 g of protein, 25-35 kcal, and 2 mg of methionine per kilogram per day. Participants remained on the experimental diet for an average of 17.3 wk (range 8-39 wk). Plasma methionine levels fell from 21.6 +/- 7.3 to 9 +/- 4 muM within 2 wk, representing a 58% decline. Serum albumin and prealbumin levels remained stable or increased. Mean energy intake increased during participation compared with baseline, and protein intake was maintained at target levels. The only side effect was weight loss of similar to0.5% of body mass index (0.5 kg) per week. We conclude that enteral dietary methionine restriction is safe and tolerable in adults with metastatic solid tumors and results in significant reduction in plasma methionine levels. C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. Texas Womans Univ, Dept Nutr & Food Sci, Houston, TX 77030 USA. RP Epner, DE (reprint author), Baylor Coll Med, Dept Med, Houston, TX 77030 USA. NR 25 TC 29 Z9 30 U1 0 U2 5 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2002 VL 42 IS 2 BP 158 EP 166 DI 10.1207/S15327914NC422_2 PG 9 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 606VT UT WOS:000178755800002 PM 12416254 ER PT J AU DeCherney, AH Bachmann, G Isaacson, K Gall, S AF DeCherney, AH Bachmann, G Isaacson, K Gall, S TI Postoperative fatigue negatively impacts the daily lives of patients recovering from hysterectomy SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID COMMUNITY ONCOLOGY; CANCER; CHEMOTHERAPY; OUTCOMES AB OBJECTIVE: To assess, from the patient's perspective, the prevalence and impact of postoperative fatigue after hysterectomy and to increase understanding of physician-patient communications before and after surgery regarding recovery and diminished postoperative energy level. METHODS: We completed a telephone survey of 300 women aged 25-50 who had undergone a hysterectomy or myomectomy within die past 2 years. The patients were recruited randomly from two national, random samples of households: 1) women aged 25-50, and 2) women taking hormone replacement therapy in the target age range. Patients were asked a series of questions about their postoperative fatigue after surgery. RESULTS: Overall, 74% of patients experienced moderate-to-severe fatigue within the first few weeks after surgery. Fatigue occurred more frequently and persisted twice as long as pain, the next most frequent symptom, which was experienced by 63% of patients overall. Fatigue was the symptom that most interfered with daily activities (37%) and also contributed to feelings of frustration (52%), to depression (37%), and to difficulty in concentrating (42%). Patients employed at the time of surgery missed an average of 5.8 weeks of work; 69% of those surveyed required 2 or more weeks of caregiver assistance. Postoperative fatigue was discussed by 68% of patients' physicians before surgery, and 57% of patients discussed postoperative fatigue with their physicians after surgery. Oral iron therapy and dietary supplements were the most frequently recommended treatments; 52% of patients were not offered any treatments or recommendations to alleviate their fatigue. CONCLUSIONS: Fatigue is a highly prevalent posthysterectomy and myomectomy symptom and has substantial negative physical, psychosocial, and economic effects on patients during recovery. (C) 2002 by the American College of Obstetricians and Gynecologists. C1 Univ Calif Los Angeles, Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA. Univ Med & Dent New Jersey, New Brunswick, NJ USA. Univ Louisville, Louisville, KY 40292 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP DeCherney, AH (reprint author), Univ Calif Los Angeles, Sch Med, Dept Obstet & Gynecol, 27-117 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. NR 23 TC 27 Z9 34 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JAN PY 2002 VL 99 IS 1 BP 51 EP 57 DI 10.1016/S0029-7844(01)01622-2 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 507XF UT WOS:000173056000010 PM 11777510 ER PT J AU Silverman, PR Baker, J Cait, CA Boerner, K AF Silverman, PR Baker, J Cait, CA Boerner, K TI The effects of negative legacies on the adjustment of parentally bereaved children and adolescents SO OMEGA-JOURNAL OF DEATH AND DYING LA English DT Article ID WIDOWED PARENTS; DEATH AB This is a report of a qualitative analysis of a sample of bereaved families in which one parent died and in which children scored in the clinical range on the Child Behavior Check List. The purpose of this analysis was to learn more about the lives of these children. They were considered to be at risk of developing emotional and behavioral problems associated with the death. We discovered that many of these "high risk" children had a continuing bond with the deceased that was primarily negative and troubling for them in contrast to a comparison group of children not at risk from the same study. Five types of legacies, not mutually exclusive, were identified: health related, role related, personal qualities, legacy of blame, and an emotional legacy. Coping behavior on the part of the surviving parent seemed to make a difference in whether or not a legacy was experienced as negative. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Cambridge City Hosp, Cambridge, MA 02138 USA. Wilfrid Laurier Univ, Fac Social Work, Waterloo, ON N2L 3C5, Canada. Lighthouse Int, New York, NY USA. RP Silverman, PR (reprint author), 18 Ingleside Rd, Lexington, MA 02420 USA. NR 33 TC 17 Z9 17 U1 0 U2 2 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, AMITYVILLE, NY 11701 USA SN 0030-2228 J9 OMEGA-J DEATH DYING JI Omega-J. Death Dying PY 2002 VL 46 IS 4 BP 335 EP 352 PG 18 WC Psychology, Multidisciplinary; Social Sciences, Biomedical SC Psychology; Biomedical Social Sciences GA 731BZ UT WOS:000185865800005 ER PT J AU Lynch, TJ AF Lynch, TJ TI Schwartz center rounds: volume 1 - Introduction SO ONCOLOGIST LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lynch, TJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 1 U2 1 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2002 VL 7 SU 2 BP 3 EP 4 DI 10.1634/theoncologist.7-suppl_2-3 PG 2 WC Oncology SC Oncology GA 567AW UT WOS:000176461300002 ER PT J AU Chabner, BA AF Chabner, BA TI Cytotoxic agents in the era of molecular targets and genomics SO ONCOLOGIST LA English DT Article; Proceedings Paper CT 2nd Symposium of Novel Molecular Targets for Cancer Therapy CY OCT 04-05, 2001 CL BUENOS AIRES, ARGENTINA SP Natl Inst Hlth, Natl Inst Dent & Craniofacial Res, Natl Inst Hlth, Natl Canc Inst, Int Soc Translat Res DE pharmacogenomics; pharmacogenetics; polymorphism; molecular targeting ID PROTEASOME INHIBITOR PS-341; GROWTH-FACTOR RECEPTOR; THIOPURINE METHYLTRANSFERASE ACTIVITY; DEHYDROGENASE DPD DEFICIENCY; NUCLEOTIDE-EXCISION-REPAIR; TYROSINE KINASE INHIBITOR; HUMAN TUMOR XENOGRAFTS; FACTOR-KAPPA-B; DIHYDROPYRIMIDINE DEHYDROGENASE; ANTITUMOR-ACTIVITY AB Cancer treatment is evolving due to the development of molecularly targeted agents and the utilization of pharmacogenomics and pharmacogenetics to identify patients who are at an increased risk for toxicity or may be uniquely responsive to cytotoxic therapies. By identifying polymorphisms in the human genome that confer changes in the ability to metabolize or activate cancer agents, a more patient-specific treatment approach can be initiated. Molecularly targeted therapies such as PS-341, flavopiridol, Iressa, and anti-vascular endothelial growth factor antibodies may help to overcome resistance to cytotoxic therapies by lowering the apoptotic threshold and increasing cytotoxicity. Using molecularly targeted agents in combination with traditional cytotoxic agents may increase the percentage of patients who achieve disease stabilization and prolonged survival. With the development of genetic tools and genotyping of tumor and patient prior to initiating treatment, antitumor efficacy may be increased with a substantial reduction in toxicity. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chabner, BA (reprint author), Hematol Oncol Associates, 100 Blossom St,Cox 640, Boston, MA 02114 USA. NR 58 TC 14 Z9 15 U1 0 U2 1 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2002 VL 7 SU 3 BP 34 EP 41 PG 8 WC Oncology SC Oncology GA 586MJ UT WOS:000177587500005 PM 12165653 ER PT J AU Mullen, JT Tanabe, KK AF Mullen, JT Tanabe, KK TI Viral oncolysis SO ONCOLOGIST LA English DT Article DE oncolysis; replication-conditional viruses; gene therapy; clinical trials ID HERPES-SIMPLEX VIRUS; REPLICATION-SELECTIVE ADENOVIRUS; PROSTATE-CANCER CELLS; HUMAN TUMOR-CELLS; PHASE-II TRIAL; GENE-THERAPY; P53 STATUS; MALIGNANT-MELANOMA; LIVER METASTASES; IN-VIVO AB The concept of using replicating viruses as anticancer agents is not a new one, but the ability to genetically modify these viruses into increasingly potent and tumor-specific vectors is a recent phenomenon. As more is learned about the functions of viral gene products in controlling the mammalian cell cycle and in disabling cellular defense mechanisms, specific viral functions can be augmented or eliminated to enhance antineoplastic efficacy. In this article, general mechanisms by which oncolytic viruses achieve their antitumor efficacy and specificity are reviewed. The paradoxical roles of the immune response are addressed with respect to oncolytic viral therapy, as it, on one hand, impedes the spread of viral infection, and on the other, augments tumor cell destruction through the recruitment of T cells "vaccinated" against tumor antigens. The most commonly used oncolytic viruses are each reviewed in turn, including adenoviruses, herpes simplex viruses, vaccinia viruses, reoviruses, and Newcastle disease viruses. Special attention is focused on the unique biology of each of these viruses as well as the status of several of these mutants in clinical trials. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Canc Ctr, Boston, MA 02114 USA. RP Tanabe, KK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Cox 626,100 Blossom St, Boston, MA 02114 USA. NR 90 TC 67 Z9 73 U1 1 U2 6 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2002 VL 7 IS 2 BP 106 EP 119 DI 10.1634/theoncologist.7-2-106 PG 14 WC Oncology SC Oncology GA 545JG UT WOS:000175213300006 PM 11961194 ER PT J AU Glaspy, J Degos, L Dicato, M Demetri, GD AF Glaspy, J Degos, L Dicato, M Demetri, GD TI Comparable efficacy of epoetin alfa for anemic cancer patients receiving platinum- and nonplatinum-based chemotherapy: A retrospective subanalysis of two large, community-based trials SO ONCOLOGIST LA English DT Article DE hemoglobin; anemia; quality of life; epoetin alfa ID QUALITY-OF-LIFE; RECOMBINANT-HUMAN-ERYTHROPOIETIN; DOUBLE-BLIND; FATIGUE; ALPHA; OUTCOMES; ONCOLOGY; THERAPY; SCALE AB Background. Data from two large, community-based clinical trials that evaluated the efficacy of epoetin alfa in anemic cancer patients receiving chemotherapy were retrospectively analyzed to determine if clinical outcomes were different depending on whether chemotherapy was platinum- or nonplatinum-based. Patients and Methods. Patients received epoetin alfa 150-300 IU/kg (Glaspy: Study 1; n = 2,342) or 10,00020,000 IU (Demetri: Study 2; n = 2,370) s.c. three times each week for 4 months. Efficacy end points were changes in transfusion requirements, hemoglobin (Hb) levels, and quality of life (QOL). A total of 4,298 out of 4,712 patients (platinum-based, n = 1,601; nonplatinum-based, n = 2,697), who both received chemotherapy and had available data, were eligible for this retrospective analysis. Results. Baseline characteristics across groups were comparable with few exceptions, which were anticipated in view of the characteristics of the two different chemotherapy types. Decreases in transfusion requirements after 2, 3, and 4 months were significant, regardless of chemotherapy type. Mean increases in Hb level from baseline to final evaluation ranged from 1.6 g/dl to 2.0 g/dl across study groups and were significant, regardless of chemotherapy type. QOL, as measured by the Linear Analog Scale Assessment (LASA), improved significantly by 20%-43%, regardless of chemotherapy type, and improvements were associated with increases in Hb. Epoetin alfa was well tolerated in both studies, regardless of chemotherapy type. Conclusion. Treatment of anemic cancer patients with epoetin alfa results in significant reduction in transfusion requirements, increase in Hb levels, and improvements in QOL, regardless of whether the chemotherapy is platinum- or nonplatinum-based. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Paris, Hop St Louis, F-75252 Paris, France. Luxembourg Med Ctr, Luxembourg, Luxembourg. Harvard Univ, Sch Med, Boston, MA USA. RP Demetri, GD (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 21 TC 19 Z9 23 U1 0 U2 0 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2002 VL 7 IS 2 BP 126 EP 135 DI 10.1634/theoncologist.7-2-126 PG 10 WC Oncology SC Oncology GA 545JG UT WOS:000175213300008 PM 11961196 ER PT J AU Chon, BH Loeffler, JS AF Chon, BH Loeffler, JS TI The effect of nonmalignant systemic disease on tolerance to radiation therapy SO ONCOLOGIST LA English DT Article DE collagen vascular disease; hypertension; diabetes; inflammatory bowel disease; radiation therapy ID GROWTH-FACTOR-BETA; INFLAMMATORY-BOWEL-DISEASE; COLLAGEN VASCULAR-DISEASE; TOTAL LYMPHOID IRRADIATION; GENE-EXPRESSION; NASOPHARYNGEAL CARCINOMA; RHEUMATOID-ARTHRITIS; TGF-BETA; FIBROSIS; RADIOTHERAPY AB Purpose. Some patients with nonmalignant systemic diseases, like collagen vascular disease (CVD), hypertension, diabetes mellitus, and inflammatory bowel disease (IBD), tolerate radiation therapy poorly. Although the mechanisms of each of these disease processes are different, they share a common microvessel pathology that is potentially exacerbated by radiotherapy. This article reviews and evaluates available data examining the effects of these benign disease processes on radiation tolerance. Methods. We conducted a thorough review of the Anglo-American medical literature from 1960 to 2001 on the effects of radiotherapy on CVD, hypertension, diabetes mellitus, and IBD. Results. Fifteen studies were identified that examined the effects of radiation therapy for cancer in patients with CVDs. Thirteen of 15 studies documented greater occurrences of acute and late toxicities (range 7%-100%). higher rates of complications were noted especially for non-rheumatoid arthritis CVDs. Nine studies evaluated the effects of hypertension and diabetes on radiation tolerance. All nine studies documented higher rates of late toxicities than in a "control" group (range 34%-100%). When patients had both diabetes and hypertension, the risk of late toxicities was even higher. Six studies examined radiation tolerance of patients with IBD irradiated to the abdomen and pelvis. Five of these six studies showed greater occurrences of acute and late toxicities for patients with IBD, even with precautionary measures like reduced fraction size and volume and patient immobilization (13%-29%). Conclusion. The majority of published studies documented lower radiation tolerance for patients who have CVD, diabetes mellitus, hypertension, and IBD. This may reflect a publication bias, as the majority of these studies are retrospective with small numbers of patients and use different scoring scales for complications. These factors may contribute to an overestimation of true radiation-induced morbidity. Although the paucity of data makes precise estimates difficult, a subset of patients, in particular, those with active CVD, IBD, or a combination of uncontrolled hypertension with type I diabetes, is likely to be at higher risk. Future prospective trials need to document these disease entities when reporting treatment-related complications and also must monitor toxicities associated with quiescent versus active IBD and CVD, type I versus type 11 diabetes, and levels of hypertension (controlled versus uncontrolled) matched for radiation-specific treatment sites, field size, fractionation, and total dose. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Loeffler, JS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. NR 39 TC 54 Z9 54 U1 0 U2 3 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2002 VL 7 IS 2 BP 136 EP 143 DI 10.1634/theoncologist.7-2-136 PG 8 WC Oncology SC Oncology GA 545JG UT WOS:000175213300009 PM 11961197 ER PT J AU Penson, RT Rauch, PK McAfee, SL Cashavelly, BJ Clair-Hayes, K Dahlin, C Green, KM Chabner, BA Lynch, TJ AF Penson, RT Rauch, PK McAfee, SL Cashavelly, BJ Clair-Hayes, K Dahlin, C Green, KM Chabner, BA Lynch, TJ TI Between parent and child: Negotiating cancer treatment in adolescents SO ONCOLOGIST LA English DT Article DE leukemia; hospice; cancer; psychosocial; communication ID PERSONAL GROWTH; LEUKEMIA AB Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital, founded the Kenneth B. Schwartz Center. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and sustenance to the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Cancer in adolescents presents an extra dynamic of psychosocial complexity. The case of a 19-year-old woman with acute myelocytic leukemia is discussed. Her disease was refractory to allogeneic transplantation, and she died with severe graft-versus-host disease. Ms. P and her mother established very different relationships with the team which supported them through the transitions in her care, and Ms. P was able to die at home, with hospice care. The personal connection with the team enabled a degree of positive adjustment through the nightmare of loss. The epidemiology of cancer in adolescents and paradigms of care are reviewed. Psychosocial aspects of adolescence, opportunities for personal growth and support, and the challenge of end-of-life care are discussed. C1 Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Penson, RT (reprint author), Cox 548,100 Blossom St, Boston, MA 02114 USA. NR 17 TC 5 Z9 5 U1 1 U2 7 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2002 VL 7 IS 2 BP 154 EP 162 DI 10.1634/theoncologist.7-2-154 PG 9 WC Oncology SC Oncology GA 545JG UT WOS:000175213300011 PM 11961199 ER PT J AU Penson, RT Green, KM Chabner, BA Lynch, TJ AF Penson, RT Green, KM Chabner, BA Lynch, TJ TI When does the responsibility of our care end: Bereavement SO ONCOLOGIST LA English DT Article DE psychosocial; oncology; hospice; abandonment; support ID OF-LIFE CARE; CANCER; DEATH; GRIEF; SURVIVAL; CRITERIA; HOSPICE; FAMILY; TIME AB Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital, founded the Kenneth B. Schwartz Center. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and sustenance to the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Two vignettes are presented of a caregiver's response to the death of a patient, contrasting the extremes of involved compassion for the family and fractured relationships. Grief for loss is an inevitable part of life and a common part of cancer care. Support of the bereaved may be one of the hardest tasks for cancer care professionals, who are confronted with the limits of modern medicine. There is a responsibility to provide grieving families with support and care; care that goes beyond the death. A compassionate response helps both those who suffer and those who care. Complicated and uncomplicated bereavement, grief reactions, resources for bereavement counseling, and the role of condolence letters are reviewed. C1 Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Penson, RT (reprint author), Cox 548,100 Blossom St, Boston, MA 02114 USA. NR 47 TC 18 Z9 18 U1 2 U2 8 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2002 VL 7 IS 3 BP 251 EP 258 PG 8 WC Oncology SC Oncology GA 563BR UT WOS:000176234200016 PM 12065799 ER PT J AU Knuti, KA Amrein, PC Chabner, BA Lynch, TJ Penson, RT AF Knuti, KA Amrein, PC Chabner, BA Lynch, TJ Penson, RT TI Faith identity, and leukemia: When blood products are not an option SO ONCOLOGIST LA English DT Article DE Jehovah's witness; autonomy; beliefs; responsibilites ID JEHOVAH-WITNESS AB Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital, founded the Kenneth B. Schwartz Center. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and sustenance to the heating process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers and gain insight and support from fellow staff members. When a competent adult patient refuses lifesaving treatment for religious or personal reasons, caregivers have a legal obligation to respect this decision. A patient's refusal of treatment adds particular challenges to the delivery of compassionate care. The case of a 50-year-old Jehovah's Witness with acute myelocytic leukemia who declined blood product support is presented. Respecting her religious beliefs during chemotherapy required balancing risk and benefit, watching her suffer while unable to intervene with what the staff saw as simple treatment, and eventually undertaking a complicated grief process. Jehovah's Witness beliefs regarding blood products are reviewed. Caregiver roles and responsibilities are discussed in the context of psychosocial, legal, familial, and ethical issues. C1 Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Penson, RT (reprint author), Cox 548,100 Blossom St, Boston, MA 02114 USA. NR 20 TC 6 Z9 8 U1 1 U2 6 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2002 VL 7 IS 4 BP 371 EP 380 DI 10.1634/theoncologist.7-4-371 PG 10 WC Oncology SC Oncology GA 587AB UT WOS:000177617400010 PM 12185299 ER PT J AU Ryan, DP Puchalski, T Supko, JG Harmon, D Maki, R Garcia-Carbonero, R Kuhlman, C Winkelman, J Merriam, P Quigley, T Jimeno, J Manola, J Demetri, GD AF Ryan, DP Puchalski, T Supko, JG Harmon, D Maki, R Garcia-Carbonero, R Kuhlman, C Winkelman, J Merriam, P Quigley, T Jimeno, J Manola, J Demetri, GD TI A phase II and pharmacokinetic study of ecteinascidin 743 in patients with gastrointestinal stromal tumors SO ONCOLOGIST LA English DT Article DE cancer; chemotherapy; clinical trials; human studies; c-kit ID SOFT-TISSUE SARCOMAS; OF-FUNCTION MUTATION; CARIBBEAN TUNICATE; KIT MUTATION; IFOSFAMIDE; COMPOUND; LEIOMYOSARCOMAS; DOXORUBICIN; ADRIAMYCIN; RESISTANCE AB Purpose. To assess the efficacy, tolerability, and pharmacokinetics of ecteinascidin 743 (ET-743) in patients with advanced gastrointestinal stromal tumors (GISTs). Patients and Methods. The study was confined to adult patients with radiographically measurable GISTs. ET-743 was administered as a 24-hour continuous i.v. infusion at a dose of 1.5 mg/m(2) repeated every 3 weeks. Pharmacokinetic blood sampling was performed during the first cycle of therapy. Tumors were restaged after every second cycle of therapy. Results. A total of 20 patients was enrolled in the study, 19 of whom were treated with 47 cycles of ET-743 (median 2, range 1-10). Severe toxicities were limited to reversible grade 3 transaminitis in 10 patients and grade 3 fatigue in one patient. There were no objective responses, and disease stabilization occurred in two patients lasting for periods of 4 and 10 months. The 1-year survival rate was 71.1%. Mean+/-standard deviation values of the maximum plasma concentration and total plasma clearance were 1.1+/-0.4 ng/ml and 44+/-16 l/h/m(2), respectively, for 19 of the 20 patients. Conclusion. This study is the first report of a prospective phase II trial to evaluate a cytotoxic agent in patients with GISTs. This study underscores the primary resistance of GISTS to chemotherapy and stands in stark contrast to the encouraging results recently achieved with STI571. The lack of response may be associated with a therapeutically ineffective exposure to the drug based upon the lower incidence of severe toxicities and greater clearance than described in phase I and II trials of ET-743. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc,Div Hematol Oncol, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Div Adult Oncol, New York, NY 10021 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Pharma Mar SA, Madrid, Spain. RP Ryan, DP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc,Div Hematol Oncol, 100 Blossom St,Cox 640, Boston, MA 02114 USA. RI IBIS, NUEVAS TERAPIA/P-3415-2015 NR 36 TC 34 Z9 36 U1 0 U2 1 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2002 VL 7 IS 6 BP 531 EP 538 DI 10.1634/theoncologist.7-6-531 PG 8 WC Oncology SC Oncology GA 628RK UT WOS:000180010200007 PM 12490740 ER PT J AU Penson, RT Benson, RC Parles, K Chabner, BA Lynch, TJ AF Penson, RT Benson, RC Parles, K Chabner, BA Lynch, TJ TI Virtual connections: Internet health care SO ONCOLOGIST LA English DT Article DE e-mail; oncology; support; psychosocial ID INFORMATION NEEDS; CANCER-PATIENTS; BREAST-CANCER; GUIDELINES; SURVIVAL AB Shortly before his death in 1995, Kenneth B. Schwartz, of the increased opportunities afforded by Internet access cancer patient at Massachusetts General Hospital while being mindful of its drawbacks and the limitations (NIGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery that provides hope to the patient, support to caregivers, and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. The 20th century success of the Internet is now translating into changes in 21st century medical practice. The changes brought about by the Internet have at once facilitated and complicated the practice of medicine. Physicians and patients are challenged to take advantage of the increased opportunities afforded by Internet access while being mindful of its drawbacks and the limitations to virtual communication. The case of Karen Parles, one of the authors, is presented. Karen developed locally advanced lung cancer and used the Internet to research her diagnosis. She found the information on lung cancer limited and confusing, and, in response, developed a website devoted to empowering lung cancer patients in their search for information and support (http://www.lungcanceronline.org). Here we discuss issues surrounding patients' use of the Internet for health information and communication with health care providers. The value of information-seeking as a coping mechanism is debated, and concerns are raised regarding confidentiality of electronic communications and the logistics of physicians adopting e-mail as a mechanism for communicating with patients. C1 Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Penson, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Cox 548,100 Blossom St, Boston, MA 02114 USA. NR 39 TC 14 Z9 14 U1 1 U2 8 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2002 VL 7 IS 6 BP 555 EP 568 DI 10.1634/theoncologist.7-6-555 PG 14 WC Oncology SC Oncology GA 628RK UT WOS:000180010200010 PM 12490743 ER PT J AU Coday, MP Warner, MA Jahrling, KV Rubin, PAD AF Coday, MP Warner, MA Jahrling, KV Rubin, PAD TI Acquired monocular vision - Functional consequences from the patient's perspective SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID ONE EYE; ENUCLEATION; PERFORMANCE; MELANOMA AB Purpose: The study is conducted to determine the effect of acquired monocular vision (enucleation, phthisis) on the daily activities of patients. Methods: Sixty-five patients in a case series completed a 30-question survey evaluating the functional consequences of monocular vision. Results: Patients with sudden visual loss adapted more slowly than those with gradual loss (8.8 versus 3.6 months). Difficulties with depth perception and cosmesis were prevalent. Unexpected consequences included neck pain, strain with reading, employment change, depression, car accidents, and alcoholism. Ninety-one percent of patients had no formal training to help them adapt. Conclusions: More than previously appreciated, there are many obstacles that patients face in making the transition to monocular vision. Few patients receive any formal instruction to help them adapt, yet many indicate that it would be beneficial. C1 Massachusetts Eye & Ear Infirm, Oculoplast & Orbital Serv, Boston, MA 02114 USA. RP Rubin, PAD (reprint author), Massachusetts Eye & Ear Infirm, Oculoplast & Orbital Serv, 243 Charles St, Boston, MA 02114 USA. NR 18 TC 11 Z9 13 U1 0 U2 3 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 JAN PY 2002 VL 18 IS 1 BP 56 EP 63 DI 10.1097/00002341-200201000-00009 PG 8 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 516KP UT WOS:000173552700009 PM 11910326 ER PT S AU Alt, C Framme, C Schnell, S Schuele, G Brinkmann, R Lin, CP AF Alt, C Framme, C Schnell, S Schuele, G Brinkmann, R Lin, CP BE Manns, F Soderberg, PG Ho, A TI In vivo and in vitro selective targeting of the retinal pigment epithelium using a laser-scanning device SO OPHTHALMIC TECHNOLOGIES XII SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT 12th Conference on Ophthalmic Technologies CY JAN 19-20, 2002 CL SAN JOSE, CA SP SPIE DE Retinal Pigment Epithelium; selective photocoagulation; melanosomes; scanning laser ID PHOTOCOAGULATION AB Background: Laser photocoagulation is a well-established treatment modality for a variety of retinal disorders, but is difficult to use near the fovea due to thermal retinal destruction. Certain diseases, such as drusen maculopathy, are thought to be caused by a dysfunction of the Retinal Pigment Epithelium. For those diseases selective targeting of the RPE, sparing the adjoining photoreceptors, might be the appropriate treatment to avoid laser scotoma, as it has been shown with application of a train of mus laser pulses by Birngruber and Roider. Material and methods: Our new approach is to use a conventional green cw laser and rapidly scan a small laser spot over the retina so as to produce mus-illumination at each RPE cell. Two scanning devices were developed using acousto-optic deflectors. Results: For the in vitro experiments the ED50 value RPE cell dam age was 170 mW with 100 exposures, scanning with a speed of 1 spot diameter/3 mus. In vivo experiments demonstrated an angiographic ED50 threshold of 66 mW for 100 exposures while scanning with an effective illumination time of 5 mus. The ophthalmoscopic threshold was higher than a factor of 2 times the angiographic ED50. Using separated scan lines we show selectivity in the form of surviving cells in between irradiated lines. Conclusion: Selective destruction of RPE cells is possible using laser-scanning devices. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Alt, C (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4350-6 J9 P SOC PHOTO-OPT INS PY 2002 VL 4611 BP 59 EP 63 DI 10.1117/12.470607 PG 5 WC Engineering, Biomedical; Ophthalmology; Optics; Physics, Applied SC Engineering; Ophthalmology; Optics; Physics GA BU92M UT WOS:000177417400008 ER PT J AU Miserocchi, E Baltatzis, S Roque, MR Ahmed, AR Foster, CS AF Miserocchi, E Baltatzis, S Roque, MR Ahmed, AR Foster, CS TI The effect of treatment and its related side effects in patients with severe ocular cicatricial pemphigoid SO OPHTHALMOLOGY LA English DT Article ID IMMUNOSUPPRESSIVE THERAPY; RHEUMATOID-ARTHRITIS; SYSTEMIC CHEMOTHERAPY; DISEASE; MANAGEMENT; DRUGS; MANIFESTATIONS; DERMATOLOGY; VULGARIS; SULFONES AB Purpose: To determine the clinical outcome of patients with ocular-cicatricial pemphigoid (OCP) and the influence of systemic treatment on clinical progression. Design: Noncomparative interventional case series. Participants: Sixty-one patients with biopsy-proven OCP. Methods: Patients with documented disease progression treated with chemotherapy and/or corticosteroids were followed between 1985 and 2000. The parameters evaluated were ocular stage at presentation, visual acuity, ocular complications, disease progression, control of ocular inflammation, and presence of extraocular involvement. Systemic treatment and related side effects were analyzed. Main Outcome Measures: Visual acuity, ocular complications, extraocular involvement, disease progression, clinical outcome, systemic treatment, and related side effects. Results: Sixty-one patients (32 female; 29 male) with a mean age of 67 years were studied. Extraocular involvement was present in 50% of patients. Sixty percent of eyes were initially seen with stage III (advanced cicatrizing) disease at first evaluation. Seven percent of involved eyes at first visit and 21% at the end of follow-up were legally blind. The most common ocular complications encountered were dry eye, corneal abnormalities, and glaucoma. Dapsone was the most commonly used drug (51 patients), followed by methotrexate (24 patients), azathioprine (23 patients), and cyclophosphamide (15 patients); prednisone, always given as adjunctive treatment, was used in 17 patients. Control of ocular inflammation (total or partial) was achieved in 90% of patients, but 46% of them needed continuation of systemic treatment to avoid disease recurrences, and 10% progressed despite different drugs used. Two agents were required in 32% of cases to control disease activity. The most common treatment-related side effects were hematologic complications (n = 34) followed by gastrointestinal (n = 17), cardiovascular (n 15), and urinary complications (n = 11). Dapsone was responsible for the greatest number of side effects (n 43); methotrexate caused the least trouble (n = 6). Corticosteroid-related complications (n = 34) were mostly cardiovascular and endocrinologic. Conclusions: Ocular-cicatricial pemphigoid is an autoimmune disease that, untreated, progresses to conjunctival scarring and blindness; systemic immunosuppression is required to control it. Long-term systemic treatment and more than one drug are frequently necessary to avoid recurrences, exposing elderly patients to a higher risk of drug toxicity. The most frequently encountered treatment-related side effects were anemia, leukopenia, liver toxicity, and hypertension. Ophthalmology 2002;109:111-118 (C) 2002 by the American Academy of Ophthalmology. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Immunol & Uveitis Serv, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Boston, MA 02115 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. NR 36 TC 52 Z9 55 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JAN PY 2002 VL 109 IS 1 BP 111 EP 118 DI 10.1016/S0161-6420(01)00863-6 PG 8 WC Ophthalmology SC Ophthalmology GA 507XK UT WOS:000173056400031 PM 11772589 ER PT J AU Miserocchi, E Baltatzis, S Ekong, A Roque, M Foster, CS AF Miserocchi, E Baltatzis, S Ekong, A Roque, M Foster, CS TI Efficacy and safety of chlorambucil in intractable noninfectious uveitis - The Massachusetts eye and ear infirmary experience SO OPHTHALMOLOGY LA English DT Article ID JUVENILE CHRONIC ARTHRITIS; NEPHROTIC SYNDROME; BEHCETS-DISEASE; SYMPATHETIC OPHTHALMIA; RHEUMATOID-ARTHRITIS; FOLLOW-UP; THERAPY; CYCLOPHOSPHAMIDE; CHEMOTHERAPY; REAPPRAISAL AB Purpose: To report our experience with the use of chlorambucil for otherwise treatment-resistant uveitis and to assess its safety and efficacy. Design: Noncomparative interventional case series. Participants; Twenty-eight patients with intractable noninfectious uveitis. Methods: We reviewed the records of 28 patients (56 eyes) with chronic noninfectious uveitis who were treated with chlorambucil from 1987 to 2000. Diagnoses included Adamantiades-Behcet's disease (ABD) (7 patients), juvenile rheumatoid arthritis (JRA)-associated uveitis (10 patients), pars planitis (2 patients), sympathetic ophthalmia (1 patient), idiopathic uveitis (6 patients), Crohn's disease (1 patient), and HLA-B27-associated uveitis (1 patient). All patients were refractory to other immunomodulatory therapy and systemic steroids. The median duration of treatment with chlorambucil was 12 months (range, 4-50 months), whereas the median daily dosage was 8 mg (range, 4-22 mg). Patients were followed for a median follow-up period of 46 months (range, 4-166 months) after chlorambucil treatment was begun and continued to be followed for relapse after cessation of therapy. Main Outcome Measures: Visual outcome, response to treatment, treatment-related side effects, drug dosage, previous and final treatment, discontinuation of systemic corticosteroids. Results. Chlorambucil was discontinued in seven patients because of side effects: two females had temporary amenorrhea develop, two patients had unacceptable gastrointestinal intolerance, one patient had infection, and 2 patients had progressive leukopenia. Nineteen patients (68%) showed positive clinical response to the treatment, four (14%) initially responded then relapsed after discontinuation of the drug, three patients with ABD had improvement of ocular disease but worsening of systemic symptoms, and two had persistent inflammation. Visual acuity was improved in 24 eyes (43%), stable in 22 (39%), and worsened in 10 eyes (18%). Systemic prednisone was successfully discontinued in 19 of the 28 patients (68%), and 14 patients were free of inflammation at the end of follow-up without any systemic medication. Conclusions: Chlorambucil can be a safe and effective alternative for preserving vision in patients with otherwise treatment resistant uveitis. (C) 2002 by the American Academy of Ophthalmology. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Ocular Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. NR 33 TC 28 Z9 33 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JAN PY 2002 VL 109 IS 1 BP 137 EP 142 DI 10.1016/S0161-6420(01)00864-8 PG 6 WC Ophthalmology SC Ophthalmology GA 507XK UT WOS:000173056400035 PM 11772593 ER PT J AU Haimovici, R D'Amico, DJ Gragoudas, ES Sokol, S AF Haimovici, R D'Amico, DJ Gragoudas, ES Sokol, S CA Deferoxamine Retinopathy Study Grp TI The expanded clinical spectrum of deferoxamine retinopathy SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Meeting of the Retina-Society CY SEP 26-27, 1998 CL WASHINGTON, D.C. SP Retina Soc ID IRON-CHELATION THERAPY; OCULAR TOXICITY; LONG-TERM; HEMODIALYZED PATIENTS; THALASSEMIA MAJOR; AUDITORY TOXICITY; ALBINO-RAT; DESFERRIOXAMINE; DEFERIPRONE; ALUMINUM AB Objective: To describe early and unusual features in 16 patients with deferoxamine-induced retinal toxicity and to assess the role of diagnostic tests in the diagnosis and management of patients with the disorder. Design: Retrospective, observational case series. Participants: Sixteen patients with deferoxamine retinopathy identified from members of the Vitreous, Retina, and Macula societies of the United States. Intervention/Testing: The patients underwent complete ophthalmologic examination. Most patients were also evaluated by fluorescein angiography and electrophysiologic testing. The diagnosis was based on the medical history, systemic and ocular findings, and the results of electrophysiologic tests. Main Outcome Measures: Ocular symptoms, ophthalmoscopic, fluoroangiographic, and electrophysiologic findings. Results: We confirmed previously reported findings in patients with established disease, including macular and/or peripheral pigmentary changes, reduced electroretinographic (ERG) amplitudes, and reduced electrooculographic (EOG) light-peak to dark-trough ratios. Peripapillary, papillomacular, and paramacular patterns of retinal pigment epithelial (RPE) degeneration were each observed in one patient. Diffuse RPE or outer retinal fluorescence by fluorescein angiography was a marker for active retinopathy both at the onset of disease and during recurrence and preceded the development of RPE pigment mottling. Conclusions: Unusual patterns of deferoxamine retinopathy may occur in addition to the foveomacular and/or peripheral patterns previously described. Fluorescein angiography is particularly useful for determining whether there is ongoing retinal/RPE injury. ERG and EOG testing may indicate earlier or more widespread injury than is suggested by funclus examination alone. Patients who do not discontinue deferoxamine after the development of retinopathy risk further retinal/RPE injury and visual deterioration. (C) 2002 by the American Academy of Ophthalmology. C1 Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, Boston, MA 02115 USA. Tufts Univ, Sch Med, New England Eye Ctr, Dept Ophthalmol, Boston, MA 02111 USA. RP Haimovici, R (reprint author), Boston Univ, Sch Med, Dept Ophthalmol, DOB-10 720 Harrison Ave, Boston, MA 02118 USA. NR 35 TC 39 Z9 40 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JAN PY 2002 VL 109 IS 1 BP 164 EP 171 DI 10.1016/S0161-6420(01)00947-2 PG 8 WC Ophthalmology SC Ophthalmology GA 507XK UT WOS:000173056400041 PM 11772599 ER PT S AU Hamblin, MR O'Donnell, DA Zahra, T Contag, CH McManus, A Hasan, T AF Hamblin, MR O'Donnell, DA Zahra, T Contag, CH McManus, A Hasan, T BE Dougherty, TJ TI Targeted photodynamic therapy for infected wounds in mice. SO OPTICAL METHODS FOR TUMOR TREATMENT AND DETECTION: MECHANISMS AND TECHNIQUES IN PHOTODYNAMIC THERAPY XI SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Optical Methods for Tumor Treatment and Detection - Mechanisms and Techniques in Photodynamic Therapy XI CY JAN 19-20, 2002 CL SAN JOSE, CA SP SPIE DE wound infection; bioluminescence imaging; Escherichia coli; Pseudomonas aeruginosa; chlorin(e6); polylysine; photosensitizer ID PSEUDOMONAS-AERUGINOSA OUTBREAK; GRAM-NEGATIVE BACTERIA; ESCHERICHIA-COLI; EFFICIENT PHOTOSENSITIZERS; STAPHYLOCOCCUS-AUREUS; RESISTANT STRAINS; PATHOGENS; MODEL; UNIT; ANTIMICROBIALS AB Although many workers have used photodynamic therapy to kill bacteria in vitro, the use of this approach has seldom been reported in vivo in animal models of infection. We report on the use of a targeted polycationic photosensitizer conjugate between poly-L-lysine and chlorin(e6) that can penetrate the Gram (-) outer membrane together with red laser light to kill Escherichia coli and Pseudomonas aeruginosa infecting excisional wounds in mice. We used genetically engineered luminescent bacteria that allowed the infection to be imaged in mouse wounds using a sensitive CCD camera. Wounds were infected with 5x10(6) bacteria, followed by application of the conjugate in solution and illumination. There was a light-dose dependent loss of luminescence as measured by image analysis in the wound treated with conjugate and light, not seen in control wounds. This strain of E coli is non-invasive and the infection in untreated wounds spontaneously resolved in a few days and all wounds healed equally well showing the photodynamic treatment did not damage the host tissue. P aeruginosa is highly invasive and mice with untreated or control wounds all died while 90% of PDT treated mice survived. PDT may have a role to play in the rapid treatment of infected wounds in view of the worldwide rise in antibiotic resistance. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, 55 Fruit St, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 NR 43 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4351-4 J9 P SOC PHOTO-OPT INS PY 2002 VL 4612 BP 48 EP 58 DI 10.1117/12.469354 PG 11 WC Oncology; Engineering, Biomedical; Optics SC Oncology; Engineering; Optics GA BU92N UT WOS:000177417600006 ER PT J AU Leuchter, I Becker, M Mickel, R Dulguerov, P AF Leuchter, I Becker, M Mickel, R Dulguerov, P TI Horner's syndrome and thyroid neoplasms SO ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES LA English DT Article DE thyroid; cancer; tumor; Horner's syndrome; sympathetic nerve system; neck ID CARCINOMA; GOITER AB Although thyroid goiter is a common condition, it rarely results in Horner's syndrome. We report a case of a patient with an intrathoracic multinodular goiter complicated by Horner's syndrome. Benign thyroid disease was confirmed pathologically, and the patient's symptoms improved after surgery. In the literature, the major cause of Horner's syndrome is neoplasia, with malignant lesions being twice as frequent as benign tumors. An extensive review of the literature demonstrates a different repartition for thyroid neoplasia: including our case, 38 cases of Horner's syndrome secondary to a benign thyroid tumor are described, against only 8 cases caused by a thyroid carcinoma. We conclude that contrary to the commonly held opinion, Horner's syndrome is more often due to benign thyroid diseases than to thyroid malignancies. Copyright (C) 2002 S, Karger AG, Basel. C1 Univ Hosp Geneva, Dept Otolaryngol Head & Neck Surg, CH-1205 Geneva, Switzerland. Univ Hosp Geneva, Div Diagnost Radiol, CH-1205 Geneva, Switzerland. Univ Calif Los Angeles, Div Head & Neck Surg, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Dulguerov, P (reprint author), Univ Hosp Geneva, Dept Otolaryngol Head & Neck Surg, 24,Rue Micheli Crest, CH-1205 Geneva, Switzerland. RI Dulguerov, Pavel/I-7325-2015 OI Dulguerov, Pavel/0000-0001-5863-3933 NR 19 TC 16 Z9 17 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-1569 J9 ORL J OTO-RHINO-LARY JI ORL-J. Oto-Rhino-Laryngol. Relat. Spec. PD JAN-FEB PY 2002 VL 64 IS 1 BP 49 EP 52 DI 10.1159/000049270 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 527KD UT WOS:000174184500012 PM 11891400 ER PT J AU Jupiter, J Ring, D AF Jupiter, J Ring, D TI Operative treatment in the management of fractures of the distal radius in active older aged patients SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PY 2002 VL 13 SU 2 MA 31 BP S12 EP S13 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 564JU UT WOS:000176311900031 ER PT J AU Ring, D Kloen, P Kadzielski, J Helfet, D Jupiter, J AF Ring, D Kloen, P Kadzielski, J Helfet, D Jupiter, J TI Locking compression plates for delayed unions and nonunions of the diaphyseal humerus SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PY 2002 VL 13 SU 2 MA 24 BP S10 EP S10 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 564JU UT WOS:000176311900024 ER PT J AU Ring, D Kloen, P Tavakolian, J Helfet, D Jupiter, J AF Ring, D Kloen, P Tavakolian, J Helfet, D Jupiter, J TI Loss of alignment after operative treatment of posterior Monteggia fractures: Salvage with dorsal contoured plating SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PY 2002 VL 13 SU 2 MA 29 BP S12 EP S12 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 564JU UT WOS:000176311900029 ER PT J AU Jensen, MP Ehde, DM Hoffman, AJ Patterson, DR Czerniecki, JM Robinson, LR AF Jensen, MP Ehde, DM Hoffman, AJ Patterson, DR Czerniecki, JM Robinson, LR TI Cognitions, coping and social environment predict adjustment to phantom limb pain SO PAIN LA English DT Article DE beliefs; appraisals; coping; phantom limb pain ID SPOUSE BEHAVIORAL INTERACTIONS; STUMP PAIN; DEPRESSION; SUPPORT; STRATEGIES; AMPUTATION; INVENTORY; BELIEFS; ATTITUDES; AMPUTEES AB Biopsychosocial models of chronic pain hypothesize a role for psychological and environmental factors in adjustment to chronic pain. To test the utility of such models for understanding phantom limb pain, 61 persons with recent amputations were administered measures of average phantom limb pain intensity. pain interference, depression, pain coping use, pain cognitions and appraisals, and social environmental variables I month post-amputation. and the measures of pain intensity. pain interference, and depression again 5 months later. Multiple regression analyses showed that the psychosocial predictors made a statistically significant contribution to the concurrent prediction of average phantom limb pain, pain interference, and depression at the initial assessment. and a significant contribution to the prediction of subsequent change in pain interference and depression over the course of 5 months. The results support the utility of studying phantom limb pain from a biopsychosocial perspective, and identify specific biopsychosocial factors (e.g., catastrophizing cognitions, social support, solicitous responses from family members, and resting as a coping response) that may play an important role in adjustment to phantom limb pain. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved. C1 Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Washington, Med Ctr Roosevelt, Ctr Multidisciplinary Pain, Seattle, WA 98105 USA. VA Puget Hlth Care Syst, Seattle, WA 98108 USA. VA Ctr Amputat Prosthet & Limb Loss Prevent, Seattle, WA 98108 USA. RP Jensen, MP (reprint author), Univ Washington, Sch Med, Dept Rehabil Med, Box 356490, Seattle, WA 98195 USA. RI Robinson , Lawrence/D-8455-2013 FU NICHD NIH HHS [P01 HD/NS 33988] NR 52 TC 119 Z9 121 U1 4 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JAN PY 2002 VL 95 IS 1-2 BP 133 EP 142 DI 10.1016/S0304-3959(01)00390-6 PG 10 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 520GK UT WOS:000173772500016 PM 11790476 ER PT J AU Tamis-LeMonda, CS Wang, SY Koutsouvanou, E Albright, M AF Tamis-LeMonda, Catherine S. Wang, Shuyuan Koutsouvanou, Eugenia Albright, Martina TI Childrearing Values in Greece, Taiwan, and the United States SO PARENTING-SCIENCE AND PRACTICE LA English DT Article AB Objective. The purpose of this investigation was to compare childrearing values in mothers of preschoolers from Greece, Taiwan and the United States. Design. Seventy-two middle-class mothers of 3- to 4-year-old children (24 per country) were interviewed about the values they wish to instill in their children using open-ended probes and an ordering task of values. Four broad categories of values were identified based on a modification of Harwood, Miller, and Irizarry's (1995) taxonomy: (1) Decency, referring to values emphasizing character, (2) Proper Demeanor, referring to values emphasizing appropriate relatedness and behaviors, (3) Self-maximization, referring to values emphasizing the development of self potential and individuality, and (4) Sociability/lovingness, referring to values emphasizing affective and social dimensions of relatedness. Results. Mothers from the three countries emphasized similar values in both tasks. However, cultural differences in value categories were evident, echoing the unique cultural frameworks of the three societies. Conclusions. Cultural ideologies are reflected in the values parents seek to instill in their young children, and different methodological approaches highlight cultural similarities and differences. C1 [Tamis-LeMonda, Catherine S.] NYU, Dept Appl Psychol, New York, NY 10003 USA. [Wang, Shuyuan] Chaoyang Univ Technol, Taichung, Taiwan. [Koutsouvanou, Eugenia] Univ Athens, GR-10679 Athens, Greece. [Albright, Martina] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Tamis-LeMonda, CS (reprint author), NYU, Dept Appl Psychol, 239 Greene St,5th Floor, New York, NY 10003 USA. EM Catherine.tamis-lemonda@nyu.edu NR 66 TC 20 Z9 20 U1 1 U2 1 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 1529-5192 J9 PARENT-SCI PRACT JI Parent.-Sci. Pract. PY 2002 VL 2 IS 3 BP 185 EP 208 AR PII 785828745 DI 10.1207/S15327922PAR0203_01 PG 24 WC Family Studies; Psychology, Developmental SC Family Studies; Psychology GA V12OE UT WOS:000207607700001 ER PT S AU Standaert, DG AF Standaert, DG BE Ronken, E VanScharrenburg, GJM TI Neurochernical changes in Parkinson's disease SO PARKINSON'S DISEASE SE SOLVAY PHARMACEUTICALS CONFERENCES LA English DT Proceedings Paper CT 1st Solvay Pharmaceuticals Conference CY OCT 25-27, 2000 CL COMO, ITALY SP Solvay Pharmaceut DE neuroanatomy; basal ganglia; glutamate; NMDA ID D-ASPARTATE RECEPTORS; MOTOR RESPONSE ALTERATIONS; EXCITATORY AMINO-ACIDS; PROTEIN-KINASE-A; BASAL GANGLIA; NMDA RECEPTOR; RAT STRIATUM; FUNCTIONAL-ANATOMY; GLUTAMATE ANTAGONISTS; TYROSINE PHOSPHORYLATION AB The primary neurochemical abnormality in the brain in Parkinson's disease, the deficiency of dopamine, is well established and is the basis for most current therapies for the disease. The loss of dopamine, however, induces a complex set of changes in the neurochemistry and function of the basal ganglia network, affecting glutamatergic, GABAergic, cholinergic and other types of synapses. Some of these changes can be accounted for by the existing models of basal ganglia function. These models have proven quite useful in understanding the effects of drugs and lesions on the activity of the basal ganglia, but clearly are not adequate to explain some of the most troubling symptoms of Parkinson's disease, particularly the long-term consequences of dopaminergic therapy: dyskinesias and wearing off effects. Recent work has demonstrated that the basis of these adverse effects of dopaminergic drugs may be modifications in glutamatergic neurotransmission, particularly the N-methyl-D-aspartate class of glutamate receptors. These receptors may represent an important new target for therapeutics in Parkinson's disease. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Standaert, DG (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 61 TC 3 Z9 3 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1566-7685 BN 1-58603-207-0 J9 SOLVAY PHARMACEUT PY 2002 VL 1 BP 17 EP 28 PG 12 WC Biochemistry & Molecular Biology; Clinical Neurology SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BU50Z UT WOS:000176202200002 ER PT S AU Carabello, BA AF Carabello, BA BE Borer, JS Isom, OW TI Selection of patients with aortic stenosis for operation: The asymptomatic patient and the patient with poor LV function SO PATHOPHYSIOLOGY, EVALUATION AND MANAGEMENT OF VALVULAR HEART DISEASES SE ADVANCES IN CARDIOLOGY LA English DT Article; Proceedings Paper CT Conference on Valves in the Heart of the Big Apple - Evaluation and Management of Valvular Heart Diseases CY MAY 10-12, 2001 CL NEW YORK, NEW YORK SP Howard Gilman Inst Valvular Heat Dis, Cornell Univ, Weill Med Coll, New York Cardiol Soc Amer Coll Cardiol, New York State Chapter ID LEFT-VENTRICULAR DYSFUNCTION; VALVE-REPLACEMENT; DOBUTAMINE ECHOCARDIOGRAPHY; SYMPTOMATIC PATIENTS; STRATIFICATION; PROGNOSIS; GRADIENTS; SURVIVAL C1 Houston VA Med Ctr, Houston, TX USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-2326 BN 3-8055-7402-9 J9 ADV CARDIOL JI Adv.Cardiol. PY 2002 VL 39 BP 49 EP 60 PG 12 WC Cardiac & Cardiovascular Systems; Surgery; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Surgery GA BW56X UT WOS:000182432700006 PM 12060923 ER PT S AU Palacios, IF AF Palacios, IF BE Borer, JS Isom, OW TI Percutaneous mutral balloon valvuloplasty. Does it really last as long and do as well as surgery SO PATHOPHYSIOLOGY, EVALUATION AND MANAGEMENT OF VALVULAR HEART DISEASES SE ADVANCES IN CARDIOLOGY LA English DT Article; Proceedings Paper CT Conference on Valves in the Heart of the Big Apple - Evaluation and Management of Valvular Heart Diseases CY MAY 10-12, 2001 CL NEW YORK, NEW YORK SP Howard Gilman Inst Valvular Heat Dis, Cornell Univ, Weill Med Coll, New York Cardiol Soc Amer Coll Cardiol, New York State Chapter ID TRANSVENOUS MITRAL COMMISSUROTOMY; FOLLOW-UP; SURGICAL COMMISSUROTOMY; CLOSED COMMISSUROTOMY; INOUE BALLOON; IMMEDIATE; TERM; STENOSIS; VALVOTOMY; MULTICENTER C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit,Dept Med, Boston, MA USA. NR 44 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-2326 BN 3-8055-7402-9 J9 ADV CARDIOL JI Adv.Cardiol. PY 2002 VL 39 BP 100 EP 113 PG 14 WC Cardiac & Cardiovascular Systems; Surgery; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Surgery GA BW56X UT WOS:000182432700012 PM 12060906 ER PT J AU Haidet, P Stone, DA Taylor, WC Makadon, HJ AF Haidet, P Stone, DA Taylor, WC Makadon, HJ TI When risk is low: primary care physicians' counseling about HIV prevention SO PATIENT EDUCATION AND COUNSELING LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 23-25, 1998 CL CHICAGO, ILLINOIS SP Soc Gen Internal Med DE counseling; primary health care; primary prevention; HIV; physician-patient relations; persuasive communication ID HUMAN-IMMUNODEFICIENCY-VIRUS; SEXUALLY-TRANSMITTED DISEASES; PROMOTION PROGRAMS; ORAL INTERCOURSE; HOMOSEXUAL MEN; CONDOM USE; SEX; INFECTION; SEROCONVERSION; COMMUNICATION AB To explore the conceptualization of risk by primary care physicians about behaviors associated with a relatively low risk of HIV transmission, we performed open-ended telephone interviews with 59 primary care physicians throughout the United States. During the interviews, physicians were asked to respond to a series of clinical vignettes presenting situations where the risk of HIV transmission is relatively low or unknown. We performed a qualitative content analysis of physicians' responses to these clinical vignettes. We found that relatively few information-gathering statements were made in an effort to elicit the patient's perspective regarding risk, and that risk counseling by physicians often followed an 'all or nothing' heuristic that manifested itself as the advice to take maximum precautions under situations of any perceived risk, no matter how small. In addition, HIV testing was often incompletely explained. When combined with the all or nothing heuristic, this created advice that was potentially harmful by using testing as a means to achieve zero risk and forgo protective strategies in settings where patients may potentially be in the HIV negative 'window' phase of infection. Published by Elsevier Science Ireland Ltd. C1 Houston Vet Affairs Med Ctr, Gen Med Sect, Houston, TX 77030 USA. Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. RP Haidet, P (reprint author), Houston Vet Affairs Med Ctr, Gen Med Sect, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. NR 46 TC 4 Z9 4 U1 4 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD JAN PY 2002 VL 46 IS 1 BP 21 EP 29 DI 10.1016/S0738-3991(01)00154-9 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 520BG UT WOS:000173759600003 PM 11804766 ER PT S AU MacLaughlin, DT Donahoe, PK AF MacLaughlin, DT Donahoe, PK BE Zderic, SA Canning, DA Carr, MC Snyder, HM TI Mullerian inhibiting substance: An update SO PEDIATRIC GENDER ASSIGNMENT: A CRITICAL REAPPRAISAL SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT Spring Conference on Pediatric Gender Assignment CY 1999 CL DALLAS, TX ID TRANSCRIPTION FACTOR GATA-4; NUCLEAR RECEPTOR SF-1; GRANULOSA-CELL TUMORS; II RECEPTOR; GONADAL DEVELOPMENT; SEX REVERSAL; OVARIAN-CANCER; DUCT SYNDROME; LEYDIG-CELLS; SERUM-LEVELS C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Pediat Surg Res Labs, Boston, MA 02114 USA. RP MacLaughlin, DT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Pediat Surg Res Labs, Boston, MA 02114 USA. NR 68 TC 12 Z9 13 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46759-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2002 VL 511 BP 25 EP 40 PG 16 WC Medicine, Research & Experimental; Pediatrics SC Research & Experimental Medicine; Pediatrics GA BW14D UT WOS:000180980900003 PM 12575754 ER PT J AU Sheridan, RL Schulz, JT Ryan, CM Schnitzer, JJ Lawlor, D Driscoll, DN Donelan, MB Tompkins, RG AF Sheridan, RL Schulz, JT Ryan, CM Schnitzer, JJ Lawlor, D Driscoll, DN Donelan, MB Tompkins, RG TI Long-term consequences of toxic epidermal necrolysis in children SO PEDIATRICS LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Burn-Association CY APR 18-21, 2001 CL BOSTON, MASSACHUSETTS SP Amer Burn Assoc DE Stevens-Johnson syndrome; toxic epidermal necrolysis; burns ID STEVENS-JOHNSON SYNDROME; LYELL SYNDROME; OCULAR COMPLICATIONS; INVOLVEMENT; MANAGEMENT; MANIFESTATIONS; CATHETERS; SPECTRUM; DISEASE AB Objective. Toxic epidermal necrolysis (TEN) is an acute inflammatory systemic condition that involves injury not just to the skin. Historically, it has been associated with a high mortality but few long-term consequences among survivors. With improved survival, long-term consequences may be becoming more apparent. The objective of this study was to define these longterm consequences and their frequency. Methods. From July 1, 1991, to June 30, 2000, 11 children with severe TEN were referred to a regional pediatric burn facility. Wounds were managed with a strategy involving prevention of wound desiccation and superinfection, including the frequent use of biological wound coverings. All children survived and have been followed in the burn clinic. The records of all children were reviewed in detail. Results. Two boys and 9 girls with an average age of 7.2 +/- 1.8 years (range: 6 months-15 years) and sloughed surface area of 76 +/- 6% of the body surface (range: 50%-95%) were admitted to the burn unit for care. Antibiotics (3 children), anticonvulsants (4 children), nonsteroidals (2 children), and viral syndrome or unknown agents (2 children) were believed to have triggered the syndrome. Six (55%) children required intubation for an average of 9.7 +/- 1.8 days (range: 2-14 days). Mucosal involvement occurred in 10 (91%) and ocular involvement in 10 (91%). Lengths of stay averaged 19 +/- 3 days (range: 6-40 days). Overall follow-up averaged 14 +/- 13 months. Three children had no apparent long-term consequences of the disease and were referred to primary care follow-up after the 2-month burn clinic visit. The remaining children had follow-up averaging 23 +/- 13 months. The most common long-term morbidity involved eyes (3 children [27%]), nails (4 children [36%]), and variegated skin depigmentation (all children). One child developed vaginal stenosis from mucosal inflammation. No esophageal strictures or recurrent TEN has been diagnosed. Conclusions. Survival has improved in children with TEN, but long-term sequelae are not infrequent. The most common long-term consequences involve the eyes, the skin, and the nails. C1 Shriners Burns Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Div Burns & Trauma, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. RP Sheridan, RL (reprint author), Shriners Burns Hosp, 51 Blossom St, Boston, MA 02114 USA. NR 40 TC 37 Z9 39 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2002 VL 109 IS 1 BP 74 EP 78 DI 10.1542/peds.109.1.74 PG 5 WC Pediatrics SC Pediatrics GA 507BJ UT WOS:000173006600029 PM 11773544 ER PT J AU Socransky, SS Haffajee, AD AF Socransky, SS Haffajee, AD TI Dental biofilms: difficult therapeutic targets SO PERIODONTOLOGY 2000 LA English DT Review ID ACTINOMYCETEMCOMITANS-ASSOCIATED PERIODONTITIS; PSEUDOMONAS-AERUGINOSA BIOFILMS; SUPRAGINGIVAL PLAQUE CONTROL; METRONIDAZOLE PLUS AMOXICILLIN; PAPILLON-LEFEVRE-SYNDROME; CENTRAL VENOUS CATHETERS; DNA-DNA HYBRIDIZATION; PROLINE-RICH PROTEINS; GORDONII DL1 CHALLIS; ACTINOMYCES-VISCOSUS C1 Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. RP Socransky, SS (reprint author), Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. RI de la Flor, Maria/B-9212-2015 FU NIDCR NIH HHS [DE-10977, DE-12108, DE-12861, DE-13232] NR 222 TC 318 Z9 349 U1 2 U2 36 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0906-6713 J9 PERIODONTOL 2000 JI Periodontol. 2000 PY 2002 VL 28 BP 12 EP 55 DI 10.1034/j.1600-0757.2002.280102.x PG 44 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 524VN UT WOS:000174033700002 PM 12013340 ER PT J AU Wu, CD Savitt, ED AF Wu, CD Savitt, ED TI Evaluation of the safety and efficacy of over-the-counter oral hygiene products for the reduction and control of plaque and gingivitis SO PERIODONTOLOGY 2000 LA English DT Article ID STANNOUS FLUORIDE DENTIFRICE; SUPRAGINGIVAL DENTAL PLAQUE; CETYLPYRIDINIUM CHLORIDE; PHARYNGEAL CANCER; MOUTHWASH USE; MOUTHRINSE PRODUCTS; SNF2 GELS; CHLORHEXIDINE; TOOTHPASTE; INHIBITION C1 Univ Illinois, Coll Dent, Dept Periodont, Chicago, IL 60680 USA. Forsyth Inst, Boston, MA USA. RP Wu, CD (reprint author), Univ Illinois, Coll Dent, Dept Periodont, Chicago, IL 60680 USA. NR 98 TC 50 Z9 54 U1 2 U2 5 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0906-6713 J9 PERIODONTOL 2000 JI Periodontol. 2000 PY 2002 VL 28 BP 91 EP 105 DI 10.1034/j.1600-0757.2002.280105.x PG 15 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 524VN UT WOS:000174033700005 PM 12013351 ER PT J AU Sullivan, SD Lew, DP Devine, EB Hakim, Z Reiber, GE Veenstra, DL AF Sullivan, SD Lew, DP Devine, EB Hakim, Z Reiber, GE Veenstra, DL TI Health state preference assessment in diabetic peripheral neuropathy SO PHARMACOECONOMICS LA English DT Article ID QUALITY-OF-LIFE; POPULATION; OUTCOMES; MELLITUS; ULCERS AB Objective: To assess patient preferences for health states associated with diabetic peripheral neuropathy (DPN). Design and intervention: Seven health states describing varying stages of disease severity in DPN were developed: mild neuropathy, painful neuropathy, severe neuropathy, minor ulcer, severe ulcer, minor amputation and major amputation. Using a computer interview, both rating scale (RS) and standard gamble (SG) preference scores were elicited from 52 patients with diabetes mellitus. Setting: A US university medical centre and a Veterans Affairs clinic. Study participants: Adult patients with type 1 and type 2 diabetes mellitus between the ages of 18 and 80 years. Patients were excluded if they had been diagnosed with DPN. Results: Preference scores decreased in accordance with greater symptomatic and functional impairment. Median RS scores ranged from 0.89 to 0.23 for the seven health states. Median SG scores ranged from 0.96 to 0.65. Conclusions: Patient preferences for health states decrease as a function of increasing disease severity in DPN. The result is robust across the RS and SG methods of preference measurement. These results may be useful in informing policy analyses for resource allocation in patients with diabetes mellitus. C1 Univ Washington, Dept Pharm, Pharmaceut Outcomes Res & Policy Program, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Kaiser Permanente, Drug Informat & Profess Serv, Oakland, CA USA. Roche Pharmaceut, Hlth Econ & Strateg Pricing, Nutley, NJ USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Sullivan, SD (reprint author), Univ Washington, Dept Pharm, Pharmaceut Outcomes Res & Policy Program, Box 357630, Seattle, WA 98195 USA. NR 25 TC 20 Z9 21 U1 1 U2 2 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-7690 J9 PHARMACOECONOMICS JI Pharmacoeconomics PY 2002 VL 20 IS 15 BP 1079 EP 1089 DI 10.2165/00019053-200220150-00004 PG 11 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 625MQ UT WOS:000179820600004 PM 12456202 ER PT J AU Reid, MS Ho, LB Hsu, K Fox, L Tolliver, BK Adams, JU Franco, A Berger, SP AF Reid, MS Ho, LB Hsu, K Fox, L Tolliver, BK Adams, JU Franco, A Berger, SP TI Evidence for the involvement of cyclooxygenase activity in the development of cocaine sensitization SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article ID VENTRAL TEGMENTAL AREA; PLATELET-ACTIVATING-FACTOR; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; INDUCED BEHAVIORAL SENSITIZATION; LONG-TERM POTENTIATION; ARACHIDONIC-ACID; RAT-BRAIN; NUCLEUS-ACCUMBENS; NORDIHYDROGUAIARETIC ACID; PHOSPHOLIPASE-A2 ACTIVITY AB Phospholipase A2 (PLA(2)) activation generates the release of arachidonic acid (AA) and platelet-activating factor (PAF), two compounds which may be involved in neuroplasticity. In previous studies, we found that PLA(2) activation is involved in the development of stimulant sensitization. In the present study, we have examined the roles of AA and PAF in the development of stimulant sensitization using agonists and antagonists selective for PAF receptors or the induction of various AA cascade-mediated eicosanoids. Sprague-Dawley rats were treated for 5 days with cocaine (30 mg/kg) or D-amphetamine (1 mg/kg) preceded 15 min earlier by various antagonists, and then tested following a 10-day withdrawal period for cocaine (15 mg/kg) or D-amphetamine (0.5 mg/kg)-induced locomotion. Consistent with our earlier work, pretreatment with the PLA(2) inhibitor quinacrine (25 mg/kg) blocked the development of cocaine and amphetamine sensitization. The lipoxygenase (LOX) inhibitors nordihydroguaiaretic acid (NDGA) (5-10 mg/kg) and MK-886 (1 mg/kg) had no effect on cocaine sensitization. The PAF receptor antagonist WEB 2086 (5-10 mg/kg) reduced the development of cocaine sensitization. The cyclooxygenase (COX) inhibitors indomethacin (1-2 mg/kg), piroxicam (0.5-1 mg/kg), 6-methoxy-2-napthylacetic acid (6-MNA; 0.5-1 mg/kg), and NS-398 (0.5-1 mg/kg) blocked the development of cocaine sensitization. The COX inhibitors indomethacin (2 mg/kg) and 6-MNA (1 mg/kg) also reduced the development of amphetamine sensitization. Rats were administered bilateral intraventral tegmental area (VTA) injections of D-amphetamine (5 mug/side) or saline coadministered with indomethacin (0.5 mug/side) or vehicle three times over 5 days and were then tested after a 10-day withdrawal for D-amphetamine (0.5 mg/kg ip)-induced locomotion. Intra-VTA amphetamine induced a robust form of amphetamine sensitization, which was blocked by coadministration of indomethacin. Unilateral intra-VTA injections of PAF (1 [g) did not significantly alter cocaine (15 mg/kg ip)-induced locomotion when tested after a 3-day withdrawal. These findings suggest that COX, and possibly PAT, activity is involved in the development of stimulant sensitization. Neuroanatomical studies demonstrate that this may occur at the level of the VTA. (C) 2002 Elsevier Science Inc. All rights reserved. C1 NYU, Sch Med, Dept Psychiat, New York Vet Affairs Med Ctr, New York, NY 10010 USA. Univ Calif San Francisco, Dept Psychiat, Psychiat Serv 116W, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Univ Cincinnati, Med Ctr, Dept Psychiat, Cincinnati, OH 45267 USA. RP Reid, MS (reprint author), NYU, Sch Med, Dept Psychiat, New York Vet Affairs Med Ctr, 423 E 23rd St, New York, NY 10010 USA. FU NIDA NIH HHS [R29 DA07376, YOIDA50038-01] NR 87 TC 18 Z9 20 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JAN-FEB PY 2002 VL 71 IS 1-2 BP 37 EP 54 DI 10.1016/S0091-3057(01)00614-1 PG 18 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 518UY UT WOS:000173687300005 PM 11812506 ER PT J AU Waterman, PR Overhaus, M Heckenkamp, J Nigri, GR Fungaloi, PFC Landis, ME Kossodo, SC LaMuraglia, GM AF Waterman, PR Overhaus, M Heckenkamp, J Nigri, GR Fungaloi, PFC Landis, ME Kossodo, SC LaMuraglia, GM TI Mechanisms of reduced human vascular cell migration after photodynamic therapy SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID SMOOTH-MUSCLE CELL; EXTRACELLULAR-MATRIX; CROSS-LINKING; INTIMAL HYPERPLASIA; GROWTH-FACTOR; ARTERIES; METALLOPROTEINASES; COLLAGEN; PROTEINS; BARRIER AB Restenosis results from intimal hyperplasia and constrictive remodeling following cardiovascular interventions. Photodynamic therapy (PDT) has been shown to inhibit intimal hyperplasia in vivo by preventing neointimal repopulation of the treated vessel. This study was undertaken in an attempt to further dissect the mechanisms by which PDT acts on secreted and extracellular matrix proteins to inhibit migration of cultured human vascular cells. PDT of three-dimensional collagen gels inhibited invasive human smooth muscle cell (SMC) migration, whereas cell-derived matrix metalloproteinase production remained unaltered. Additionally, PDT generated cross-links in the collagen gels, a result substantiated in an ex vivo model whereby PDT rendered the treated vessels resistant to pepsin digestion and inhibited invasive migration of SMC and fibroblasts. These data support the premise that by inducing matrix protein cross-links, rendering the vessel resistant to degradation, in vivo PDT inhibits repopulation of the vessel and therefore intimal hyperplasia. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP LaMuraglia, GM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg, WAC 464, Boston, MA 02114 USA. NR 24 TC 14 Z9 15 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 JAN PY 2002 VL 75 IS 1 BP 46 EP 50 DI 10.1562/0031-8655(2002)075<0046:MORHVC>2.0.CO;2 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 515YX UT WOS:000173525200007 PM 11841040 ER PT J AU Hamblin, MR O'Donnell, DA Murthy, N Contag, CH Hasan, T AF Hamblin, MR O'Donnell, DA Murthy, N Contag, CH Hasan, T TI Rapid control of wound infections by targeted photodynamic therapy monitored by in vivo bioluminescence imaging SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID MESOSUBSTITUTED CATIONIC PORPHYRINS; GRAM-NEGATIVE BACTERIA; STAPHYLOCOCCUS-AUREUS; RESISTANCE AB The worldwide rise in antibiotic resistance necessitates the development of novel antimicrobial strategies. In this study we report on the first use of a photochemical approach to destroy bacteria infecting a wound in an animal model. Following topical application, a targeted polycationic photosensitizer conjugate between poly-L-lysine and chlorin(e6) penetrated the Gram (-) outer bacterial membrane, and subsequent activation with 660 nm laser light rapidly killed Escherichia coli infecting excisional wounds in mice. To facilitate real-time monitoring of infection, we used bacteria that expressed the lux operon from Photorhabdus luminescens; these cells emitted a bioluminescent signal that allowed the infection to be rapidly quantified, using a low-light imaging system. There was a light-dose dependent loss of luminescence in the wound treated with conjugate and light, not seen in untreated wounds. Treated wounds healed as well as control wounds, showing that the photodynamic treatment did not damage the host tissue. Our study points to the possible use of this methodology in the rapid control of wounds and other localized infections. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, 50 Blossom St,BAR 314B, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 NR 39 TC 158 Z9 170 U1 4 U2 30 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 JAN PY 2002 VL 75 IS 1 BP 51 EP 57 DI 10.1562/0031-8655(2002)075<0051:RCOWIB>2.0.CO;2 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 515YX UT WOS:000173525200008 PM 11837327 ER PT J AU Calvert, PD Makino, CL AF Calvert, PD Makino, CL TI The time course of light adaptation in vertebrate retinal rods SO PHOTORECEPTORS AND CALCIUM SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article ID PROTEIN-KINASE-C; CGMP-GATED CHANNEL; CYCLIC-GMP PHOSPHODIESTERASE; CYTOPLASMIC CALCIUM; OUTER SEGMENTS; SALAMANDER RODS; PHOTOTRANSDUCTION CASCADE; PHOTORECEPTOR CELLS; SATURATING FLASHES; RHODOPSIN KINASE AB The photoresponse of a rod wanes over time in steady illumination, as light loses its efficacy in generating the response. Such desensitization is adaptive because it extends the range of ambient light levels over which the rod signals changes in light intensity by several orders of magnitude. Adaptation begins to unfold rapidly after the onset of light with a time constant of similar to1 s, causing the rod's sensitivity to steady light to decrease by nearly two log units. Thereafter, a much slower phase of adaptation evolves with a time constant of 9 s. During this phase the rod's sensitivity decreases by an additional log unit. Both phases are dependent upon the light-induced fall in intracellular Ca2+. The fast phase of light adaptation can be attributed to Ca2+ feedback processes regulating the lifetime of photoactivated rhodopsin, cGMP synthesis and sensitivity of the cGMP-gated channel to cGMP. Although the mechanism(s) of the slow phase is not yet known, it appears to include further regulation of the lifetime of photoactivated rhodopsin. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Calvert, PD (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. FU NEI NIH HHS [EY06857, EY12944] NR 60 TC 10 Z9 10 U1 2 U2 5 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2002 VL 514 BP 37 EP 60 PG 24 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BW92B UT WOS:000183600900003 PM 12596914 ER PT J AU Endo, A Seo, M Cheng, WH Sheen, J Koshiba, T AF Endo, A Seo, M Cheng, WH Sheen, J Koshiba, T TI Arabidopsis ABA2 is a novel short-chain dehydrogenase/reductase catalyzing the conversion of xanthoxin to abscisic aldehyde SO PLANT AND CELL PHYSIOLOGY LA English DT Meeting Abstract C1 Tokyo Metropolitan Univ, Dept Biol Sci, Tokyo, Japan. Massachusetts Gen Hosp, Dept Biol Mol, 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 0032-0781 J9 PLANT CELL PHYSIOL JI Plant Cell Physiol. PY 2002 VL 43 SU S BP S43 EP S43 PG 1 WC Plant Sciences; Cell Biology SC Plant Sciences; Cell Biology GA 536XD UT WOS:000174726400150 ER PT J AU Rolland, F Moore, B Sheen, J AF Rolland, F Moore, B Sheen, J TI Sugar sensing and signaling in plants SO PLANT CELL LA English DT Review ID SNF1 PROTEIN-KINASE; YEAST SACCHAROMYCES-CEREVISIAE; 3' UNTRANSLATED REGION; PHOSPHORYLATED NITRATE REDUCTASE; ADP-GLUCOSE PYROPHOSPHORYLASE; SYSTEMIC ACQUIRED-RESISTANCE; CARBON CATABOLITE REPRESSION; TREHALOSE 6-PHOSPHATE LEVELS; TRANSGENIC TOBACCO PLANTS; INDUCIBLE GENE-EXPRESSION C1 Harvard Univ, Sch Med, Dept Biol Mol, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Sheen, J (reprint author), Harvard Univ, Sch Med, Dept Biol Mol, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM sheen@molbio.mgh.harvard.edu FU NIGMS NIH HHS [R01 GM060493, GM 60493] NR 259 TC 382 Z9 418 U1 5 U2 78 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 1040-4651 J9 PLANT CELL JI Plant Cell PY 2002 VL 14 SU S BP S185 EP S205 DI 10.1105/tpc.010455 PG 21 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA 562FV UT WOS:000176187500013 PM 12045277 ER PT J AU Liberman, AM Best, SR Metzler, TJ Fagan, JA Weiss, DS Marmar, CR AF Liberman, AM Best, SR Metzler, TJ Fagan, JA Weiss, DS Marmar, CR TI Routine occupational stress and psychological distress in police SO POLICING-AN INTERNATIONAL JOURNAL OF POLICE STRATEGIES & MANAGEMENT LA English DT Article DE police; stress; USA; work study ID EMERGENCY SERVICES PERSONNEL; SOCIAL SUPPORT; OFFICERS; TRAUMA; DISORDER; IMPACT; WOMEN; DESIRABILITY; PREVALENCE; COMMUNITY AB The relationship between routine work stress and psychological distress was investigated among 733 police officers in three US cities, during 1998-1999. The Work Environment Inventory (WEI) was developed to assess exposure to routine work stressors, while excluding duty-related traumatic stressors (critical incidents). The WEI and its general properties are presented The relationship between routine work stress exposure and psychological distress is then explored. Exposure to routine work stressors predicted general psychological distress (r = 0.46), as well as post-traumatic stress symptoms following officers' most traumatic career incident (rs = 0.26 to 0.39). Multivariate analyses found that these effects were independent of and larger than, the effects of cumulative critical incident exposure. (Time since the most traumatic event, social support, and social desirability effects were also controlled statistically.) Routine occupational stress exposure appears to be a significant risk factor for psychological distress among police officers, and a surprisingly strong predictor of post-traumatic stress symptoms. C1 Natl Inst Justice, Washington, DC 20531 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Columbia Univ, New York, NY USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RP Liberman, AM (reprint author), Natl Inst Justice, Washington, DC 20531 USA. NR 55 TC 65 Z9 67 U1 1 U2 13 PU EMERALD PI BRADFORD PA 60/62 TOLLER LANE, BRADFORD BD8 9BY, W YORKSHIRE, ENGLAND SN 1363-951X J9 POLICING JI Policing-An Int J Police Strategies & Manag. PY 2002 VL 25 IS 2 BP 421 EP 439 DI 10.1108/13639510210429446 PG 19 WC Criminology & Penology SC Criminology & Penology GA 574FY UT WOS:000176879100012 ER PT J AU Stoddard, AM Fox, SA Costanza, ME Lane, DS Andersen, MR Urban, N Lipkus, I Rimer, BK AF Stoddard, AM Fox, SA Costanza, ME Lane, DS Andersen, MR Urban, N Lipkus, I Rimer, BK CA NCI Breast Screening Consortium TI Effectiveness of telephone counseling for mammography: Results from five randomized trials SO PREVENTIVE MEDICINE LA English DT Article DE mammography; transtheoretical model; women's health; telephone counseling ID INCREASE MAMMOGRAPHY; PROMOTING MAMMOGRAPHY; SCREENING MAMMOGRAPHY; BREAST-CANCER; SELF-REPORTS; WOMEN; INTERVENTIONS; ACCURACY; BEHAVIOR; MODELS AB Background. Women over age 50 continue to be underscreened for breast cancer. The purpose of this report is to compare the effectiveness of a barrier-specific telephone counseling intervention across the five study sites of the Breast Cancer Screening Consortium (BCSC). Methods. Each of the BCSC projects was a randomized study of the effectiveness of telephone counseling (TC) in comparison to a control condition. Eligible underusers were identified and surveyed by telephone before and after the implementation of the interventions. Data from a total of 3,461 underusers were analyzed. We tested whether significantly more women randomized to TC than to control were regular mammography users at the follow-up survey. Data were analyzed separately by site. Results. Overall, TC was not significantly more effective than control in encouraging regular mammography. The pooled consortium-wide odds ratio was 1.08 (95% confidence interval: 0.91 to 1.27). Conclusions. TC has the potential to support maintenance of mammogram use. Modifications are needed to maximize this potential and additional methods should be used in conjunction with TC to reach women who are underusers of mammography. (C) 2002 American Health Foundation and Elsevier Science. C1 Univ Massachusetts, Amherst, MA 01003 USA. Univ Calif Los Angeles, Los Angeles, CA 90095 USA. Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Washington, Seattle, WA 98195 USA. Duke Univ, Med Ctr, Durham, NC 27701 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RAND Corp, Santa Monica, CA 90406 USA. RP Stoddard, AM (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R01-CA60129, R01-CA65880, R01-CA63782, R01-CA60131, R01-CA60130] NR 30 TC 23 Z9 23 U1 2 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD JAN PY 2002 VL 34 IS 1 BP 90 EP 99 DI 10.1006/pmed.2001.0960 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 510YN UT WOS:000173235300012 PM 11749101 ER PT B AU Sutton, JP Jamieson, IMD AF Sutton, JP Jamieson, IMD BE Caulfield, HJ Chen, SH Duro, R Honavar, V Kerre, EE Lu, M Romay, MG Shih, TK Ventura, D Wang, PP Yang, YY TI Reconfigurable networking for coordinated multi-agent sensing and communications SO PROCEEDINGS OF THE 6TH JOINT CONFERENCE ON INFORMATION SCIENCES LA English DT Proceedings Paper CT 6th Joint Conference on Information Sciences CY MAR 08-13, 2002 CL RES TRIANGLE PK, NC SP Assoc Intelligent Machinery, Informat Sci Journal, Duke Univ, Acad Affairs, Tamkang Univ, N Carolina Biotechnol Ctr, GalxoSmithKline, George Mason Univ C1 Massachusetts Gen Hosp, Harvard MIT Div Hlth Sci & Technol, Neural Syst Grp, Charlestown, MA 02129 USA. RP Sutton, JP (reprint author), Massachusetts Gen Hosp, Harvard MIT Div Hlth Sci & Technol, Neural Syst Grp, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ASSOC INTELLIGENT MACHINERY PI DURHAM PA PO BOX 90291, DURHAM, NC 27708-0291 USA BN 0-9707890-1-7 PY 2002 BP 36 EP 39 PG 4 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Software Engineering; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BV54W UT WOS:000179331800011 ER PT J AU Petersen, T Dording, C Neault, NB Kornbluh, R Alpert, JE Nierenberg, AA Rosenbaum, JF Fava, M AF Petersen, T Dording, C Neault, NB Kornbluh, R Alpert, JE Nierenberg, AA Rosenbaum, JF Fava, M TI A survey of prescribing practices in the treatment of depression SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE antidepressants; prescribing practices; survey ID PRIMARY-CARE PHYSICIANS; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND TRIAL; ATYPICAL DEPRESSION; MAJOR DEPRESSION; ANTIDEPRESSANT EFFICACY; SUSTAINED-RELEASE; FLUOXETINE; PSYCHIATRISTS; SERTRALINE AB Background: With the increasing number and type of antidepressants available to clinicians, there is a need to better understand current prescribing practices and to what degree these practices reflect research findings. The purpose of this study was to examine prescribing practices in a sample of psychiatrists attending a psychopharmacology review course and compare these results with empirical evidence. Method: 439 of 800 clinicians asked (55%) responded to a 10-item questionnaire that was given prior to beginning the review course. Items covered three major content areas: first-line preferences in the treatment of depression, antidepressant agents most associated with certain side effects, and first-line preferences in the treatment of certain depressive subtypes. Results: 214 (49%) clinicians indicated a belief that one antidepressant type is more efficacious than others. Of these 214 clinicians, 103 (48%) indicated selective serotonin reuptake inhibitors (SSRIs) as being most efficacious, while 53 (25%) indicated venlafaxine as being most efficacious; 378 (93%) clinicians indicated SSRIs as their first-line treatment preference. Mirtazapine (56%) was endorsed as most likely to be associated with weight gain, fluoxetine (57%) with sexual dysfunction, paroxetine (48%) with a discontinuation syndrome, and fluoxetine (52%) with agitation. For the treatment of anxious, atypical, and melancholic depression, SSRIs were the first choice of treatment (58%, 57%, and 57%), and for depression with prominent insomnia, mirtazapine and nefazadone (31 % and 27%) were the first choices of treatment. Conclusions: Despite the lack of evidence of a significant difference in efficacy between older and newer agents, clinicians perceive the newer agents to be more efficacious than the older drugs [tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs)] even in the melancholic and anxious depressive subtypes. Similarly, although sexual dysfunction and agitation appear to occur at similar rates with all the SSRIs, fluoxetine was perceived to be most likely to cause these side effects. These findings are significant as they highlight the discrepancy between empirical evidence and clinical practices and suggest that other factors influence clinicians' medication choices in the treatment of depression. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Petersen, T (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,WAC 812, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X NR 56 TC 38 Z9 41 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD JAN PY 2002 VL 26 IS 1 BP 177 EP 187 DI 10.1016/S0278-5846(01)00250-0 PG 11 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 506UU UT WOS:000172990800026 PM 11853110 ER PT J AU Mischoulon, D AF Mischoulon, D TI The herbal anxiolytics kava and valerian for anxiety and insomnia SO PSYCHIATRIC ANNALS LA English DT Article ID PIPER-METHYSTICUM; ENRICHED EXTRACT; BRAIN; GABA; MICE; (+/-)-KAVAIN; SYNAPTOSOMES; INHIBITION; REMEDIES; PYRONES C1 Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mischoulon, D (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, WAC 812,15 Parkman St, Boston, MA 02114 USA. NR 51 TC 4 Z9 4 U1 0 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD JAN PY 2002 VL 32 IS 1 BP 55 EP 60 PG 6 WC Psychiatry SC Psychiatry GA 512TX UT WOS:000173340600007 ER PT J AU Meyer, EA Kieran, MW AF Meyer, EA Kieran, MW TI Psychological adjustment of 'surgery-only' pediatric neuro-oncology patients: A retrospective analysis SO PSYCHO-ONCOLOGY LA English DT Article ID BRAIN-TUMORS; QUALITY; LIFE AB A recent increase in diagnoses of pediatric neuro-oncology tumors combined with recent advancements in medical treatment of such tumors has resulted in a growing cohort of pediatric brain tumor survivors. These survivors are at risk for short and long-term psychological adjustment problems. Most studies regarding these survivors have focused on children who have received combinations of surgery, radiation, and chemotherapy as medical treatment. The sub-group of pediatric neuro-oncology patients who receive surgery Lis the only form of medical treatment has not been closely followed for adjustment problems. In this study, data ere retrospectively collected from semi-structured clinical interviews with 34 'surgery-only' pediatric neuro-oncology patients, who were 2 weeks to 5 years off medical treatment for their tumor. These data suggest that these survivors may be experiencing significant short and long-term mood, behavioral, and academic adjustment problems in comparison to national averages for children regarding these issues. Additional research examining the psychological adjustment process for surgery-only pediatric neuro-oncology patients is needed to validate these preliminary findings and facilitate the development of targeted interventions to address the identified adjustment problems. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Harvard Univ, Dana Farber Canc Inst, Sch Med, Cambridge, MA 02138 USA. RP Meyer, EA (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Cambridge, MA 02138 USA. OI Kieran, Mark/0000-0003-2184-7692 NR 9 TC 20 Z9 20 U1 0 U2 0 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 JAN-FEB PY 2002 VL 11 IS 1 BP 74 EP 79 DI 10.1002/pon.553 PG 6 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 518BR UT WOS:000173647100007 PM 11835594 ER PT J AU Caplan, D Waters, G AF Caplan, D Waters, G TI Working memory and connectionist models of parsing: A reply to MacDonald and Christiansen (2002) SO PSYCHOLOGICAL REVIEW LA English DT Article ID SYNTACTIC AMBIGUITY RESOLUTION; SHORT-TERM-MEMORY; INDIVIDUAL-DIFFERENCES; SENTENCE COMPREHENSION; LANGUAGE COMPREHENSION; READING-COMPREHENSION; CAPACITY THEORY; CONSTRAINTS; CODES AB The authors take issue with 3 claims made by M. C. MacDonald and M. H. Christiansen (2002): (a) that connectionist models of syntactic processing do not have components that function in the same way as limitations on working memory (WM) in production system models of psychological processes; (b) that individual differences in WM are related to the efficiency of syntactic processing because both are affected by reading experience; and (c) that individual differences in the nature of phonological representations affect the efficiency of syntactic processing. The authors argue that the concept of WM cannot be eliminated from models of language processing and that the literature supports the view that syntactic processing involves a specialized WM system. C1 Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. Boston Univ, Dept Commun Disorders, Boston, MA 02215 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Vincent Burnham 827,55 Fruit St, Boston, MA 02114 USA. NR 30 TC 27 Z9 28 U1 1 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0033-295X J9 PSYCHOL REV JI Psychol. Rev. PD JAN PY 2002 VL 109 IS 1 BP 66 EP 74 DI 10.1037//0033-295X.109.1.66 PG 9 WC Psychology; Psychology, Multidisciplinary SC Psychology GA 521LA UT WOS:000173840400005 ER PT J AU Mendelson, JH Mello, NK Sholar, MB Siegel, AJ Mutschler, N Halpern, J AF Mendelson, JH Mello, NK Sholar, MB Siegel, AJ Mutschler, N Halpern, J TI Temporal concordance of cocaine effects on mood states and neuroendocrine hormones SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE cocaine; euphoria; heart rated; adrenocorticotropin hormone (ACTH); cortisol; dihydroepiandrosterone (DHEA) ID CORTICOTROPIN-RELEASING HORMONE; ADRENOCORTICOTROPIN ACTH SECRETION; PITUITARY-ADRENAL AXIS; MALE RHESUS-MONKEYS; PLASMA ADRENOCORTICOTROPIN; INDUCED ELEVATION; BETA-ENDORPHIN; FACTOR CRF; RATS; CORTICOSTERONE AB Cocaine stimulates the release of adrenocorticotropin hormone (ACTH) and cortisol in both clinical and preclinical studies, but the temporal sequence of cocaine-induced changes in other hormones and affective states is unclear. The purpose of this study was to analyze the pattern and temporal concordance of cocaine-induced changes in ACTH, cortisol, dihydroepiandrosterone (DHEA), epinephrine, heart rate and subjective reports of euphoria. Six healthy men who met Diagnostic and Statistical Manual-IV (DSM-IV) criteria for cocaine abuse provided informed consent for participation. Cocaine (0.4 mg/kg) or saline placebo was infused intravenously over 1 min under double-blind conditions. Euphoria, ACTH, epinephrine and heart rate increased significantly within 8 to 12 min after i.v. cocaine administration in all subjects (P<0.01-0.001). Moreover, the increases in euphoria, ACTH, epinephrine and heart rate each were significantly correlated with increases in plasma cocaine levels (P<0.001). Euphoria increased significantly within 2 min after i.v. cocaine injection, as plasma cocaine levels were increasing, and peak euphoria was reported at 10 min (P<0.001). Peak ACTH values were measured at 8.7 (+/-0.8) min after cocaine injection (P<0.01). Peak levels of epinephrine were measured at 10 (+/-1) min after cocaine injection (P<0.05). Peak increases in heart rate occurred at 11.7 (+/-1.1) min after cocaine injection (P<0.05). Peak levels of cortisol and DHEA were measured at 36 (+/-4.0) and 28.7 (+/-4.3) min after cocaine injection (P<0.01 and P<0.01). The temporal concordance between cocaine-induced stimulation of ACTH, epinephrine and subjective euphoria suggests that these hormonal changes are significant concomitants of the abuse-related effects of cocaine. The similarities between these hormonal profiles, the subjective effects of cocaine and the effects of "stress" are discussed. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 McLean Hosp, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Mendelson, JH (reprint author), McLean Hosp, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02178 USA. EM jmendel@mclean.harvard.edu FU NIDA NIH HHS [T32-DA07252, R01-DA10757, KO5-DA00101, P50-DA04059, K23-DA00494] NR 45 TC 43 Z9 44 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JAN-FEB PY 2002 VL 27 IS 1-2 BP 71 EP 82 DI 10.1016/S0306-4530(01)00036-1 PG 12 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 518CQ UT WOS:000173649400005 PM 11750770 ER PT J AU Yehuda, R Halligan, SL Bierer, LM AF Yehuda, R Halligan, SL Bierer, LM TI Cortisol levels in adult offspring of Holocaust survivors: relation to PTSD symptom severity in the parent and child SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE PTSD; Holocaust; cortisol; depression ID POSTTRAUMATIC-STRESS-DISORDER; GLUCOCORTICOID RECEPTORS; MAJOR DEPRESSION; MATERNAL-CARE; COMORBIDITY; RESPONSES; RAT AB We have previously demonstrated lower mean 24-h urinary cortisol excretion in adult offspring of Holocaust survivors with parental posttraumatic stress disorder (and lifetime PTSD), compared to offspring without parental PTSD, and to demographically similar comparison subjects. In the current study, we re-analyze data from our previously published report, plus four new subjects, to further examine the relationship between cortisol and severity of PTSD symptoms in offspring and their parents. We also examine the contribution of current depressive disorder to cortisol levels. Two-way analysis of variance revealed lifetime PTSD to be associated with significantly lower cortisol levels, while depressive disorder was associated with higher cortisol levels. The presence of parental PTSD was associated with lower cortisol excretion in the offspring only if both parents were affected. There were significant negative correlations between severity of parental PTSD and offspring urinary cortisol excretion, and between severity of offspring PTSD symptoms and urinary cortisol levels. The findings amplify our earlier descriptions of children of Holocaust survivors with PTSD as a sample 'at risk' for PTSD by demonstrating relationships between lowered cortisol excretion in these offspring and their experience of their parents' PTSD symptoms. Published by Elsevier Science Ltd. C1 Bronx Vet Affairs Med Ctr, Psychiat OOMH, Bronx, NY 10468 USA. CUNY Mt Sinai Sch Med, Traumat Stress Studies Program, New York, NY 10029 USA. RP Yehuda, R (reprint author), Bronx Vet Affairs Med Ctr, Psychiat OOMH, 130 W Kingsbridge Rd,, Bronx, NY 10468 USA. OI Halligan, Sarah/0000-0002-3436-3358 FU NIMH NIH HHS [MH-49555] NR 20 TC 81 Z9 86 U1 3 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JAN-FEB PY 2002 VL 27 IS 1-2 BP 171 EP 180 DI 10.1016/S0306-4530(01)00043-9 PG 10 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 518CQ UT WOS:000173649400012 PM 11750777 ER PT J AU Aikins, D Craske, M AF Aikins, D Craske, M TI Increased heart rate variability in nocturnal panic after cognitive behavioral therapy: Contributions from the mind and the body SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Yale Univ, New Haven, CT 06520 USA. Natl Ctr PTSD, Boston, MA USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2002 VL 39 SU 1 BP S18 EP S18 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 592LT UT WOS:000177939700067 ER PT J AU Aikins, D Craske, M AF Aikins, D Craske, M TI Contribution of reduced heart rate variability in panic disorder with and without nocturnal panic attacks SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Yale Univ, New Haven, CT 06520 USA. Natl Ctr PTSD, Boston, MA USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2002 VL 39 SU 1 BP S17 EP S17 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 592LT UT WOS:000177939700066 ER PT J AU Aikins, D AF Aikins, D TI A procedure for recording heart rate variability during functional magnetic resonance imaging SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Yale Univ, New Haven, CT 06520 USA. Natl Ctr PTSD, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2002 VL 39 SU 1 BP S17 EP S17 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 592LT UT WOS:000177939700065 ER PT J AU Fung, MT Raine, A Lynam, DR Steinhauer, SR Loeber, R Stouthamer-Loeber, M AF Fung, MT Raine, A Lynam, DR Steinhauer, SR Loeber, R Stouthamer-Loeber, M TI Reduced anticipatory and reactive skin conductance: Evidence for an adolescent analog of psychopathy SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Univ So Calif, Los Angeles, CA 90089 USA. Univ Kentucky, Lexington, KY 40506 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RI Lynam, Donald/J-5755-2014 OI Lynam, Donald/0000-0001-8306-498X NR 0 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2002 VL 39 SU 1 BP S37 EP S37 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 592LT UT WOS:000177939700144 ER PT J AU Spencer, KM Weinstein, D Niznikiewicz, MA McCarley, RW AF Spencer, KM Weinstein, D Niznikiewicz, MA McCarley, RW TI P300 source localization using lead-field modeling and focused inversion SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Cambridge, MA 02138 USA. Univ Utah, Salt Lake City, UT 84112 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2002 VL 39 SU 1 BP S79 EP S79 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 592LT UT WOS:000177939700312 ER PT J AU Johnston-Brooks, CH Lewis, MA Garg, S AF Johnston-Brooks, CH Lewis, MA Garg, S TI Self-efficacy impacts self-care and HbA1c in young adults with Type I diabetes SO PSYCHOSOMATIC MEDICINE LA English DT Article DE diabetes; self-efficacy; self-esteem; HbA1c; self-care; mediation ID SHORT-TERM; COMPLICATIONS TRIAL; BEHAVIORS; MELLITUS; THERAPY; ESTEEM; ADOLESCENTS; MANAGEMENT; PREDICTORS; ADHERENCE AB Objective: The present study examined self-efficacy and self-esteem as basic aspects of the self that influence self-care and physiological outcomes among young adults with Type I diabetes. The two aims of this study were 1) to examine the cross-sectional and longitudinal role of the self-variables as they predict self-care and HbA1c and 2) to test whether self-care mediates the association between the self variables and HbA1c using cross-sectional and longitudinal data. Methods: One hundred ten participants were recruited from a regional diabetes outpatient clinic. Inclusion criteria were age (18-35 years) and duration of diabetes (>1 year before recruitment). Participants were 61% female and 88% white. In addition, the sample had an average annual income between $24,999 and $34,999, and 85% had completed some or all of college. The average duration of diabetes was 15 years. Results: Using multiple regression analyses we found that, compared with self-esteem, self-efficacy was a better predictor of all aspects of self-care and HbA1c in cross-sectional analyses, in addition to diet and exercise self-care, and a better predictor of HbA1c in longitudinal analyses. The data also supported the cross-sectional and longitudinal mediational model in which better self-care helped account for the association between greater self-efficacy and better HbA1c. Conclusions: Self-efficacy is an important factor for management of self-care practices and physiological outcomes among young adults with Type I diabetes, and self-care may be an important mechanism by which self-efficacy influences HbA1c levels. C1 Denver VAMC, Denver, CO 80220 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. RP Johnston-Brooks, CH (reprint author), Denver VAMC, Routing 116 B,1055 Clermont St, Denver, CO 80220 USA. NR 59 TC 92 Z9 96 U1 3 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JAN-FEB PY 2002 VL 64 IS 1 BP 43 EP 51 PG 9 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 520BM UT WOS:000173760200007 PM 11818585 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 Association between pretransplant psychological assessments and posttransplant psychiatric disorders in living-related transplantation SO PSYCHOSOMATICS LA English DT Article ID TORONTO-ALEXITHYMIA-SCALE; KIDNEY-TRANSPLANTATION; SECONDARY ALEXITHYMIA; TREE; VALIDITY; LIVER AB The authors examined pretransplant assessment in order to predict posttransplant occurrence of psychiatric disorders in living-related transplantation (LRT). Before LRT, the authors administered the Integrated House-Tree-Person Drawing Test (1-HTP) and 20-item Toronto Alexithymia Scale (TAS-20) to 31 donor-recipient pairs undergoing living-related liver transplantation (LRLT) and 65 pairs undergoing living-related kidney transplantation (LRKT). After LRT the authors examined the occurrence of psychiatric disorders for the recipients and donors. Pretransplant, two psychological indicators,-alexithymia, a lack of verbalized emotion and abnormal projective drawings such as truncated tree representation-we re significantly related to the manifestation of paradoxical psychiatric syndrome (PPS) in LRLT and LRKT The occurrence of PPS was significantly related to recipients' guilt feelings toward living donors, but these were strongly superseded by recipients' desires to escape front approaching death just before LRT These results suggest that pretransplant psychological assessment is useful for predicting posttransplant occurrence of psychiatric disorders. C1 Tokyo Metropolitan Org Med Res, Tokyo Inst Psychiat, Setagaya Ku, Tokyo 156, Japan. Univ Tokyo, Fac Med, Dept Surg 2, Tokyo 113, Japan. Univ Tokyo, Fac Med, Dept Pediat Surg, Tokyo 113, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Fukunishi, I (reprint author), Tokyo Metropolitan Org Med Res, Tokyo Inst Psychiat, Setagaya Ku, 2-1-8 Kamikitazawa, Tokyo 156, Japan. EM fukunisi@prit.go.jp RI 幕内, 雅敏/A-2140-2012 NR 20 TC 43 Z9 45 U1 0 U2 1 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 JAN-FEB PY 2002 VL 43 IS 1 BP 49 EP 54 DI 10.1176/appi.psy.43.1.49 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 530CA UT WOS:000174337000008 PM 11927758 ER PT J AU Eastwood, JD Lev, MH Azhari, T Lee, TY Barboriak, DP Delong, DM Fitzek, C Herzau, M Wintermark, M Meuli, R Brazier, D Provenzale, JM AF Eastwood, JD Lev, MH Azhari, T Lee, TY Barboriak, DP Delong, DM Fitzek, C Herzau, M Wintermark, M Meuli, R Brazier, D Provenzale, JM TI CT perfusion scanning with deconvolution analysis: Pilot study in patients with acute middle cerebral artery stroke SO RADIOLOGY LA English DT Article DE brain, blood flow; brain, CT; brain, infarction; brain, perfusion ID ACUTE ISCHEMIC STROKE; DYNAMIC COMPUTED-TOMOGRAPHY; BLOOD-FLOW; TRANSIT-TIME; VOLUME; BRAIN; INFARCTION; VALIDATION; MRI AB PURPOSE: To measure mean cerebral blood flow (CBF) in ischemic and nonisch- emic territories and in low-attenuation regions in patients with acute stroke by using deconvolution-derived hemodynamic imaging. MATERIALS AND METHODS: Twelve. patients with acute middle cerebral artery stroke and 12 control patients were. examined by using single-section computed tomography (CT) perfusion scanning. Analysis was performed with a deconvolution-based algorithm. Comparisons of mean CBF, cerebral blood volume (CBV), and mean transit time (MTT) were determined, between hemispheres in all patients and between low- and normal-attenuation regions in patients with acute stroke. Two independent readers examined the images for extent of visually apparent regional perfusion abnormalities. The data were compared with extent of final infarct in seven patients with acute stroke who underwent follow-up CT or magnetic reso- nance imaging. RESULTS: Significant decreases in CBF (-50%, P = .001) were found in the affected hemispheres of patients with acute stroke. Significant changes in CBV (-26%, P = .03) and MTT (+ 111 %, P = .004) were also,seen. Significant alterations in perfusion were also seen in low- compared with normal-attenuation areas. Pearson correlation between readers for extent of CBF abnormality was 0.94 (P =,.001). Intraobserver variation was 8.9% for CBF abnormalities. CONCLUSION: Deconvolution analysis of CT perfusion data is a promising method for evaluation of cerebral hemodynamics in, patients with acute stroke. C1 Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Univ Jena, Inst Diagnost & Intervent Radiol, D-6900 Jena, Germany. John P Robarts Res Inst, Imaging Res Labs, London, ON N6A 5K8, Canada. Univ Lausanne Hosp, Dept Diagnost & Intervent Radiol, Lausanne, Switzerland. Royal N Shore Hosp, Dept Radiol, St Leonards, NSW 2065, Australia. RP Eastwood, JD (reprint author), Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. RI Lee, Ting-Yim/M-1721-2013; OI Wintermark, Max/0000-0002-6726-3951 NR 32 TC 167 Z9 192 U1 0 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2002 VL 222 IS 1 BP 227 EP 236 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 504YW UT WOS:000172884800034 PM 11756730 ER PT J AU Ludemann, HC Redmond, RW Hillenkamp, F AF Ludemann, HC Redmond, RW Hillenkamp, F TI Singlet-singlet annihilation in ultraviolet matrix-assisted laser desorption/ionization studied by fluorescence spectroscopy SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID MOLECULES AB Laser-induced fluorescence spectroscopy was carried out on microcrystalline samples of three typical matrices under conditions of matrix-assisted laser desorption/ionization (MALDI). The emitted fluorescence intensity was determined as a function of incident laser fluence and a sublinear increase of the fluorescence intensity with laser fluence was found. A very good fit was obtained when the experimental fluorescence vs. fluence data were compared with a numerical model assuming that under typical MALDI fluence conditions a large fraction of molecules in the excited singlet state undergoes singlet-singlet annihilation. Throughout the fluence range relevant for MALDI, however, the experimental data could not be fit well to a model assuming resonant two-photon absorption as the process depopulating the singlet state. In a separate set of experiments, the singlet lifetimes of several typical crystalline MALDI matrices were determined and found to be considerably shorter than previously reported. While both singlet-singlet annihilation and resonant two-photon absorption have been discussed in the literature as candidates for pathways to primary matrix ion generation in MALDI, the data presented here suggest that singlet-singlet annihilation is the dominant mechanism for depopulating the singlet state in a matrix crystal excited at typical MALDI fluences. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Univ Munster, Inst Med Phys & Biophys, D-48149 Munster, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP Hillenkamp, F (reprint author), Univ Munster, Inst Med Phys & Biophys, Robert Koch Str 31, D-48149 Munster, Germany. NR 13 TC 27 Z9 27 U1 0 U2 10 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 2002 VL 16 IS 13 BP 1287 EP 1294 DI 10.1002/rcm.712 PG 8 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 570HM UT WOS:000176652900006 PM 12112256 ER PT J AU Maulik, G Salgia, R Makrigiorgos, GM AF Maulik, G Salgia, R Makrigiorgos, GM TI Flow cytometric determination of lipid peroxidation using fluoresceinated phosphoethanolamine SO REDOX CELL BIOLOGY AND GENETICS, PART A SE METHODS IN ENZYMOLOGY LA English DT Review ID OXIDATIVE STRESS; MALONALDEHYDE; ERYTHROCYTES; DAMAGE; ACID C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Maulik, G (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL 57150-01] NR 21 TC 5 Z9 5 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2002 VL 352 BP 80 EP 91 PN A PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BU93G UT WOS:000177426500007 PM 12125379 ER PT J AU Oberley, TD AF Oberley, TD TI Ultrastructural localization and relative quantification of 4-hydroxynonenal-modified proteins in tissues and cell compartments SO REDOX CELL BIOLOGY AND GENETICS, PART A SE METHODS IN ENZYMOLOGY LA English DT Review ID OXIDATIVE DAMAGE; ADDUCTS; KIDNEY C1 Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Madison, WI 53705 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Oberley, TD (reprint author), Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Madison, WI 53705 USA. NR 13 TC 10 Z9 10 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2002 VL 352 BP 373 EP 377 PN A PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BU93G UT WOS:000177426500032 PM 12125364 ER PT S AU Faustman, DL AF Faustman, DL BE Sipe, JD Kelley, CA McNicol, LA TI Reversal of established autoimmune diabetes by in situ beta-cell regeneration SO REPARATIVE MEDICINE: GROWING TISSUES AND ORGANS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Symposium on Reparative Medicine - Growing Tissues and Organs CY JUN 25-26, 2001 CL BETHESDA, MARYLAND SP NIH Bioengn Consortium, Natl Eye Inst, NICHHD, Natl Inst Bioimaging & Biomed Engn DE autoimmune diabetes; B-cell regeneration C1 Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Faustman, DL (reprint author), Massachusetts Gen Hosp, Immunobiol Lab, Bldg 149,13th St,Room 3601, Charlestown, MA 02129 USA. NR 1 TC 3 Z9 3 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-382-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 961 BP 40 EP 40 PG 1 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Engineering; Science & Technology - Other Topics GA BU82Q UT WOS:000177134500004 PM 12081859 ER PT S AU Glowacki, J Yates, KE Warden, S Allemann, F Peretti, G Strongin, D MacLean, R Zaleske, D AF Glowacki, J Yates, KE Warden, S Allemann, F Peretti, G Strongin, D MacLean, R Zaleske, D BE Sipe, JD Kelley, CA McNicol, LA TI Engineering a biological joint SO REPARATIVE MEDICINE: GROWING TISSUES AND ORGANS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Symposium on Reparative Medicine - Growing Tissues and Organs CY JUN 25-26, 2001 CL BETHESDA, MARYLAND SP NIH Bioengn Consortium, Natl Eye Inst, NICHHD, Natl Inst Bioimaging & Biomed Engn DE bioengineering; joints ID MURINE OSTEOSARCOMA CELLS; HUMAN DERMAL FIBROBLASTS; DEMINERALIZED BONE; 3-DIMENSIONAL CULTURE; IN-VITRO; CHONDROINDUCTION; COLLAGEN C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, MGH Skeletal Biol Res Ctr, Boston, MA 02114 USA. RP Glowacki, J (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, 75 Francis St, Boston, MA 02115 USA. RI Peretti, Giuseppe/K-6358-2016 OI Peretti, Giuseppe/0000-0001-9341-7187 FU NIAMS NIH HHS [R01 AR 45870] NR 6 TC 1 Z9 1 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-382-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 961 BP 123 EP 125 PG 3 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Engineering; Science & Technology - Other Topics GA BU82Q UT WOS:000177134500024 PM 12081879 ER PT S AU Toner, M Kocsis, J AF Toner, M Kocsis, J BE Sipe, JD Kelley, CA McNicol, LA TI Storage and translational issues in reparative medicine SO REPARATIVE MEDICINE: GROWING TISSUES AND ORGANS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Symposium on Reparative Medicine - Growing Tissues and Organs CY JUN 25-26, 2001 CL BETHESDA, MARYLAND SP NIH Bioengn Consortium, Natl Eye Inst, NICHHD, Natl Inst Bioimaging & Biomed Engn DE cryopreservation; freeze-thaw protocol; vitrification; desiccation; tissue-engineered products ID LONG-TERM STORAGE; DESICCATION TOLERANCE; VASCULAR GRAFTS; HUMAN-CELLS; TREHALOSE; CRYOPRESERVATION; WATER C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA USA. Yale Univ, Sch Med, Ctr Res Neurosci, West Haven, CT 06516 USA. RP Toner, M (reprint author), Shriners Burns Hosp, 51 Blossom St, Boston, MA 02114 USA. NR 17 TC 8 Z9 8 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-382-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 961 BP 258 EP 262 PG 5 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Engineering; Science & Technology - Other Topics GA BU82Q UT WOS:000177134500057 PM 12081912 ER PT J AU Marder, SR Essock, SM Miller, AL Buchanan, RW Davis, JM Kane, JM Lieberman, J Schooler, NR AF Marder, SR Essock, SM Miller, AL Buchanan, RW Davis, JM Kane, JM Lieberman, J Schooler, NR TI The Mount Sinai conference on the pharmacotherapy of schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Article DE schizophrenia; antipsychotics; tardive dyskinesia; evidence-based practice; clozapine ID REFRACTORY SCHIZOPHRENIA; TARDIVE-DYSKINESIA; RESISTANT SCHIZOPHRENIA; WEIGHT-GAIN; CLOZAPINE; HALOPERIDOL; RISPERIDONE; OLANZAPINE; BLIND; ANTIPSYCHOTICS AB This report summarizes the recommendations from a consensus meeting that focused on specific questions regarding the pharmacotherapy of schizophrenia. The issues were selected because there was evidence that experts had recently disagreed about the evidence supporting a particular practice or when there were substantial variations in a clinical practice indicating that there was disagreement among clinicians. The group of experts was able to reach a consensus regarding the evidence base pertaining to the following issues: First generation (FGAs) and second generation (SGAs) antipsychotics as first line agents; the duration of antipsychotic trials; the effectiveness of clozapine and other agents for treatment refractory schizophrenia; risk of tardive dyskinesia on FGAs and SGAs; differences among antipsychotics for different dimensions of psychopathology; and side effect monitoring for various antipsychotics. C1 VA Desert Pacific, MIRECC, Los Angeles, CA USA. VA Greater Los Angeles Hlth Care Syst, Dept Chair Psychiat, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. NYU, Dept Psychiat, Div Hlth Serv Res, Mt Sinai Sch Med, New York, NY 10016 USA. Vet Affairs New York Healthcare Syst, Mental Illness Res Educ & Clin Ctr, New York, NY USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. Univ Illinois, Chicago, IL USA. N Shore Long Isl Jewish Hlth Syst, Behav Hlth Serv, New York, NY USA. Albert Einstein Coll Med, New York, NY USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. Hillside Hosp, Glen Oaks, NY 11004 USA. RP Marder, SR (reprint author), W Los Angeles VA Hlth Care Ctr, MIRECC 210A, 11301 Wiltshire Blvd, Los Angeles, CA 90073 USA. NR 46 TC 89 Z9 93 U1 1 U2 1 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 2002 VL 28 IS 1 BP 5 EP 16 PG 12 WC Psychiatry SC Psychiatry GA 553CT UT WOS:000175658500002 PM 12047022 ER PT J AU Marder, SR AF Marder, SR TI Can clinical practice guide a research agenda? SO SCHIZOPHRENIA BULLETIN LA English DT Article DE schizophrenia; antipsychotic; clozapine; evidence-based practice; polypharmacy AB Articles from this issue of the Bulletin indicate that clinicians are frequently adopting clinical practices that have not been supported by an evidence base. Examples of these practices are prescribing more than one antipsychotic and reserving clozapine for patients who have had multiple antipsychotic trials. This commentary suggests that these practices can be used to define important research questions. C1 VA Greater Los Angeles Hlth Care Syst, Dept Chair Psychiat, VA Desert Pacific MIRECC, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. RP Marder, SR (reprint author), W Los Angeles VA Hlth Care Ctr, MIRECC-210A,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 7 TC 6 Z9 6 U1 1 U2 1 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 2002 VL 28 IS 1 BP 127 EP 129 PG 3 WC Psychiatry SC Psychiatry GA 553CT UT WOS:000175658500013 PM 12047012 ER PT J AU Marder, SR Aravagiri, M Wirshing, WC Wirshing, DA Lebell, M Mintz, J AF Marder, SR Aravagiri, M Wirshing, WC Wirshing, DA Lebell, M Mintz, J TI Fluphenazine plasma level monitoring for patients receiving fluphenazine decanoate SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; antipsychotic; fluphenazine ID RELAPSE; SCHIZOPHRENIA; THERAPY AB Background: Finding a dose of an antipsychotic for maintenance therapy that is both safe and effective can be difficult because clinicians are unable to titrate dose against clinical response in patients who are already stable. Therapeutic monitoring of antipsychotic plasma levels has the potential for helping clinicians in dosage selection. With this in mind, we evaluated the usefulness of monitoring fluphenazine plasma levels for patients with schizophrenia who were receiving maintenance treatment with fluphenazine decanoate. Method: Thirty-one patients with schizophrenia were randomly assigned to low, medium, or high (0.1-0.3, 0.3-0.6, 0.6-1.0 ng/ml) plasma levels of fluphenazine. The dose of fluphenazine decanoate was adjusted in order to maintain patients in their assigned range. Side effects, psychopathology, and psychotic exacerbations were measured during the year following randomization. Results: All of the psychotic exacerbations occurred during the first eight weeks following randomization, before patients had adequate time to reach their plasma level assignments. We did not find a relationship between plasma levels of fluphenazine and clinical outcomes or side effects. Conclusion: Our results do not provide support for the usefulness of monitoring fluphenazine plasma levels for patients receiving fluphenazine decanoate. (C) 2002 Elsevier Science B.V. All rights reserved. C1 W Los Angeles Hlth Ctr, VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Marder, SR (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,MIRECC-210A, Los Angeles, CA 90073 USA. NR 16 TC 11 Z9 11 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN 1 PY 2002 VL 53 IS 1-2 BP 25 EP 30 DI 10.1016/S0920-9964(00)00184-5 PG 6 WC Psychiatry SC Psychiatry GA 507ZE UT WOS:000173060900004 PM 11728835 ER PT S AU Sun, CH Migliorini, C Munn, LL AF Sun, CH Migliorini, C Munn, LL GP IEEE IEEE IEEE TI Influence of vessel geometry on leukocyte adhesion: A lattice-Boltzmann model SO SECOND JOINT EMBS-BMES CONFERENCE 2002, VOLS 1-3, CONFERENCE PROCEEDINGS: BIOENGINEERING - INTEGRATIVE METHODOLOGIES, NEW TECHNOLOGIES SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 24th Annual International Conference of the Engineering-in-Medicine-and-Biology-Society/Annual Fall Meeting of the Biomedical-Engineering-Society (EMBS 2002 BMES) CY OCT 23-26, 2002 CL HOUSTON, TX SP Engn Med & Biol Soc, Biomed Engn Soc, Natl Sci Fdn, Natl Inst Hlth, Natl Inst Biomed Imaging & Bioengn, Whitaker Fdn ID ERYTHROCYTES; ARREST AB Leukocytes roll and arrest on the vascular endothelium in both normal and pathological immune responses, but the particulate, non-Newtonian nature of blood renders traditional mathematical models of these processes intractable. Here we present a Lattice-Boltzmann approach to quantify the fluid dynamics and forces involved as white blood cells interact with red blood cells in "virtual" blood vessels of various geometries. We report that the normal force imparted by erythrocytes is sufficient to increase leukocyte binding, and that increases in tangential force and torque can promote rolling of previously adherent leukocytes. The ratio of cell diameter to vessel diameter is an important determinant of the form of the interaction. This novel approach can be applied to a large number of biological and industrial problems involving the complex flow of particulate suspensions. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Sun, CH (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 7 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-7612-9 J9 P ANN INT IEEE EMBS PY 2002 BP 373 EP 374 PG 2 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging GA BV84T UT WOS:000180194800178 ER PT S AU Walton, SP Jayaraman, A Yarmush, ML Roth, CM AF Walton, SP Jayaraman, A Yarmush, ML Roth, CM GP IEEE IEEE IEEE TI Characterization of molecular and cellular events limiting the effectiveness of antisense oligonucleotides SO SECOND JOINT EMBS-BMES CONFERENCE 2002, VOLS 1-3, CONFERENCE PROCEEDINGS: BIOENGINEERING - INTEGRATIVE METHODOLOGIES, NEW TECHNOLOGIES SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 24th Annual International Conference of the Engineering-in-Medicine-and-Biology-Society/Annual Fall Meeting of the Biomedical-Engineering-Society (EMBS 2002 BMES) CY OCT 23-26, 2002 CL HOUSTON, TX SP Engn Med & Biol Soc, Biomed Engn Soc, Natl Sci Fdn, Natl Inst Hlth, Natl Inst Biomed Imaging & Bioengn, Whitaker Fdn DE RNA folding; hybridization; real-time PCR ID TARGET AB Antisense oligonucleotides (AS ONs) are a powerful means to inhibit the expression of specific genes, but their effectiveness is limited by factors including cellular delivery, biochemical attack, and poor binding to target. We are developing rational approaches to improve effectiveness through high affinity binding. We developed a molecular thermodynamic model based on ON and mRNA folding that predicts accurately the affinity of ON-mRNA binding, and we have found that it successfully selects those ONs that are most successful in cell culture. We have experimentally measured both thermodynamic and kinetic binding events in solution and found strong correlation between association kinetics and binding affinity. Binding association rates as a function of temperature have provided evidence for our hypothesis that RNA restructuring is the limiting step in ON binding. We are currently integrating these results with additional measurements on delivery and ribonuclease H cleavage of RNA in DNA-RNA duplexes to form a whole cell model that can serve as the basis for optimization of ON chemistry, dosing and timing. Taken together, these tools may help accelerate the development of this promising technology. C1 Shriners Burns Hosp, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA USA. RP Walton, SP (reprint author), Shriners Burns Hosp, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA USA. OI Walton, S. Patrick/0000-0003-1708-8603; Roth, Charles/0000-0002-4924-0721 NR 7 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-7612-9 J9 P ANN INT IEEE EMBS PY 2002 BP 610 EP 611 PG 2 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging GA BV84T UT WOS:000180194800295 ER PT S AU Kang, YH Dwarakanath, B Berthiaume, F Yarmush, ML AF Kang, YH Dwarakanath, B Berthiaume, F Yarmush, ML GP IEEE IEEE IEEE TI In vitro primary hepatocyte proliferation with nonparenchymal liver cell activation SO SECOND JOINT EMBS-BMES CONFERENCE 2002, VOLS 1-3, CONFERENCE PROCEEDINGS: BIOENGINEERING - INTEGRATIVE METHODOLOGIES, NEW TECHNOLOGIES SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 24th Annual International Conference of the Engineering-in-Medicine-and-Biology-Society/Annual Fall Meeting of the Biomedical-Engineering-Society (EMBS 2002 BMES) CY OCT 23-26, 2002 CL HOUSTON, TX SP Engn Med & Biol Soc, Biomed Engn Soc, Natl Sci Fdn, Natl Inst Hlth, Natl Inst Biomed Imaging & Bioengn, Whitaker Fdn DE primary hepatocyte; proliferation; nonparenchymal cells; regeneration AB The construction of a tissue engineered liver requires the ready availability of an immunocompatible cell source capable of replacing lost physiological functions. Primary autologous hepatocytes would be an ideal choice for such a device, however, it is not yet known how to induce proliferation of these cells in vitro. We investigated the effect of culture medium containing known liver regeneration factors (HGF, EGF, VEGF, IL-6) pre-conditioned by culture with nonparenchymal cells (NPCs) on the proliferation of primary hepatocytes in collagen sandwich culture. Morphological evidence indicated an increase in the density of hepatocytes when supplemented with proliferation factor-conditioned NPC media. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shriners Hosp Children,Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. RP Kang, YH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shriners Hosp Children,Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-7612-9 J9 P ANN INT IEEE EMBS PY 2002 BP 780 EP 781 PG 2 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging GA BV84T UT WOS:000180194800374 ER PT S AU Baust, JM Toner, M AF Baust, JM Toner, M GP IEEE IEEE IEEE TI The effect of cell culture substrate on cell tolerance to desiccation SO SECOND JOINT EMBS-BMES CONFERENCE 2002, VOLS 1-3, CONFERENCE PROCEEDINGS: BIOENGINEERING - INTEGRATIVE METHODOLOGIES, NEW TECHNOLOGIES SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 24th Annual International Conference of the Engineering-in-Medicine-and-Biology-Society/Annual Fall Meeting of the Biomedical-Engineering-Society (EMBS 2002 BMES) CY OCT 23-26, 2002 CL HOUSTON, TX SP Engn Med & Biol Soc, Biomed Engn Soc, Natl Sci Fdn, Natl Inst Hlth, Natl Inst Biomed Imaging & Bioengn, Whitaker Fdn DE anhydrobiosis; desiccation; extra cellular matrix; biopreservation; trehalose; tissue engineering AB The biopreservation sciences have typically relied on the utilization of low temperature to suppress or arrest cellular physiological function in an attempt to extend biological time. Recently, however, several reports have detailed successful anhydrobiotic (dry-state) preservation of cellular systems through the utilization of stabilizing molecules such as trehalose. In this study we investigated the influence of cell-substrate interaction during and following desiccation on cell survival in a human fibroblast model. Cells were dried on differing culture surfaces after allowing 10min for cell attachment. Desiccated samples (15% residual moisture) were rehydrated and then culture on differing extracellular matrices. Cells cultured on biologically active matrices (collagen, fibronectin, and laminin) following desiccation resulted in a significant improvement (>15%) in cell survival in comparison with poly-L-lysine and plasma treated tissue culture surfaces. Further, both desiccation and subsequent culture of samples on biologically active surfaces resulted in similar to30% increase in overall cell survival in comparison with standard culture. These findings indicate that cell-substrate interactions may play a substantial role in the success of anhydrobiotic preservation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. RP Baust, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-7612-9 J9 P ANN INT IEEE EMBS PY 2002 BP 790 EP 791 PG 2 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging GA BV84T UT WOS:000180194800379 ER PT S AU Acker, JP Fowler, A Toner, M AF Acker, JP Fowler, A Toner, M GP IEEE IEEE IEEE TI Media composition affects the survival of desiccated mammalian cells SO SECOND JOINT EMBS-BMES CONFERENCE 2002, VOLS 1-3, CONFERENCE PROCEEDINGS: BIOENGINEERING - INTEGRATIVE METHODOLOGIES, NEW TECHNOLOGIES SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 24th Annual International Conference of the Engineering-in-Medicine-and-Biology-Society/Annual Fall Meeting of the Biomedical-Engineering-Society (EMBS 2002 BMES) CY OCT 23-26, 2002 CL HOUSTON, TX SP Engn Med & Biol Soc, Biomed Engn Soc, Natl Sci Fdn, Natl Inst Hlth, Natl Inst Biomed Imaging & Bioengn, Whitaker Fdn DE fibroblasts; biopreservation; intracellular trehalose; desiccation AB Efforts to improve the tolerance of mammalian cells to desiccation have focused on the role that sugars have in protecting cells from lethal injury. The objective of this study was to examine the effect that the composition of intra- and extracellular trehalose solutions has on the survival of dried 3T3 fibroblasts. Trehalose was introduced into 3T3 fibroblasts using a genetically-engineered mutant of the pore-forming hemolysin from Staphylococcus aureus. Cells were dried using natural convection at ambient temperatures. Plasma membrane integrity and the ability to grow and divide in culture were used to assess cell survival. We found that the post-rehydration membrane integrity was a function of the residual moisture content of the cells following drying. Adjusting the initial osmolality of the intra- and extracellular sugar solutions to be isotonic by reducing the concentration of buffer resulted in a significant improvement in the membrane integrity and growth of dried cells. In an isotonic solution of 0.2 M trehalose, approximately 80% of cells survived drying. Understanding the biological response to desiccation will be critical in developing effective strategies for the drying of mammalian cells. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. RP Acker, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-7612-9 J9 P ANN INT IEEE EMBS PY 2002 BP 792 EP 793 PG 2 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging GA BV84T UT WOS:000180194800380 ER PT S AU Mokuno, Y Berthiaume, F Yarmush, ML AF Mokuno, Y Berthiaume, F Yarmush, ML GP IEEE IEEE IEEE TI Reconditioning of fatty livers for transplantation increased survival of recipients in a rat model SO SECOND JOINT EMBS-BMES CONFERENCE 2002, VOLS 1-3, CONFERENCE PROCEEDINGS: BIOENGINEERING - INTEGRATIVE METHODOLOGIES, NEW TECHNOLOGIES SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 24th Annual International Conference of the Engineering-in-Medicine-and-Biology-Society/Annual Fall Meeting of the Biomedical-Engineering-Society (EMBS 2002 BMES) CY OCT 23-26, 2002 CL HOUSTON, TX SP Engn Med & Biol Soc, Biomed Engn Soc, Natl Sci Fdn, Natl Inst Hlth, Natl Inst Biomed Imaging & Bioengn, Whitaker Fdn DE fatty liver; steatosis; transplantation; perfusion; rat ID ISCHEMIA AB Fatty livers a very sensitive to ischemia-reperfusion and cold preservation-related injuries, which makes them unaccepatble for liver transplantation. We hypothesized that removal of the excess fat storage from fatty livers can restore their ability to undergo liver transplantation. We obtained fatty livers from rats fed a choline and methionine-deficient diet (CMDD) for 6 wk, stored them in cold hetastarch-free University of Wisconsin solution for 6 h, and transplanted them into normal recipient rats. While recipient rats had a 90% rate of survival after transplantation of control normal "lean" livers, they all died when receiving CMDD rat livers. If CMDD rats were returned to a normal diet for 3 or 7 days prior to donating livers, effectively reducing the fat content of the livers by 33% and 85%, respectively, the recipients survived at rates similar to the controls. Furthermore, we found that it is possible to eliminate excess fat storage from fatty livers by short-term perfusion of fatty livers ex vivo. These results support the notion that liver perfusion could be used to recondition fatty livers and make them suitable for transplantation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. RP Mokuno, Y (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-7612-9 J9 P ANN INT IEEE EMBS PY 2002 BP 794 EP 795 PG 2 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging GA BV84T UT WOS:000180194800381 ER PT S AU Rosinski, M Goumnerov, B Rahme, LG Yarmush, ML Berthiaume, F AF Rosinski, M Goumnerov, B Rahme, LG Yarmush, ML Berthiaume, F GP IEEE IEEE IEEE TI Effect of sepsis after burn injury on the dynamics of granulopoiesis in mice SO SECOND JOINT EMBS-BMES CONFERENCE 2002, VOLS 1-3, CONFERENCE PROCEEDINGS: BIOENGINEERING - INTEGRATIVE METHODOLOGIES, NEW TECHNOLOGIES SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 24th Annual International Conference of the Engineering-in-Medicine-and-Biology-Society/Annual Fall Meeting of the Biomedical-Engineering-Society (EMBS 2002 BMES) CY OCT 23-26, 2002 CL HOUSTON, TX SP Engn Med & Biol Soc, Biomed Engn Soc, Natl Sci Fdn, Natl Inst Hlth, Natl Inst Biomed Imaging & Bioengn, Whitaker Fdn DE granulopoiesis; bone marrow; burn injury; sepsis AB Rational strategies for the treatment of burn injury and infection require an improved understanding of the mechanisms by which immune suppression and pro-inflammatory signals interact. Here we study the dynamics of granulopoiesis in the bone marrow (13M) using a mouse burn/infection model to identify the roles that apoptosis, differentiation, proliferation and release play in the etiology of the immunologic response to burns and superimposed infection. We demonstrate that there is a rapid loss of mature granulocytes (CD11b(+) Ly6G(+)) from the marrow during a primarily septic injury using a clinical isolate of Pseudomonas aeruginosa (PA-14). Due to the short timescale involved massive and specific release of granulocytes from the marrow is the most likely mechanism for the observed dynamics. There is also clear evidence of a drop in the bone marrow cellularity for animals with superimposed burn and sepsis. Using a simple population balance approach we demonstrate that a decreased cell residence time in the mature bone marrow pool could explain the observed rapid decline in its size. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. RP Rosinski, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-7612-9 J9 P ANN INT IEEE EMBS PY 2002 BP 796 EP 797 PG 2 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging GA BV84T UT WOS:000180194800382 ER PT S AU Shito, M Tilles, AW Tompkins, RG Yarmush, ML Toner, M AF Shito, M Tilles, AW Tompkins, RG Yarmush, ML Toner, M GP IEEE IEEE IEEE TI In vivo experience with an extracorporeal flat-plate bioartificial liver: Demonstration of efficacy in treating fulminant hepatic failure SO SECOND JOINT EMBS-BMES CONFERENCE 2002, VOLS 1-3, CONFERENCE PROCEEDINGS: BIOENGINEERING - INTEGRATIVE METHODOLOGIES, NEW TECHNOLOGIES SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 24th Annual International Conference of the Engineering-in-Medicine-and-Biology-Society/Annual Fall Meeting of the Biomedical-Engineering-Society (EMBS 2002 BMES) CY OCT 23-26, 2002 CL HOUSTON, TX SP Engn Med & Biol Soc, Biomed Engn Soc, Natl Sci Fdn, Natl Inst Hlth, Natl Inst Biomed Imaging & Bioengn, Whitaker Fdn DE hepatocyte; bioreactor; animal model; liver failure AB An extracorporeal bioartificial liver (BAL) device has the potential to provide temporary support for patients with fulminant hepatic failure (FHF). The authors developed a flat-plate BAL with an internal membrane oxygenator in which porcine hepatocytes were cultured as a monolayer. The efficacy of this device was tested in an experimental animal model of FHF. Twenty-four hours after cannulation of the left carotid artery and right jugular vein, FHF was induced in rats by administering two intraperitoneal injections of D-galactosamine (GalN) (1.2 g/kg) at a 12 hour interval. The rats were connected to a BAL device 24 hours after the first GalN injection, and underwent extracorporeal perfusion for a duration of 10 hours. Liver-specific markers and animal survival up to 168 hours (7 days) were examined. Significant reductions occurred in the plasma ammonia levels and prothrombin times in the group treated with the seeded BAL device. Animal survival in the group treated with the seeded BAL device was significantly higher (50.0%) than in the control animal group treated with an unseeded BAL device (11.1%). In conclusion, this flat-plate BAL with an internal membrane oxygenator and cultured porcine hepatocytes has yielded encouraging results in the treatment of rats with GalN-induced FHF. C1 Massachusetts Gen Hosp, Shriners Hosp Children, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. RP Shito, M (reprint author), Massachusetts Gen Hosp, Shriners Hosp Children, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-7612-9 J9 P ANN INT IEEE EMBS PY 2002 BP 877 EP 878 PG 2 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging GA BV84T UT WOS:000180194800422 ER PT S AU Vidal-Melo, M Layfield, D Harris, RS Venegas, JG AF Vidal-Melo, M Layfield, D Harris, RS Venegas, JG GP IEEE IEEE IEEE TI Distributions of V/Q heterogeneity during bronchoconstriction measured with pet: Contribution of subresolution heterogeneity to gas exchange impairment SO SECOND JOINT EMBS-BMES CONFERENCE 2002, VOLS 1-3, CONFERENCE PROCEEDINGS: BIOENGINEERING - INTEGRATIVE METHODOLOGIES, NEW TECHNOLOGIES SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 24th Annual International Conference of the Engineering-in-Medicine-and-Biology-Society/Annual Fall Meeting of the Biomedical-Engineering-Society (EMBS 2002 BMES) CY OCT 23-26, 2002 CL HOUSTON, TX SP Engn Med & Biol Soc, Biomed Engn Soc, Natl Sci Fdn, Natl Inst Hlth, Natl Inst Biomed Imaging & Bioengn, Whitaker Fdn DE functional imaging; pulmonary gas exchange; PET; ventilation; perfusion; heterogeneity AB Positron emission tomography (PET) imaging of i.v. injected N-13-labeled saline was used to quantify V/Q heterogeneity and estimate arterial blood gases in methacholine bronchoconstricted sheep. Imaging data were analyzed assuming a uniform V/Q distribution within the resolution elements, and assuming a double compartment model of sub-resolution heterogeneity. Results indicate that V/Q heterogeneity is present within volumes smaller than a spatial resolution of 2.2 cm(3) and that such heterogeneity is responsible for approximately 30% of the total alveolar-arterial O-2 and CO2 gradients. Tracer kinetics analysis of PET images provides a quantitative assessment of global V/Q heterogeneity including that corresponding to length scales smaller than the spatial resolution of the imaging method. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Vidal-Melo, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-7612-9 J9 P ANN INT IEEE EMBS PY 2002 BP 1495 EP 1496 PG 2 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging GA BV84T UT WOS:000180194800732 ER PT S AU Winkler, T Martinez, M Layfield, D Venegas, JG AF Winkler, T Martinez, M Layfield, D Venegas, JG GP IEEE IEEE IEEE TI Estimation of noise-corrected pulmonary blood flow heterogeneity using Positron Emission Tomography SO SECOND JOINT EMBS-BMES CONFERENCE 2002, VOLS 1-3, CONFERENCE PROCEEDINGS: BIOENGINEERING - INTEGRATIVE METHODOLOGIES, NEW TECHNOLOGIES SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 24th Annual International Conference of the Engineering-in-Medicine-and-Biology-Society/Annual Fall Meeting of the Biomedical-Engineering-Society (EMBS 2002 BMES) CY OCT 23-26, 2002 CL HOUSTON, TX SP Engn Med & Biol Soc, Biomed Engn Soc, Natl Sci Fdn, Natl Inst Hlth, Natl Inst Biomed Imaging & Bioengn, Whitaker Fdn DE estimation; heterogeneity; Positron Emission Tomography; pulmonary blood flow ID PET AB The coefficient of Variation (CoV) is frequently used to describe functional or structural heterogeneity but is overestimated by the contribution of noise from the measurement method. We evaluated a method to estimate a noise-corrected heterogeneity. It delivers results with a narrow confidence interval. That method has been used to estimate heterogeneity of pulmonary blood flow in humans as well as in animals. C1 Harvard Univ, Sch Med, Mass Gen Hosp, Dept Anesthesia & Biomed Engn, Boston, MA 02115 USA. RP Winkler, T (reprint author), Harvard Univ, Sch Med, Mass Gen Hosp, Dept Anesthesia & Biomed Engn, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-7612-9 J9 P ANN INT IEEE EMBS PY 2002 BP 1521 EP 1522 PG 2 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging GA BV84T UT WOS:000180194800745 ER PT S AU Toner, M AF Toner, M GP IEEE IEEE IEEE TI Integration of living cells into microsystems technology SO SECOND JOINT EMBS-BMES CONFERENCE 2002, VOLS 1-3, CONFERENCE PROCEEDINGS: BIOENGINEERING - INTEGRATIVE METHODOLOGIES, NEW TECHNOLOGIES SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 24th Annual International Conference of the Engineering-in-Medicine-and-Biology-Society/Annual Fall Meeting of the Biomedical-Engineering-Society (EMBS 2002 BMES) CY OCT 23-26, 2002 CL HOUSTON, TX SP Engn Med & Biol Soc, Biomed Engn Soc, Natl Sci Fdn, Natl Inst Hlth, Natl Inst Biomed Imaging & Bioengn, Whitaker Fdn C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02115 USA. RP Toner, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02115 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-7612-9 J9 P ANN INT IEEE EMBS PY 2002 BP 1698 EP 1699 PG 2 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging GA BV84T UT WOS:000180194800836 ER PT J AU Jaeckel, E AF Jaeckel, E TI Animal models of autoimmune hepatitis SO SEMINARS IN LIVER DISEASE LA English DT Review DE experimental autoimmune hepatitis; tolerance; anergy; deletion; immune regulation; cytokines; regulatory cells ID T-CELL TOLERANCE; SINUSOIDAL ENDOTHELIAL-CELLS; VIRUS TRANSGENIC MICE; TUMOR-NECROSIS-FACTOR; POLYGLANDULAR SYNDROME TYPE-1; MEMBRANE LIPOPROTEIN LSP; DEPENDENT LIVER-INJURY; CONCANAVALIN-A; IN-VIVO; PERIPHERAL TOLERANCE AB Autoimmune hepatitis (AIH) is difficult to study in humans because of the late diagnosis, the heterogenic genetic background and the lack of tissue specimens. Therefore, animal models have been used for more than 90 years to study liver-specific immune regulation. This article summarizes how early studies of experimental AIH established the importance of T cells for causing the liver injury and how regulatory pathways were detected. Studies in transgenic models demonstrated that T cells can be tolerant to liver antigens by ignorance, deletion, anergy, and receptor downregulation. They furthermore defined functions in antigen presentation for hepatocytes and sinusoidal endothelial cells. Studies in cytokine-induced models show common effector cascades resulting from T-cell activation and the interaction of innate and adaptive immune response. The use of animal models of AIH will improve our understanding of the pathophysiology of the disease and might help to explore new possibilities for therapy and prevention. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Jaeckel, E (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Smith 734,1 Jimmy Fund Way, Boston, MA 02115 USA. NR 93 TC 18 Z9 21 U1 0 U2 4 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PY 2002 VL 22 IS 4 BP 325 EP 337 DI 10.1055/s-2002-35703 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 617NC UT WOS:000179366900003 PM 12447705 ER PT B AU Sang, CN AF Sang, CN BE Yezierski, RP Burchiel, KJ TI Glutamate receptor antagonists in central neuropathic pain following spinal cord injury SO SPINAL CORD INJURY PAIN: ASSESSMENT, MECHANISMS, MANAGEMENT SE PROGRESS IN PAIN RESEARCH AND MANAGEMENT LA English DT Proceedings Paper CT 3rd International-Association-for-the-Study-of-Pain-Research Symposium CY APR 16-19, 2001 CL PHOENIX, AZ SP Int Assoc Stud Pain, Barrow Neurol Fdn, Elan Pharmaceut, Endo Pharmaceut, Janssen Pharmaceut, Kent Waldrep Natl Paraly Fdn, Medtron Corp, Paralyzed Vet Amer, Pfizer Pharmaceut, Pharmac Corp, Purdue Fredrick, Miami Project ID METHYL-D-ASPARTATE; DOSE-ESCALATION SAFETY; DOUBLE-BLIND; ORAL KETAMINE; POSTHERPETIC NEURALGIA; NMDA ANTAGONIST; CENTRAL SENSITIZATION; REMACEMIDE HYDROCHLORIDE; MEDIATED NEUROTOXICITY; SECONDARY HYPERALGESIA C1 Massachusetts Gen Hosp, Clin Trials Program, MGH Pain Ctr, Boston, MA 02114 USA. RP Sang, CN (reprint author), Harvard Univ, Sch Med, Dept Anaesthesia, 55 Fruit St,Clin 3, Boston, MA 02114 USA. NR 115 TC 2 Z9 2 U1 0 U2 0 PU INT ASSOC STUDY PAIN (IASP) PRESS PI SEATTLE PA 909 NE 43RD ST, SUITE 304, SEATTLE, WA 98105 USA BN 0-931092-43-4 J9 PROG PAIN RES MANAG PY 2002 VL 23 BP 365 EP 377 PG 13 WC Anesthesiology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA BU79V UT WOS:000177028900022 ER PT J AU Preffer, FI Dombkowski, D Sykes, M Scadden, D Yang, YG AF Preffer, FI Dombkowski, D Sykes, M Scadden, D Yang, YG TI Lineage-negative side-population (SP) cells with restricted hematopoietic capacity circulate in normal human adult blood: Immunophenotypic and functional characterization SO STEM CELLS LA English DT Article DE stem cells; hematopoietic stem cells; T cells; NK cells ID BONE-MARROW CELLS; COMPLEMENT REGULATORY PROTEINS; STEM-CELLS; IN-VIVO; DENDRITIC CELLS; T-CELLS; REPOPULATING ACTIVITY; NATURAL-KILLER; DYE EFFLUX; MICE AB Side-population (SP) cells are a recently described rare cell population detected in selected tissues of various mammalian species, but not yet described in the peripheral circulation. In the present study, we have identified for the first time SP cells in lineage-negative adult human blood and have provided an extensive functional and immunophenotypic characterization of these cells. Adult peripheral blood was depleted of mature leukocyte cell types by density gradient and immunomagnetic separation. The SP cell population was identified by its characteristic Hoechst 33342 pro. rile. Immunophenotypic analysis revealed that blood SP cells expressed high levels of CD45, CD59, CD43, CD49d, CD31, and integrin markers and lacked CD34. Highly purified SP cells were put into cobblestone area-forming cell (CAFC), long-term culture-initiating cell (LTC-IC), and liquid cell culture assays; repopulating assays were performed utilizing nonobesc diabetic/severe combined immunodeficient mice. Circulating SP cells were shown to exhibit verapamil sensitivity and a low growth rate. LTC-IC, CAFC, and engraftment assays indicated that circulating SP cells had lost the multipotentiality described in murine bone marrow SP cells. However, outgrowth of mature cell types from liquid cell culture suggests the presence of common lymphoid (T and natural killer) and dendritic cell precursor(s) within circulating SP cell populations. The absence of SP cell growth in the LTC-IC, CAFC, and repopulating assays might be intrinsic to the tissue source (marrow versus blood) or species (mouse versus human) tested. Thus, human blood SP cells, although rare, may serve as a source of selected leukocyte progenitor cells. The immunophenotype of circulating SP cells may provide clues to their seeding and homing capacity. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Dept Pathol, Charlestown, MA USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Charlestown, MA USA. Massachusetts Gen Hosp, AIDS Res Ctr, Dept Med, Charlestown, MA USA. RP Preffer, FI (reprint author), Massachusetts Gen Hosp E, Dept Pathol, Charlestown Navy Yard 7140,149 13th St, Charlestown, MA 02129 USA. NR 45 TC 42 Z9 47 U1 0 U2 3 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2002 VL 20 IS 5 BP 417 EP 427 DI 10.1634/stemcells.20-5-417 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 599PF UT WOS:000178343700006 PM 12351812 ER PT J AU Figlewicz, DP Van Dijk, G Wilkinson, CW Gronbeck, P Higgins, M Zavosh, A AF Figlewicz, D. P. Van Dijk, G. Wilkinson, C. W. Gronbeck, P. Higgins, M. Zavosh, A. TI Effects of Repetitive Hypoglycemia on Neuroendocrine Response and Brain Tyrosine Hydroxylase Activity in the Rat SO STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS LA English DT Article DE Catecholamines; Glucocorticoids; Neuroglucopenia; Stress ID DEPENDENT DIABETES-MELLITUS; INTENSIVE INSULIN THERAPY; VENTROMEDIAL HYPOTHALAMUS; PARAVENTRICULAR NUCLEUS; GENE-EXPRESSION; UNAWARENESS; RELEASE; COUNTERREGULATION; CORTICOSTERONE; STRESS AB Hypoglycemia-associated autonomic failure (HAAF) is a syndrome of acute adaptation to a metabolic stressor, in which neuroendocrine responses to repetitive hypoglycemic bouts are blunted. The CNS mechanisms that contribute to HAAF are unknown. In the present study, we modeled HAAF in the rat and measured the activity of tyrosine hydroxylase (TH) as an index of acute noradrenergic activation, to test the hypothesis that noradrenergic activation of the hypothalamus might be impaired. In association with a significant counter-regulatory response to a single bout of hypoglycemia (elevated corticosterone, catecholamines, and glucagon), TH activity was elevated overall in brainstem NE cell body areas and hypothalamus. With multiple hypoglycemic episodes in a 24 h period, the counter-regulatory response was blunted, and hypothalamic TH activity was comparable to that of saline-infused controls. In a similar paradigm, multiple bouts of CNS neuroglucopenia did not blunt the hyperglycemic or corticosterone responses, and were required for elevation of TH activity. This alternate response pattern suggests that insulin-induced hypoglycemia and cerebral neuroglucopenia represent somewhat different metabolic stressors at the CNS. C1 [Figlewicz, D. P.; Gronbeck, P.; Higgins, M.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Figlewicz, D. P.; Zavosh, A.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Van Dijk, G.] Univ Groningen, Dept Anim Physiol, NL-9750 AA Haren, Netherlands. [Wilkinson, C. W.] VA Puget Sound Hlth Care Syst, GRECC, Seattle, WA 98195 USA. [Wilkinson, C. W.] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. RP Figlewicz, DP (reprint author), VA Puget Sound Hlth Care Syst, 1660 So Columbian Way, Seattle, WA 98108 USA. EM latte@u.washington.edu OI van Dijk, Gertjan/0000-0002-6565-4019 FU American Diabetes Association; Juvenile Diabetes Foundation; NIH [DK40963]; Department of Veterans Affairs; Dutch Diabetes Foundation FX The authors gratefully acknowledge the technical assistance of Libby Colasurdo, Carl Sikkema, Laura Beth Johnson, Anne Ferrel, and Rachael Bomar in these studies. Support for these studies was provided by the American Diabetes Association and the Juvenile Diabetes Foundation; and by NIH DK40963; the Department of Veterans Affairs; and the Dutch Diabetes Foundation. NR 34 TC 9 Z9 9 U1 1 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1025-3890 J9 STRESS JI Stress PY 2002 VL 5 IS 3 BP 217 EP 226 DI 10.1080/1025389021000010558 PG 10 WC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences SC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences & Neurology GA V19RV UT WOS:000208090400007 PM 12186684 ER PT J AU Yamada, K Wu, O Gonzalez, RG Bakker, D Ostergaard, L Copen, WA Weisskoff, RM Rosen, BR Yagi, K AF Yamada, K Wu, O Gonzalez, RG Bakker, D Ostergaard, L Copen, WA Weisskoff, RM Rosen, BR Yagi, K TI Magnetic resonance perfusion-weighted imaging of acute cerebral infarction - Effect of the calculation methods and underlying vasculopathy SO STROKE LA English DT Article DE brain; diffusion; magnetic resonance imaging; perfusion; stroke, acute ID HIGH-RESOLUTION MEASUREMENT; CAROTID-ARTERY OCCLUSION; TRACER BOLUS PASSAGES; BLOOD-FLOW; HYPERACUTE STROKE; CEREBROVASCULAR-DISEASE; COMPUTED-TOMOGRAPHY; COMBINED DIFFUSION; DWI/PWI MISMATCH; TRANSIT-TIME AB Background and Purpose-Various calculation methods are available to estimate the transit-time on MR perfusion-weighted imaging (PWI). Each method may affect the results of PWI. Steno-occlusive disease in the parent vessels is another factor that may affect the results of the PWI. The purpose of this study was to elucidate the effect of the calculation methods and underlying vasculopathy on PWI. Methods-From a pool of 113 patients who had undergone PWI during the study period, a total of 12 patients with nonlacunar ischemic strokes who were scanned within 24 hours after onset of symptom were selected for the study. The patient population consisted of 6 patients who had extracranial internal carotid artery stenosis (>70%) and 6 individuals without stenosis. Seven different postprocessing methods were evaluated: first moment, ratio of area to peak, time to peak (TTP), relative TTP, arrival time, full-width at half-maximum, and deconvolution methods. Follow-up MR or CT images were used to determine the areas that evolved into infarcts, which served as the gold standard. Sensitivity and specificity of each transit time technique were calculated. Results-Calculation methods with high sensitivity were the first moment (sensitivity, 74%), TTP (sensitivity, 77%), and deconvolution methods (sensitivity, 81% to 94%). Between the 2 groups with and without internal carotid artery stenosis, the specificity of most of the techniques was lower in the internal carotid artery stenosis group. The first moment and deconvolution methods maintained relatively high specificity even in the stenosis group. Conclusions-The calculation technique and presence of underlying, vasculopathy have a direct impact on the results of PWI. The methods with high sensitivity even in the presence of steno-occlusive disease were the first moment and deconvolution methods with arterial input function derived from the peri-infarct arteries; the deconvolution method was the superior choice because of higher lesion conspicuity. C1 Kyoto Prefectural Univ Med, Dept Radiol, Kamigyo Ku, Kyoto 6028566, Japan. Kyoto Prefectural Univ Med, Dept Math, Kyoto 6028566, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Boston, MA USA. Aarhus Univ Hosp, Dept Neuroradiol, DK-8000 Aarhus, Denmark. RP Yamada, K (reprint author), Kyoto Prefectural Univ Med, Dept Radiol, Kamigyo Ku, Kajii Cho,Kawaramachi Hirokoji Sagaru, Kyoto 6028566, Japan. RI Bonefeld, Birgit/B-7936-2010; Ostergaard, Leif/A-9281-2008 OI Ostergaard, Leif/0000-0003-2930-6997 NR 29 TC 86 Z9 87 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 BP 87 EP 94 DI 10.1161/hs0102.101893 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700019 PM 11779894 ER PT J AU Rosand, J Hylek, EM Knudsen, KA Cho, HS Greenberg, SM AF Rosand, J Hylek, EM Knudsen, KA Cho, HS Greenberg, SM TI Factor XIII Val34Leu and protection from warfarin-related intracerebral hemorrhage SO STROKE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 MA 14 BP 344 EP 344 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700087 ER PT J AU Sumii, T Lo, EH AF Sumii, T Lo, EH TI Involvement of matrix metalloproteinase in thrombolysis-associated hemorrhagic transformation after embolic focal ischemia in rats SO STROKE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 MA 29 BP 347 EP 347 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700102 ER PT J AU Schaefer, PW Hassankhani, A Ronald, C Koroshetz, WJ Rordorf, G Schwamm, LH Buonanno, F Gonzalez, RG AF Schaefer, PW Hassankhani, A Ronald, C Koroshetz, WJ Rordorf, G Schwamm, LH Buonanno, F Gonzalez, RG TI Partial reversal of DWI abnormalities in stroke patients undergoing thrombolysis: Evidence of DWI and ADC thresholds SO STROKE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 MA 84 BP 357 EP 357 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700157 ER PT J AU McDonald, CT O'Donnell, J Bemporad, J Greer, D Lee, KE Ougorets, I Rosand, J Buonanno, F Schwamm, LH Rordorf, G Putman, C Koroshetz, WJ AF McDonald, CT O'Donnell, J Bemporad, J Greer, D Lee, KE Ougorets, I Rosand, J Buonanno, F Schwamm, LH Rordorf, G Putman, C Koroshetz, WJ TI The clinical utility of intravenous integrilin combined with intra-arterial tissue plasminogen activator in acute ischemic stroke: The MGH experience SO STROKE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 MA 96 BP 359 EP 359 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700169 ER PT J AU Huang, ZH Fujioka, M Liao, JK Moskowitz, MA AF Huang, ZH Fujioka, M Liao, JK Moskowitz, MA TI Dexamethasone decreased infarct size after focal ischemia by eNOS dependent mechanisms SO STROKE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 MA 101 BP 360 EP 360 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700174 ER PT J AU Lev, MH Hunter, GJ Hamberg, LM Schwamm, LH Buonanno, FS Zaatari, M Kim, J McDonald, CT Rordorf, GA Koroshetz, WJ Gonzalez, RG Schaefer, PW AF Lev, MH Hunter, GJ Hamberg, LM Schwamm, LH Buonanno, FS Zaatari, M Kim, J McDonald, CT Rordorf, GA Koroshetz, WJ Gonzalez, RG Schaefer, PW TI CT versus MRI in acute stroke: Comparison of perfusion abnormalities at the infarct core SO STROKE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Hariri High Sch II, Beirut, Lebanon. Mt Sinai Sch Med, New York, NY 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 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 MA P36 BP 368 EP 368 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700215 ER PT J AU Swap, CJ Lev, MH McDonald, CT Koroshetz, WJ Rordorf, GA Buonanno, FS Rosand, J Bemporad, J O'Donnell, J Putman, CM Schwamm, LH AF Swap, CJ Lev, MH McDonald, CT Koroshetz, WJ Rordorf, GA Buonanno, FS Rosand, J Bemporad, J O'Donnell, J Putman, CM Schwamm, LH TI Degree of oligemia by perfusion-weighted CT and risk of hemorrhage after IA thrombolysis SO STROKE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 MA P40 BP 369 EP 369 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700219 ER PT J AU Topcuoglu, MA Singhal, AB Buonanno, FS AF Topcuoglu, MA Singhal, AB Buonanno, FS TI Stroke in endocarditis: Analysis of 101 cases SO STROKE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 MA P69 BP 374 EP 374 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700248 ER PT J AU Huang, ZH Austin, S Salomone, S Plumier, JC FitzGerald, G Bonventre, J Moskowitz, MA AF Huang, ZH Austin, S Salomone, S Plumier, JC FitzGerald, G Bonventre, J Moskowitz, MA TI Enhanced susceptibility to focal ischemic injury in mice lacking prostacyclin receptors SO STROKE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Univ Penn, Philadelphia, PA 19104 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 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 MA P81 BP 376 EP 376 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700260 ER PT J AU Schlaug, G Feske, SK Babikian, VL Safi, C Thaler, D Henderson, GV Kase, CS O'Donoghue, M Levine, J Larson, R Moyer, P Schwamm, LH AF Schlaug, G Feske, SK Babikian, VL Safi, C Thaler, D Henderson, GV Kase, CS O'Donoghue, M Levine, J Larson, R Moyer, P Schwamm, LH TI Components of intra-hospital delay times in patients eligible for t-PA SO STROKE LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Med Ctr, Boston, MA USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. St Elizabeths Med Ctr, Boston, MA USA. Faulkner Hosp, Boston, MA USA. Boston EMS, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 MA P108 BP 381 EP 381 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700287 ER PT J AU Feske, SK Schlaug, G Schwamm, LH Thaler, D Kase, CS Safi, C Mitchell, PM Linfante, R Levine, J Babikian, VL AF Feske, SK Schlaug, G Schwamm, LH Thaler, D Kase, CS Safi, C Mitchell, PM Linfante, R Levine, J Babikian, VL TI Factors affecting delivery of thrombolytics in the city of Boston SO STROKE LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Boston Med Ctr, Boston, MA USA. Boston EMS, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 MA P145 BP 388 EP 388 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700324 ER PT J AU Sugimori, H Wada, K Finklestein, SP AF Sugimori, H Wada, K Finklestein, SP TI The effect of endogenous vs. exogenous basic fibroblast growth factor in reducing infarct volume following focal cerebral ischemia in mice SO STROKE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 MA P210 BP 399 EP 399 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700388 ER PT J AU Maynard, KI Ayoub, IA AF Maynard, KI Ayoub, IA TI Nicotinamide reduces cerebral infarction and improves neurological deficits following transient focal cerebral ischemia: Therapeutic window SO STROKE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Aventis Pharmaceut Inc, Bridgewater, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 MA P231 BP 403 EP 403 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700409 ER PT J AU Wang, XY Mori, T Sumii, T Lo, EH AF Wang, XY Mori, T Sumii, T Lo, EH TI Profiles of caspase activation and effects of caspase inhibitors after hemoglobin exposure in rat cortical neurons SO STROKE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Med Sch, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 MA P229 BP 403 EP 403 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700407 ER PT J AU Asahi, M Sumil, T Itohara, S Fini, ME Lo, EH AF Asahi, M Sumil, T Itohara, S Fini, ME Lo, EH TI Matrix metalloproteinase 2 gene knockout has no effect on brain injury after focal cerebral ischemia SO STROKE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Tufts Univ, Boston, MA 02111 USA. RIKEN, Hiroshima, Japan. RI Itohara, Shigeyoshi/I-8769-2012 OI Itohara, Shigeyoshi/0000-0002-2410-9989 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 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 MA P251 BP 407 EP 407 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700429 ER PT J AU Magura, S Schildhaus, S Rosenblum, A Gastfriend, D AF Magura, S Schildhaus, S Rosenblum, A Gastfriend, D TI Substance user treatment program quality: Selected topics SO SUBSTANCE USE & MISUSE LA English DT Article DE substance dependency treatment; program quality; treatment outcomes; cocaine dependency treatment; patient placement matching; evidence-based treatment ID DRUG-ABUSE TREATMENT; OUTPATIENT BEHAVIORAL TREATMENT; FOLLOW-UP OUTCOMES; COCAINE ABUSERS; METHADONE PATIENTS; DEPENDENCE; ADDICTION; PSYCHOTHERAPY; ABSTINENCE; ISSUES AB This panel explores the "state of the art" in conceptualization and research pertinent to program quality in substance user treatment. First, seven critical questions for program quality are identified and discussed. Second, a recent national evaluation of treatment examines the implications of long-term patient outcomes for treatment quality. Third, a large number of clinical trials of behavioral and pharmacological treatments for cocaine dependence were conducted during the 1990s; this research is synthesized and interpreted. Fourth, progress is reported in improving the quality of treatment through standardized criteria for patient placement matching. C1 Natl Dev & Res Inst, New York, NY 10010 USA. Univ Chicago, NORC, Washington, DC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Dept Psychiat, Boston, MA 02115 USA. RP Magura, S (reprint author), Natl Dev & Res Inst, 71 W 23rd St,8th Floor, New York, NY 10010 USA. FU NIDA NIH HHS [5 R01 DA06959, DA08781] NR 70 TC 10 Z9 10 U1 0 U2 3 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2002 VL 37 IS 8-10 BP 1185 EP 1214 DI 10.1081/JA-120004179 PG 30 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 581XG UT WOS:000177319400016 PM 12180561 ER PT J AU Daley, J AF Daley, J TI Invited commentary: Quality of care and the volume-outcome relationship - What's next for surgery? SO SURGERY LA English DT Editorial Material ID IMPROVE C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Partners Healthcare Syst, Boston, MA USA. RP Daley, J (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. NR 15 TC 27 Z9 27 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD JAN PY 2002 VL 131 IS 1 BP 16 EP 18 DI 10.1067/msy.2002.120237 PG 3 WC Surgery SC Surgery GA 520GF UT WOS:000173772100003 PM 11812958 ER PT J AU Sweeney, T Rattner, DW AF Sweeney, T Rattner, DW TI Robotically assisted minimally invasive biliary surgery in a porcine model SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE robotics; laparoscopic surgery; bile duct injury; laparoscopic cholecystectomy; laparoscopic common bile duct exploration AB Background: A robotic surgery system has the potential both to reduce the effects of tremor and fatigue and to enhance dexterity in the performance of complex, fine endo-surgical tasks. We report a prospective study of robotically assisted minimally invasive biliary surgery in a porcine model using the Zeus robotic surgical system (Computer Motion, Goleta, Ca. USA). Methods: For this study, 50-kg domestic swine were used. Minimally invasive robotically assisted cholecystectomy was performed in 16 animals. either longitudinal or transverse common bile duct incision, T-tube placement, and suture repair of the common bile duct. Retrieval of 12 simulated bile duct calculi was attempted. Eight animals were monitored for 6 weeks postoperatively. Liver function tests and cholangiography were performed 2 and 6 weeks after surgery. Results: The median setup time for the robotic system was 45 min (range, 10-120 min). The median operative time was 40 min (range, 25-60 min) for cholecystectomy and 80 min (range, 40-165 min) for bile duct dissection. exploration. and repair. Of 12 bile duct calculi. I I were retrieved successfully. Cholangiography demonstrated no leaks, and the anastomotic stenotic index (diameter of the proximal bile duct divided by the diameter of distal bile duct) at 6 weeks was 0.98. The results of the liver function tests remained normal in all animals. One postoperative death unrelated to operative technique occurred. Complications included one minor splenic laceration and two intraoperative gallbladder perforations. Conclusions: Robotically assisted minimally invasive biliary surgery in this animal model is both feasible and safe. The Zeus system provides enhanced dexterity, which facilitates precise laparoscopic suture repair of small bile ducts. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Wang ACC, Harvard Ctr Minimally Invas Surg, Boston, MA 02114 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Dept Surg, 337 Parkman St, Boston, MA 02114 USA. NR 8 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD JAN PY 2002 VL 16 IS 1 BP 138 EP 141 DI 10.1007/s00464-001-8110-1 PG 4 WC Surgery SC Surgery GA 507ZA UT WOS:000173060500032 PM 11961624 ER PT J AU Pham, W Weissleder, R Tung, CH AF Pham, W Weissleder, R Tung, CH TI Intermolecular [8+2] cycloaddition reactions of 2H-3-methoxycarbonylcyclohepta[b]furan-2-one with vinyl ethers: an approach to bicyclo[5.3.0]azulene derivatives SO TETRAHEDRON LETTERS LA English DT Article ID ANALOGS AB Substituted bicyclo[5,3,0]azulene compounds are synthesized by intermolecular [8+2] cycloaddition reactions of lactone 1 with vinyl ethers-acetal decomposition products-are described. The reactions were found to be temperature and solvent dependent. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Tung, CH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St, Charlestown, MA 02129 USA. OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [R21 CA088365, R21 CA088365-01, R33 CA088365] NR 8 TC 10 Z9 10 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD JAN 1 PY 2002 VL 43 IS 1 BP 19 EP 20 DI 10.1016/S0040-4039(01)02061-5 PG 2 WC Chemistry, Organic SC Chemistry GA 503YC UT WOS:000172828400006 PM 20740048 ER PT J AU Delgado, JC Baena, A Thim, S Yunis, EJ Goldfeld, AE AF Delgado, JC Baena, A Thim, S Yunis, EJ Goldfeld, AE TI The effect of aspartic acid in position 57 of the beta chain of HLA-DQ on the rate of progression to pulmonary tuberculosis SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. Cambodian Hlth Comm, Phnom Penh, Cambodia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PY 2002 VL 59 SU 2 BP 31 EP 31 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 564JM UT WOS:000176311300095 ER PT J AU Anaya, VI Romero, T Pinto, C Husain, Z Sofia, DR Flores-Villanueva, P Yunis, EJ AF Anaya, VI Romero, T Pinto, C Husain, Z Sofia, DR Flores-Villanueva, P Yunis, EJ TI HLA-DQB1*0602 is a marker for patients with convulsive disorders SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Wallace Labs, Cranbury, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PY 2002 VL 59 SU 2 BP 56 EP 56 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 564JM UT WOS:000176311300177 ER PT J AU Azocar, J Clavijo, O Yunis, EJ AF Azocar, J Clavijo, O Yunis, EJ TI HLA class II associations with control of HCV viremia SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PY 2002 VL 59 SU 2 BP 68 EP 68 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 564JM UT WOS:000176311300218 ER PT J AU Gutierrez, M Yunis, E Burdett, L Stoddard, J Ng, J Fernandez-Vina, M Hartzman, RJ AF Gutierrez, M Yunis, E Burdett, L Stoddard, J Ng, J Fernandez-Vina, M Hartzman, RJ TI Low frequency of null alleles in bone marrow registry donors investigated by comparison of serologic testing with 13th IWH trays and sequence based methods SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 CW Bill Young DoD Marrow Program, Kensington, NSW, Australia. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PY 2002 VL 59 SU 2 BP 94 EP 95 PG 2 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 564JM UT WOS:000176311300309 ER PT J AU Romero, T Husain, Z Yu, N Pinto, C Yunis, EJ AF Romero, T Husain, Z Yu, N Pinto, C Yunis, EJ TI Linkage disequilibrium of HLA-E alleles with HLA-A and HLA-B SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 Amer Red Cross, Dedham, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PY 2002 VL 59 SU 2 BP 97 EP 97 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 564JM UT WOS:000176311300317 ER PT J AU Goldfeld, AE Baena, A Leung, JY Sullivan, AD Landires, I Vasquez-Luna, N Quinones-Berrocal, J Fraser, PA Uko, GP Delgado, JC Thim, S Meshnick, SR Nyirenda, T Yunis, EJ AF Goldfeld, AE Baena, A Leung, JY Sullivan, AD Landires, I Vasquez-Luna, N Quinones-Berrocal, J Fraser, PA Uko, GP Delgado, JC Thim, S Meshnick, SR Nyirenda, T Yunis, EJ TI TNF-alpha promoter single nucleotide polymorphisms are markers of human ancestry SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 Ctr Blood Res, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Hosp Antonio Lorena, Cuzco, Peru. Univ Mangochi, Dist Hosp, Mangochi, Malawi. Cambodian Hlth Comm, Phnom Penh, Cambodia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PY 2002 VL 59 SU 2 BP 131 EP 131 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 564JM UT WOS:000176311300426 ER PT J AU Vamvakas, EC Carven, JH AF Vamvakas, EC Carven, JH TI Exposure to allogeneic plasma and risk of postoperative pneumonia and/or wound infection in coronary artery bypass graft surgery SO TRANSFUSION LA English DT Article ID RAT CARDIAC ALLOGRAFTS; HLA CLASS-I; BLOOD-TRANSFUSION; FAS LIGAND; INTRATHYMIC INOCULATION; COLORECTAL-CARCINOMA; WHOLE-BLOOD; CANCER; RECURRENCE; TOLERANCE AB BACKGROUND: A relationship may exist between the immunomodulatory effects of allogeneic blood transfusion and the volume of transfused allogeneic plasma and/or the number of transfused plasma-containing units. STUDY DESIGN AND METHODS: The records of 416 consecutive patients undergoing coronary artery bypass graft operations at the Massachusetts General Hospital were reviewed. Exposure to allogeneic plasma in units of transfused RBCs, platelets, FFP, and cryoprecipitate was recorded, and diagnoses of postoperative pneumonia and wound infection were made by CDC criteria. The association between postoperative infection and exposure to allogeneic plasma was calculated by logistic regression analyses adjusting for the effects of confounding factors that related to severity of illness, difficulty of operation, and risk of postoperative pneumonia. RESULTS: Two hundred seventy-four patients received (mean +/- SE) 636.2 +/- 64.3 mL of allogeneic plasma, contained in 8.5 +/- 0.7 units of blood components. Sixty-four patients (15.4%) developed pneumonia and/or wound infection, and 54 (13.0%) developed pneumonia. Patients who did (n = 64) or did not develop infection received 956.6 +/- 180.6 and 321.3 +/- 39.6 mL of plasma, respectively (p<0.0001). In multivariate analyses, the volume of transfused allogeneic plasma was not associated with postoperative pneumonia and/or wound infection (p = 0.24), pneumonia (p = 0.21), or wound infection (p = 0.74), Similarly, the number of transfused plasma-containing units was not associated with these outcomes (p = 0.08, p = 0.08, and p = 0.46, respectively). CONCLUSION. A relationship between the exposure to allogeneic plasma and the risk of postoperative pneumonia and/or wound infection was not detected in this study population. C1 NYU, Med Ctr, Blood Bank, Sch Med,Dept Pathol, New York, NY 10016 USA. Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. RP Vamvakas, EC (reprint author), NYU, Med Ctr, Blood Bank, Sch Med,Dept Pathol, RRG-17,400 E 34th St, New York, NY 10016 USA. NR 40 TC 23 Z9 23 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 JAN PY 2002 VL 42 IS 1 BP 107 EP 113 DI 10.1046/j.1537-2995.2002.00001.x PG 7 WC Hematology SC Hematology GA 522TQ UT WOS:000173913400017 PM 11896321 ER PT J AU Friedmann, AM Sengul, H Lehmann, H Schwartz, C Goodman, S AF Friedmann, AM Sengul, H Lehmann, H Schwartz, C Goodman, S TI Do basic laboratory tests or clinical observations predict bleeding in thrombocytopenic oncology patients? SO TRANSFUSION MEDICINE REVIEWS LA English DT Review ID PROPHYLACTIC PLATELET TRANSFUSION; ACUTE MYELOID-LEUKEMIA; DOSE-RESPONSE; DOUBLE-BLIND; THRESHOLD; POLICY; CONTROVERSIES; 20,000/MU-L; MEDICINE; CHILDREN AB The purpose of this study was to determine which clinical and laboratory features correlate with serious hemorrhage in thrombocytopenic oncology patients. A retrospective review was conducted of all thrombocytopenic adult patients admitted to the Johns Hopkins Oncology Center, Baltimore, MD, over the last 10 years. We performed multiple logistic regression analysis on 2942 patients looking at the frequency of serious bleeding as a function of platelet count and numerous features that may correlate with hemorrhage. Multivariate analyses showed no relationship between either the first morning platelet count or the lowest platelet count of the day and the risk of hemorrhage. Of the other features we examined, several correlated independently with bleeding, including uremia (odds ratio [OR] 1.64; 95% confidence interval [CI], 1.40 to 1.92), hypoalbuminemia (OR 1.54,95% Cl, 1.33 to 1.79), recent bone marrow transplantation (OR 1.32; 95% Cl, 1.22 to 1.43), and recent hemorrhage (OR 6.72; 95% Cl, 5.53 to 8.18). Leukopenia was associated with a decreased risk of bleeding (OR 0.70; 95% Cl, 0.60 to 0.82). Although this large study identified a number of clinical and laboratory features that correlated significantly with bleeding, the ORs of these factors were not large and all were much less than previous bleeding. These findings suggest that the major goal of transfusion support should be the aggressive therapeutic use of blood products rather than prophylactic use based on such weak clinical correlates and on the platelet count, which was not a correlate at all in multivariate analysis. Copyright (C) 2002 by W.B. Saunders Company. C1 Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. RP Friedmann, AM (reprint author), Massachusetts Gen Hosp, 55 Fruit St,WAC-712, Boston, MA 02114 USA. FU NCI NIH HHS [CA01709] NR 33 TC 73 Z9 75 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 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD JAN PY 2002 VL 16 IS 1 BP 34 EP 45 DI 10.1053/tmrv.2002.29403 PG 12 WC Hematology SC Hematology GA 511JL UT WOS:000173260800004 PM 11788928 ER PT J AU Manis, JP Tian, M Alt, FW AF Manis, JP Tian, M Alt, FW TI Mechanism and control of class-switch recombination SO TRENDS IN IMMUNOLOGY LA English DT Review ID IMMUNOGLOBULIN CLASS-SWITCH; CYTIDINE DEAMINASE AID; DOUBLE-STRAND BREAKS; HEAVY-CHAIN LOCUS; SOMATIC HYPERMUTATION; B-CELLS; CIRCULAR DNA; SACCHAROMYCES-CEREVISIAE; GERMLINE TRANSCRIPTION; REGION RECOMBINATION AB Class-switch recombination (CSR) occurs by an unusual and intriguing mechanism that has not been clearly elucidated as yet. Currently, we know that this mechanism involves recombination between large and highly repetitive switch (S) regions, is targeted by S-region transcription and requires the activity of the newly discovered activation-induced deaminase (AID). In this review, we discuss the potential role of these factors in CSR, discuss potential relationships between CSR and somatic hypermutation, and speculate how CSR and related mechanisms might contribute to genomic instability. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. FU NIAID NIH HHS [AI31541] NR 91 TC 272 Z9 275 U1 1 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD JAN PY 2002 VL 23 IS 1 BP 31 EP 39 DI 10.1016/S1471-4906(01)02111-1 PG 9 WC Immunology SC Immunology GA 510GR UT WOS:000173200800006 PM 11801452 ER PT J AU Taylor, KJW Merritt, C Piccoli, C Schmidt, R Rouse, G Fornage, B Rubin, E Georgian-Smith, D Winsberg, F Goldberg, B Mendelson, E AF Taylor, KJW Merritt, C Piccoli, C Schmidt, R Rouse, G Fornage, B Rubin, E Georgian-Smith, D Winsberg, F Goldberg, B Mendelson, E TI Ultrasound as a complement to mammography and breast examination to characterize breast masses SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE breast cancer; mammography; ultrasound; breast biopsy ID FOLLOW-UP; SONOGRAPHIC APPEARANCE; DUPLEX SONOGRAPHY; CANCER DETECTION; DOPPLER; DIAGNOSIS; LESIONS; BIOPSY; BENIGN; FIBROADENOMA AB This study was designed to determine if complementary ultrasound (US) imaging and Doppler could decrease the number of biopsies for benign masses. A total of 761 breast masses were sequentially scored on a level of suspicion (LOS) of 1-5, where 1 represented low, and 5 was a high suspicion of malignancy, for mammography, US, and color flow with pulse Doppler (DUS). After biopsy, the results were analyzed using 2 X 2 contingency tables and ROC analysis, for mammography alone and in combination with US and DUS. The addition of US increased the specificity from 51.4% to 66.4% at a prevalence of 31.3% malignancy. ROC analysis showed that the addition of US significantly improved the performance over mammography alone in women < 55 years old (p=0.049); > 55 years old (p=0.029); masses < 1 cm (p=0.016) and masses > 1 cm (p=0.016). These results show that the addition of US to mammography alone could substantially reduce the number of breast biopsies for benign disease. (E-mail: Kenneth.Taylor@yale.edu) (C) 2002 World Federation for Ultrasound In Medicine Biology. C1 Yale Univ, Sch Med, New Haven, CT 06520 USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. NYU, New York, NY USA. Loma Linda Univ, Loma Linda, CA 92350 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Alabama, Birmingham, AL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Chicago, Chicago, IL 60637 USA. Western Penn Hosp, Pittsburgh, PA 15224 USA. RP Taylor, KJW (reprint author), Yale Univ, Sch Med, 333 Cedar St, New Haven, CT 06520 USA. NR 38 TC 68 Z9 70 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD JAN PY 2002 VL 28 IS 1 BP 19 EP 26 AR PII S0301-5629(01)00491-4 DI 10.1016/S0301-5629(01)00491-4 PG 8 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 529UL UT WOS:000174317900002 PM 11879948 ER PT J AU Platz, EA Krithivas, K Kantoff, PW Stampfer, MJ Giovannucci, E AF Platz, EA Krithivas, K Kantoff, PW Stampfer, MJ Giovannucci, E TI ATAAA repeat upstream of glutathione S-transferase P1 and prostate cancer risk SO UROLOGY LA English DT Article ID GSTP1 GENE; PI-GENE; METHYLATION; ASSOCIATION; CARCINOMA; POLYMORPHISMS; EXPRESSION; ISOENZYMES; BLADDER; ISLAND AB Objectives. Expression of glutathione S-transferase pi (GSTP1), a detoxification enzyme that also binds steroid hormones, is diminished or absent in human prostate tumors possibly because of promoter hypermethylation. Upstream of its promoter is a polymorphic ATAAA repeat of unknown functional significance. We evaluated whether this polymorphism is associated with prostate cancer. Methods. Incident prostate cancer cases (n=186) and controls (n=398) were identified among participants in the Physicians' Health Study. DNA was extracted from peripheral whole blood, and the region encompassing the repeat was amplified using fluorescent-labeled primers. The fragments were run on polyacrylamide gels and sized by Genescan software. Alleles were designated by polymerase chain reaction fragment size. We estimated the relative risk of prostate cancer for the GSTP1 gene ATAAA alleles and genotype from logistic regression models controlling for age and cigarette smoking status. Results. Fifteen GSTP1 ATAAA alleles were observed; C (19 repeats), G (21 repeats), and 1 (22 repeats) accounted for 80% among the controls. Compared with C, the relative risks for prostate cancer were I. 1 (95% confidence interval 0.7 to 1.7) for G and 0.8 (95% confidence interval 0.6 to 1.2) for 1. The relative risks were also not statistically significantly elevated for the less common alleles. Compared with CC, the most common genotype, none of the other genotypes appeared to be associated with an increased risk of prostate cancer. Conclusions. The results of this study do not support an important role of the ATAAA repeat polymorphism upstream from the GSTP1 promoter in prostate cancer incidence. Urology 59: 159-164, 2002. (C) 2002, Elsevier Science Inc. C1 Johns Hopkins Univ, Bloomsburg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Dept Adult Oncol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA 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. RP Platz, EA (reprint author), Johns Hopkins Univ, Bloomsburg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,Room E6143, Baltimore, MD 21205 USA. FU NCI NIH HHS [CA-42182]; NHLBI NIH HHS [HL-34595, HL-26490] NR 26 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD JAN PY 2002 VL 59 IS 1 BP 159 EP 164 DI 10.1016/S0090-4295(01)01498-4 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 513DP UT WOS:000173362900038 PM 11796315 ER PT B AU Sands, BE AF Sands, BE BE Rachmilewitz, D Modigliani, R Sachar, DB Podolsky, DK Tozun, N TI Thalidomide: is it justified for usage in Crohn's disease? SO VI INTERNATIONAL SYMPOSIUM ON INFLAMMATORY BOWEL DISEASES SE FALK SYMPOSIUM LA English DT Proceedings Paper CT Falk Symposium 123/6th International Symposium on Inflammatory Bowel Diseases CY SEP 02-05, 2001 CL ISTANBUL, TURKEY ID NECROSIS-FACTOR-ALPHA; ESOPHAGEAL ULCERS; CHIRAL INVERSION; HIV; ANGIOGENESIS; ENANTIOMERS; GENERATION; ADULTS; TRIAL C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Sands, BE (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St GRJ-7, Boston, MA 02114 USA. NR 34 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-8773-2 J9 FALK SYMP PY 2002 VL 123 BP 149 EP 158 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BU95J UT WOS:000177476000018 ER PT B AU Podolsky, DK AF Podolsky, DK BE Rachmilewitz, D Modigliani, R Sachar, DB Podolsky, DK Tozun, N TI Investing in the future of inflammatory bowel disease research: if I had 10 million dollars, how would I spend it? SO VI INTERNATIONAL SYMPOSIUM ON INFLAMMATORY BOWEL DISEASES SE FALK SYMPOSIUM LA English DT Proceedings Paper CT Falk Symposium 123/6th International Symposium on Inflammatory Bowel Diseases CY SEP 02-05, 2001 CL ISTANBUL, TURKEY C1 Massachusetts Gen Hosp, Ctr Study IBD, Unit G1, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Ctr Study IBD, Unit G1, 55 Fruit St,RJ-719, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-8773-2 J9 FALK SYMP PY 2002 VL 123 BP 225 EP 231 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BU95J UT WOS:000177476000026 ER PT J AU Barnes, E Lauer, G Walker, B Klenerman, P AF Barnes, E Lauer, G Walker, B Klenerman, P TI T cell failure in hepatitis C virus infection SO VIRAL IMMUNOLOGY LA English DT Review ID IMMUNE-RESPONSE; LYMPHOCYTE RESPONSES; EFFECTOR FUNCTION; PERSISTENCE; CARRIERS; ANTIGEN; HEALTHY; EPITOPE; MICE; SPECIFICITY C1 Univ Oxford, Nuffield Dept Med, Oxford OX1 3SY, England. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Barnes, E (reprint author), Univ Oxford, Nuffield Dept Med, Peter Medwar Bldg Pathogen Res,S Parks Rd, Oxford OX1 3SY, England. NR 41 TC 18 Z9 19 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0882-8245 J9 VIRAL IMMUNOL JI Viral Immunol. PY 2002 VL 15 IS 2 BP 285 EP 293 DI 10.1089/08828240260066233 PG 9 WC Immunology; Virology SC Immunology; Virology GA 563QZ UT WOS:000176268200005 PM 12081013 ER PT J AU Dinh, T Pham, H Veves, A AF Dinh, T Pham, H Veves, A TI Emerging treatments in diabetic wound care SO WOUNDS-A COMPENDIUM OF CLINICAL RESEARCH AND PRACTICE LA English DT Article ID FIBROBLAST GROWTH-FACTOR; CULTURED EPIDERMAL ALLOGRAFTS; HUMAN SKIN EQUIVALENT; FOOT ULCERS; VENOUS ULCERS; DOUBLE-BLIND; DRESSINGS; KERATINOCYTES; EXPRESSION; MANAGEMENT AB This paper reviews the physiology of wound healing and properties of the "ideal" dressing and also reviews advanced wound therapeutics and dressings, such as growth factors and biological skin substitutes. C1 Beth Israel Deaconess Med Ctr, Microcirculat Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Beth Israel Deaconess Foot Ctr, Boston, MA USA. Joslin Beth Israel Deaconess Foot Ctr, Dept Surg, Boston, MA USA. RP Veves, A (reprint author), Beth Israel Deaconess Med Ctr, Microcirculat Lab, Palmer 317,W Campus,1 Deaconess Rd, Boston, MA 02215 USA. OI Pham, Hau/0000-0003-4583-9873 NR 47 TC 7 Z9 9 U1 2 U2 5 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1044-7946 J9 WOUNDS JI Wounds-Compend. Clin. Res. Pract. PD JAN-FEB PY 2002 VL 14 IS 1 BP 2 EP 10 PG 9 WC Dermatology; Surgery SC Dermatology; Surgery GA 607QE UT WOS:000178801600003 ER PT J AU Buhler, L Deng, S O'Neil, J Kitamura, H Koulmanda, M Baldi, A Rahier, J Alwayn, IPJ Appel, JZ Awwad, M Sachs, DH Weir, G Squifflet, JP Cooper, DKC Morel, P AF Buhler, L Deng, S O'Neil, J Kitamura, H Koulmanda, M Baldi, A Rahier, J Alwayn, IPJ Appel, JZ Awwad, M Sachs, DH Weir, G Squifflet, JP Cooper, DKC Morel, P TI Adult porcine islet transplantation in baboons treated with conventional immunosuppression or a non-myeloablative regimen and CD154 blockade SO XENOTRANSPLANTATION LA English DT Article DE anti-CD154 monoclonal antibody; diabetes; islets of Langerhans; pancreatectomy; pig-to-primate model; xenotransplantation ID BONE-MARROW TRANSPLANTATION; HUMAN-FETAL PANCREAS; XENOGRAFT REJECTION; ANTI-GAL-ALPHA-1-3GAL ANTIBODY; TOLERANCE INDUCTION; IN-VITRO; T-CELLS; PIG; MICE; MACROPHAGE AB The aim of the present study was to assess the survival of adult porcine islets transplanted into baboons receiving either (1) conventional triple drug immunosuppressive therapy or (2) a non-myeloablative regimen and an anti-CD154 monoclonal antibody (mAb) aimed at tolerance-induction. Group 1 baboons (n=3) were pancreatectomized prior to intraportal injection of 10 000 porcine islet equivalents (IE)/kg and immunosuppressed with anti-thymocyte globulin (ATG), cyclosporine and azathioprine. In Group 2 (n=2), non-pancreatectomized baboons underwent induction therapy with whole body and thymic irradiation, and ATG. Extracorporeal immunoadsorption (EIA) of anti-Galphalalphal,3Gal (Gal) antibody was carried out. Maintenance therapy was with cobra venom factor, cyclosporine, mycophenolate mofetil, methylprednisolone and anti-CD154 mAb. Porcine islets were injected intraportally (14 000 and 32 000 IE/kg, respectively) and high-dose pig mobilized peripheral blood proigenitor cells (3 x 10(10) cells/kg) were infused into a systemic vein. Porcine islets were also implanted in the sternomastoid muscle to facilitate subsequent biopsies. In both groups, porcine C-peptide was measured, and histological examination of liver or sternomastoid muscle biopsies was performed at regular intervals. In Group 1, total pancreatectomy reduced human C-peptide to <0.1 ng/ml and induced insulin-requiring diabetes. The transplantation of porcine islets was followed by normalization of glycemia for 15-24 h, Porcine C-peptide was detected only transiently immediately after porcine islet injection (maximum 0.12 ng/ml). Histological examination of liver biopsies taken between days 2 and 19 did not reveal viable islets, but necrotic cell structures with mononuclear cell infiltrates were identified in portal venules. In Group 2, injection of porcine islets into non-pancreatectomized recipients induced a transient hypoglycemia (2-4 h) requiring concentrated intravenous dextrose administration. Porcine C-peptide was detectable for 5 and 3 days (maximum 2.8 and 1.0 ng/ml), respectively. Baboon #4 died on day 12 from small bowel intussusception. Liver and sternomastoid muscle biopsies showed well-preserved porcine islets, staining positive for insulin and glucacon, without signs of rejection. In baboon 95, viable islets were detected in the sternomastoid muscle biopsy on day 14, but not on day 28 or thereafter. A progressive mononuclear cell and macrophage infiltration was seen in the biopsies. In conclusion, conventional immunosuppression allowed survival of porcine islets in baboons for < 24 h. The non-myeloablative regimen prolonged survival of porcine islets for > 14 days. However, despite depletion of T cells. anti-Gal antibody and complement, and CD154-blockade. porcine islets were rejected by day 28. These results suggest that powerful innate immune responses are involved in rejection of discordant xenogeneic islets. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Univ Geneva, Hop Cantonal, Chirurg Digest Clin, CH-1211 Geneva 4, Switzerland. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplant Unit, Boston, MA USA. Univ Louvain, Dept Renal & Pancreat Transplantat & Pathol, Brussels, Belgium. Immerge Biotherapeut Inc, Charlestown, MA USA. RP Buhler, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [5P01 AI39755] NR 33 TC 63 Z9 66 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JAN PY 2002 VL 9 IS 1 BP 3 EP 13 DI 10.1034/j.1399-3089.2002.1o044.x PG 11 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 523TC UT WOS:000173970800001 PM 12005102 ER PT B AU Huang, PL Zhang, L Huang, PL Lee-Huang, S AF Huang, PL Zhang, L Huang, PL Lee-Huang, S GP MONDUZZI EDITORE MONDUZZI EDITORE MONDUZZI EDITORE TI cDNA microarrays of host cell gene expression during HIV-1 infection and with antiviral treatment SO XIV INTERNATIONAL AIDS CONFERENCE: BASIC SCIENCES LA English DT Proceedings Paper CT 14th International AIDS Conference CY JUL 07-12, 2002 CL BARCELONA, SPAIN SP Univ N Carolina, Gen Clin Res Ctr, UNC Ctr AIDS Res, Natl Inst Hlth, Swiss Natl AIDS Res Program, Bristol-Myers Squibb Co, Boehringer Ingelheim, GlaxoWellcome Res & Dev, HIV Antiviral Res ID MAP30; INHIBITION; AGENTS; VIRUS; GAP31 AB We used pathway-specific cDNA microarrays to define the expression profiles of cellular genes in MT2 HIV target cells that were uninfected, infected with HIV-1, and infected and treated with anti-HIV agents MAP30 and GAP31. We analyzed the expression profiles of 92 genes from signal transduction, apoptosis, cell cycle and cytokine pathways, and identified 18 genes modulated by HIV-1 infection. HIV-1 infection downregulates the expression of caspase 3, caspase 6, Fas, gadd45, NFkappaB, DR5, and TRAIL. On the other hand, HIV-1 infection upregulates heat shock protein genes hsp27, hsp90, and the human homolog of mdm2. Treatment with the anti-HIV agents MAP30 and GAP31 prevents these changes. MAP30 and GAP31 also upregulate the expression of ATF-2, Egr-1, cyclin B1, cyclin D2, IL-1alpha, IL-6, IL-12alpha and TNFbeta genes. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Huang, PL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY PY 2002 BP 169 EP 172 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA BV88Y UT WOS:000180303800031 ER PT J AU Vazquez, F Grossman, SR Takahashi, Y Rokas, MV Nakamura, N Sellers, WR AF Vazquez, F Grossman, SR Takahashi, Y Rokas, MV Nakamura, N Sellers, WR TI Phosphorylation of the PTEN tail acts as an inhibitory switch by preventing its recruitment into a protein complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; TYROSINE-PHOSPHATASE; PDZ DOMAIN; GENE; BINDING; GROWTH AB PTEN is a tumor suppressor protein that functions, in large part, by dephosphorylating the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate and by doing so antagonizing the action of phosphoinositide 3-kinase. PTEN structural domains include an N-terminal phosphatase domain, a lipid-binding C2 domain, and a 50-amino acid C-terminal tail that contains a PDZ binding sequence. We showed previously that phosphorylation of the PTEN tail negatively regulates PTEN activity. We now show that phosphorylated PTEN exists in a monomeric "closed" conformation and has low affinity for PDZ domain-containing proteins. Conversely, when unphosphorylated, PTEN is in an "open" conformation, is recruited into a high molecular weight complex (PTEN-associated complex), and strongly interacts with PDZ-containing proteins such as MAGI-2. As a consequence, when compared with wild-type PTEN, the phosphorylation-deficient mutant form of PTEN strongly cooperates with MAGI-2 to block Akt activation. These results indicate that phosphorylation of the PTEN tail causes a conformational change that results in the masking of the PDZ binding domain. Consequently, the ability of PTEN to bind to PDZ domain-containing proteins is reduced dramatically. These data suggest that phosphorylation of the PTEN tail suppresses the activity of PTEN by controlling the recruitment of PTEN into the PTEN-associated complex. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Adult Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Sellers, WR (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Adult Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. NR 21 TC 253 Z9 264 U1 2 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 28 PY 2001 VL 276 IS 52 BP 48627 EP 48630 DI 10.1067/jbc.C100556200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 522XK UT WOS:000173922100004 PM 11707428 ER PT J AU Keire, DA Anton, P Faull, KF Ruth, E Walsh, JH Chew, P Quisimoro, D Territo, M Reeve, JR AF Keire, DA Anton, P Faull, KF Ruth, E Walsh, JH Chew, P Quisimoro, D Territo, M Reeve, JR TI Diethyl phthalate, a chemotactic factor secreted by Helicobacter pylori SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DI(2-ETHYLHEXYL) PHTHALATE; GASTRIC-CARCINOMA; PROTEIN-1 MCP-1; INFECTION; METABOLITES; CHEMOKINES; LEUKOCYTES; MUCOSA; IDENTIFICATION; HEMODIALYSIS AB The structure of a small-molecule, non-peptide chemotactic factor has been determined from activity purified to apparent homogeneity from Helicobacter pylori supernatants. H. pylori was grown in brucella broth media until one liter of solution had 0.9 absorbance units. The culture was centrifuged, and the bacteria re-suspended in physiological saline and incubated at 37 degreesC for 4 h. A monocyte migration bioassay revealed the presence of a single active chemotactic factor in the supernatant from this incubation. The chemotactic factor was concentrated by solid phase chromatography and purified by reverse phase high pressure liquid chromatography. The factor was shown to be indistinguishable from diethyl phthalate (DEP) on the basis of multiple criteria including nuclear magnetic resonance spectroscopy, electron impact mass spectroscopy, UV visible absorption spectrometry, GC and high pressure liquid chromatography retention times, and chemotactic activity toward monocytes. Control experiments with incubated culture media without detectable bacteria did not yield detectable DEP, suggesting it is bacterially derived. It is not known if the bacteria produce diethyl phthalate de novo or if it is a metabolic product of a precursor molecule present in culture media. DEP produced by H. pylori in addition to DEP present in man-made products may contribute to the high levels of DEP metabolites observed in human urine. DEP represents a new class of chemotactic factor. C1 Vet Affairs Greater Los Angeles Hlth Care Syst, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Civil & Environm Engn, Environm Engn Analyt Chem Lab, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Chem & Biochem, Pasarow Mass Spectrometry Lab, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Div Hematol Oncol, Los Angeles, CA 90024 USA. City Hope Res Inst, Beckman Res Inst, Div Immunol, Duarte, CA 91010 USA. Univ Calif Los Angeles, Sch Med, Div Digest Dis, Los Angeles, CA 90024 USA. RP Reeve, JR (reprint author), Vet Affairs Greater Los Angeles Hlth Care Syst, CURE Digest Dis Res Ctr, Bldg 115,Rm 115,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCI NIH HHS [CA3572]; NIAID NIH HHS [K-24 AI 01610, AI 28697]; NIDDK NIH HHS [DK-41301] NR 52 TC 11 Z9 18 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 28 PY 2001 VL 276 IS 52 BP 48847 EP 48853 DI 10.1074/jbc.M109811200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 522XK UT WOS:000173922100031 PM 11677249 ER PT J AU Shimizu, N Guo, J Gardella, TJ AF Shimizu, N Guo, J Gardella, TJ TI Parathyroid hormone (PTH)-(1-14) and -(1-11) analogs conformationally constrained by alpha-aminoisobutyric acid mediate full agonist responses via the juxtamembrane region of the PTH-1 receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID (PTH)/PTH-RELATED PEPTIDE RECEPTOR; N-TERMINAL REGION; EXTRACELLULAR LOOP; CROSS-LINKING; LIGAND; FRAGMENTS; PROTEIN; PTH-(1-34); SITE; SELECTIVITY AB The N-terminal portion of parathyroid hormone is critical for PTH-1 receptor (P1R) activation and has been postulated to be a-helical when bound to the receptor. We investigated whether substitution of the sterically hindered and helix-promoting amino acid a-aminoisobutyric acid (Aib) in N-terminal PTH oligopeptides would improve the capacity of the peptide to activate the P1R. Analysis of the effects of individual Aib substitutions at each position in [Ala 3,12 Gln(10), Har(11),Trp(14)]PTH(1-14)NH2, ([M]PTH(1-14)) on cAMP-stimulating potency in HKRK-B28 cells revealed that Aib at most positions diminished potency; however, Aib at positions 1 and 3 enhanced potency. Thus [Aib(1,3)M]PTH(1-14) was similar to100-fold more potent than [M]PTH(1-14) (EC50 = 1.1 +/- 0.1 and 100 +/- 20 rim, respectively), similar to100,000-fold more potent than native PTH(1-14), and 2-fold more potent than PTH(1-34). The shorter peptide, [Aib(1,) M-3]PTH(1-11), was also fully efficacious and 1,000-fold more potent than [M]PTH(1-11) (EC50 4 +/- 1 nM versus 3 +/- 1 mum). In cAMP stimulation assays performed in COS-7 cells expressing P1R-delNt, a receptor that lacks most of the N-terminal extracellular domain, [Aib(1,3)M]PTH(1-14) was 50-fold more potent than [M]PTH(1-14) (EC50 = 0.7 +/- 0.2 versus 40 +/- 2 nm) and 1,000-fold more potent than PTH(1-34) (EC50 = 700 rim). [Aib(1,3),M]PTH(1-14), but not PTH(1-34), inhibited the binding of I-125[Aib(1),(3),Nle(8),Gln(10),Har(11),Ala(12) Trp(14),Arg(19),Tyr(21)]PTH(1-21)NH2 to hP1R-delNt (IC50 = 1,600 200 nm). The Aib(1),(3) substitutions in otherwise unmodified PTH(1-34) enhanced potency and binding affinity on hP1R-delNt, but they had no effect for this peptide on hP1R-WT. Circular dichroism spectroscopy demonstrated that the Aib-1,3 substitutions increased helicity in all peptides tested, including PTH(1-34). The overall data thus suggest that the N-terminal residues of PTH are intrinsically disordered but become conformationally constrained, possibly as an a-helix, upon interaction with the activation domain of the PTH-1 receptor. C1 Massachusetts Gen Hosp, Endocrine Unit, 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 46 TC 63 Z9 65 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 28 PY 2001 VL 276 IS 52 BP 49003 EP 49012 DI 10.1074/jbc.M106827200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 522XK UT WOS:000173922100052 PM 11604398 ER PT J AU Eskandar, EN Cosgrove, GR Shinobu, L AF Eskandar, EN Cosgrove, GR Shinobu, L TI Surgical treatment of Parkinson disease SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID DEEP BRAIN-STIMULATION; HIGH-FREQUENCY STIMULATION; TERM FOLLOW-UP; SUBTHALAMIC NUCLEUS; POSTEROVENTRAL PALLIDOTOMY; GLOBUS-PALLIDUS; STEREOTAXIC PALLIDOTOMY; UNILATERAL PALLIDOTOMY; ELECTRICAL-STIMULATION; THALAMIC-STIMULATION C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Cosgrove, GR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, 15 Parkman St,ACC 331, Boston, MA 02114 USA. NR 61 TC 13 Z9 13 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 26 PY 2001 VL 286 IS 24 BP 3056 EP 3059 DI 10.1001/jama.286.24.3056 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 505QM UT WOS:000172927100002 PM 11754653 ER PT J AU Dolor, RJ Witsell, DL Hellkamp, AS Williams, JW Califf, RM Simel, DL AF Dolor, RJ Witsell, DL Hellkamp, AS Williams, JW Califf, RM Simel, DL CA CAFFS Investigators TI Comparison of cefuroxime with or without intranasal fluticasone for the treatment of rhinosinusitis - The CAFFS trial: A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE MAXILLARY SINUSITIS; ORAL ANTIBIOTIC-THERAPY; CULTURES; SPRAY; IRRIGATION; CHILDREN; VALIDITY; ADJUNCT AB Context It is not known whether intranasal corticosteroids are beneficial to treat acute rhinosinusitis in patients with a history of chronic or recurrent sinus symptoms. Objective To assess whether the addition of an intranasal corticosteroid to antibiotic therapy affects the speed and rate of recovery of such patients with acute rhinosinusitis. Design, Setting, and Patients A double-blind, randomized, placebo-controlled multicenter trial of 95 patients (median age, 39 years) with a history of recurrent sinusitis or chronic rhinitis and evidence of acute infection by sinus radiograph or nasal endoscopy, which was conducted from October 1998 through April 2000 at 22 sites (12 primary care and 10 otolaryngology). Intervention Two puffs (total dose, 200 mug) of fluticasone propionate (n=47) or placebo nasal spray (n=48) in each nostril once daily for 21 days; all received 2 puffs of xylometazoline hydrochloride in each nostril twice daily for 3 days and 250 mg of cefuroxime axetil twice daily for 10 days. Main Outcome Measure Time to clinical success (patient reported cured or much improved) during telephone follow-up at 10, 21, and 56 days. Results A total of 88 patients (93%) completed follow-up. Patients recorded their symptoms, work assessment, and compliance during the 3-week treatment phase. Patients receiving fluticasone achieved a significantly higher rate of clinical success than patients receiving placebo (93.5% vs 73.9%; P=.009). Patients treated with fluticasone improved significantly more rapidly (median of 6.0 days to clinical success) vs patients in the placebo group (median of 9.5 days; P=.01). Conclusions The addition of fluticasone to xylometazoline and antimicrobial therapy with cefuroxime improves clinical success rates and accelerates recovery of patients with a history of chronic rhinitis or recurrent sinusitis who present for treatment of acute rhinosinusitis. C1 Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27705 USA. Durham Vet Affairs Med Ctr, Dept Med, Durham, NC USA. Durham Vet Affairs Med Ctr, Dept Surg, Div Internal Med, Durham, NC USA. Duke Univ, Med Ctr, Div Otolaryngol, Durham, NC USA. Univ Texas, Hlth Sci Ctr, Audie L Murphy Div, S Texas Vet Affairs Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Div Internal Med, San Antonio, TX USA. RP Dolor, RJ (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 31 TC 96 Z9 101 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 26 PY 2001 VL 286 IS 24 BP 3097 EP 3105 DI 10.1001/jama.286.24.3097 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 505QM UT WOS:000172927100027 PM 11754675 ER PT J AU Battelli, L Cavanagh, P Intriligator, J Tramo, MJ Henaff, MA Michel, F Barton, JJS AF Battelli, L Cavanagh, P Intriligator, J Tramo, MJ Henaff, MA Michel, F Barton, JJS TI Unilateral right parietal damage leads to bilateral deficit for high-level motion SO NEURON LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; FIRST-ORDER MOTION; BRAIN-DAMAGE; APPARENT MOTION; VISUAL EXTINCTION; SELECTIVE IMPAIRMENT; ATTENTIVE TRACKING; 2ND-ORDER MOTION; NEGLECT PATIENTS; SPATIAL NEGLECT AB Patients with right parietal damage demonstrate a variety of attentional deficits in their left visual field contralateral to their lesion. We now report that patients with right lesions also show a severe loss in the perception of apparent motion in their "good" right visual field ipsilateral to their lesion. Three tests of attention were conducted, and losses were found only in the contralesional fields for a selective attention and a multiple object tracking task. Losses in apparent motion, however, were bilateral in all cases. The deficit in apparent motion in the parietal patients supports previous claims that this relatively effortless percept is mediated by attention. However, the bilateral deficit suggests that the disruption is due to a bilateral loss in the temporal resolution of attention to transient events that drive the apparent motion percept. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Beth Israel Deaconess Med Ctr, Dept Neurol & Opthalmol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. INSERM, U280, F-69008 Lyon, France. RP Battelli, L (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. RI Barton, Jason/A-6362-2012 FU NEI NIH HHS [EY09258] NR 62 TC 102 Z9 104 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD DEC 26 PY 2001 VL 32 IS 6 BP 985 EP 995 DI 10.1016/S0896-6273(01)00536-0 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 504ZT UT WOS:000172886800007 PM 11754832 ER PT J AU Cooley, J Takayama, TK Shapiro, SD Schechter, NM Remold-O'Donnell, E AF Cooley, J Takayama, TK Shapiro, SD Schechter, NM Remold-O'Donnell, E TI The serpin MNEI inhibits elastase-like and chymotrypsin-like serine proteases through efficient reactions at two active sites SO BIOCHEMISTRY LA English DT Article ID HUMAN ALPHA-1-PROTEINASE INHIBITOR; PROSTATE-SPECIFIC ANTIGEN; MUCUS PROTEINASE-INHIBITOR; HUMAN-LEUKOCYTE ELASTASE; MAST-CELL CHYMASE; NEUTROPHIL ELASTASE; CATHEPSIN-G; HUMAN-SEMEN; GRANZYME-B; COMPLEX-FORMATION AB MNEI (monocyte/neutrophil elastase inhibitor) is a 42 kDa serpin superfamily protein characterized initially as a fast-acting inhibitor of neutrophil elastase. Here we show that MNEI has a broader specificity, efficiently inhibiting proteases with elastase- and chymotrypsin-like specificities. Reaction of MNEI with neutrophil proteinase-3, an elastase-like protease, and porcine pancreatic elastase demonstrated rapid inhibition rate constants >10(7) M-1 s(-1). similar to that observed for neutrophil elastase. Reactions of MNEI with chymotrypsin-like proteases were also rapid: cathepsin G from neutrophils (>10(6) M-1 s(-1)), mast cell chymase (>10(5) M-1 s(-1)), chymotrypsin (>10(6) M-1 s(-1)), and prostate-specific antigen (PSA), which had the slowest rate constant at similar to10(4) M-1 s(-1). Inhibition of trypsin-like (plasmin, granzyme A, and thrombin) and caspase-like (granzyme B) serine proteases was not observed or highly inefficient (trypsin), nor was inhibition of proteases from the cysteine (caspase-1 and caspase-3) and metalloprotease (macrophage elastase, MMP-12) families. The stoichiometry of inhibition for all inhibitory reactions was near 1, and inhibitory complexes were resistant to dissociation by SDS, further indicating the specificity of MNEI for elastase- and chymotrypsin-like proteases. Determination of the reactive site of MNEI by N-terminal sequencing and mass analysis of reaction products identified two reactive sites, each with a different specificity. CyS344, which corresponds to Met(358), the P-1 site of alpha1-antitrypsin, was the inhibitory site for elastase-like proteases and PSA, while the preceding residue, Phe(343), was the inhibitory site for chymotrypsin-like proteases. This study demonstrates that MNEI has two functional reactive sites corresponding to the predicted P-1 and P-2 Positions of the reactive center loop. The data suggest that MNEI plays a regulatory role at extravascular sites to limit inflammatory damage due to proteases of cellular origin. C1 Ctr Blood Res, Boston, MA 02115 USA. Univ Washington, Dept Biochem, Seattle, WA 98195 USA. Univ Washington, Dept Urol, Seattle, WA 98195 USA. Brigham & Womens Hosp, Dept Pulm & Crit Care Med, Boston, MA 02115 USA. Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. EM remold@cbr.med.harvard.edu FU NHLBI NIH HHS [HL41579, HL48065]; NIAMS NIH HHS [AR42931]; NIDDK NIH HHS [DK02447] NR 75 TC 94 Z9 97 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 25 PY 2001 VL 40 IS 51 BP 15762 EP 15770 DI 10.1021/bi0113925 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 509NF UT WOS:000173153300035 PM 11747453 ER PT J AU Wieczorek, TJ Krane, JF Domanski, HA Akerman, M Carlen, B Misdraji, J Granter, SR AF Wieczorek, TJ Krane, JF Domanski, HA Akerman, M Carlen, B Misdraji, J Granter, SR TI Cytologic findings in granular cell tumors, with emphasis on the diagnosis of malignant granular cell tumor by fine-needle aspiration biopsy SO CANCER CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT 90th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 03-09, 2001 CL ATLANTA, GEORGIA SP US & Canadian Acad Pathol DE granular cell tumor; fine-needle aspiration biopsy; hyperchromasia; coarse chromatin; malignant AB BACKGROUND. Granular cell tumors (GCTs) are uncommon tumors of putative schwannian derivation that are rarely malignant. Although recent studies have addressed a histologic correlation with malignant behavior, similar studies have not been done on cytologic material. METHODS. The authors evaluated 3 malignant GCTs and 17 benign GCTs (comprising 17 fine-needle aspiration biopsy samples and 3 samples from direct scrapes) for the following cytologic features: hyperchromasia; coarse chromatin; nuclear-to-cytoplasmic (N/C) ratio; nuclear pleomorphism; and vesicular nuclei with enlarged nucleoli, mitoses, necrosis, and spindle cell morphology. RESULTS. Hyperchromasia, coarse chromatin, increased N/C ratio, nuclear pleomorphism, and vesicular nuclei with enlarged nucleoli and spindle cell morphology were associated the most closely with malignancy when they were present throughout the cytologic sample. All were diffusely present in three of three malignant tumors, except vesicular nuclei and spindle cell morphology, which were present diffusely in two tumors and focally in one tumor. By contrast, although one to five of these features were present focally in 8 of 17 benign GCTs, none was present diffusely in any benign GCTs, with one exception, which had a combination of focal nuclear pleomorphism and hyperchromasia together with diffuse vesicular nuclei, large nucleoli, and coarse chromatin. The N/C ratio in this tumor was not increased, and there were no spindle cells or mitoses. Mitoses were present in 2 of 3 malignant GCTs and absent from all 17 benign GCTs. Necrosis was not seen in any tumors. CONCLUSIONS. Malignant GCTs have characteristic cytologic features that differ from those of benign GCTs. However, morphologic heterogeneity precludes definitive classification of some tumors by cytologic features alone. Cancer (Cancer Cytopathol) 2001;93:398-408. (C) 2001 American Cancer Society. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Lund Hosp, Dept Pathol & Cytol, S-22185 Lund, Sweden. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Granter, SR (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 29 TC 17 Z9 19 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD DEC 25 PY 2001 VL 93 IS 6 BP 398 EP 408 DI 10.1002/cncr.10143 PG 11 WC Oncology; Pathology SC Oncology; Pathology GA 504BZ UT WOS:000172838500007 PM 11748580 ER PT J AU Hemler, ME AF Hemler, ME TI Specific tetraspanin functions SO JOURNAL OF CELL BIOLOGY LA English DT Review ID SUPERFAMILY TM4SF PROTEINS; HEPATITIS-C VIRUS; TRANSMEMBRANE-4 SUPERFAMILY; ALPHA-3-BETA-1 INTEGRIN; CD81-DEFICIENT MICE; CELL-SURFACE; CD81; CD9; COMPLEXES; CD151 AB Relatively little attention has been given to the large family of abundantly expressed transmembrane proteins known as tetraspanins. Now, the importance of tetraspanins is strongly supported by emerging genetic evidence, coupled with new insights into the biochemistry and functions of tetraspanin protein complexes. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Rm D-1430,44 Binney St, Boston, MA 02115 USA. NR 56 TC 270 Z9 282 U1 4 U2 9 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 DEC 24 PY 2001 VL 155 IS 7 BP 1103 EP 1107 DI 10.1083/jcb.200108061 PG 5 WC Cell Biology SC Cell Biology GA 507JJ UT WOS:000173023500006 PM 11756464 ER PT J AU Lin, HJ de Carvalho, P Kho, D Tai, CY Pierre, P Fink, GR Pellman, D AF Lin, HJ de Carvalho, P Kho, D Tai, CY Pierre, P Fink, GR Pellman, D TI Polyploids require Bik1 for kinetochore-microtubule attachment SO JOURNAL OF CELL BIOLOGY LA English DT Article DE kinetechore; microtubule; ploidy; Bik1; plus end-tracking protein ID CEREVISIAE MITOTIC SPINDLE; SACCHAROMYCES-CEREVISIAE; BUDDING YEAST; IN-VIVO; PRECOCIOUS SEPARATION; DYNAMIC INSTABILITY; CYTOPLASMIC DYNEIN; BINDING PROTEIN; FISSION YEAST; HUMAN CANCERS AB The attachment of kinetochores to spindle microtubules (MTs) is essential for maintaining constant ploidy in eukaryotic cells. Here, biochemical and imaging data is presented demonstrating that the budding yeast CLIP-170 orthologue Bik1 is a component of the kinetochore-MT binding interface. Strikingly, Bik1 is not required for viability in haploid cells, but becomes essential in polyploids. The ploidy-specific requirement for BIK1 enabled us to characterize BIK1 without eliminating nonhomologous genes, providing a new approach to circumventing the overlapping function that is a common feature of the cytoskeleton. In polyploid cells, Bilk1 is required before anaphase to maintain kinetochore separation and therefore contributes to the force that opposes the elastic recoil of attached sister chromatids. The role of Bik1 in kinetochore separation appears to be independent of the role of Bik1 in regulating MT dynamics. The finding that a protein involved in kinetochore-MT attachment is required for the viability of polyploids has potential implications for cancer therapeutics. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. CNRS Marseille Luminy, INSERM, Ctr Immunol, Marseille, France. MIT, Cambridge, MA 02142 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Pellman, D (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Rm M621A,44 Binney St, Boston, MA 02115 USA. OI pierre, philippe/0000-0003-0863-8255 FU NIGMS NIH HHS [R01 GM55772] NR 76 TC 78 Z9 79 U1 0 U2 2 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 DEC 24 PY 2001 VL 155 IS 7 BP 1173 EP 1184 DI 10.1083/jcb.200108119 PG 12 WC Cell Biology SC Cell Biology GA 507JJ UT WOS:000173023500014 PM 11756471 ER PT J AU Berney, T Buhler, L Caulfield, A Oberholzer, J Toso, C Alejandro, R Cooper, DKC Ricordi, C Morel, P AF Berney, T Buhler, L Caulfield, A Oberholzer, J Toso, C Alejandro, R Cooper, DKC Ricordi, C Morel, P TI Transplantation of islets of Langerhans: new developments SO SWISS MEDICAL WEEKLY LA English DT Review DE diabetes; islets of Langerhans; transplantation; xenotransplantation ID PORCINE ENDOGENOUS RETROVIRUS; TYPE-1 DIABETES-MELLITUS; LONG-TERM SURVIVAL; FETAL PANCREAS; STEM-CELLS; HUMANIZED ANTI-CD154; LYMPHOCYTES-T; RAT ISLETS; IN-VITRO; ALLOGRAFTS AB The clinical results recently reported by the Edmonton group in recipients of allogeneic islet grafts, all of whom achieved at least temporary insulin independence, has rekindled interest in transplantation of islets of Langerhans as a means to cure diabetes. Long-term islet graft survival has been achieved in a non-human primate pre-clinical model with a protocol of T-cell signaling-blockade using a new monoclonal antibody. Islet xenotransplantation (namely the use of animal islets, with the aim of transplanting them into humans), or stem cell technology (the controlled differentiation of stem cells to obtain specialised cells for the treatment of diabetes) are other procedures currently being evaluated in animal models. The recent clinical success suggests that, in the near future, diabetes might be treated by islet transplantation early in the clinical course of the disease before the development of complications, and without the risks associated with conventional immunosuppression. C1 Univ Hosp Geneva, Dept Surg, Clin Chirurg Digest, CH-1211 Geneva 14, Switzerland. Univ Miami, Sch Med, Diabet Res Inst, Miami, FL USA. Harvard Univ, Med Sch, Massachusetts Gen Hosp, Transplatat Biol Res Ctr, Boston, MA USA. RP Buhler, L (reprint author), Univ Hosp Geneva, Dept Surg, Clin Chirurg Digest, CH-1211 Geneva 14, Switzerland. OI Ricordi, Camillo/0000-0001-8092-7153 NR 85 TC 12 Z9 13 U1 1 U2 3 PU E M H SWISS MEDICAL PUBLISHERS LTD PI BASEL PA STEINENTORSTRASSE 13, CH-4-10 BASEL, SWITZERLAND SN 1424-7860 J9 SWISS MED WKLY JI Swiss Med. Wkly. PD DEC 22 PY 2001 VL 131 IS 47-48 BP 671 EP 680 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 541WV UT WOS:000175009700001 PM 11875751 ER PT J AU Geng, LP Rudd, C AF Geng, LP Rudd, C TI Adaptor ADAP (adhesion- and degranulation-promoting adaptor protein) regulates beta 1 integrin clustering on mast cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID T-CELLS; TYROSINE PHOSPHORYLATION; PLATELET ACTIVATION; COLLAGEN RECEPTOR; MOLECULAR-CLONING; CUTTING EDGE; SLP-76; CYTOSKELETON; LYMPHOCYTES; SUBSTRATE AB Aggregation of the high-affinity IgE receptor (FcepsilonRI) activates a tyrosine phosphorylation cascade needed for enhanced adhesion and degranulation events on mast cells. We previously identified the adaptor ADAP (otherwise known as FYB/SLAP) as a modulator of integrin-mediated adhesion of T-cells and mast cells. However, the molecular basis for the effect on beta1 integrin adhesion on mast cells was unclear. In this study, we demonstrate that ADAP can promote the kinetics of beta1 integrin clustering on mast cells. By contrast, the clustering of the FcepsilonRI receptor was unaffected by transfected ADAP, indicating that the promoting effect on clustering was selective for beta1 integrins. These findings extend the modulatory effect of ADAP from beta2 to beta1 members of the integrin family, and provide a molecular basis for the modulatory effect of ADAP on mast cell adhesion. (C) 2001 Elsevier Science. C1 Dana Farber Canc Inst, Dept Canc Immunol, Div Tumor Immunol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Rudd, C (reprint author), Dana Farber Canc Inst, Dept Canc Immunol, Div Tumor Immunol, Boston, MA 02115 USA. NR 38 TC 11 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 21 PY 2001 VL 289 IS 5 BP 1135 EP 1140 DI 10.1006/bbrc.2001.6117 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 513XQ UT WOS:000173406500034 PM 11741310 ER PT J AU Komatsuzaki, K Terashita, K Kinane, TB Nishimoto, I AF Komatsuzaki, K Terashita, K Kinane, TB Nishimoto, I TI Somatostatin type V receptor activates c-Jun N-terminal kinases via G alpha(12) family G proteins SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE somatostatin; somatostatin receptor type V; G(12) family G proteins; c-Jun N-terminal kinases ID TYROSINE PHOSPHATASE SHP-1; STRESS FIBER FORMATION; CELL-PROLIFERATION; FUNCTIONAL-CHARACTERIZATION; SIGNAL-TRANSDUCTION; ADENYLYL-CYCLASE; PITUITARY-CELLS; SUBTYPES SSTR1; ALPHA-SUBUNITS; INHIBITION AB Somatostatin is a neurotransmitter with diverse effects including anti-proliferation in a wide range of normal and neoplastic cells, and occasionally growth stimulatory and neurotrophic actions. Stress-activated protein kinase or c-Jun N-terminal kinase (SAPK/JNK) can also induce growth arrest and occasionally growth stimulation. However, the relationship between somatostatin and SAPK/JNK is less clear. Here we report that the binding of somatostatin to the somatostatin receptor type V (SSTR5) upregulates SAPK/JNK activity. We also show that this activation is mediated by Galpha(12) and Galpha(13). This study demonstrates that SSTR5 is the heptahelical receptor that activates SAPK/JNK via the G(12) family G proteins. (C) 2001 Elsevier Science. C1 Keio Univ, Sch Med, Dept Pharmacol & Neurosci, Shinjuku Ku, Tokyo 1608582, Japan. Massachusetts Gen Hosp, Dept Pediat, Pediat Pulm Serv, Boston, MA 02114 USA. RP Nishimoto, I (reprint author), Keio Univ, Sch Med, Dept Pharmacol, Shinjuku Ku, Tokyo 1608582, Japan. NR 54 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 21 PY 2001 VL 289 IS 5 BP 1211 EP 1217 DI 10.1006/bbrc.2001.6085 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 513XQ UT WOS:000173406500046 PM 11741322 ER PT J AU Gruber, A Wheat, JC Kuhen, KL Looney, DJ Wong-Staal, F AF Gruber, A Wheat, JC Kuhen, KL Looney, DJ Wong-Staal, F TI Differential effects of HIV-1 protease inhibitors on dendritic cell immunophenotype and function. SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; CD4(+) T-CELLS; IN-VITRO; ANTIGEN PRESENTATION; VIRAL PROTEASE; INFECTION; ACTIVATION; RECEPTOR; PATHWAY; SUSCEPTIBILITY AB Recent findings show that human immunodeficiency virus (HIV)-1 protease inhibitors designed to specifically inhibit the aspartic protease of HIV-1 nonetheless exert various effects on immune cell function in vitro and in vivo. Dendritic cells (DC), central players of the immune system, express several aspartic proteases that are important for DC function. In the present study, we demonstrate that all of the HIV-1 protease inhibitors tested affect DC maturation. In addition, saquinavir had a strong inhibitory effect on the T-cell stimulatory capacity of mature DC. In contrast, indinavir had only a slight effect on DC induced T-cell proliferation and allowed efficient transduction of DC with a replication-incompetent HIV-1 vector designed for DC-based immunotherapy. HIV-1 protease inhibitors that have little or no effect on DC function may be preferable for combination with immunotherapy for HIV/AIDS. C1 Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Vet Adm Med Ctr, Infect Dis Div, La Jolla, CA 92093 USA. RP Gruber, A (reprint author), Dana Farber Canc Inst, 44 Binney St,JFB-809,Rm 426, Boston, MA 02115 USA. FU NIAID NIH HHS [AI45992, AI44372, P30 AI36214-06] NR 40 TC 26 Z9 26 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 21 PY 2001 VL 276 IS 51 BP 47840 EP 47843 DI 10.1074/jbc.M105582200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505QL UT WOS:000172927000017 PM 11602580 ER PT J AU Criss, AK Silva, M Casanova, JE McCormick, BA AF Criss, AK Silva, M Casanova, JE McCormick, BA TI Regulation of Salmonella-induced neutrophil transmigration by epithelial ADP-ribosylation factor 6 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOTIDE EXCHANGE FACTOR; PROTEIN-KINASE-C; PHOSPHOLIPASE-D ACTIVITY; CANINE KIDNEY-CELLS; PHOSPHATIDIC-ACID; PLASMA-MEMBRANE; INTESTINAL EPITHELIA; ACTIN CYTOSKELETON; MAMMALIAN-CELLS; FACTOR ARNO AB Salmonella typhimurium elicits an acute inflammatory response in the host intestinal epithelium, characterized by the movement of polymorphonuclear leukocytes (PMN) across the epithelial monolayer to the intestinal lumen. It was recently shown that SipA, a protein secreted by S. typhimurium, is necessary and sufficient to drive PMN transmigration across model intestinal epithelia (Lee, C. A., Silva, M., Siber, A. M., Kelly, A. J., Galyov, E., and McCormick, B. A (2000) Proc. Natl. Acad Sci. USA 97, 12283-12288). However, the epithelial factors responsible for this process have not been identified. Here, for the first time, we demonstrate that S. typhimurium-induced PMN transmigration across Madin-Darby canine kidney-polarized monolayers is regulated by the GTPase ARF6. Apically added S. typhimurium promoted the translocation of ARF6 and its exchange factor ARNO to the apical surface. Overexpression of a dominant-negative mutant of ARF6 inhibited Salmonella-induced PMN transmigration, which was due to a reduction in apical release of the PMN chemoattractant PEEC (pathogen-elicited epithelial chemoattractant), without affecting bacterial internalization. Furthermore, ARF6 and its effector phospholipase D (PLD) were both required for bacteria-induced translocation of protein kinase C (PKC) to membranes. These results describe a novel signal transduction pathway, in which Salmonella initiates an ARF6- and PLD-dependent lipid signaling cascade that, in turn, directs activation of PKC, release of PEEC, and subsequent transepithelial PMN movement. C1 Univ Virginia, Hlth Sci Ctr, Dept Cell Biol, Charlottesville, VA 22908 USA. Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. RP Casanova, JE (reprint author), Univ Virginia, Hlth Sci Ctr, Dept Cell Biol, Box 800732, Charlottesville, VA 22908 USA. FU NIAID NIH HHS [AI-32991]; NIDDK NIH HHS [DK-33506, DK-58536, DK-56754] NR 61 TC 31 Z9 32 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 21 PY 2001 VL 276 IS 51 BP 48431 EP 48439 DI 10.1074/jbc.M106969200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505QL UT WOS:000172927000095 PM 11641400 ER PT J AU Shin, JM Goldshleger, R Munson, KB Sachs, G Karlish, SJD AF Shin, JM Goldshleger, R Munson, KB Sachs, G Karlish, SJD TI Selective Fe2+-catalyzed oxidative cleavage of gastric H+,K+-ATPase - Implications for the energy transduction mechanism of P-type cation pumps SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSPORT ADENOSINE-TRIPHOSPHATASE; SARCOPLASMIC-RETICULUM; ALPHA-SUBUNIT; CONFORMATIONAL TRANSITIONS; STRUCTURAL ASPECTS; CRYSTAL-STRUCTURE; + K+)-ATPASE; H,K ATPASE; H,K-ATPASE; NA,K-ATPASE AB In the presence of ascorbate/H2O2, Fe2+ ions or the ATP-Fe2+ complex catalyze selective cleavage of the alpha subunit of gastric H+, K+-ATPase. The electrophoretic mobilities of the fragments and dependence of the cleavage patterns on E-1 and E-2 conformational states are essentially identical to those described previously for renal Na+, K+-ATPase. The cleavage pattern of H+, K+-ATPase by Fe2+ ions is consistent with the existence of two Fe2+ sites: site I within highly conserved sequences in the P and A domains, and site 2 at the cytoplasmic entrance to trans-membrane segments M3 and MI. The change in the pattern of cleavage catalyzed by Fe2+ or the ATP-Fe2+ complex induced by different ligands provides evidence for large conformational movements of the N, P, and A cytoplasmic domains of the enzyme. The results are consistent with the Ca2+-ATPase crystal structure (Protein Data Bank identification code 1EUL; Toyoshima, C., Nakasako, M., Nomura, H., and Ogawa, H. (2000) Nature 405, 647-655), an E1Ca2+ conformation, and a theoretical model of Ca2+-ATPase in an E2 conformation (Protein Data Bank identification code 1FQU). Thus, it can be presumed that the movements of N, P, and A cytoplasmic domains, associated with the E-1 <----> E-2 transitions, are similar in all P-type ATPases. Fe-2-catalyzed cleavage patterns also reveal sequences involved in phosphate, Mg2+, and ATP binding, which have not yet been shown in crystal structures, as well as changes which occur in E-1 <----> E2 transitions, and subconformations induced by H+, K+-ATPase-specific ligands such as SCH28080. C1 Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. Univ Calif Los Angeles, Dept Physiol, Membrane Biol Lab, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Karlish, SJD (reprint author), Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. FU NIDDK NIH HHS [DK53462, DK41301, DK17294, DK46917] NR 54 TC 24 Z9 24 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 21 PY 2001 VL 276 IS 51 BP 48440 EP 48450 DI 10.1074/jbc.M106864200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505QL UT WOS:000172927000096 PM 11585827 ER PT J AU Mori, T Wang, XY Kline, AE Siao, CJ Dixon, CE Tsirka, SE Lo, EH AF Mori, T Wang, XY Kline, AE Siao, CJ Dixon, CE Tsirka, SE Lo, EH TI Reduced cortical injury and edema in tissue plasminogen activator knockout mice after brain trauma SO NEUROREPORT LA English DT Article DE blood-brain barrier; brain edema; extracellular matrix; neuroprotection; proteolysis ID FOCAL CEREBRAL-ISCHEMIA; CENTRAL-NERVOUS-SYSTEM; NEURONAL DEATH; GENE; MATRIX-METALLOPROTEINASE-9; HIPPOCAMPUS; APOPTOSIS; SEIZURE; DAMAGE; STROKE AB Tissue plasminogen activator (tPA) may play a deleterious role after brain injury. Here, we compared the response to traumatic brain injury in tPA knockout (KO) and wildtype (WT) mice after controlled cortical impact. At 6 h after trauma, blood-brain barrier permeability was equally increased in all mice. However, by 24 h specific gravity measurements of brain edema were significantly worse in WT mice than in KO mice. At 1 and 2 days post-trauma, mice showed deficits in rotarod performance, but by day 7 all mice recovered motor function and there were no differences between WT and KO mice. At 7 days, cortical lesion volumes were significantly reduced in KO mice compared with WT mice. However, there were no significant differences: in CA3 hippocampal neuron survival. These data suggest that tPA amplifies cortical brain damage and edema in this mouse model of traumatic brain injury. NeuroReport 12:4117-4120 (C) 2001 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Neuroprotect Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Charlestown, MA 02129 USA. Univ Pittsburgh, Dept Neurol Surg, Brain Trauma Res Ctr, Pittsburgh, PA 15260 USA. SUNY Stony Brook, Dept Pharmacol, Stony Brook, NY 11794 USA. RP Lo, EH (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, MGH E 149-2322, Charlestown, MA 02129 USA. NR 28 TC 35 Z9 36 U1 0 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 DEC 21 PY 2001 VL 12 IS 18 BP 4117 EP 4120 DI 10.1097/00001756-200112210-00051 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 502LT UT WOS:000172745600062 PM 11742249 ER PT J AU Hooper, BA LaVerde, GC Von Ramm, OT AF Hooper, BA LaVerde, GC Von Ramm, OT TI Design and construction of an evanescent optical wave device for the recanalization of vessels SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT LA English DT Article; Proceedings Paper CT 22nd International Free Electron Laser Conference/7th FEL Users Workshop (FEL 2000) CY AUG 13-18, 2000 CL DUKE UNIV, FREE ELECT LASER LAB, DURHAM, NORTH CAROLINA HO DUKE UNIV, FREE ELECT LASER LAB DE evanescent waves; ablation; atherosclerotic plaque; catheter; free-electron laser ID TRANSMISSION AB Removing atherosclerotic material without transecting the vessel wall is a common problem for vascular surgeons and interventional cardiologists. The goal of this project is to design and construct a device that uses evanescent optical waves for precise, controlled laser ablation. For laser light incident at an angle to an optic-tissue interface greater than or equal to the critical angle, an evanescent optical wave is launched into the tissue. With evanescent optical waves, there is no free-beam propagation and the laser energy can be confined to a layer less than one wavelength thick at the optic-tissue interface. Several device designs have been proposed and constructed. The Duke University Mark III Infrared Free-Electron Laser is used to study energy deposition and ablation mechanisms at sapphire-tissue and zinc sulfide-tissue interfaces. Ablation experiments on human low-density lipoprotein and aorta tissue are presented. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. Duke Univ, Ctr Emerging Cardiovasc Technol, Durham, NC 27708 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Cambridge, MA 02138 USA. RP Hooper, BA (reprint author), Duke Univ, Dept Biomed Engn, Box 90319, Durham, NC 27708 USA. NR 7 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-9002 J9 NUCL INSTRUM METH A JI Nucl. Instrum. Methods Phys. Res. Sect. A-Accel. Spectrom. Dect. Assoc. Equip. PD DEC 21 PY 2001 VL 475 IS 1-3 BP 645 EP 649 DI 10.1016/S0168-9002(01)01691-6 PG 5 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Nuclear; Physics, Particles & Fields SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA 507DN UT WOS:000173011900117 ER PT J AU Usuka, J Grupe, A Germer, S Aud, D Belknap, JK Klein, RF Ahluwalia, MK Peltz, G AF Usuka, J Grupe, A Germer, S Aud, D Belknap, JK Klein, RF Ahluwalia, MK Peltz, G TI In silico mapping of mouse quantitative trait loci - Response SO SCIENCE LA English DT Editorial Material C1 Roche Biosci, Dept Genet & Genom, Palo Alto, CA 94303 USA. Roche Mol Syst, Alameda, CA 94501 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. RP Usuka, J (reprint author), Roche Biosci, Dept Genet & Genom, Palo Alto, CA 94303 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 21 PY 2001 VL 294 IS 5551 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 505QU UT WOS:000172927700003 ER PT J AU Chen, YC Taghian, AG Rosenberg, AE O'Connell, J Okunieff, P Suit, HD AF Chen, YC Taghian, AG Rosenberg, AE O'Connell, J Okunieff, P Suit, HD TI Predictive value of histologic tumor necrosis after radiation SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE radiation; human tumor xenograft; histology; tumor control ID ADVANCED BREAST CANCERS; NEOADJUVANT CHEMOTHERAPY; PEDIATRIC OSTEOSARCOMA; EWINGS-SARCOMA; XENOGRAFTS; EXTREMITIES; EXPERIENCE; CARCINOMAS; CISPLATIN; THERAPY AB Postsurgical evaluation of histologic changes of tumors after preoperative chemotherapy and/or radiotherapy has been a routine clinical practice of pathologists and oncologists. There appears to be secure evidence that the extent of tumor necrosis vs. viable tumor cells postchemotherapy is a clinically useful predictor of outcome. The significance of histologic tumor necrosis after radiotherapy, however, has not been clearly established and deserves further investigation. We investigated the correlation between histological extent of tumor necrosis, survival of tumor transplants, and radiation doses in an experimental model using three human tumor xenografts. Three human tumor cell lines were investigated: STS-26, SCC-21, and HGL-21. Tumors were grown subcutaneously in athymic nude mice and received external beam radiation of different doses. Tumors were excised 2 weeks postirradiation. One-half of the tumor was divided into 1-mm(3) fragments and transplanted to naive mice. The other half was examined for histologic tumor necrosis. Transplant survival was strongly correlated with radiation dose, TCDp (radiation dose that results in local tumor control in proportion, p, to irradiated tumors). In contrast, there was no clear association between transplant survival rate and the extent of tumor necrosis. The experimental model demonstrated a strong inverse correlation between radiation doses and tumor transplant survival. Histologic tumor necrosis did not correlate well with radiation doses or transplant survival rates. Despite common practices in histologic examination of tumors posttherapy, clinical interpretations and implications of histologic tumor necrosis after radiotherapy should be considered with caution. (C) 2001 Wiley-Liss, Inc. C1 Univ Rochester, Med Ctr, Dept Radiat Oncol, James P Wilmot Canc Ctr, Rochester, NY 14642 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Chen, YC (reprint author), Univ Rochester, Med Ctr, Dept Radiat Oncol, James P Wilmot Canc Ctr, 601 Elmwood Ave,Box 647, Rochester, NY 14642 USA. NR 21 TC 2 Z9 3 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 20 PY 2001 VL 96 IS 6 BP 334 EP 340 DI 10.1002/ijc.1041 PG 7 WC Oncology SC Oncology GA 499QR UT WOS:000172582300002 PM 11745503 ER PT J AU King, IFG Kingston, RE AF King, IFG Kingston, RE TI Molecular biology - Specifying transcription SO NATURE LA English DT Editorial Material ID CHROMATIN-REMODELING COMPLEX; SWI/SNF SUBUNITS; IN-VITRO C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP King, IFG (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. NR 10 TC 3 Z9 3 U1 0 U2 0 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 20 PY 2001 VL 414 IS 6866 BP 858 EP + DI 10.1038/414858a PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 503RB UT WOS:000172813300031 PM 11780046 ER PT J AU Meier, DE Back, AL Morrison, RS AF Meier, DE Back, AL Morrison, RS TI The inner life of physicians and care of the seriously ill SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID DOCTOR-PATIENT COMMUNICATION; ASSISTED SUICIDE; MEDICAL-STUDENTS; PALLIATIVE CARE; PERSONAL GROWTH; NATIONAL SURVEY; SEXUAL CONTACT; STRESS; DEATH; COUNTERTRANSFERENCE AB Seriously ill persons are emotionally vulnerable during the typically protracted course of an illness. Physicians respond to such patients' needs and emotions with emotions of their own, which may reflect a need to rescue the patient, a sense of failure and frustration when the patient's illness progresses, feelings of powerlessness against illness and its associated losses, grief, fear of becoming ill oneself, or a desire to separate from and avoid patients to escape these feelings. These emotions can affect both the quality of medical care and the physician's own sense of well-being, since unexamined emotions may also lead to physician distress, disengagement, burnout, and poor judgment. In this article, which is intended for the practicing, nonpsychiatric clinician, we describe a model for increasing physician self-awareness, which includes identifying and working with emotions that may affect patient care. Our approach is based on the standard medical model of risk factors, signs and symptoms, differential diagnosis, and intervention. Although it is normal to have feelings arising from the care of patients, physicians should take an active role in identifying and controlling those emotions. C1 CUNY Mt Sinai Sch Med, Dept Geriatr & Adult Dev, Hertzberg Palliat Care Inst, New York, NY 10029 USA. Univ Washington, Sch Med, Dept Med Hist & Eth, Dept Med,VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Meier, DE (reprint author), CUNY Mt Sinai Sch Med, Dept Geriatr & Adult Dev, Hertzberg Palliat Care Inst, Box 1070, New York, NY 10029 USA. NR 95 TC 243 Z9 248 U1 4 U2 26 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 DEC 19 PY 2001 VL 286 IS 23 BP 3007 EP 3014 DI 10.1001/jama.286.23.3007 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 502VY UT WOS:000172764500036 PM 11743845 ER PT J AU Jain, RK Forbes, NS AF Jain, RK Forbes, NS TI Commentary - Can engineered bacteria help control cancer? SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID DELIVERY SYSTEM; BIFIDOBACTERIUM-LONGUM; ANAEROBIC-BACTERIA; SOLID TUMORS; GENE-THERAPY; IN-VIVO; ANGIOGENESIS; DETERMINANTS; SALMONELLA C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. NR 34 TC 61 Z9 65 U1 3 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 18 PY 2001 VL 98 IS 26 BP 14748 EP 14750 DI 10.1073/pnas.261606598 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 504GK UT WOS:000172848800002 PM 11752416 ER PT J AU Thomas, DA Scorrano, L Putcha, GV Korsmeyer, SJ Ley, TJ AF Thomas, DA Scorrano, L Putcha, GV Korsmeyer, SJ Ley, TJ TI Granzyme B can cause mitochondrial depolarization and cell death in the absence of BID, BAX, and BAK SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CYTOCHROME-C RELEASE; PERMEABILITY TRANSITION PORE; CASPASE ACTIVATION; INDUCED APOPTOSIS; CYCLOSPORINE; INDUCTION; CLEAVAGE AB Granzyme B (GzmB) is a serine protease that is used by activated cytoltoxic T lymphocytes to induce target cell apoptosis. Although GzmB directly cleaves the Bcl2 family member BID on target cell entry, Bid-deficient (and Bax, Bak doubly deficient) cells are susceptible to GzmB-induced death, even though they fail to release cytochrome c from mitochondria. GzmB still induces mitochondrial depolarization in Bax, Bak double knockout cells without cytochrome c release or opening of the permeability transition pore. Because GzmB cannot directly cause depolarization of isolated mitochondria, novel intracellular factor(s) may be required for GzmB to depolarize mitochondria in situ. GzmB therefore utilizes two distinct mitochondrial pathways to amplify the proapoptotic signal that it delivers to target cells. C1 Washington Univ, Sch Med, Div Oncol, Dept Med,Siteman Canc Ctr, St Louis, MO 63110 USA. Washington Univ, Sch Med, Div Oncol, Dept Genet,Siteman Canc Ctr, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Mol Biol & Pharmacol, St Louis, MO 63110 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Dept Med, Boston, MA 02115 USA. RP Ley, TJ (reprint author), 660 S Euclid Ave,Campus Box 8007, St Louis, MO 63110 USA. RI Scorrano, Luca/A-6652-2008 OI Scorrano, Luca/0000-0002-8515-8928 FU NCI NIH HHS [CA50239, R01 CA050239, R37 CA050239]; NHLBI NIH HHS [T32 HL007088, T32 HL07088]; NIDDK NIH HHS [DK49786, R01 DK049786] NR 34 TC 84 Z9 87 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 18 PY 2001 VL 98 IS 26 BP 14985 EP 14990 DI 10.1073/pnas.261581498 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 504GK UT WOS:000172848800046 PM 11752447 ER PT J AU Ramaswamy, S Tamayo, P Rifkin, R Mukherjee, S Yeang, CH Angelo, M Ladd, C Reich, M Latulippe, E Mesirov, JP Poggio, T Gerald, W Loda, M Lander, ES Golub, TR AF Ramaswamy, S Tamayo, P Rifkin, R Mukherjee, S Yeang, CH Angelo, M Ladd, C Reich, M Latulippe, E Mesirov, JP Poggio, T Gerald, W Loda, M Lander, ES Golub, TR TI Multiclass cancer diagnosis using tumor gene expression signatures SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SUPPORT VECTOR MACHINES; MOLECULAR CLASSIFICATION; PATTERNS AB The optimal treatment of patients with cancer depends on establishing accurate diagnoses by using a complex combination of clinical and histopathological data. In some instances, this task is difficult or impossible because of atypical clinical presentation or histopathology. To determine whether the diagnosis of multiple common adult malignancies could be achieved purely by molecular classification, we subjected 218 tumor samples, spanning 14 common tumor types, and 90 normal tissue samples to oligonucleotide microarray gene expression analysis. The expression levels of 16,063 genes and expressed sequence tags were used to evaluate the accuracy of a multiclass classifier based on a support vector machine algorithm. Overall classification accuracy was 78%, far exceeding the accuracy of random classification (91%). Poorly differentiated cancers resulted in low-confidence predictions and could not be accurately classified according to their tissue of origin, indicating that they are molecularly distinct entities with dramatically different gene expression patterns compared with their well differentiated counterparts. Taken together, these results demonstrate the feasibility of accurate, multiclass molecular cancer classification and suggest a strategy for future clinical implementation of molecular cancer diagnostics. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, McGovern Inst, Ctr Brain & Computat Learning, Cambridge, MA 02139 USA. MIT, Artificial Intelligence Lab, Cambridge, MA 02139 USA. RP Golub, TR (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. OI Mukherjee, Sayan/0000-0002-6715-3920 NR 30 TC 1192 Z9 1240 U1 4 U2 43 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 18 PY 2001 VL 98 IS 26 BP 15149 EP 15154 DI 10.1073/pnas.211566398 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 504GK UT WOS:000172848800074 PM 11742071 ER PT J AU Plesnila, N Zinkel, S Le, DA Amin-Hanjani, S Wu, YQ Qiu, JH Chiarugi, A Thomas, SS Kohane, DS Korsmeyer, SJ Moskowitz, MA AF Plesnila, N Zinkel, S Le, DA Amin-Hanjani, S Wu, YQ Qiu, JH Chiarugi, A Thomas, SS Kohane, DS Korsmeyer, SJ Moskowitz, MA TI BID mediates neuronal cell death after oxygen/glucose deprivation and focal cerebral ischemia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MITOCHONDRIAL CYTOCHROME-C; CASPASE ACTIVATION; APOPTOSIS; RELEASE; BRAIN; DAMAGE; MICE; OVEREXPRESSION; MECHANISMS; INHIBITION AB Mitochondria and cytochrome c release play a role in the death of neurons and glia after cerebral ischemia. In the present study, we investigated whether BID, a proapoptotic promoter of cytochrome c release and caspase 8 substrate, was expressed in brain, activated after an ischemic insult in vivo and in vitro, and contributed to ischemic cell death. We detected BID in the cytosol of mouse brain and primary cultured mouse neurons and demonstrated, by using recombinant caspase 8, that neuronal BID also is a caspase 8 substrate. After 2 h of oxygen/glucose deprivation, BID cleavage was detected in neurons concurrent with caspase 8 activation but before caspase 3 cleavage. Bid(-/-) neurons were resistant to death after oxygen/glucose deprivation, and caspase 3 cleavage was significantly reduced; however, caspase 8 cleavage did not differ from wild type. In vivo, BID was cleaved 4 h after transient middle cerebral artery occlusion. Infarct volumes and cytochrome c release also were less in Bid(-/-) mice (-67% and -41%, respectively) after mild focal ischemia. These findings suggest that BID and the mitochondrial-amplification pathway promoting caspase activation contributes importantly to neuronal cell death after ischemic insult. C1 Harvard Univ, Sch Med, Stroke & Neurovasc Regulat Lab, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Dept Med, Boston, MA 02115 USA. RP Moskowitz, MA (reprint author), Harvard Univ, Sch Med, Stroke & Neurovasc Regulat Lab, Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [F32 NS010828, K08NS02162, NS10828, NS374141-02, P01 NS010828, P50 NS010828] NR 34 TC 173 Z9 184 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 18 PY 2001 VL 98 IS 26 BP 15318 EP 15323 DI 10.1073/pnas.261323298 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 504GK UT WOS:000172848800103 PM 11742085 ER PT J AU Shin, LM Whalen, PJ Pitman, RK Bush, G Macklin, ML Lasko, NB Orr, SP McInerney, SC Rauch, SL AF Shin, LM Whalen, PJ Pitman, RK Bush, G Macklin, ML Lasko, NB Orr, SP McInerney, SC Rauch, SL TI An fMRI study of anterior cingulate function in posttraumatic stress disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE medial prefrontal cortex; modified Stroop; insula; emotion; neuroimaging; anxiety disorder ID SCRIPT-DRIVEN IMAGERY; POSITRON-EMISSION-TOMOGRAPHY; MEDIAL PREFRONTAL CORTEX; CHILDHOOD SEXUAL ABUSE; VIETNAM COMBAT VETERANS; CEREBRAL BLOOD-FLOW; INTERFERENCE TASK; COUNTING STROOP; RETROSPLENIAL CORTEX; CONDITIONED FEAR AB Background: Several recent neuroimaging studies have provided data consistent with functional abnormalities ill anterior cingulate cortex in posttraumatic stress disorder (PTSD). In our study, we implemented a cognitive activation paradigm to test the functional integrity of anterior cingulate cortex in PTSD. Methods: Eight Vietnam combat veterans with PTSD (PTSD Group) and eight Vietnam combat veterans without PTSD (non-PTSD Group) underwent functional magnetic resonance imaging (fMRI) while performing the Emotional Counting Stroop. In separate conditions, subjects counted the number of combat-related (Combat), generally negative (General Negative), and neutral (Neutral) words presented on a screen and pressed a button indicating their response. Results: In the Combat versus General Negative comparison, the non-PTSD group exhibited significant fMRI blood oxygenation level-dependent signal increases in rostral anterior cingulate cortex, but the PTSD group did not. Conclusions: These findings suggest a diminished response in rostral anterior cingulate cortex in the presence of emotionally relevant stimuli in PTSD. We speculate that diminished recruitment of this region in PTSD may, in part, mediate symptoms such as distress and arousal upon exposure to reminders of trauma. Biol Psychiatry 2001; 50; 932-942 (C) 2001 Society of Biological Psychiatry . C1 Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA. Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA. VA Res Serv, Manchester, NH USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Shin, LM (reprint author), Tufts Univ, Dept Psychol, Medford, MA 02155 USA. FU NIMH NIH HHS [K01 MH-01611, K01 MH-01866, MH-60219] NR 88 TC 345 Z9 361 U1 8 U2 31 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 2001 VL 50 IS 12 BP 932 EP 942 DI 10.1016/S0006-3223(01)01215-X PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 504DD UT WOS:000172841300002 PM 11750889 ER PT J AU Cheng, T Shen, H Rodrigues, N Stier, S Scadden, DT AF Cheng, T Shen, H Rodrigues, N Stier, S Scadden, DT TI Transforming growth factor beta 1 mediates cell-cycle arrest of primitive hematopoietic cells independent of p21(Cip1/Waf1) or p27(Kip1) SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; STEM/PROGENITOR CELLS; GENE-EXPRESSION; CDK-INHIBITORS; MESSENGER-RNA; STEEL FACTOR; IN-VIVO; DIFFERENTIATION; P21; PROGENITORS AB The regulation of stem cell proliferation is a poorly understood process balancing rapid, massive blood cell production in times of stress with maintenance of a multipotent stem cell pool over decades of life. Transforming growth factor beta1 (TGF-pl) has pleiotropic effects on hematopoietic cells, including the inhibition of primitive cell proliferation. It was recently demonstrated that the cyclin-dependent kinase inhibitors, p21(Clp1/Waf1) (p21) and p27(Kip1) (p27), can inhibit the proliferation of hematopoietic stem cells and progenitor cells, respectively. The relation of TGF-beta1 stimulation to p21 and p27 was examined using a fine-mapping approach to gene expression in individual cells. Abundant TGF-beta1 expression and p21 expression were documented in quiescent, cytokine-resistant hematopoietic stem cells and in terminally differentiated mature blood cells, but not in proliferating progenitor cell populations. TGF-beta1 receptor (TPR II) was expressed ubiquitously without apparent modulation. Cell-cycle-synchronized 32D cells exposed to TGF-beta1 demonstrated a marked antiproliferative effect of TGF-beta1, yet neither the level of p21 mRNA nor the protein level of either p21 or p27 was altered. To corroborate these observations in primary cells, bone marrow mononuclear cells derived from mice engineered to be deficient in p21 or p27 were assessed. Progenitor and primitive cell function was inhibited by TGF-beta1 equivalently in -/- and +/+ littermate controls. These data indicate that TGF-beta1 exerts its inhibition on cell cycling independent of p21 and p27 in hematopoietic cells. TGF-beta1 and p21 or p27 participate in independent pathways of stem cell regulation, suggesting that targeting each may provide complementary strategies for enhancing stem or progenitor cell expansion and gene transduction. (C) 2001 by The American Society of Hematology. C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, AIDS Res Ctr, Massachusetts Gen Hosp, Boston, MA USA. Univ Pittsburgh, Pittsburgh Canc Inst, Pittsburgh, PA USA. RP Scadden, DT (reprint author), Massachusetts Gen Hosp, Bldg 149,Rm 5212,13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL55718, HL44851]; NIDDK NIH HHS [DK50234, KO8 DK02761] NR 53 TC 50 Z9 55 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2001 VL 98 IS 13 BP 3643 EP 3649 DI 10.1182/blood.V98.13.3643 PG 7 WC Hematology SC Hematology GA 500AX UT WOS:000172604700019 PM 11739168 ER PT J AU Yagasaki, H Adachi, D Oda, T Garcia-Higuera, I Tetteh, N D'Andrea, AD Futaki, M Asano, S Yamashita, T AF Yagasaki, H Adachi, D Oda, T Garcia-Higuera, I Tetteh, N D'Andrea, AD Futaki, M Asano, S Yamashita, T TI A cytoplasmic serine protein kinase binds and may regulate the Fanconi anemia protein FANCA SO BLOOD LA English DT Article ID KAPPA-B ACTIVATION; GROUP-A PROTEIN; NUCLEAR-COMPLEX; PHOSPHOINOSITIDE 3-KINASE; GROUP-C; COMPLEMENTATION ANALYSIS; POSITIONAL CLONING; GENE-PRODUCT; IN-VIVO; FORM AB Fanconi anemia (FA) is an autosomal recessive disease with congenital anomalies, bone marrow failure, and susceptibility to leukemia. Patient cells show chromosome instability and hypersensitivity to DNA cross-linking agents. At least 8 complementation groups (A-G) have been identified and 6 FA genes (for subtypes A, C, D2, E, F, and G) have been cloned. Increasing evidence indicates that a protein complex assembly of multiple FA proteins, including FANCA and FANCG, plays a crucial role in the FA pathway. Previously, it was reported that FANCA was phosphorylated in lymphoblasts from normal controls, whereas the phosphorylation was defective in those derived from patients with FA of multiple complementation groups. The present study examined phosphorylation of FANCA ectopically expressed in FANCA(-) cells. Several patient-derived mutations abrogated in vivo phosphorylation of FANCA in this system, suggesting that FANCA phosphorylation is associated with its function. In vitro phosphorylation studies indicated that a physiologic protein kinase for FANCA (FANCA-PK) forms a complex with the substrate. Furthermore, at least a part of FANCA-PK as well as phosphorylated FANCA were included in the FANCA/FANCG complex. Thus, FANCA-PK appears to be another component of the FA protein complex and may regulate function of FANCA. FANCA-PK was characterized as a cytoplasmic serine kinase sensitive to wortmannin. Identification of the protein kinase Is expected to elucidate regulatory mechanisms that control the FA pathway. (C) 2001 by The American Society of Hematology. C1 Univ Tokyo, Inst Med Sci, Div Genet Diag, Minato Ku, Tokyo 1088639, Japan. Univ Tokyo, Inst Med Sci, Dept Mol Therapy, Adv Clin Res Ctr, Tokyo 1088639, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Yamashita, T (reprint author), Univ Tokyo, Inst Med Sci, Div Genet Diag, Minato Ku, 4-6-1 Shirokanedai, Tokyo 1088639, Japan. RI Garcia-Higuera, Irene/L-5004-2014 NR 54 TC 12 Z9 12 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 DEC 15 PY 2001 VL 98 IS 13 BP 3650 EP 3657 DI 10.1182/blood.V98.13.3650 PG 8 WC Hematology SC Hematology GA 500AX UT WOS:000172604700020 PM 11739169 ER PT J AU Deguillien, M Huang, SC Moriniere, M Dreumont, N Benz, EJ Baklouti, F AF Deguillien, M Huang, SC Moriniere, M Dreumont, N Benz, EJ Baklouti, F TI Multiple cis elements regulate an alternative splicing event at 4.1R pre-mRNA during erythroid differentiation SO BLOOD LA English DT Article ID TRACT BINDING-PROTEIN; MESSENGER-RNA; EXON SEQUENCES; HETEROLOGOUS EXON; TERNARY COMPLEX; FACTORS ASF/SF2; SITE SELECTION; IN-VIVO; ENHANCER; GENE AB The inclusion of exon 16 in the mature protein 4.1 R messenger RNA (mRNA) is a critical event in red blood cell membrane biogenesis. It occurs during late erythroid development and results in inclusion of the 10-kd domain needed for stabilization of the spectrin/actin lattice. In this study, an experimental model was established in murine erythroleukemia cells that reproduces the endogenous exon 16 splicing patterns from a transfected minigene. Exon 16 was excluded in predifferentiated and predominantly included after induction. This suggests that the minigene contained exon and abutting intronic sequences sufficient for splicing regulation. A systematic analysis of the cls-acting regulatory sequences that reside within the exon and flanking introns was performed. Results showed that (1) the upstream intron of 4.1 R pre-mRNA is required for exon recognition and it displays 2 enhancer elements, a distal element acting in differentiating cells and a proximal constitutive enhancer that resides within the 25 nucleotides preceding the acceptor site; (2) the exon itself contains a strong constitutive splicing silencer; (3) the exon has a weak 5' splice site; and (4) the downstream intron contains at least 2 splicing enhancer elements acting in differentiating cells, a proximal element at the vicinity of the 5' splice site, and a distal element containing 3 copies of the UGCAUG motif. These results suggest that the interplay between negative and positive elements may determine the inclusion or exclusion of exon 16. The activation of the enhancer elements in late erythroid differentiation may play an important role in the retention of exon 16. (C) 2001 by The American Society of Hematology. C1 Univ Lyon 1, CNRS, UMR 5534, Ctr Genet Mol & Cellulaire, F-69622 Villeurbanne, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Baklouti, F (reprint author), Univ Lyon 1, CNRS, UMR 5534, Ctr Genet Mol & Cellulaire, 43 Blvd 11 Novembre 1918, F-69622 Villeurbanne, France. RI BAKLOUTI, Faouzi/E-7670-2013 FU NHLBI NIH HHS [HL 24385] NR 47 TC 48 Z9 49 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 DEC 15 PY 2001 VL 98 IS 13 BP 3809 EP 3816 DI 10.1182/blood.V98.13.3809 PG 8 WC Hematology SC Hematology GA 500AX UT WOS:000172604700041 PM 11739190 ER PT J AU Liu, G Miller, DP Zhou, W Thurston, SW Fan, R Xu, LL Lynch, TJ Wain, JC Su, L Christiani, DC AF Liu, G Miller, DP Zhou, W Thurston, SW Fan, R Xu, LL Lynch, TJ Wain, JC Su, L Christiani, DC TI Differential association of the codon 72 p53 and GSTM1 polymorphisms on histological subtype of non-small cell lung carcinoma SO CANCER RESEARCH LA English DT Article ID ENVIRONMENTAL TOBACCO-SMOKE; HUMAN-PAPILLOMAVIRUS; NONSMOKING WOMEN; CANCER RISK; CERVICAL-CANCER; UNITED-STATES; SUSCEPTIBILITY; CYP1A1; GENES; ADENOCARCINOMA AB Traditionally, non-small cell lung cancer (NSCLC) has been evaluated as a unique entity in genotyping studies. However, recent biological data suggest that different NSCLC subtypes, specifically adenocarcinomas (AC) and squamous cell carcinomas (SCC), differentially alter cancer behavior. Several studies have associated a p53 polymorphism at codon 72 with NSCLC susceptibility,. This study investigated whether different p53 genotypes altered the overall risk of developing AC versus SCC. Poly morphisms in metabolizing enzymes, together with prolonged exposure to tobacco carcinogens, can result in accumulation of DNA damage;, these effects may potentiate the effects of subtle differences in p53 function. Thus, interactions between polymorphisms of p53 and either GSTM1 or GSTT1 were also evaluated. We analyzed 1168 incident lung cancer cases and 1256 control subjects using multiple logistic regression. Histological data were available for 1144 cases (98%): 585 with AC, 284 with SCC, and 275 with other histological subtypes (large cell, small cell, mixed, and other). An increase in the NSCLC risk posed by the p53 Pro allele (versus Arg/Arg) was seen in AC compared with controls [adjusted odds ratio (OR), 1.36; 95% confidence interval (CI), 1.1-1.7] but not in SCC (adjusted OR, 1.04; 95% CI, 0.8-1.4). Among AC and SCC cancer patients, individuals with the GSTM1-null genotype had an OR of 1.80 (95% Cl, 1.1-2.8; case-only, analysis) of having AC versus SCC if they also carried a p53 Pro allele. We conclude that different genotype combinations of p53 and GSTM1 increase the risk of developing specific histological subtypes of NSCLC. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Thorac Surg Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Pulm Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Crit Care Unit, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, 665 Huntington Ave, Boston, MA 02115 USA. RI Liu, Geoffrey/N-4421-2016 FU FIC NIH HHS [TW00828]; NCI NIH HHS [CA74396]; NIEHS NIH HHS [ES T3207069, ES00002] NR 48 TC 84 Z9 90 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 DEC 15 PY 2001 VL 61 IS 24 BP 8718 EP 8722 PG 5 WC Oncology SC Oncology GA 505CU UT WOS:000172894500020 PM 11751390 ER PT J AU Gadd, M Pisc, C Branda, J Ionescu-Tiba, V Nikolic, Z Yang, CW Wang, T Shackleford, GM Cardiff, RD Schmidt, EV AF Gadd, M Pisc, C Branda, J Ionescu-Tiba, V Nikolic, Z Yang, CW Wang, T Shackleford, GM Cardiff, RD Schmidt, EV TI Regulation of cyclin D1 and p16(INK4A) is critical for growth arrest during mammary involution SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER RISK; D-DEPENDENT KINASES; TRANSGENIC MICE; CELL-CYCLE; TUMOR VIRUS; CANDIDATE ONCOGENE; CDK INHIBITORS; MOUSE; EXPRESSION; DIFFERENTIATION AB A coordinated growth arrest during mammary involution completes the dramatic changes in mammary cell proliferation seen during pregnancy and lactation. Signals regulating this arrest are poorly understood, despite their potential relevance to oncogenesis. Here we report that the arrest involves a unique pulse of p16(INK4A) expression in vivo, which accompanies decreased cyclin D1 expression and a shift to an active repressor E2F4 complex. We used INK4A/ARF-/- mice as well as cyclin D1 and p16(INK4A) transgenic strains to examine the physiological significance of these patterns. p16(INK4A) directly regulated the in vivo transition from E2F3 to E2F4 as the major E2F DNA binding activity, and its contribution to growth arrest was independent of cyclin D1. Transgenic cyclin D1 expression prevented normal terminal differentiation by ablating the p16(INK4A) pulse, abolishing the shift from E2F3 to E2F4, derepressing E2F target genes, and expanding a stem cell population. The effects of cyclin D1 were reversed by restoring p16(INK4A) but were not seen in INK4A/ARF-/- mice. Our results indicate that cyclin Dl may contribute to tumorigenesis by altering cell differentiation and demonstrate a significant function for p16(INK4A) in development in vivo. These regulatory mechanisms used during mammary involution offer a potential explanation for the protective effect of pregnancy against breast cancer. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Univ Massachusetts Mem Healthcare, Dept Med, Worcester, MA 01655 USA. Univ Calif Davis, Sch Med, Dept Pathol, Davis, CA 95616 USA. Massachusetts Gen Hosp, Serv Pediat, Boston, MA 02114 USA. Childrens Hosp Los Angeles, Div Hematol Oncol, Los Angeles, CA 90027 USA. RP Schmidt, EV (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [R01 CA69069] NR 51 TC 30 Z9 31 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2001 VL 61 IS 24 BP 8811 EP 8819 PG 9 WC Oncology SC Oncology GA 505CU UT WOS:000172894500033 PM 11751403 ER PT J AU Zimonjic, D Brooks, MW Popescu, N Weinberg, RA Hahn, WC AF Zimonjic, D Brooks, MW Popescu, N Weinberg, RA Hahn, WC TI Derivation of human tumor cells in vitro without widespread genomic instability SO CANCER RESEARCH LA English DT Article ID LARGE T-ANTIGEN; EPITHELIAL-CELLS; MICROSATELLITE INSTABILITY; COLORECTAL-CANCER; TRANSFORMATION; ANEUPLOIDY; DNA; KERATINOCYTES; CHROMOSOMES; EXPRESSION AB The majority of adult human epithelial cancers exhibit evidence of genetic instability, and it is widely believed that the genetic instability manifested by aneuploidy or microsatellite instability plays an essential role in the genesis of these tumors. Indeed, most experimental models of cancer also show evidence of genomic instability. The resulting genetic chaos, which has widespread effects on many genes throughout the genome, confounds attempts to determine the precise cohort of genetic changes that are required for the transformation of normal human cells to a tumorigenic state. Here we show that genetic transformation of human kidney epithelial cells can occur in the absence of extensive aneuploidy, chromosomal translocations, and microsatellite instability. These observations demonstrate that the in vitro oncogenic transformation of human cells can proceed without widespread genomic instability. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. NCI, Mol Cytogenet Sect, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20815 USA. RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. EM william_hahn@dfci.harvard.edu FU NCI NIH HHS [K01 CA94223, R01 CA78461] NR 39 TC 83 Z9 83 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2001 VL 61 IS 24 BP 8838 EP 8844 PG 7 WC Oncology SC Oncology GA 505CU UT WOS:000172894500036 PM 11751406 ER PT J AU Zachary, KC Hanna, GJ D'Aquila, RT AF Zachary, KC Hanna, GJ D'Aquila, RT TI Human immunodeficiency virus type 1 hypersusceptibility to amprenavir in vitro can be associated with virus load response to treatment in vivo SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID PROTEASE INHIBITOR; RESISTANCE AB The human immunodeficiency virus type 1 protease mutation N88S, which is occasionally selected by treatment with nelfinavir or indinavir, confers hypersusceptibility to amprenavir in vitro. The clinical relevance of this observation is unclear. We report a case of N88S developing after virologic failure of both indinavir- and nelfinavir-containing regimens that was managed successfully with a regimen that contained amprenavir. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Partners AIDS Res Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Zachary, KC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 32 Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [AI29193, AI44619, AI40350, AI01696, AI27659] NR 9 TC 14 Z9 14 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2001 VL 33 IS 12 BP 2075 EP 2077 DI 10.1086/324510 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 494QN UT WOS:000172297500019 PM 11700580 ER PT J AU Hellsten, E Evans, JP Bernard, DJ Janne, PA Nussbaum, RL AF Hellsten, E Evans, JP Bernard, DJ Janne, PA Nussbaum, RL TI Disrupted sperm function and fertilin beta processing in mice deficient in the inositol polyphosphate 5-phosphatase Inpp5b SO DEVELOPMENTAL BIOLOGY LA English DT Article DE phosphoinositide; inositol polyphosphate 5-phosphatase; fertilization; sperm; epididymis; fertilin beta ID MALE-INFERTILITY; MOUSE FERTILIN; TYROSINE PHOSPHORYLATION; SEQUENCE-ANALYSIS; EPIDIDYMAL SPERM; CRE RECOMBINASE; ZONA-PELLUCIDA; ALPHA; MATURATION; ROLES AB Inpp5b is an ubiquitously expressed type 11 inositol polyphosphate 5-phosphatase. We have disrupted the Inpp5b gene in mice and found that homozygous mutant males are infertile. Here we examine the causes for the infertility in detail. We demonstrate that sperm from Inpp5b(-/-) males have reduced motility and reduced ability to fertilize eggs, although capacitation and acrosome exocytosis appear to be normal. In addition, fertilin 13, a sperm surface protein involved in sperm-egg membrane interactions that is normally proteolytically processed during sperm transit through the epididymis, showed reduced levels of processing in the Inpp5b(-/-) animals. Inpp5b was expressed in the Sertoli cells and epididymis and at low levels in the developing germ cells; however, mice lacking Inpp5b in spermatids and not in other cell types generated by conditional gene targeting, were fully fertile. The abnormalities in mutant sperm function and maturation appear to arise from defects in the functioning of Sertoli and epididymal epithelial cells. Our results directly demonstrate a previously unknown role for phosphoinositides in normal sperm maturation beyond their previously characterized involvement in the acrosome reaction. Inpp5b(-/-) mice provide an excellent model to study the role of Sertoli and epididymal epithelial cells in the differentiation and maturation of sperm. (C) 2001 Elsevier Science. C1 Natl Human Genome Res Inst, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biochem & Mol Biol, Div Reprod Biol, Baltimore, MD 21205 USA. Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. RP Nussbaum, RL (reprint author), Natl Human Genome Res Inst, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. FU NICHD NIH HHS [HD 37696] NR 51 TC 27 Z9 28 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD DEC 15 PY 2001 VL 240 IS 2 BP 641 EP 653 DI 10.1006/dbio.2001.0476 PG 13 WC Developmental Biology SC Developmental Biology GA 510PK UT WOS:000173216300025 PM 11784089 ER PT J AU Jackson, EL Willis, N Mercer, K Bronson, RT Crowley, D Montoya, R Jacks, T Tuveson, DA AF Jackson, EL Willis, N Mercer, K Bronson, RT Crowley, D Montoya, R Jacks, T Tuveson, DA TI Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras SO GENES & DEVELOPMENT LA English DT Article DE K-ras; lung cancer; mouse models; Cre-loxP ID LARGE T-ANTIGEN; ATYPICAL ADENOMATOUS HYPERPLASIA; TRANSGENIC MICE; PULMONARY ADENOCARCINOMAS; MOUSE LUNG; II CELL; CARCINOMA; GENE; CYTODIFFERENTIATION; DIFFERENTIATION AB Adenocarcinoma of the lung is the most common form of lung cancer, but the cell of origin and the stages of progression of this tumor type are not well understood. We have developed a new model of lung adenocarcinoma in mice harboring a conditionally activatable allele of oncogenic K-ras. Here we show that the use of a recombinant adenovirus expressing Cre recombinase (Adeno-Cre) to induce K-ras G12D expression in the lungs of mice allows control of the timing and multiplicity of tumor initiation. Through the ability to synchronize tumor initiation in these mice, we have been able to characterize the stages of tumor progression. Of particular significance, this system has led to the identification of a new cell type contributing to the development of pulmonary adenocarcinoma. C1 MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. Tufts Univ, Sch Med & Vet Med, Dept Pathol, Boston, MA 02111 USA. RP Jacks, T (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. NR 25 TC 811 Z9 827 U1 1 U2 29 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 DEC 15 PY 2001 VL 15 IS 24 BP 3243 EP 3248 DI 10.1101/gad.943001 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 504WP UT WOS:000172879200003 PM 11751630 ER PT J AU Sauty, A Colvin, RA Wagner, L Rochat, S Spertini, F Luster, AD AF Sauty, A Colvin, RA Wagner, L Rochat, S Spertini, F Luster, AD TI CXCR3 internalization following T cell-endothelial cell contact: Preferential role of IFN-Inducible T cell alpha chemoattractant (CXCL11) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHEMOKINE RECEPTOR CXCR3; INDUCED PROTEIN IP-10; I-TAC; INTERFERON; EXPRESSION; LYMPHOCYTES; ENDOCYTOSIS; BINDING; MIG; MECHANISMS AB Chemokine receptors are rapidly desensitized and internalized following ligand binding, a process that attenuates receptor-mediated responses. However, the physiological settings in which this process occurs are not clear. Therefore, we examined the fate of CXCR3, a chemokine receptor preferentially expressed on activated T cells following contact with endothelial cells. By immunofluorescence microscopy and How cytometry, we found that CXCR3 was rapidly internalized when T cells were incubated with IFN-gamma -activated human saphenous vein endothelial cells (HSVEC), but not with resting HSVEC. Similar results were obtained using human CXCR3-transfected murine 300-19 B cells. CXCR3 down-regulation was significantly more pronounced when T cells were in contact with HSVEC than with their supernatants, suggesting that CXCR3 ligands were efficiently displayed on the surface of HSVEC. Using neutralizing mAbs to IFN-induced protein-10 (CXCL10), monokine induced by IFN-gamma (CXCL9), and IFN-inducible T cell alpha chemoattractant (I-TAC; CXCL11), we found that even though I-TAC was secreted from IFN-gamma -activated HSVEC to lower levels than IFN-induced protein-10 or the monokine induced by IFN-gamma, it was the principal chemokine responsible for CXCR3 internalization. This correlated with studies using recombinant chemokines, which revealed that I-TAC was the most potent inducer of CXCR3 down-regulation and of transendothelial migration. Known inhibitors of chemokine-induced chemotaxis, such as pertussis toxin or wortmannin, did not reduce ligand-induced internalization, suggesting that a distinct signal transduction pathway mediates internalization. Our data demonstrate that I-TAC is the physiological inducer of CXCR3 internalization and suggest that chemokine receptor internalization occurs in physiological settings, such as leukocyte contact with an activated endothelium. C1 Harvard Univ, Sch Med,Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. Univ Lausanne Hosp, Immunol & Allergy Div, Lausanne, Switzerland. RP Luster, AD (reprint author), Harvard Univ, Sch Med,Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA69212]; NIDDK NIH HHS [DK50305] NR 37 TC 94 Z9 98 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2001 VL 167 IS 12 BP 7084 EP 7093 PG 10 WC Immunology SC Immunology GA 500ER UT WOS:000172613400049 PM 11739530 ER PT J AU Rasmussen, RA Montefiori, DC Robinson, HL McClure, HM Ruprecht, RM AF Rasmussen, RA Montefiori, DC Robinson, HL McClure, HM Ruprecht, RM TI Heterologous neutralizing antibody induction in a simian-human immunodeficiency virus primate model: Lack of original antigenic sin SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID VACCINATION; HIV-1 AB According to the principle of original antigenic sin, neutralizing antibodies (NAbs) initially directed against a single virus strain compromise the immune system's ability to subsequently mount adequate responses against antigenically divergent virus strains. In this study, rhesus macaques, after vaccination and breakthrough infection with homologous simian-human immunodeficiency virus (SHIV), developed strong SHIV-IIIB strain-directed NAb responses that were mostly V3 loop specific. After superinfection with heterologous SHIV89.6P, all macaques developed high-titer SHIV89.6P-specific NAbs without significant boosting of SHIVIIIB-specific NAbs. These results indicate that prior B cell responses against a single immunodeficiency virus strain do not preclude the later development of NAbs against a divergent strain of the same virus. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Duke Univ, Med Ctr, Durham, NC USA. Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30322 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCRR NIH HHS [RR-000165]; NIAID NIH HHS [AI-4304, AI-48240, AI-85343] NR 13 TC 15 Z9 15 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2001 VL 184 IS 12 BP 1603 EP 1607 DI 10.1086/324582 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 498ZW UT WOS:000172545000015 PM 11740737 ER PT J AU Ploghaus, A Narain, C Beckmann, CF Clare, S Bantick, S Wise, R Matthews, PM Rawlins, JNP Tracey, I AF Ploghaus, A Narain, C Beckmann, CF Clare, S Bantick, S Wise, R Matthews, PM Rawlins, JNP Tracey, I TI Exacerbation of pain by anxiety is associated with activity in a hippocampal network SO JOURNAL OF NEUROSCIENCE LA English DT Article DE hyperalgesia; hippocampus; classical fear conditioning; anterior cingulate; insula; causal associative learning; medial temporal lobe; surprise; aversive emotional learning; anticipation; functional neuroimaging ID ANTERIOR CINGULATE CORTEX; EVENT-RELATED FMRI; POSITRON-EMISSION-TOMOGRAPHY; HUMAN BRAIN; CORTICAL REPRESENTATION; STIMULATION; ACTIVATION; RESPONSES; EXPRESSION; ANALGESIA AB It is common clinical experience that anxiety about pain can exacerbate the pain sensation. Using event-related functional magnetic resonance imaging (FMRI), we compared activation responses to noxious thermal stimulation while perceived pain intensity was manipulated by changes in either physical intensity or induced anxiety. One visual signal, which reliably predicted noxious stimulation of moderate intensity, came to evoke low anxiety about the impending pain. Another visual signal was followed by the same, moderate-intensity stimulation on most of the trials, but occasionally by discriminably stronger noxious stimuli, and came to evoke higher anxiety. We found that the entorhinal cortex of the hippocampal formation responded differentially to identical noxious stimuli, dependent on whether the perceived pain intensity was enhanced by pain-relevant anxiety. During this emotional pain modulation, entorhinal responses predicted activity in closely connected, affective (perigenual cingulate), and intensity coding (mid-insula) areas. Our finding suggests that accurate preparatory information during medical and dental procedures alleviates pain by disengaging the hippocampus. It supports the proposal that during anxiety, the hippocampal formation amplifies aversive events to prime behavioral responses that are adaptive to the worst possible outcome. C1 Univ Oxford, John Radcliffe Hosp, Dept Clin Neurol, Oxford Ctr Funct Magnet Resonance Imaging Brain, Oxford OX3 9DU, England. Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. RP Ploghaus, A (reprint author), Massachusetts Gen Hosp, Dept Neuroradiol, 13th St,Bldg 149, Charlestown, MA 02129 USA. RI Wise, Richard/A-3869-2010; Beckmann, Christian/E-6374-2012; OI Wise, Richard/0000-0003-1700-2144; Matthews, Paul M/0000-0002-1619-8328 NR 97 TC 389 Z9 401 U1 4 U2 31 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 15 PY 2001 VL 21 IS 24 BP 9896 EP 9903 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 500XW UT WOS:000172654800039 PM 11739597 ER PT J AU Takahashi, MP Cannon, SC AF Takahashi, MP Cannon, SC TI Mexiletine block of disease-associated mutations in S6 segments of the human skeletal muscle Na+ channel SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID HYPERKALEMIC PERIODIC PARALYSIS; CARDIAC SODIUM-CHANNELS; PARAMYOTONIA-CONGENITA; SLOW INACTIVATION; LIDOCAINE BLOCK; LOCAL-ANESTHETICS; CELL-LINE; MYOTONIA; STATE; BATRACHOTOXIN AB 1. Over twenty different missense mutations in the alpha-subunit of the adult skeletal muscle Na+ channel (hSkM1) have been identified as a cause of myotonia or periodic paralysis. We examined state-dependent mexiletine block for mutations involving the putative binding site in S6 segments (V445M, S804F, V1293I, V1589M and M1592V). Whole-cell Na+ currents were measured from wild-type (WT) and mutant channels transiently expressed in HEK cells. 2. Use-dependent block (10 ms pulses to -10 mV, at 20 Hz) in 100 eta(M) mexiletine was reduced modestly by mutations in IVS6 (V1589M, M1592V) and enhanced by the mutation in IS6 (V445M). For mutations in IIS6 (S804F) and IIIS6 (V1293I) use-dependent block was not statistically different from that of wild-type channels. 3. Resting-state block (10 ms pulses to -10 mV from -150 mV, at 0.1 Hz) of S6 mutants was comparable to that of WT (dissociation constant for resting channels, K-R = 650 +/- 40 mu(M) , n = 9). The S6 mutant with the greatest change in K-R was V445M (K-R = 794 +/- 45 mu(M), n = 5), but this difference was only marginally significant (P = 0.047). 4. A modified technique for estimating local anaesthetic affinity of inactivated channels was developed to reduce errors due to slow inactivation and to failure of drug binding to reach equilibrium. Mexiletine affinity for inactivated channels was reduced by mutations in IVS6 (V1589M: dissociation constant for the inactivated state (K-I) = 44.7 mu(M) ; M1592V: K-I = 40.0 mu(M)) and increased by the mutation in IS6 (V445M: K-I = 15.0 mu(M)), compared to wild-type channels (K-I = 28.3 mu(M)) 5. We conclude that, the disease-associated S6 mutations in domains I-IV cause at most a 2-fold change in inactivated state affinity and have even less of an effect oil resting block. Model simulations show that the reduced use-dependent block of IVS6 mutants derives primarily from an increased of off-rate at hyperpolarized potentials, whereas the enhanced use-dependent block of the IS6 mutant was due to a higher affinity for inactivated V445M channels. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02114 USA. RP Cannon, SC (reprint author), Massachusetts Gen Hosp, Dept Neurol, Wellman 423, Boston, MA 02114 USA. FU NIAMS NIH HHS [R01-AR42703, R01 AR042703] NR 39 TC 28 Z9 28 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD DEC 15 PY 2001 VL 537 IS 3 BP 701 EP 714 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 511PH UT WOS:000173274400006 PM 11744749 ER PT J AU DeMeo, DL Ginns, LC AF DeMeo, DL Ginns, LC TI Clinical status of lung transplantation SO TRANSPLANTATION LA English DT Review ID BRONCHIOLITIS OBLITERANS SYNDROME; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE; QUALITY-OF-LIFE; EXTRACORPOREAL MEMBRANE-OXYGENATION; BRONCHIAL ANASTOMOTIC COMPLICATIONS; PRIMARY PULMONARY-HYPERTENSION; MUSCLE OXIDATIVE CAPACITY; CYSTIC-FIBROSIS PATIENTS; HEART-BEATING CADAVER; PRIMARY GRAFT FAILURE C1 Massachusetts Gen Hosp, Lung Transplant Program, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Ginns, LC (reprint author), Massachusetts Gen Hosp, Lung Transplant Program, Pulm & Crit Care Unit, Bigelow 808,55 Fruit St, Boston, MA 02114 USA. NR 172 TC 16 Z9 18 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 15 PY 2001 VL 72 IS 11 BP 1713 EP 1724 DI 10.1097/00007890-200112150-00001 PG 12 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 504ET UT WOS:000172844900001 PM 11740377 ER PT J AU Buhler, L Yamada, K Kitamura, H Alwayn, IPJ Basker, M Appel, JZ Colvin, RB White-Scharf, ME Sachs, DH Robson, SC Awwad, M Cooper, DKC AF Buhler, L Yamada, K Kitamura, H Alwayn, IPJ Basker, M Appel, JZ Colvin, RB White-Scharf, ME Sachs, DH Robson, SC Awwad, M Cooper, DKC TI Pig kidney transplantation in baboons: Anti-Gal alpha 1-3Gal IgM alone is associated with acute humoral xenograft rejection and disseminated intravascular coagulation SO TRANSPLANTATION LA English DT Article ID RENAL-ALLOGRAFT REJECTION; HEMATOPOIETIC-CELL TRANSPLANTATION; MONOCLONAL-ANTIBODY; CARDIAC TRANSPLANTS; TOLERANCE INDUCTION; NONHUMAN-PRIMATES; CD40 LIGAND; IN-VITRO; PORCINE; XENOTRANSPLANTATION AB Background. Kidneys harvested from miniature swine or pigs transgenic for human decay-accelerating factor (hDAF) were transplanted into baboons receiving an anti-CD154 monoclonal antibody (mAb) and either a whole body irradiation (WBI)- or cyclophosphamide (CPP)-based immunosuppressive regimen. Methods. Group 1 baboons (n=3) underwent induction therapy with WBI and thymic irradiation, pretransplantation antithymocyte globulin, and immunoadsorption of anti-Gal alpha1-3Gal (Gal) antibody (Ab). After transplantation of a miniature swine kidney, maintenance therapy comprised cobra venom factor, mycophenolate mofetil, and an anti-CD154 mAb (for 14-28 days). In group 2 (n=2), WBI was replaced by CPP in the induction protocol. Group 3 (n=3) animals received the group 2 regimen, but underwent transplantation with hDAF pig kidneys. Results. Group 1 and 2 animals developed features of disseminated intravascular coagulation (DIC), with reductions of fibrinogen and platelets and increases of prothrombin time, partial thromboplastin time, and fibrin split products. Graft survival was for 6-13 days. Histology showed mild acute humoral xenograft rejection (AHXR) of the kidneys, but severe rejection of the ureters. Group 3 animals developed features of DIC in two of three cases during the fourth week, with AHXR in the third case. Graft survival was for 28 (n=1) or 29 (n=2) days. Histology of day 15 biopsy specimens showed minimal focal mononuclear cellular infiltrates, with predominantly CD3(+) cells. By days 28 and 29, kidneys showed mild-to-moderate features of AHXR. In all groups, the humoral response was manifest by reappearance of anti-Gal IgM below baseline level, with no or low return of anti-Gal IgG. All excised kidneys showed IgM deposition, but no complement and no or minimal IgG deposition. No baboon showed a rebound of anti-Gal Ab immediately after excision of the graft, and anti-Gal Ab increased over pretransplantation levels only when anti-CD154 mAb was discontinued. Conclusions. DIC was observed with WBI- or CPP-based therapy, and after miniature swine or hDAF kidney transplantation. AHXR +/- DIC was observed in all recipients even in the absence of complement and no or low levels of anti-Gal IgG, but was significantly delayed in the hDAF recipients. These results confirm our earlier observation that CD154 blockade prevents T cell-dependent sensitization in baboons to pig antigens, but that baseline natural anti-Gal Ab production is not inhibited. We suggest that IgM deposition, even in the absence of IgG and complement, leads to endothelial cell activation with the development of DIC, even when there are only minimal histologic changes of AHXR. C1 Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Massachusetts Gen Hosp, Boston, MA 02129 USA. Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Massachusetts Gen Hosp, Boston, MA 02129 USA. Biotransplant Inc, Charlestown, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Immunobiol, Boston, MA 02115 USA. RP Cooper, DKC (reprint author), Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Massachusetts Gen Hosp, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [R01 HL57307]; PHS HHS [5P01 A139755] NR 38 TC 71 Z9 73 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 15 PY 2001 VL 72 IS 11 BP 1743 EP 1752 DI 10.1097/00007890-200112150-00007 PG 10 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 504ET UT WOS:000172844900007 PM 11740383 ER PT J AU Buhler, L Alwayn, IPJ Basker, M Oravec, G Thall, A White-Scharf, ME Sachs, DH Awwad, M Cooper, DKC AF Buhler, L Alwayn, IPJ Basker, M Oravec, G Thall, A White-Scharf, ME Sachs, DH Awwad, M Cooper, DKC TI CD40-CD154 pathway blockade requires host macrophages to induce humoral unresponsieveness to pig hematopoietic cells in baboons SO TRANSPLANTATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; RENAL-ALLOGRAFT REJECTION; NONHUMAN-PRIMATES; ANTI-GAL-ALPHA-1-3GAL ANTIBODY; XENOGRAFT REJECTION; CARDIAC TRANSPLANTS; TOLERANCE INDUCTION; PORCINE KIDNEY; IN-VITRO; CD40 AB The effect of CD154 blockade and macrophage depletion or inhibition on baboon humoral and cellular immune responses to pig antigens was studied in a pig-to-baboon peripheral blood mobilized progenitor cell (PEPC) transplantation model aimed at inducing tolerance. We in-fused pig PBPCs in baboons pretreated with a nonmyeloablative regimen along with murine antihuman CD154 monoclonal antibody (mAb) and macrophage-depleting or -inhibiting agents. Group 1 baboons (n=2) underwent a nonmyeloablative regimen and immunoadsorption of anti-Gal alpha1,3Gal (Gal) antibody (Ab) before intravenous infusion of high doses (1.3-4.6x10 10cells/kg) of PBPCs. In group 2 (n=5), cyclosporine was replaced by 8 doses of anti-CD154 mAb over 14 days. Group 3 (n=3) received the group 2 regimen plus medronate liposomes (n=2) or commercially available human intravenous immunoglobulin G depleted of anti-Gal Ab (n=1) to deplete/inhibit recipient macrophages. Group 1 developed sensitization to Gal and also developed new Ab to non-Gal porcine antigens within 10 to 20 days. In group 2, no sensitization to Gal or non-Gal determinants was seen, but Gal-reactive antibodies did return to their preleukocyte transplantation levels. CD154 blockade, therefore, induced humoral unresponsiveness to pig cells. In group 3, sensitization to Gal was seen in all three baboons at 20 days, and Abs against new porcine determinants developed in one baboon. The depletion or inhibition of host macrophages, therefore, prevented the induction of humoral unresponsiveness by CD154 blockade. These results suggest that CD154 blockade induces humoral unresponsiveness by a mechanism that involves the indirect pathway of antigen presentation. In vitro investigation of baboon anti-pig mixed lymphocyte reaction confirmed that only the indirect pathway is efficiently blocked by anti-CD154 mAb. The mechanism in which blockade of the CD40-CD154 pathway induces its effect remains to be determined, but it could involve the generation of regulatory cells capable of suppressing the direct pathway. C1 Harvard Univ, Dept Pathol, Transplantat Biol Res Ctr, Massachusetts Gen Hosp,Sch Med, Boston, MA 02129 USA. Biotransplant Inc, Charlestown, MA USA. RP Cooper, DKC (reprint author), Harvard Univ, Dept Pathol, Transplantat Biol Res Ctr, Massachusetts Gen Hosp,Sch Med, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [5P01 AI39755] NR 34 TC 18 Z9 19 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 DEC 15 PY 2001 VL 72 IS 11 BP 1759 EP 1768 DI 10.1097/00007890-200112150-00009 PG 10 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 504ET UT WOS:000172844900009 PM 11740385 ER PT J AU Cao, YX Bonizzi, G Seagroves, TN Greten, FR Johnson, R Schmidt, EV Karin, M AF Cao, YX Bonizzi, G Seagroves, TN Greten, FR Johnson, R Schmidt, EV Karin, M TI IKK alpha provides an essential link between RANK signaling and cyclin D1 expression during mammary gland development SO CELL LA English DT Article ID NF-KAPPA-B; BREAST-CANCER; MICE LACKING; SPLENIC MICROARCHITECTURE; LIVER DEGENERATION; IMMUNE-RESPONSES; BETA SUBUNIT; CELL-GROWTH; ACTIVATION; KINASE AB To identify functions of the IKK alpha subunit of I kappaB kinase that require catalytic activity, we generated an Ikk alpha (AA) knockin allele containing alanines instead of serines in the activation loop. Ikk alpha (AA/AA) mice are healthy and fertile, but females display a severe lactation defect due to impaired proliferation of mammary epithelia[ cells. IKK alpha. activity is required for NF-kappaB activation in mammary epithelial cells during pregnancy and in response to RANK ligand but not TNF alpha. IKK alpha and NF-kappaB activation are also required for optimal cyclin Dl induction. Defective RANK signaling or cyclin D1 expression results in the same phenotypic effect as the Ikk alpha (AA) mutation, which is completely suppressed by a mammary specific cyclin D1 transgene. Thus, IKK alpha is a critical intermediate in a pathway that controls mammary epithelial proliferation in response to RANK signaling via cyclin D1. C1 Univ Calif San Diego, Sch Med, Dept Pharmacol, Lab Gene Regulat & Signal Transduct, La Jolla, CA 92093 USA. Univ Calif San Diego, Div Biol, Mol Biol Sect, La Jolla, CA 92093 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Childrens Serv, Charlestown, MA 02129 USA. RP Karin, M (reprint author), Univ Calif San Diego, Sch Med, Dept Pharmacol, Lab Gene Regulat & Signal Transduct, 9500 Gilman Dr, La Jolla, CA 92093 USA. NR 50 TC 314 Z9 329 U1 4 U2 13 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD DEC 14 PY 2001 VL 107 IS 6 BP 763 EP 775 DI 10.1016/S0092-8674(01)00599-2 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 502ZC UT WOS:000172771800009 PM 11747812 ER PT J AU Chen, NY Ma, WY She, QB Wu, E Liu, GM Bode, AM Dong, ZG AF Chen, NY Ma, WY She, QB Wu, E Liu, GM Bode, AM Dong, ZG TI Transactivation of the epidermal growth factor receptor is involved in 12-O-tetradecanoylphorbol-13-acetate-induced signal transduction SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; ACID RESPONSE ELEMENT; TUMOR PROMOTION; METALLOPROTEINASE CLEAVAGE; INDUCED TRANSFORMATION; RETINOIC ACID; AP-1 ACTIVITY; EGF RECEPTOR; FACTOR-ALPHA; SKIN TUMORS AB The mechanism of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumor promotion is still not well understood even though it is thought to be related to the protein kinase C/mitogen-activated protein kinase/AP-1 pathway. Recently, TPA was also found to induce epidermal growth factor receptor (EGFR) activity. Here, we investigated whether the EGFR is a necessary component for TPA-induced signal transduction associated with tumor promotion. We demonstrated that potent inhibitors of the EGFR, PD153035 and AG1478, blocked TPA-induced phosphorylation of extracellular signal-regulated kinases (ERKs), AP-1 activity, and cell transformation. Egfr gene deficiency blocked TPA-induced ERK activity and AP-1 binding activity. The blocking of the ectodomain of the EGFR by a monoclonal antibody depressed TPA-induced ERK activity and AP-1 DNA binding activity. The use of a neutralizing antibody for heparin-binding EGF, one of the ligands of EGFR, blocked TPA-induced phosphorylation of ERKs. BB-94, a potent inhibitor of matrix metalloproteinases, which are activators of ectodomain shedding of EGFR ligands, also blocked TPA-induced ERK activity, AP-1 DNA binding, and cell transformation but had no effect on EGF-induced signal transduction. Anti-EGFR, anti-heparin-binding EGF, and BB-94 each blocked TPA-induced EGFR phosphorylation, but only anti-EGFR could block EGF-induced EGFR phosphorylation. Based on these results, we conclude that the EGFR is required for mediating TPA-induced signal transduction. EGFR transactivation induced by TPA is a mechanism by which the EGFR mediates TPA-induced tumor promotion-relate signal transduction. C1 Univ Minnesota, Hormel Inst, Austin, MN 55912 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Dong, ZG (reprint author), Univ Minnesota, Hormel Inst, 801 16th Ave NE, Austin, MN 55912 USA. FU NCI NIH HHS [CA 74916, CA 77646, CA 81064] NR 43 TC 54 Z9 55 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 14 PY 2001 VL 276 IS 50 BP 46722 EP 46728 DI 10.1074/jbc.M107156200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 502XR UT WOS:000172768500008 PM 11592962 ER PT J AU Gao, Y Xing, J Streuli, M Leto, TL Zheng, Y AF Gao, Y Xing, J Streuli, M Leto, TL Zheng, Y TI Trp(56) of Rac1 specifies interaction with a subset of guanine nucleotide exchange factors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DBL HOMOLOGY DOMAIN; CRYSTAL-STRUCTURE; RHO-GTPASES; ONCOGENIC DBL; GTP ANALOG; FAMILY; TRIO; PROTEIN; ACTIVATION; KINASE AB Signaling specificity of Rho GTPase pathways is achieved in part by selective interaction between members of the Dbl family guanine nucleotide exchange factors (GEFs) and their Rho GTPase substrates. For example, Trio, GEF-H1, and Tiam1 are a subset of GEFs that specifically activate Rac1 but not the closely related Cdc42. The Rac1 specificity of these GEFs appears to be governed by Rac1-GEF binding interaction. To understand the detailed mechanism underlying the GEF specificity issue, we have analyzed a panel of chimeras made between Rac1 and Cdc42 and examined a series of point mutants of Racl made at the switch I, switch II, and beta (2)/beta (3) regions for their ability to interact with and to be activated by the GEFs. The results reveal that Rac1 residues of both the switch I and switch II regions are involved in GEF docking and GEF-mediated nucleotide disruption, because mutation of Asp(38), Asn(39), Gln(61), Tyr(64), or Arg(66)/Leu(67) into Ala results in the loss of GEF binding, whereas mutation at Tyr(32), Asp(65), or Leu(70)/ Ser(71) leads to the loss of GEF catalysis while retaining the binding capability. The region between amino acids 53-72 of Rac1 is required for specific recognition and activation by the GEFs, and Trp(56) in beta (3), appears to be the critical determinant. Introduction of Trp(56) to Cdc42 renders it fully responsive to the Rac-specific GEF in vitro and in cells. Further, a polypeptide derived from the beta (3) region of Rac1 including the Trp,56 residue serves as a specific inhibitor for Rac1 interaction with the GEFs. Taken together, these results indicate that Trp-56 is the necessary and sufficient determinant of Rac1 for discrimination by the subset of Rac1-specific GEFs and suggest that a compound mimicking Trp 56 action could be explored as an interfering reagent specifically targeting Rac1 activation. C1 Univ Tennessee, Ctr Hlth Sci, Dept Mol Sci, Memphis, TN 38163 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Zheng, Y (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Mol Sci, Memphis, TN 38163 USA. EM yzheng@utmem.edu RI Xing, Jinchuan/A-2489-2012; Zheng, Yi/J-7235-2015 OI Zheng, Yi/0000-0001-7089-6074 FU NIGMS NIH HHS [GM 53943, GM 60523] NR 41 TC 63 Z9 63 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 14 PY 2001 VL 276 IS 50 BP 47530 EP 47541 DI 10.1074/jbc.M108865200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 502XR UT WOS:000172768500112 PM 11595749 ER PT J AU Dimitroff, CJ Lee, JY Schor, KS Sandmaier, BM Sackstein, R AF Dimitroff, CJ Lee, JY Schor, KS Sandmaier, BM Sackstein, R TI Differential L-selectin binding activities of human hematopoietic cell L-selectin ligands, HCELL and PSGL-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CUTANEOUS LYMPHOCYTE ANTIGEN; P-SELECTIN; GLYCOPROTEIN LIGAND-1; PROGENITOR CELLS; ADHESION MOLECULES; EXPRESSION CLONING; PLATELET RECOVERY; PERIPHERAL-BLOOD; CD34(+) CELLS; T-CELLS AB Expression of L-selectin on human hematopoietic cells (HC) is associated with a higher proliferative activity and a more rapid engraftment after hematopoietic stem cell transplantation. Two L-selectin ligands are expressed on human HCs, P-selectin glycoprotein ligand-1 (PSGL-1) and a specialized glycoform of CD44 (hematopoietic cell E- and L-selectin ligand, HCELL). Although the structural biochemistry of HCELL and PSGL-1 is well characterized, the relative capacity of these molecules to mediate L-selectin-dependent adhesion has not been explored. In this study, we examined under shear stress conditions L-selectin-dependent leukocyte adhesive interactions mediated by HCELL and PSGL-1, both as naturally expressed on human HC membranes and as purified molecules. By utilizing both Stamper-Woodruff and parallel-plate flow chamber assays, we found that HCELL displayed a 5-fold greater capacity to support L-selectin-dependent leukocyte adherence across a broad range of shear stresses compared with that of PSGL-1. Moreover, L-selectin-mediated leukocyte binding to immunopurified HCELL was consistently > 5-fold higher than leukocyte binding to equivalent amounts of PSGL-1. Taken together, these data indicate that HCELL is a more avid L-selectin ligand than PSGL-1 and may be the preferential mediator of L-selectin-dependent adhesive interactions among human HCs in the bone marrow. C1 Harvard Univ, Brigham & Womens Hosp, Dept Dermatol, Skin Dis Res Ctr, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dept Med, Skin Dis Res Ctr, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Dept Med, Div Clin Res, Seattle, WA 98109 USA. RP Sackstein, R (reprint author), Harvard Univ, Inst Med, Skin Dis Res Ctr, Dept Dermatol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA 84156]; NHLBI NIH HHS [HL 36444, R01 HL 60528] NR 38 TC 32 Z9 34 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 14 PY 2001 VL 276 IS 50 BP 47623 EP 47631 DI 10.1074/jbc.M105997200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 502XR UT WOS:000172768500123 PM 11591704 ER PT J AU Mathis, D Vence, L Benoist, C AF Mathis, D Vence, L Benoist, C TI beta-cell death during progression to diabetes SO NATURE LA English DT Review ID TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE PRODUCTION; CD8 T-CELL; HUMAN PANCREATIC-ISLETS; TRANSGENIC MICE; FAS LIGAND; NOD MICE; PSAMMOMYS-OBESUS; AUTOIMMUNE DESTRUCTION; CYTOTOXIC PATHWAYS AB The hallmark of type 1 diabetes is specific destruction of pancreatic islet beta -cells. Apoptosis of beta -cells may be crucial at several points during disease progression, initiating leukocyte invasion of the islets and terminating the production of insulin in islet cells. beta -Cell apoptosis may also be involved in the occasional evolution of type 2 into type 1 diabetes. C1 Brigham & Womens Hosp, Joslin Diabet Ctr, Dept Med, Sect Immunol & Innumogenet, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Mathis, D (reprint author), Brigham & Womens Hosp, Joslin Diabet Ctr, Dept Med, Sect Immunol & Innumogenet, 1 Joslin Pl, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu NR 100 TC 555 Z9 591 U1 5 U2 45 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD DEC 13 PY 2001 VL 414 IS 6865 BP 792 EP 798 DI 10.1038/414792a PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 501GD UT WOS:000172676200059 PM 11742411 ER PT J AU Saltiel, AR Kahn, CR AF Saltiel, AR Kahn, CR TI Insulin signalling and the regulation of glucose and lipid metabolism SO NATURE LA English DT Review ID PROTEIN-KINASE-B; PHOSPHOINOSITIDE 3-KINASE P85-ALPHA; GLYCOGEN-SYNTHASE KINASE-3; RECEPTOR SUBSTRATE-1; PHOSPHATIDYLINOSITOL 3-KINASE; MICE LACKING; 3T3-L1 ADIPOCYTES; TARGETED DISRUPTION; DIABETES-MELLITUS; TYROSINE PHOSPHORYLATION AB The epidemic of type 2 diabetes and impaired glucose tolerance is one of the main causes of morbidity and mortality worldwide. In both disorders, tissues such as muscle, fat and liver become less responsive or resistant to insulin. This state is also linked to other common health problems, such as obesity, polycystic ovarian disease, hyperlipidaemia, hypertension and atherosclerosis. The pathophysiology of insulin resistance involves a complex network of signalling pathways, activated by the insulin receptor, which regulates intermediary metabolism and its organization in cells. But recent studies have shown that numerous other hormones and signalling events attenuate insulin action, and are important in type 2 diabetes. C1 Univ Michigan, Sch Med, Dept Med, Inst Life Sci, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Saltiel, AR (reprint author), Univ Michigan, Sch Med, Dept Med, Inst Life Sci, Ann Arbor, MI 48109 USA. OI Saltiel, Alan/0000-0002-9726-9828 NR 100 TC 2309 Z9 2422 U1 107 U2 762 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 13 PY 2001 VL 414 IS 6865 BP 799 EP 806 DI 10.1038/414799a PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 501GD UT WOS:000172676200060 PM 11742412 ER PT J AU Amato, AA Sanelli, PC Anderson, MP Jeyapalan, S AF Amato, AA Sanelli, PC Anderson, MP Jeyapalan, S TI A 51-year-old woman with lung cancer and neuropsychiatric abnormalities. Lymphocytic meningitis and lymphocytic encephalomyelitis with sensory neuronopathy and ganglionitis. Small-cell carcinoma of the lung (treated). SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ANTI-HU ANTIBODY; ANTINEURONAL NUCLEAR AUTOANTIBODIES; PARANEOPLASTIC ENCEPHALOMYELITIS; NERVOUS-SYSTEM; TUMOR; NEUROPATHY; SERUM C1 Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Neuromuscular Div, Boston, MA 02115 USA. Massachusetts Gen Hosp, Neuromuscular Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Amato, AA (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. NR 33 TC 2 Z9 2 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 13 PY 2001 VL 345 IS 24 BP 1758 EP 1765 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 500YK UT WOS:000172656100007 PM 11742051 ER PT J AU Lee, RYN Hench, J Ruvkun, G AF Lee, RYN Hench, J Ruvkun, G TI Regulation of C-elegans DAF-16 and its human ortholog FKHRL1 by the daf-2 insulin-like signaling pathway SO CURRENT BIOLOGY LA English DT Article ID CAENORHABDITIS-ELEGANS; TRANSCRIPTION FACTOR; DAUER FORMATION; LIFE-SPAN; GENE; LONGEVITY AB C. elegans insulin-like signaling regulates metabolism, development, and life span. This signaling pathway negatively regulates the activity of the forkhead transcription factor DAF-16. daf-16 encodes multiple isoforms that are expressed in distinct tissue types and are probable orthologs of human FKHRL1, FKHR, and AFX. We show that human FKHRL1 can partially replace DAF-16, proving the orthology. In mammalian cells, insulin and insulin-like growth factor signaling activate AKT/PKB kinase to negatively regulate the nuclear localization of DAF-16 homologs (reviewed in [1]). We show that the absence of AKT consensus sites on DAF-16 is sufficient to cause dauer arrest in daf-2(+) animals, proving that daf-16 is the major output of insulin signaling in C. elegans. FKHR, FKRHL1, and AFX may similarly be the major outputs of mammalian insulin signaling. daf-2 insulin signaling, via AKT kinases, negatively regulates DAF-16 by controlling its nuclear localization. Surprisingly, we find that daf-7 TGF-beta signaling also regulates DAF-16 nuclear localization specifically at the time when the animal makes the commitment between diapause and reproductive development. daf-16 function is supported by the combined action of two distinct promoter/enhancer elements, whereas the coding sequences of two major DAF-16 isoforms are interchangeable. Together, these observations suggest that the combined effects of transcriptional and posttranslational regulation of daf-16 transduce insulin-like signals in C. elegans and perhaps more generally. C1 Harvard Univ, Sch Med, Dept Genet, Massachusetts Gen Hosp,Dept Mol Biol, Boston, MA 02114 USA. RP Ruvkun, G (reprint author), CALTECH, Div Biol, WormBase, 156-29, Pasadena, CA 91125 USA. FU NIA NIH HHS [AG14161] NR 24 TC 287 Z9 297 U1 1 U2 23 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD DEC 11 PY 2001 VL 11 IS 24 BP 1950 EP 1957 DI 10.1016/S0960-9822(01)00595-4 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 502QR UT WOS:000172754700023 PM 11747821 ER PT J AU O'Neill, GN Aoki, M Brown, RH AF O'Neill, GN Aoki, M Brown, RH TI ABCD1 translation-initiator mutation demonstrates genotype-phenotype correlation for AMN SO NEUROLOGY LA English DT Article ID X-LINKED ADRENOLEUKODYSTROPHY; PEROXISOMAL MEMBRANE-PROTEIN; MONOZYGOTIC TWINS; GENE; TRANSPORTERS; EXPRESSION; HETEROGENEITY; INACTIVATION; THERAPY; FAMILY AB Background: Inherited mutations of the X-linked adrenoleukodystrophy (X-ALD) gone (ABCD1) cause two neuropathologically distinct disorders: cerebral adrenoleukodystrophy (ALD) and adrenomycloneuropathy (AMN). The biochemical hallmark of these disorders is a reduction of very long chain fatty acid (VLCFA) beta -oxidation with accumulation of VLCFA esters in neural white matter. More than 300 mutations of the ABCD1 gene have been described. Genotype-phenotype correlation in X-ALD has not been demonstrated; indeed, the two disorders coexist in individual pedigrees and in homozygotic twin pairs. Methods: The authors have identified one large kindred with a highly concordant AMN phenotype resembling an X-linked dominant hereditary spastic paraparesis. All obligate female carriers are clinically affected. The ABCD1 gene was examined by direct sequencing of genomic DNA and full-length cDNA. Mutant gene transcription was analyzed by reverse transcriptase PCR. ALD protein (ALDP) expression was tested by Western blotting and indirect immunofluorescence. VLCFA beta -oxidation was examined by in vitro assay. Results: The authors have identified a novel deletion of the ABCD1 gene ATG translation initiation codon. The authors have demonstrated that an N-terminal truncated ALDP, missing the first 65 amino acids, is expressed by internal initiation of translation and is correctly trafficked to peroxisomes. They have documented complete penetrance of this mutant in all female carriers. They have also shown that VLCFA beta -oxidation is reduced to 20% of normal in association with this mutant ALDP. Conclusion: It appears that initiation of translation at an internal AUG codon generates a truncated ALDP that uniformly leads to an AMN phenotype in this family. Possible models for action of this truncated ALDP and full disease penetrance in heterozygotes are reviewed. C1 Massachusetts Gen Hosp, Cecil B Day Lab Neuromuscular Res, Boston, MA 02114 USA. Tohoku Univ, Sch Med, Dept Neurol, Sendai, Miyagi 980, Japan. RP O'Neill, GN (reprint author), Massachusetts Gen Hosp E, Cecil B Day Lab, Room 3125,Bldg 114,16th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG12992-05]; NINDS NIH HHS [NS02017, NS37912-02] NR 34 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 11 PY 2001 VL 57 IS 11 BP 1956 EP 1962 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 500AP UT WOS:000172603900004 PM 11739809 ER PT J AU Gallardo, E Rojas-Garcia, R de Luna, N Pou, A Brown, RH Illa, I AF Gallardo, E Rojas-Garcia, R de Luna, N Pou, A Brown, RH Illa, I TI Inflammation in dysferlin myopathy: Immunohistochemical characterization of 13 patients SO NEUROLOGY LA English DT Article ID GIRDLE MUSCULAR-DYSTROPHY; GENE; 2B AB Inflammation was detected in 9 of 13 patients with different phenotypes of dysferlin myopathy. Endomysial or perivascular infiltrates consisted of 11.1% +/- 6.6% C8(+) cells, 40.6% +/- 22.8% CD4(+) cells, 36.7% +/- 23.7% macrophages, and no B cells. Major histocompatibility complex class I was not upregulated in normal muscle fibers. In young patients with sporadic proximal weakness, very high creatine kinase levels, necrotic fibers and inflammation in the muscle biopsy, a diagnosis of dysferlin myopathy should be considered. C1 Hosp Santa Creu & Sant Pau, Dept Neurol, UAB, Barcelona 08025, Spain. Hosp Santa Creu & Sant Pau, Neuromuscular Unit, Barcelona 08025, Spain. Hosp Santa Creu & Sant Pau, Lab Expt Neurol, Barcelona 08025, Spain. Univ Autonoma Barcelona, Inst Recerca, HSCSP, E-08193 Barcelona, Spain. Hosp del Mar, Dept Neurol, Barcelona, Spain. Massachusetts Gen Hosp, Day Neuromuscular Res Lab, Charlestown, MA USA. RP Illa, I (reprint author), Hosp Santa Creu & Sant Pau, Dept Neurol, UAB, Sant Antoni Ma Claret,167, Barcelona 08025, Spain. OI Gallardo, Eduard/0000-0002-3942-3436 NR 10 TC 120 Z9 122 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 11 PY 2001 VL 57 IS 11 BP 2136 EP 2138 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 500AP UT WOS:000172603900039 PM 11739845 ER PT J AU Amano, S Akutsu, N Matsunaga, Y Kadoya, K Nishiyama, T Champliaud, MF Burgeson, RE Adachi, E AF Amano, S Akutsu, N Matsunaga, Y Kadoya, K Nishiyama, T Champliaud, MF Burgeson, RE Adachi, E TI Importance of balance between extracellular matrix synthesis and degradation in basement membrane formation SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE laminin 5; type IV collagen; type VII collagen; basement membrane; MMPs ID VII COLLAGEN; EPIDERMOLYSIS-BULLOSA; ANCHORING FIBRILS; METALLOPROTEINASE-3 STROMELYSIN; TISSUE INHIBITOR; SKIN; INTEGRIN; ALPHA-3-BETA-1; KERATINOCYTES; EXPRESSION AB The epidermal basement membrane (BM) plays important roles in adhesion between epidermis and dermis and in controlling epidermal differentiation. In a skin-equivalent (SE), components of the epidermal BM such as laminin 5 and type IV and VII collagens were detected in conditioned media and in basal keratinocytes. Despite production of these BM components, however, BM was rarely observed at the dermal-epidermal junction. One possible explanation for the absence of BM in SEs is that matrix metalloproteinases (MMPs) degrade newly synthesized extracellular matrices. In fact, several MMPs, such as MMPs-1, 2,9, and 9, were observed to be present in conditioned media and some of them were in active forms. Tissue inhibitor of metalloproteinase (TIMP)-2 was not detected, although TIMP-1 was present. BM degradation activity presumably exceeds BM formation activity in the SE, resulting in the absence of lamina densa at the dermal-epidermal junction. Synthetic MMP inhibitors CGS27023A and MMP inhibitor I, which inhibit MAIN 1, 2, 3, and 9, markedly augmented deposition of laminin 5 and type IV and VII collagens at the dermal-epidermal junction, resulting in formation of continuous epidermal BAI. These results suggest that the balance between synthesis and degradation of BM components is important for BM formation. (C) 2001 Elsevier Science. C1 Shiseido Life Sci Res Ctr, Skin BIol Res Labs, Kanazawa Ku, Yokohama, Kanagawa 2368643, Japan. Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Boston, MA 02129 USA. Kitasato Univ, Grad Sch Med Sci, Dept Mol Morphol, Sagamihara, Kanagawa 2288555, Japan. RP Amano, S (reprint author), Shiseido Life Sci Res Ctr, Skin BIol Res Labs, Kanazawa Ku, 2-12-1 Fukuura, Yokohama, Kanagawa 2368643, Japan. RI Nishiyama, Toshio/C-5434-2013 NR 46 TC 50 Z9 55 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE 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 DEC 10 PY 2001 VL 271 IS 2 BP 249 EP 262 DI 10.1006/excr.2001.5387 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 502NK UT WOS:000172749500006 PM 11716537 ER PT J AU Tsuang, DW Skol, AD Faraone, SV Bingham, S Young, KA Prabhudesai, S Haverstock, SL Mena, F Menon, AS Bisset, D Pepple, J Sauter, F Baldwin, C Weiss, D Collins, J Boehnke, M Schellenberg, GD Tsuang, MT AF Tsuang, DW Skol, AD Faraone, SV Bingham, S Young, KA Prabhudesai, S Haverstock, SL Mena, F Menon, AS Bisset, D Pepple, J Sauter, F Baldwin, C Weiss, D Collins, J Boehnke, M Schellenberg, GD Tsuang, MT TI Examination of genetic linkage of chromosome 15 to schizophrenia in a large veterans affairs cooperative study sample SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE chromosome 15; schizophrenia; linkage; genetics; nicotinic cholinergic receptor ID GENOME SCAN; DIAGNOSTIC INTERVIEW; SUSCEPTIBILITY GENES; NO EVIDENCE; LOCUS; RELATIVES; FAMILIES; CHRNA7; CONSORTIUM; EXPRESSION AB Previous studies have reported genetic linkage evidence for a schizophrenia gene on chromosome 15q. Here, chromosome 15 was examined by genetic linkage analysis using 166 schizophrenia families, each with two or more affected subjects. The families, assembled from multiple centers by the Department of Veterans Affairs Cooperative Study Program, consisted of 392 sampled affected subjects and 216 affected sibling pairs. By DSM-III-R criteria, 360 subjects (91.8%) had a diagnosis of schizophrenia and 32 (8.2%) were classified as schizo-affective disorder, depressed. Participating families had diverse ethnic backgrounds. The largest single group were northern European American families (n = 62, 37%), but a substantial proportion was African American kindreds (n = 60, 36%). The chromosome 15 markers tested were spaced at intervals of approximately 10 cM over the entire chromosome and 2-5 cM for the region surrounding the alpha -7 nicotinic cholinergic receptor subunit gene (CHRNA7). These markers were genotyped and the data analyzed using semiparametric affecteds-only linkage analysis. In the European American families, there was a maximum Z-score of 1.65 between markers D15S165 and D15S1010. These markers are within 1 cM from CHRNA-7, the site previously implicated in schizophrenia. However, there was no evidence for linkage to this region in the African America kindreds. Published 2001 Wiley-Liss, Inc.(dagger). C1 Mental Illness Res Educ & Clin Ctr, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. Brockton W Roxbury Vet Affairs Med Ctr, Brockton, MA USA. Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Vet Affairs Med Ctr, Cooperat Studies Program Coordinating Ctr, Perry Point, MD USA. Vet Affairs Med Ctr, Waco, TX USA. Vet Affairs Med Ctr, Danville, IL USA. Vet Affairs Med Ctr, Augusta, GA USA. Vet Affairs Med Ctr, Tuskegee, AL USA. Vet Affairs Med Ctr, Perry Point, MD USA. Ctr Geriatr Res Educ & Clin, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Gerontol, Seattle, WA 98195 USA. Univ Washington, Dept Geriatr Med, Seattle, WA 98195 USA. Vet Affairs Med Ctr, New Orleans, LA USA. Vet Affairs Med Ctr, Northport, NY USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Schellenberg, GD (reprint author), Mental Illness Res Educ & Clin Ctr, Vet Affairs Puget Sound Hlth Care Syst, 182 GRECC,1660 S Columbian Way, Seattle, WA 98108 USA. RI Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Faraone, Stephen/0000-0002-9217-3982 NR 40 TC 54 Z9 55 U1 2 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 8 PY 2001 VL 105 IS 8 BP 662 EP 668 DI 10.1002/ajmg.1550 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 497TE UT WOS:000172470900003 PM 11803512 ER PT J AU Freedman, R Leonard, S Olincy, A Kaufmann, CA Malaspina, D Cloninger, CR Svrakic, D Faraone, SV Tsuang, MT AF Freedman, R Leonard, S Olincy, A Kaufmann, CA Malaspina, D Cloninger, CR Svrakic, D Faraone, SV Tsuang, MT TI Evidence for the multigenic inheritance of schizophrenia SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE schizophrenia; bipolar disorder; genetics; linkage analysis; chromosomes human pair 6, 10, and 15 ID GENETICALLY COMPLEX TRAITS; CHRNA7 GENE REGION; SUSCEPTIBILITY LOCUS; LINKAGE ANALYSIS; CHROMOSOME-15 LOCUS; VULNERABILITY LOCUS; SUGGESTIVE EVIDENCE; NO EVIDENCE; PEDIGREES; FAMILIES AB Schizophrenia is assumed to have complex inheritance because of its high prevalence and sporadic familial transmission. Findings of linkage on different chromosomes in various studies corroborate this assumption. It is not known whether these findings represent heterogeneous inheritance, in which various ethnic groups inherit illness through different major gene effects, or multigenic inheritance, in which affected individuals inherit several common genetic abnormalities. This study therefore examined inheritance of schizophrenia at different genetic loci in a nationally collected European American and African American sample. Seventy-seven families were previously genotyped at 458 markers for the NIMH Schizophrenia Genetics Initiative. Initial genetic analysis tested a dominant model, with schizophrenia and schizoaffective disorder, depressed type, as the affected phenotype. The families showed one genome-wide significant linkage (Z = 3.97) at chromosome 15q14, which maps within 1 cM of a previous linkage at the alpha7-nicotinic receptor gene. Chromosome 10p13 showed suggestive linkage (Z = 2.40). Six others (6q21, 9q32, 13q32, 15q24, 17p12, 20q13) were positive, with few differences between the two ethnic groups. The probability of each family transmitting schizophrenia through two genes is greater than expected from the combination of the independent segregation of each gene. Two trait-locus linkage analysis supports a model in which genetic alleles associated with schizophrenia are relatively common in the general population and affected individuals inherit risk for illness through at least two different loci. (C) 2001 Wiley-Liss, Inc. C1 Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Denver VA Med Ctr, Dept Psychiat, Denver, CO USA. Denver VA Med Ctr, Dept Pharmacol, Denver, CO USA. Columbia Univ, Dept Psychiat, New York, NY 10032 USA. Washington Univ, Dept Psychiat, St Louis, MO 63130 USA. Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Freedman, R (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Psychiat, C268-71, Denver, CO 80262 USA. RI Cloninger, Claude/F-5357-2012; OI Cloninger, Claude/0000-0003-3096-4807; Faraone, Stephen/0000-0002-9217-3982 NR 50 TC 74 Z9 76 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 8 PY 2001 VL 105 IS 8 BP 794 EP 800 DI 10.1002/ajmg.10100 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 497TE UT WOS:000172470900024 PM 11803533 ER PT J AU Gunshin, H Allerson, CR Polycarpou-Schwarz, M Rofts, A Rogers, JT Kishi, F Hentze, W Rouault, TA Andrews, NC Hediger, MA AF Gunshin, H Allerson, CR Polycarpou-Schwarz, M Rofts, A Rogers, JT Kishi, F Hentze, W Rouault, TA Andrews, NC Hediger, MA TI Iron-dependent regulation of the divalent metal ion transporter SO FEBS LETTERS LA English DT Article DE divalent cation transporter 1; divalent metal ion transporter 1; natural resistance associated macrophage protein 2; iron responsive element; iron regulatory protein; iron ID FERRITIN MESSENGER-RNA; RESPONSIVE ELEMENT; HEREDITARY HEMOCHROMATOSIS; UNTRANSLATED REGION; PROTEIN-BINDING; NRAMP2; IDENTIFICATION; EXPRESSION; TRANSLATION; METABOLISM AB The first step in intestinal iron absorption is mediated by the H+-coupled Fe2+ transporter called divalent cation transporter 1/divalent metal ion transporter 1 (DCT1/DMT1) (also known as natural resistance-associated macrophage protein 2). DCT1/DMT1 mRNA levels in the duodenum strongly increase in response to iron depletion. To study the mechanism of iron-dependent DCT1/DMT1 mRNA regulation, we investigated the endogenous expression of DCT1/DMT1 mRNA in various cell types. We found that only the iron responsive element (IRE)containing form, which corresponds to one of two splice forms of DCT1/DMT1, is responsive to iron treatment and this responsiveness was cell type specific. We also examined the interaction of the putative 3'-UTR IRE with iron responsive binding proteins (IRP1 and IRP2), and found that IRP1 binds to the DCT1/DMT1-IRE with higher affinity compared to IRP2. This differential binding of IRP1 and IRP2 was also reported for the IREs of transferrin receptors, erythroid 5-aminolevulinate synthase and mitochondrial aconitase. We propose that regulation of DCT1/DMT1 mRNA by iron involves post-transcriptional regulation through the binding of IRP1 to the transporter's IRE, as well as other as yet unknown factors. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies. C1 Brigham & Womens Hosp, Membrane Biol Program, Boston, MA 02115 USA. Brigham & Womens Hosp, Renal Div, Boston, MA 02115 USA. Harvard Univ, Sch Med, Inst Med, Boston, MA 02115 USA. Childrens Hosp, Hematol Oncol Div, Boston, MA 02115 USA. Natl Inst Child, Cell Biol & Metab Branch, Boston, MA USA. Massachusetts Gen Hosp, Genet & Aging Unit, Boston, MA 02114 USA. Yamaguchi Univ, Yamaguchi 753, Japan. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Gunshin, H (reprint author), Brigham & Womens Hosp, Membrane Biol Program, 77 Ave Louis Pasteur, Boston, MA 02115 USA. OI Andrews, Nancy/0000-0003-0243-4462; Hentze, Matthias/0000-0002-4023-7876 FU NIDDK NIH HHS [KO1DK02804, R01 DK053813, R01 DK053813-10, R01DK53813, R01DK57782] NR 40 TC 200 Z9 208 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD DEC 7 PY 2001 VL 509 IS 2 BP 309 EP 316 DI 10.1016/S0014-5793(01)03189-1 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 502RX UT WOS:000172757500031 PM 11741608 ER PT J AU Watson, PA Nesterova, A Burant, CF Klemm, DJ Reusch, JEB AF Watson, PA Nesterova, A Burant, CF Klemm, DJ Reusch, JEB TI Diabetes-related changes in cAMP response element-binding protein content enhance smooth muscle cell proliferation and migration SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIGH GLUCOSE; CARDIOVASCULAR-DISEASE; KINASE PATHWAY; CYCLIC-AMP; VITAMIN-E; TRANSCRIPTION; ACTIVATION; GROWTH; CREB; CBP AB We hypothesized that diabetes and glucose-induced reactive oxygen species lead to depletion of cAMP response element-binding protein (CREB) content in the vasculature. In primary cultures of smooth muscle cells (SMC) high medium glucose decreased CREB function but increased SMC chemokinesis and entry into the cell cycle. These effects were blocked by pretreatment with the antioxidants. High glucose increased intracellular reactive oxygen species detected by CM-H(2)DCFA. SMC exposed to oxidative stress (H2O2) demonstrated a 3.5-fold increase in chemokinesis (p < 0.05) and accelerated entry into cell cycle, accompanied by a significant decrease in CREB content. Chronic oxidative challenge similar to the microenvironment in diabetes (glucose oxidase treatment) decreases CREB content (40-50%). Adenoviral-mediated expression of constitutively active CREB abolished the increase in chemokinesis and cell cycle progression induced by either high glucose or oxidative stress. Analysis of vessels from insulin resistant or diabetic animals indicates that CREB content is decreased in the vascular stroma. Treatment of insulin-resistant animals with the insulin sensitizer rosiglitazone restores vessel wall CREB content toward that observed in normal animals. In summary, high glucose and oxidative stress decrease SMC CREB content increase chemokinesis and entry into the cell cycle, which is blocked by antioxidants or restoration of CREB content. Thus, decreased vascular CREB content could be one of the molecular mechanisms leading to increased atherosclerosis in diabetes. C1 Denver Vet Affairs Med Ctr, Denver Res Inst, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Div Endocrinol, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Cardiovasc Pulm Res Sect, Denver, CO 80220 USA. Pfizer Inc, Ann Arbor, MI 48105 USA. RP Reusch, JEB (reprint author), Denver Vet Affairs Med Ctr, Denver Res Inst, Rm 9C-120,1055 Clermont St, Denver, CO 80220 USA. OI Burant, Charles/0000-0001-9189-5003 FU NIDDK NIH HHS [R01 DK53969, K08 DK02351] NR 55 TC 54 Z9 55 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 DEC 7 PY 2001 VL 276 IS 49 BP 46142 EP 46150 DI 10.1074/jbc.M104770200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 499LR UT WOS:000172573100089 PM 11560925 ER PT J AU Boeuf, H Merienne, K Jacquot, S Duval, D Zeniou, M Hauss, C Reinhardt, B Huss-Garcia, Y Dierich, A Frank, DA Hanauer, A Kedinger, C AF Boeuf, H Merienne, K Jacquot, S Duval, D Zeniou, M Hauss, C Reinhardt, B Huss-Garcia, Y Dierich, A Frank, DA Hanauer, A Kedinger, C TI The ribosomal S6 kinases, cAMP-responsive element-binding, and STAT3 proteins are regulated by different leukemia inhibitory factor signaling pathways in mouse embryonic stem cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; INDUCED TRANSCRIPTIONAL ACTIVATION; SERINE PHOSPHORYLATION; CREB PHOSPHORYLATION; SELF-RENEWAL; MAPK PATHWAY; DNA-BINDING; RECEPTOR; GENE; LIF AB Mouse embryonic stem (ES) cells remain "pluripotent" in vitro in the continuous presence of leukemia inhibitory factor (LIF). In the absence of LIF, ES cells are irreversibly committed to differentiate into various lineages. In this study we have set up an in vitro assay based on the anti-apoptotic activity of LIF to distinguish pluripotent from "differentiation-committed" ES cells. We have examined the phosphorylation profiles of known (STAT3 and ERKs) and identified new (ribosomal S6 kinases (RSKs) and cAMP-responsive element-binding protein (CREB)) LIF-regulated targets in ES and in ES-derived neuronal cells. We have demonstrated that although STAT3, a crucial player in the maintenance of ES cell pluripotency, is induced by LIF in all cell types tested, the LIF-dependent activation of RSKs is restricted to ES cells. We have shown that LIF-induced phosphorylation of RSKs in ES cells is dependent on ERKs, whereas STAT3 phosphorylation is not mediated by any known MAPK activities. Our results also demonstrate that the LIF-dependent phosphorylation of CREB is partially under the control of the RSK2 kinase. C1 Univ Strasbourg 1, Inst Genet & Biol Mol & Cellulaire, CNRS, INSERM, F-67404 Illkirch Graffenstaden, France. Univ Zurich, Div Neuroanat & Behav, Inst Anat, Zurich, Switzerland. Ecole Super Biotechnol Strasbourg, FRE 2370, F-67400 Strasbourg, France. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Kedinger, C (reprint author), Univ Strasbourg 1, Inst Genet & Biol Mol & Cellulaire, CNRS, INSERM, BP 163, F-67404 Illkirch Graffenstaden, France. RI DUVAL, David/B-8586-2011 NR 85 TC 44 Z9 47 U1 1 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 DEC 7 PY 2001 VL 276 IS 49 BP 46204 EP 46211 DI 10.1074/jbc.M106718200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 499LR UT WOS:000172573100097 PM 11581263 ER PT J AU Gori, F Divieti, P Demay, MB AF Gori, F Divieti, P Demay, MB TI Cloning and characterization of a novel WD-40 repeat protein that dramatically accelerates osteoblastic differentiation. SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BONE MORPHOGENETIC PROTEIN-2; MARROW STROMAL CELLS; TRANSCRIPTIONAL REPRESSION; WD-REPEAT; SACCHAROMYCES-CEREVISIAE; PTH/PTHRP RECEPTOR; FAMILY MEMBERS; BETA-SUBUNITS; YEAST; GENE AB The bone morphogenetic proteins (BMPs) play a pivotal role in endochondral bone formation. Using differential display polymerase chain reaction, we have identified a novel gene, named BIG-3 (BMP-2-induced gene 3 kb), that is induced as a murine prechondroblastic cell line, MLB13MYC clone 17, acquires osteoblastic features in response to BMP-2 treatment. The 3-kilobase mRNA encodes a 34-kDa protein containing seven WD-40 repeats. Northern and Western analyses demonstrated that BIG-3 mRNA and protein were induced after 24 h of BMP-2 treatment. BIG-3 mRNA was expressed in conditionally immortalized murine bone marrow stromal cells, osteoblasts, osteocytes, and growth plate chondrocytes, as well as in primary calvarial osteoblasts. Immunohistochemistry demonstrated that BIG-3 was expressed in the osteoblasts of calvariae isolated from mouse embryos. To identify a role for BIG-3 in osteoblast differentiation, MC3T3-E1 cells were stably transfected with the full-length coding region of BIG-3 (MC3T3E1-BIG-3) cloned downstream of a cytomegalovirus promoter in pcDNA3.1. Pooled MC3T3E1-BlG-3 clones expressed alkaline phosphatase activity earlier and achieved a peak level of activity 10-fold higher than cells transfected with the empty vector (MC3T3E1-EV) at 14 days. Cyclic AMP production in response to parathyroid hormone was increased 10- and 14-fold at 7 and 14 days, respectively, in MC3T3E1-BlG-3 clones, relative to MC3T3E1-EV clones. This increase in cAMP production was associated with an increase in PTH binding. Expression of BIG-3 increased mRNA levels encoding Cbfa1, type I collagen, and osteocalcin and accelerated formation of mineralized nodules. In conclusion, we have identified a novel WD-40 protein, induced by BMP-2 treatment, that dramatically accelerates the program of osteoblastic differentiation in stably transfected MC3T3E1 cells. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. RP Demay, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. FU NIDCR NIH HHS [1 F32 DE-05754]; NIDDK NIH HHS [1 KO8 DK02889, DK36597] NR 47 TC 59 Z9 62 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 DEC 7 PY 2001 VL 276 IS 49 BP 46515 EP 46522 DI 10.1074/jbc.M105757200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 499LR UT WOS:000172573100137 PM 11551928 ER PT J AU Gruendler, C Lin, Y Farley, J Wang, TW AF Gruendler, C Lin, Y Farley, J Wang, TW TI Proteasomal degradation of Smad1 induced by bone morphogenetic proteins. SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TGF-BETA FAMILY; ORNITHINE DECARBOXYLASE; DEPENDENT DEGRADATION; SIGNALING PATHWAYS; I RECEPTORS; SUBUNIT; FKBP12; REGULATORS; ANTIZYME; CLONING AB The bone morphogenetic proteins (BMPs) regulate early embryogenesis and morphogenesis of multiple organs, such as bone, kidney, limbs, and muscle. Smad1 is one of the key signal transducers of BMPs and is responsible for transducing receptor activation signals from the cytoplasm to the nucleus, where Smad1 serves as a transcriptional regulator of various BMP-responsive genes. Based upon the ability of Smad1 to bind multiple proteins involved in proteasome-mediated degradation pathway, we investigated whether Smad1 could be a substrate for proteasome. We found that Smad1 is targeted to proteasome for degradation in response to BMP type I receptor activation. The targeting of Smad1 to proteasome involves not only the receptor activation-induced Smad1 ubiquitination but also the targeting functions of the ornithine decarboxylase antizyme and the proteasome beta subunit HsN3. Our studies provide the first evidence for BMP-induced proteasomal targeting and degradation of Smad1 and also reveal new players and novel mechanisms involved in this important aspect of Smad1 regulation and function. C1 Virginia Mason Res Ctr, Seattle, WA 98101 USA. Univ Washington, Dept Immunol, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. RP Wang, TW (reprint author), Virginia Mason Res Ctr, 1201 9th Ave, Seattle, WA 98101 USA. NR 44 TC 64 Z9 68 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 DEC 7 PY 2001 VL 276 IS 49 BP 46533 EP 46543 DI 10.1074/jbc.M105500200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 499LR UT WOS:000172573100139 PM 11571290 ER PT J AU Xu, GM Sikaneta, T Sullivan, BM Zhang, QH Andreucci, M Stehle, T Drummond, L Arnaout, MA AF Xu, GM Sikaneta, T Sullivan, BM Zhang, QH Andreucci, M Stehle, T Drummond, L Arnaout, MA TI Polycystin-1 interacts with intermediate filaments. SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PKD1 GENE-PRODUCT; KIDNEY-DISEASE; IN-VITRO; PROTEIN PHOSPHATASE; MEMBRANE-FUSION; MDCK CELLS; DESMOSOMES; DOMAIN; IDENTIFICATION; MICE AB Polycystin-1, the protein defective in a majority of patients with autosomal dominant polycystic kidney disease, is a ubiquitously expressed multi-span transmembrane protein of unknown function. Subcellular localization studies found this protein to be a component of various cell junctional complexes and to be associated with the cytoskeleton, but the specificity and nature of such associations are not known. To identify proteins that interact with the polycystin-1 C-tail (P1CT), this segment was used as bait in a yeast two-hybrid screening of a kidney epithelial cell library. The intermediate filament (IF) protein vimentin was identified as a strong polycystin-1-interacting partner. Cytokeratins K8 and K18 and desmin were also found to interact with P1CT. These interactions were mediated by coiled-coil motifs in polycystin-1 and IF proteins. Vimentin, cytokeratins K8 and K18, and desmin also bound directly to P1CT in GST pull-down and in in vitro filament assembly assays. Two observations confirmed these interactions in vivo: (i) a cell membrane-anchored form of recombinant P1CT decorated the IF network and was found to associate with the cytoskeleton in detergent-solubilized cells and (ii) endogenous polycystin-1 distributed with IF at desmosomal junctions. Polycystin-1 may utilize this association for structural, storage, or signaling functions. C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Arnaout, MA (reprint author), Massachusetts Gen Hosp, Renal Unit, Bldg 149,13th St, Boston, MA 02129 USA. FU NIDDK NIH HHS [P01 DK54711] NR 74 TC 51 Z9 55 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 DEC 7 PY 2001 VL 276 IS 49 BP 46544 EP 46552 DI 10.1074/jbc.M107828200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 499LR UT WOS:000172573100140 PM 11581269 ER PT J AU Rosenthal, MJ Hwang, IK Song, MK AF Rosenthal, MJ Hwang, IK Song, MK TI Effects of arachidonic acid and cyclo (his-pro) on zinc transport across small intestine and muscle tissues SO LIFE SCIENCES LA English DT Article DE zinc; arachidonic acid; cyclo (his-pro); rat; muscle tissue; small intestine ID THYROTROPIN-RELEASING-HORMONE; DEPENDENT DIABETES-MELLITUS; GLUCOSE-TOLERANCE; INSULIN; RAT; METABOLISM; COPPER; CYCLO(HIS-PRO); SUPPLEMENTS; CALCIUM AB Previously we have shown that arachidonic acid (AA) plus zinc or cyclo (his-pro) (CHP) plus zinc improve clinical signs of diabetes in streptozotocin-induced diabetic rats. Since streptozotocin destroys pancreatic P-cells, we hypothesize that the effect of either AA or CHP, plus zinc on glucose metabolism is via mobilization of intracellular zinc which in turn stimulates glucose uptake by peripheral tissues. We now report the relationship between zinc and AA and between zinc and CHP in controlling zinc influx and efflux across hindlimb muscle cells isolated from three-month old rats. Although CHP increased muscle zinc influx in a dose-dependent manner, AA was not effective. However, AA was more effective in stimulating zinc efflux than CHP. We have previously demonstrated that AA stimulates intestinal zinc uptake and absorption, and now present evidence that CHP also influences intestinal zinc transport. These results suggest that both AA and CHP affect glucose uptake in muscle cells via stimulating intestinal zinc absorption and muscle cell zinc flux. (C) 2001 Elsevier Science Inc. All rights reserved. C1 VA Greater Los Angeles Healthcare Syst, Sepulveda VA Med Ctr, Geriatr Res & Educ Ctr 11E, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Ctr Human Nutr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. RP Rosenthal, MJ (reprint author), VA Greater Los Angeles Healthcare Syst, Sepulveda VA Med Ctr, Geriatr Res & Educ Ctr 11E, Sepulveda, CA 91343 USA. FU NIDDK NIH HHS [1 R43 DK 56546-01] NR 45 TC 16 Z9 17 U1 0 U2 0 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 DEC 7 PY 2001 VL 70 IS 3 BP 337 EP 348 DI 10.1016/S0024-3205(01)01395-9 PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 500PR UT WOS:000172636400009 PM 12005266 ER PT J AU van den Brink, GR Barbara, PD Roberts, DJ AF van den Brink, GR Barbara, PD Roberts, DJ TI Development - Epithelial cell differentiation - a mather of Choice SO SCIENCE LA English DT Editorial Material ID HEDGEHOG; SIGNALS; GENES C1 Univ Amsterdam, Acad Med Ctr, Dept Expt Internal Med, NL-1105 AZ Amsterdam, Netherlands. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP van den Brink, GR (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Expt Internal Med, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. NR 16 TC 35 Z9 35 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 7 PY 2001 VL 294 IS 5549 BP 2115 EP 2116 DI 10.1126/science.1067751 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 500VQ UT WOS:000172647700036 PM 11739944 ER PT J AU Becerra, L Breiter, HC Wise, R Gonzalez, RG Borsook, D AF Becerra, L Breiter, HC Wise, R Gonzalez, RG Borsook, D TI Reward circuitry activation by noxious thermal stimuli SO NEURON LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; ANTERIOR CINGULATE CORTEX; NUCLEUS-ACCUMBENS NEURONS; HUMAN BRAIN; PREFRONTAL CORTEX; ELECTROPHYSIOLOGICAL EVIDENCE; PERIAQUEDUCTAL GRAY; PAIN PERCEPTION; SOMATOSENSORY CORTEX; ORBITOFRONTAL CORTEX AB Using functional magnetic resonance imaging (fMRI), we observed that noxious thermal stimuli (46 degreesC) produce significant signal change in putative reward circuitry as well as in classic pain circuitry. Increases in signal were observed in the sublenticular extended amygdala of the basal forebrain (SLEA) and the ventral tegmentum/periaqueductal gray (VT/PAG), while foci of increased signal and decreased signal were observed in the ventral striatum and nucleus accumbens (NAc). Early and late phases were observed for signals in most brain regions, with early activation in reward related regions such as the SLEA, VT/PAG, and ventral striatum, In contrast, structures associated with somatosensory perception, including SI somatosensory cortex, thalamus, and insula, showed delayed activation. These data support the notion that there may be a shared neural system for evaluation of aversive and rewarding stimuli. C1 Massachusetts Gen Hosp, Ctr Funct Pain Neuroimaging & Therapy Res, Boston, MA 02129 USA. Massachusetts Gen Hosp, Motivat & Emot Neurosci Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02129 USA. NIDA, NIH, Baltimore, MD 21224 USA. RP Borsook, D (reprint author), Massachusetts Gen Hosp, Ctr Funct Pain Neuroimaging & Therapy Res, Boston, MA 02129 USA. RI Wise, Roy/A-6465-2012 FU PHS HHS [00265, 01258, 034626, 09467, 13650] NR 121 TC 298 Z9 299 U1 1 U2 34 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD DEC 6 PY 2001 VL 32 IS 5 BP 927 EP 946 DI 10.1016/S0896-6273(01)00533-5 PG 20 WC Neurosciences SC Neurosciences & Neurology GA 501RW UT WOS:000172700700017 PM 11738036 ER PT J AU Ozen, M Giri, D Ropiquet, F Mansukhani, A Ittmann, M AF Ozen, M Giri, D Ropiquet, F Mansukhani, A Ittmann, M TI Role of fibroblast growth factor receptor signaling in prostate cancer cell survival SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID EPITHELIAL-CELLS; OVER-EXPRESSION; FGF RECEPTORS; IN-VITRO; APOPTOSIS; PROLIFERATION; TRANSDUCTION; SUPPRESSION; GENE AB Background: Expression of fibroblast growth factors (FGFs) is increased in a substantial fraction of human prostate cancers in vivo and in prostate cancer cell lines. Altered FGF signaling can potentially have a variety of effects, including stimulating cell proliferation and inhibiting cell death. To determine the biologic significance of altered FGF signaling in human prostate cancer, we disrupted signaling by expression of a dominant-negative (DN) FGF receptor in prostate cancer cell lines. Methods: PC-3, LNCaP, and DU145 prostate cancer cells were stably transfected with DN FGFR constructs, and LNCaP and DU145 cells were infected with a recombinant adenovirus expressing DN FGFR-1. The effect of DN FGFR-1 expression was assessed by colony-formation assays, cell proliferation assays, flow cytometry, and cytogenetic analysis. Key regulators involved in the G(2)-to-M cell cycle transition were assessed by western blotting to examine cyclin B1 expression and by in vitro kinase assay to assess cdc2 kinase activity. Results: Stable transfection of the DN FGFR-1 construct inhibited colony formation by more than 99% in all three cell lines. Infection of LNCaP and DU145 prostate cancer cells with adenovirus expressing DN FGFR-1 led to extensive cell death within 48 hours. Flow cytometry and cytogenetic analysis revealed that the DN FGFR-1 receptor led to arrest in the G(2) phase of the cell cycle before cell death. Cyclin B1 accumulated in DN FGFR-1-infected LNCaP cells, but cdc2 kinase activity was decreased. Conclusions: These findings reveal an unexpected dependence of prostate cancer cells on FGF receptor signal transduction to traverse the G(2)/M checkpoint. The mechanism for the G(2) arrest is not clear. Our results raise the possibility that FGF-signaling antagonists might enhance the cell death induced by other prostate cancer therapies. C1 Houston Dept Vet Affairs Med Ctr, Res Serv, Houston, TX 77030 USA. NYU, Sch Med, Dept Microbiol, New York, NY USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. RP Ittmann, M (reprint author), Houston Dept Vet Affairs Med Ctr, Res Serv, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 27 TC 60 Z9 64 U1 1 U2 2 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 DEC 5 PY 2001 VL 93 IS 23 BP 1783 EP 1790 DI 10.1093/jnci/93.23.1783 PG 8 WC Oncology SC Oncology GA 498DN UT WOS:000172494700008 PM 11734594 ER PT J AU Taghian, AG Assaad, SI Niemierko, A Kuter, I Younger, J Schoenthaler, R Roche, M Powell, SN AF Taghian, AG Assaad, SI Niemierko, A Kuter, I Younger, J Schoenthaler, R Roche, M Powell, SN TI Risk of pneumonitis in breast cancer patients treated with radiation therapy and combination chemotherapy with paclitaxel SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CONSERVATIVE SURGERY; MITOTIC ARREST; TAXOL; LUNG; RADIORESPONSE; APOPTOSIS AB Background: Some chemotherapy (CT) drugs, including, taxanes, may enhance the effectiveness of radiation therapy (RT)., However, combining these therapies may increase the incidence of radiation pneumonitis, a lung inflammation. In a retrospective cohort study, we evaluated the incidence of radiation pneumonitis in breast cancer patients treated with RT and standard adjuvant CT by use of doxorubicin (Adriamycin) and cyclophosphamide, with and without paclitaxel., Methods: Forty-one patients with breast cancer were treated with RT and adjuvant CT, including paclitaxel. Paclitaxel and RT (to breast-chest wall in all and lymph nodes in some) were delivered sequentially in 20 patients, and concurrently in 21 patients. Paclitaxel was given weekly in some patients and every 3 weeks in other patients. The incidence of radiation, pneumonitis, was compared with that among patients in our database whose treatments did not include paclitaxel (n = 1286). The percentage of the lung volume irradiated was, estimated. The Cox proportional. hazards model was used to find covariates, that may be associated with the observed outcomes. All P values were two-sided. Results: Radiation pneumonitis, developed in six of the 41 patients,. Three patients received paclitaxel concurrently with RT., and three received it sequentially (P = .95). The mean percentage of lung volume irradiated was 20% in patients who developed radiation pneumonitis and 22% in those who did not (P = .6). For patients treated with CT including paclitaxel, the crude rate of developing radiation pneumonitis, was 14.6% (95% confidence interval [CI] = 5.6% to 29.2%). For patients treated with CT without paclitaxel, the crude rate of pneumonitis was, 1.1% (95% CI = 0.2% to 2.3%)., The difference between the crude rates with or without paclitaxel is highly statistically significant (P < .0001). The mean time to develop radiation pneumonitis in patients treated concurrently with RT and paclitaxel was statistically significantly shorter in patients receiving paclitaxel weekly than in those receiving it every 3 weeks (P = .002). Conclusions: The use of paclitaxel and RT in the primary treatment of breast cancer should be undertaken with caution. Clinical trials with the use of combination CT, including paclitaxel plus RT, whether concurrent or sequential, must evaluate carefully the incidence, of radiation pneumonitis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biostat, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med Oncol, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Cox 3,100 Blossom St, Boston, MA 02114 USA. FU NCI NIH HHS [CA 21239, CA 50628] NR 28 TC 96 Z9 98 U1 0 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 DEC 5 PY 2001 VL 93 IS 23 BP 1806 EP 1811 DI 10.1093/jnci/93.23.1806 PG 6 WC Oncology SC Oncology GA 498DN UT WOS:000172494700011 PM 11734597 ER PT J AU Wang, LI Miller, DP Sai, Y Liu, G Su, L Wain, JC Lynch, TJ Christiani, DC AF Wang, LI Miller, DP Sai, Y Liu, G Su, L Wain, JC Lynch, TJ Christiani, DC TI Manganese superoxide dismutase alanine-to-valine polymorphism at codon 16 and lung cancer risk SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MITOCHONDRIAL TARGETING SEQUENCE; MALIGNANT PHENOTYPE; CELLS; EXPRESSION; DISEASE; GENE; OVEREXPRESSION; MNSOD; CARCINOGENESIS; SUSCEPTIBILITY C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Hematol Oncol Unit, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Thorac Surg Unit, Cambridge, MA 02138 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Epidemiol, 665 Huntington Ave,Bldg 1,Rm 1402, Boston, MA 02115 USA. RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [CA 74386]; NIEHS NIH HHS [ES 00002, ES-CA 06409] NR 37 TC 91 Z9 95 U1 0 U2 3 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 DEC 5 PY 2001 VL 93 IS 23 BP 1818 EP 1821 DI 10.1093/jnci/93.23.1818 PG 4 WC Oncology SC Oncology GA 498DN UT WOS:000172494700013 PM 11734599 ER PT J AU Penson, DF Albertsen, PC Nelson, PS Barry, M Stanford, JL AF Penson, DF Albertsen, PC Nelson, PS Barry, M Stanford, JL TI Determining cause of death in prostate cancer: Are death certificates valid? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MORTALITY; INFORMATION C1 Univ Washington, Sch Med, US Dept Vet Affairs Pugent Sound Hlth Care Syst, Urol Sect, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Connecticut, Sch Med, Farmington, CT USA. Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. RP Penson, DF (reprint author), Univ Washington, Sch Med, US Dept Vet Affairs Pugent Sound Hlth Care Syst, Urol Sect, 112-UR,1660 S Columbian Way, Seattle, WA 98195 USA. FU AHRQ HHS [HS 08397] NR 14 TC 98 Z9 98 U1 1 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 DEC 5 PY 2001 VL 93 IS 23 BP 1822 EP 1823 DI 10.1093/jnci/93.23.1822 PG 2 WC Oncology SC Oncology GA 498DN UT WOS:000172494700014 PM 11734600 ER PT J AU Sabatine, MS Braunwald, E AF Sabatine, MS Braunwald, E TI Will diabetes save the platelet blockers? SO CIRCULATION LA English DT Editorial Material ID PERCUTANEOUS CORONARY INTERVENTION; MELLITUS; HYPERINSULINEMIA; AGGREGATION; ABCIXIMAB; DISEASE; BLOOD; RISK C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med, Boston, MA 02115 USA. RP Sabatine, MS (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. NR 23 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 4 PY 2001 VL 104 IS 23 BP 2759 EP 2761 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 499NN UT WOS:000172577400004 PM 11733390 ER PT J AU McQuillan, BM Picard, MH Leavitt, M Weyman, AE AF McQuillan, BM Picard, MH Leavitt, M Weyman, AE TI Clinical correlates and reference intervals for pulmonary artery systolic pressure among echocardiographically normal subjects SO CIRCULATION LA English DT Article DE hypertension, pulmonary; obesity; aging; sex; echocardiography ID TRICUSPID REGURGITATION; NONINVASIVE ESTIMATION; DOPPLER ULTRASOUND; HYPERTENSION; HEMODYNAMICS; MORTALITY AB Background-Data in normal human subjects on the factors affecting pulmonary artery systolic pressure (PASP) are limited. We determined the correlates of and established a reference range for PASP as determined by Doppler transthoracic echocardiography (TTE) from a clinical echocardiographic database of 102 818 patients, of whom 15 596 (15%) had a normal Doppler TTE study. Methods and Results-A normal TTE was based on normal cardiac structure and function during complete Doppler TTE studies. The PASP was calculated by use of the modified Bernoulli equation, with right atrial pressure assumed to be 10 mm Hg. Among TTE normal subjects, 3790 subjects (2432 women, 1358 men) from 1 to 89 years old had a measured PASP. The mean PASP was 28.3 +/-4.9 mm Hg (range 15 to 57 mm Hg). PASP was independently associated with age, body mass index (BMI), male sex, left ventricular posterior wall thickness, and left ventricular ejection fraction (P <0.001). The estimated upper 95% limit for PASP among lower-risk subjects was 37.2 mm fig. A PASP > 40 mm Hg was found in 6% of those > 50 years old and 5% of those with a BMI > 30 kg/m(2). Conclusions-Among 3790 echocardiographically normal subjects, PASP was associated with age, BMI, sex, wall thickness, and ejection fraction. Of these subjects, 28% had a PASP > 130 mm Hg, and the expected upper limit of PASP may include 40 min Hg in older or obese subjects. These findings support the use of age- and BMI-corrected values in establishing the expected normal range for PASP. C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Weyman, AE (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St, Boston, MA 02114 USA. RI McQuillan, Brendan/B-8271-2013; OI McQuillan, Brendan/0000-0002-2130-8114; Picard, Michael/0000-0002-9264-3243 NR 22 TC 334 Z9 363 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 4 PY 2001 VL 104 IS 23 BP 2797 EP 2802 DI 10.1161/hc4801.100076 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 499NN UT WOS:000172577400011 PM 11733397 ER PT J AU Cao, H Krishnan, G Goumnerov, B Tsongalis, J Tompkins, R Rahme, LG AF Cao, H Krishnan, G Goumnerov, B Tsongalis, J Tompkins, R Rahme, LG TI A quorum sensing-associated virulence gene of Pseudomonas aeruginosa encodes a LysR-like transcription regulator with a unique self-regulatory mechanism SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SUBCELLULAR-LOCALIZATION; BACILLUS-SUBTILIS; BETA-LACTAMASE; EFFLUX OPERON; PROTEIN; IDENTIFICATION; CONSTRUCTION; AUTOINDUCER; RESISTANCE; ACTIVATION AB The human opportunistic pathogen Pseudomonas aeruginosa strain PA14 infects both plants and animals. Previously, using plants to screen directly for P. aeruginosa virulence-attenuated mutants, we identified a locus, pho34B12, relevant in mammalian pathogenesis. Here, nonsense point mutations in the two opposing DRFs identified in the pho34B12 locus revealed that one of them, mvfR (multiple virulence factor Regulator), is able to control all of the phenotypes that mutant phoA34B12 displays. Both genetic and biochemical evidence demonstrate that the mvfR gene encodes a LysR-like transcriptional factor that positively regulates the production of elastase, phospholipase, and of the autoinducers, 3-oxo-dodecanoyl homoserine lactone (PAI I) and 2-heptyl-3-hydroxy-4-quinolone (PQS), as well as the expression of the phnAB operon, involved in phenazine biosynthesis. We demonstrate that the MvfR protein is membrane-associated and acts as a transcriptional activator until cells reach stationary phase, when a unique negative feedback mechanism is activated to signal the downregulation of the MvfR protein. This work reveals an unprecedented virulence mechanism of P. aeruginosa and identifies a unique indispensable player in the P, aeruginosa quorum-sensing cascade. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Boston Shriners Inst, Boston, MA 02114 USA. RP Rahme, LG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 50 Blossom St, Boston, MA 02114 USA. NR 38 TC 158 Z9 164 U1 0 U2 12 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 4 PY 2001 VL 98 IS 25 BP 14613 EP 14618 DI 10.1073/pnas.251465298 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 499NH UT WOS:000172576900077 PM 11724939 ER PT J AU Renno, RZ Miller, JW AF Renno, RZ Miller, JW TI Photo sensitizer delivery for photodynamic therapy of choroidal neovascularization (vol 52, pg 63, 2001) SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Correction C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Angiogenesis Lab,Retina Serv, Boston, MA 02114 USA. RP Miller, JW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Angiogenesis Lab,Retina Serv, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD DEC 3 PY 2001 VL 53 IS 1 BP 131 EP 131 DI 10.1016/S0169-409X(01)00238-1 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 501XZ UT WOS:000172712500009 ER PT J AU Li, SG Couvillon, AD Brasher, BB Van Etten, RA AF Li, SG Couvillon, AD Brasher, BB Van Etten, RA TI Tyrosine phosphorylation of Grb2 by Bcr/Abl and epidermal growth factor receptor: a novel regulatory mechanism for tyrosine kinase signaling SO EMBO JOURNAL LA English DT Article DE Abelson; chronic myeloid leukemia; CML; SH3 ID BCR-ABL ONCOGENE; SRC SH3 DOMAIN; INSULIN-RECEPTOR; NUCLEOTIDE EXCHANGE; BINDING PROTEIN-2; ADAPTER PROTEIN; EGF-RECEPTOR; RAS PATHWAY; IN-VIVO; TRANSFORMATION AB Growth factor receptor-binding protein-2 (Grb2) plays a key role in signal transduction initiated by Bcr/Abl oncoproteins and growth factors, functioning as an adaptor protein through its Src homology 2 and 3 (SH2 and SH3) domains. We found that Grb2 was tyrosine-phosphorylated in cells expressing BCR/ABL and in A431 cells stimulated with epidermal growth factor (EGF). Phosphorylation of Grb2 by Bcr/Abl or EGF receptor reduced its SH3-dependent binding to Sos in vivo, but not its SH2-dependent binding to Bcr/Abl. Tyr209 within the C-terminal SH3 domain of Grb2 was identified as one of the tyrosine phosphorylation sites, and phosphorylation of Tyr209 abolished the binding of the SH3 domain to a proline-rich Sos peptide in vitro. In vivo expression of a Grb2 mutant where Tyr209 was changed to phenylalanine enhanced BCR/ABL-induced ERK activation and fibroblast transformation, and potentiated and prolonged Grb2-mediated activation of Ras, mitogen-activated protein kinase and c-Jun N-terminal kinase in response to EGF stimulation. These results suggest that tyrosine phosphorylation of Grb2 is a novel mechanism of down-regulation of tyrosine kinase signaling. C1 Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Genet, Ctr Blood Res, Boston, MA 02115 USA. RP Li, SG (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. FU NCI NIH HHS [CA72465, CA90576, R01 CA090576] NR 47 TC 60 Z9 60 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 3 PY 2001 VL 20 IS 23 BP 6793 EP 6804 DI 10.1093/emboj/20.23.6793 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 500LM UT WOS:000172629100024 PM 11726515 ER PT J AU Han, AP Yu, C Lu, LR Fujiwara, Y Browne, C Chin, G Fleming, M Leboulch, P Orkin, SH Chen, JJ AF Han, AP Yu, C Lu, LR Fujiwara, Y Browne, C Chin, G Fleming, M Leboulch, P Orkin, SH Chen, JJ TI Heme-regulated eIF2 alpha kinase (HRI) is required for translational regulation and survival of erythroid precursors in iron deficiency SO EMBO JOURNAL LA English DT Article DE apoptosis; erythropoiesis; heme-regulated eIF2 alpha kinase; iron deficiency; translation ID DEPENDENT PROTEIN-KINASE; EUKARYOTIC INITIATION FACTOR-2-ALPHA; FACTOR 2-ALPHA KINASE; HEMOGLOBIN-H DISEASE; BETA-GLOBIN CHAINS; EIF-2-ALPHA KINASE; ERYTHROPOIETIC CELLS; ELECTRON-MICROSCOPE; MAMMALIAN HOMOLOG; THALASSEMIA AB Although the physiological role of tissue-specific translational control of gene expression in mammals has long been suspected on the basis of biochemical studies, direct evidence has been lacking. Here, we report on the targeted disruption of the gene encoding the heme-regulated eIF2 alpha kinase (HRI) in mice. We establish that HRI, which is expressed predominantly in erythroid cells, regulates the synthesis of both alpha -and beta -globins in red blood cell (RBC) precursors by inhibiting the general translation initiation factor eIF2. This inhibition occurs when the intracellular concentration of heme declines, thereby preventing the synthesis of globin peptides in excess of heme. In iron-deficient HRI-/- mice, globins devoid of heme aggregated within the RBC and its precursors, resulting in a hyperchromic, normocytic anemia with decreased RBC counts, compensatory erythroid hyperplasia and accelerated apoptosis in bone marrow and spleen. Thus, HRI is a physiological regulator of gene expression and cell survival in the erythroid lineage. C1 MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Chen, JJ (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RI Lu, Linrong/A-1429-2013 FU NIDDK NIH HHS [DK-16272, R01 DK016272, R56 DK016272] NR 52 TC 161 Z9 165 U1 0 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 3 PY 2001 VL 20 IS 23 BP 6909 EP 6918 DI 10.1093/emboj/20.23.6909 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 500LM UT WOS:000172629100035 PM 11726526 ER PT J AU Klein, U Tu, YH Stolovitzky, GA Mattioli, M Cattoretti, G Husson, H Freedman, A Inghirami, G Cro, L Baldini, L Neri, AN Califano, A Dalla-Favera, R AF Klein, U Tu, YH Stolovitzky, GA Mattioli, M Cattoretti, G Husson, H Freedman, A Inghirami, G Cro, L Baldini, L Neri, AN Califano, A Dalla-Favera, R TI Gene expression profiling of B cell chronic lymphocytic leukemia reveals a homogeneous phenotype related to memory B cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE somatic hypermutation; germinal center; CD5; DNA microarray; cluster analysis ID GROWTH-FACTOR-BETA; VARIABLE REGION GENES; V-H GENES; SOMATIC HYPERMUTATION; SACCHAROMYCES-CEREVISIAE; CD27; MUTATION; CLONING; ANTIGEN; MARKER AB B cell-derived chronic lymphocytic leukemia (B-CLL) represents a common malignancy whose cell derivation and pathogenesis are unknown. Recent studies have shown that > 50% of CLLs display hypermutated immunoglobulin variable region (IgV) sequences and a more favorable prognosis, suggesting that they may represent a distinct subset of CLLs which have transited through germinal centers (GCs), the physiologic site of IgV hypermutation. To further investigate the phenotype of CLLs, their cellular derivation and their relationship to normal B cells, we have analyzed their gene expression profiles using oligonucleotide-based DNA chip microarrays representative of similar to 12,000 genes. The results show that CLLs display a common and characteristic gene expression profile that is largely independent of their IgV genotype. Nevertheless, a restricted number of genes (< 30) have been identified whose differential expression can distinguish IgV mutated versus unmutated cases and identify them in independent panels of cases. Comparison of CLL profiles with those of purified normal B cell subpopulations indicates that the common CLL profile is more related to memory B cells than to those derived from naive B cells, CD5(+) B cells, and GC centroblasts and centrocytes. Finally, this analysis has identified a subset of genes specifically expressed by CLL cells of potential pathogenetic and clinical relevance. C1 Columbia Univ, Inst Canc Genet, Dept Pathol, New York, NY 10032 USA. Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA. IBM Corp, Thomas J Watson Res Ctr, Yorktown Hts, NY 10598 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NYU, Med Ctr, Dept Pathol, New York, NY 10016 USA. Osped Maggiore, IRCCS, Dept Hematol, I-20122 Milan, Italy. First GeneticTrust, Lyndhurst, NJ 07071 USA. RP Dalla-Favera, R (reprint author), Columbia Univ, Inst Canc Genet, Dept Pathol, 1150 St Nicholas Ave, New York, NY 10032 USA. RI Califano, Andrea/F-7239-2012; Mattioli, Michela/K-3951-2013; OI Mattioli, Michela/0000-0002-1692-9178; neri, antonino/0000-0001-9047-5912; Cattoretti, Giorgio/0000-0003-3799-3221 FU NCI NIH HHS [P01 CA066996, CA66996] NR 56 TC 603 Z9 618 U1 1 U2 18 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 3 PY 2001 VL 194 IS 11 BP 1625 EP 1638 DI 10.1084/jem.194.11.1625 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 500ZX UT WOS:000172659500008 PM 11733577 ER PT J AU Bannert, N Craig, S Farzan, M Sogah, D Santo, NV Choe, H Sodroski, J AF Bannert, N Craig, S Farzan, M Sogah, D Santo, NV Choe, H Sodroski, J TI Sialylated O-glycans and sulfated tyrosines in the NH2-terminal domain of CC chemokine receptor 5 contribute to high affinity binding of chemokines SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE CCR5; O-glycosylation; sialic acid; tyrosine sulfation; HIV ID HAMSTER OVARY CELLS; IMMUNODEFICIENCY-VIRUS TYPE-1; SELECTIN GLYCOPROTEIN LIGAND-1; LINKED CARBOHYDRATE CHAINS; AMINO-TERMINAL DOMAIN; P-SELECTIN; CORECEPTOR FUNCTION; HIV-1 CORECEPTOR; N-GLYCOSYLATION; GP120 BINDING AB The chemokine receptor CCR5 plays an important role in leukocyte chemotaxis and activation, and also acts as a coreceptor for human and simian immunodeficiency viruses (HIV-1, HIV-2, and SIV). We provide evidence that CCR5 is O-glycosylated on serine 6 in the NH2 terminus. The O-linked glycans, particularly sialic acid moieties, significantly contribute to binding of the chemokine ligands. By contrast, removal of O-linked oligosaccharide exerted little effect on HIV-1 infection, Sulfation of specific tyrosine residues in the CCR5 NH2 terminus was important for efficient beta -chemokine binding. Thus, as has been observed for the binding of selectins and their ligands, O-linked carbohydrates and tyrosine sulfates play major roles in promoting the interaction of chemokines with CCR5. The resulting flexible arrays of negative charges on the CCR5 surface may allow, specific, high-affinity interactions with diverse chemokine ligands. Although this is the first example of O-linked oligosaccharides and tyrosine sulfates playing a role in chemokine binding, the high density of serines, threonines and tyrosines in the N-termini of many CC chemokine receptors suggests that these posttranslational modifications may commonly contribute to chemokine binding. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div Aids, Boston, MA 02215 USA. Harvard Univ, Sch Med, Childrens Hosp, Perlmutter Lab,Dept Med, Boston, MA 02115 USA. Harvard Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. FU NIAID NIH HHS [R01 AI041851, AI28691, AI41851, P30 AI028691, R01 AI043891] NR 55 TC 94 Z9 97 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 3 PY 2001 VL 194 IS 11 BP 1661 EP 1673 DI 10.1084/jem.194.11.1661 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 500ZX UT WOS:000172659500011 PM 11733580 ER PT J AU Martin, M Schneider, H Azouz, A Rudd, CE AF Martin, M Schneider, H Azouz, A Rudd, CE TI Cytotoxic T lymphocyte antigen 4 and CD28 modulate cell surface raft expression in their regulation of T cell function SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE T cell function; CD28; CTLA-4; lipid rafts; LAT ID KINASE PHOSPHATIDYLINOSITOL 3-KINASE; LIPID RAFTS; CTLA-4; ACTIVATION; RECEPTOR; BINDING; STIMULATION; REORGANIZATION; COSTIMULATION; LOCALIZATION AB Coreceptors CD28 and cytotoxic T lymphocyte antigen (CTLA)-4 have opposing effects on TcR/CD3 activation of T cells. While CD28 enhances and CTLA-4 inhibits activation, the underlying molecular basis of these effects has yet to be established. In this context, ganglioside and cholesterol enriched membrane microdomains (rafts, GEMs) serve as centers of signaling in T cells. Although CD28 can promote TcR/raft colocalization, evidence is lacking on whether the surface expression of membrane rafts can be targeted by CTLA-4 in its modulation of T cell responses. In this study, we demonstrate that both CD28 and CTLA-4 profoundly alter the surface expression of membrane rafts during T cell activation. While CD28 increased expression and the number of peripheral T cells induced to express surface rafts in response to TcR ligation, CTLA-4 potently inhibited both TcR and TcR x CD28 induced raft expression on the surface of T cells. Consistent with this, CD28 increased the presence of the linker of activated T cells (LAT) in purified membrane rafts, while CTLA-4 coligation effectively blocked this increase. Further, the reversal of the CTLA-4 block with CD3/CD28 ligation was accompanied by an increase in surface raft expression and associated LAT. Our observations demonstrate for the first time that CTLA-4 targets the release of rafts to the surface of T cells, and provides a mechanism for the opposing effects of CD28 and CTLA-4 on costimulation. C1 Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Haematol, Hammersmith Hosp, London W12 ONN, England. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Rudd, CE (reprint author), Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Haematol, Hammersmith Hosp, Du Cane Rd, London W12 ONN, England. RI Martin, Margarita/H-2025-2015 OI Martin, Margarita/0000-0002-9245-4899 NR 34 TC 91 Z9 96 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 3 PY 2001 VL 194 IS 11 BP 1675 EP 1681 DI 10.1084/jem.194.11.1675 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 500ZX UT WOS:000172659500012 PM 11733581 ER PT J AU Parekh, R Beresin, EV AF Parekh, R Beresin, EV TI Looking for love? Take a cross-cultural walk through the personals SO ACADEMIC PSYCHIATRY LA English DT Article ID LONELY HEARTS ADVERTISEMENTS; MATCHMAKING; PEOPLE AB Personal advertisements are powerful windows into understanding individuals, societal trends, and cultural values. "Personals" in the United States and elsewhere offer a unique opportunity to understand societal changes and cross-cultural issues. As one study demonstrates, personals reflect the societal importance placed oil thinness in American women. A cross-cultural study shows how personals are used in understanding the American value of individualism and the Chinese values of family and society. Personals in all Indian newspaper and all Indian-American newspaper both demonstrate Indian values, yet the latter shows hints of American acculturation. For psychiatrists, the personals may be all important way to understand patients anti their social and cultural contexts. Patients' ads may help the psychiatrist and patient understand the patients' values and fantasies, aid in treatment, and help form relationships. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Parekh, R (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WAC 725C,55 Fruit St, Boston, MA 02114 USA. NR 11 TC 1 Z9 1 U1 1 U2 6 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 WIN PY 2001 VL 25 IS 4 BP 223 EP 233 DI 10.1176/appi.ap.25.4.223 PG 11 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 503HF UT WOS:000172792500004 ER PT J AU Udris, EM Au, DH McDonell, MB Chen, LW Martin, DC Tierney, WM Fihn, SD AF Udris, EM Au, DH McDonell, MB Chen, LW Martin, DC Tierney, WM Fihn, SD TI Comparing methods to identify general internal medicine clinic patients with chronic heart failure SO AMERICAN HEART JOURNAL LA English DT Article ID PRACTICE GUIDELINES; PHARMACY RECORDS; DECISION-SUPPORT; MANAGEMENT; OUTCOMES; MORTALITY; ENALAPRIL; DYSFUNCTION; CARVEDILOL; MORBIDITY AB Objectives Identification of patients with left ventricular systolic dysfunction is the first step in identifying which patients may benefit from clinical practice guidelines. The purpose of this study was to develop and validate a computerized tool using clinical information that is commonly available to identify patients with left ventricular systolic dysfunction (LVSD). Methods We performed a cross-sectional study of patients seen in a Department of Veterans Affairs General Internal Medicine Clinic who had echocardiography or radionuclide ventriculography performed as part of their clinical care. Results We identified 2246 subjects who had at least one cardiac imaging study. A total of 778 (34.6%) subjects met study criteria for LVSD. Subjects with LVSD were slightly older than subjects without LVSD (70 years vs 68 years, P = .00002) but were similar with regard to sex and race. Subjects with LVSD were more likely to have prescriptions for angiotensin-converting enzyme (ACE) inhibitors, carvedilol, digoxin, loop diuretics, hydralazine, nitrates, and angiotensin II receptor antagonists. Of the variables included in the final predictive model, ACE inhibitors, loop diuretics, and digoxin exerted the greatest predictive power. Discriminant analysis demonstrated that models containing pharmacy information were consistently more accurate (75% accurate [65% sensitivity, 81% specificity]) than those models that contained only International Classification of Diseases, 9th revision (ICD-9), codes, including ICD-9 codes for congestive heart failure (72% accurate [80% sensitivity, 68% specificity]). Conclusions We demonstrated that an automated, computer-driven algorithm identifying LVSD permits simple, rapid, and timely identification of patients with congestive heart failure by use of only routinely collected data. Future research is needed to develop accurate electronic identification of heart failure and other common chronic conditions. C1 Vet Affairs Puget Sound Hlth Care Syst, NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Rochester, Dept Med, Div Cardiol, Rochester, NY USA. Richard L Roudebush Vet Affairs Med Ctr, Hlth Serv Res & Dev Program, Indianapolis, IN USA. Indiana Univ, Sch Med, Dept Med, Div Gen Internal Med & Geriatr, Indianapolis, IN USA. RP Udris, EM (reprint author), Vet Affairs Puget Sound Hlth Care Syst, NW Hlth Serv Res & Dev Ctr Excellence, 1660 S Columbian Way, Seattle, WA 98108 USA. EM ed.udris@med.va.gov NR 31 TC 14 Z9 14 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD DEC PY 2001 VL 142 IS 6 BP 1003 EP 1009 DI 10.1067/mhj.2001.119130 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 500JQ UT WOS:000172623900013 PM 11717604 ER PT J AU Tomiak, A Vincent, M Earle, CC Johnston, PG Kocha, W Taylor, M Maroun, J Eidus, L Whiston, F Stitt, L AF Tomiak, A Vincent, M Earle, CC Johnston, PG Kocha, W Taylor, M Maroun, J Eidus, L Whiston, F Stitt, L TI Thymidylate synthase expression in stage II and III colon cancer - A retrospective review SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE thymidylate synthase; colon cancer; prognostic factor; predictive factor ID INDEPENDENT PROGNOSTIC FACTOR; SURGICAL ADJUVANT BREAST; COLORECTAL-CANCER; RECTAL-CANCER; DUKES-B; FLUOROURACIL; CHEMOTHERAPY; LEUCOVORIN; CARCINOMA; SURVIVAL AB This study is a retrospective analysis of thymidylate synthase (TS) levels in patients with stage If (T3 or T4) and III colon cancer. Two groups of patients were identified: one undergoing surgery alone (98 patients) and the second receiving adjuvant 5-fluorouracil chemotherapy (112 patients). TS analyses were carried out using the 106 monoclonal antibody and a published grading system dividing staining into high and low intensity. The distribution of patients with low versus high TS levels was similar in the two groups. There was no association between TS staining intensity and grade, stage or location of primary. Seventy-nine patients have relapsed: 46 (48%) in the surgery only group, 33 (30%) in the adjuvant therapy group median follow-up: 51 and 61 months). Similar proportions relapsed when analyzed according to TS: in the surgery only group, of patients with low TS, 48% with high TS; in the adjuvant group, 31% with low TS, 30% with high TS. In the surgery only group, a trend toward improved disease-free survival (DFS) was seen in the low TS group (84 versus 63% at 2 years, p = 0,08). No difference was seen in overall survival. There were no differences in DFS or overall survival in patients receiving adjuvant therapy according to TS intensity. The trend for worse outcome in patients with high TS is consistent with previous reports. The lack of difference in outcome for patients with low and high TS receiving chemotherapy suggests that high TS levels may predict greater benefit from adjuvant treatment. C1 London Reg Canc Ctr, London, ON N6A 4L6, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Queens Univ Belfast, Belfast, Antrim, North Ireland. Ottawa Reg Canc Ctr, Ottawa, ON K1Y 4K7, Canada. RP Tomiak, A (reprint author), Kingston Reg Canc Ctr, 25 King St W, Kingston, ON K7L 5P9, Canada. NR 30 TC 29 Z9 30 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD DEC PY 2001 VL 24 IS 6 BP 597 EP 602 DI 10.1097/00000421-200112000-00014 PG 6 WC Oncology SC Oncology GA 508XW UT WOS:000173115900014 PM 11801762 ER PT J AU Metz, DC Forsmark, C Lew, EA Starr, JA Soffer, EF Bochenek, W Pisegna, JR AF Metz, DC Forsmark, C Lew, EA Starr, JA Soffer, EF Bochenek, W Pisegna, JR TI Replacement of oral proton pump inhibitors with intravenous pantoprazole to effectively control gastric acid hypersecretion in patients with Zollinger-Ellison syndrome SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID OMEPRAZOLE; MANAGEMENT; RESECTION; SECRETION AB OBJECTIVES: In patients with Zollinger-Ellison syndrome (ZES) or other conditions requiring oral doses of proton pump inhibitors, it frequently becomes necessary to use parenterally administered gastric acid inhibitors. However, i.v. histamine-2 receptor antagonists are not effective at usual doses and lose their effectiveness because of tachyphlaxis. With the approval in the United States of i.v. pantoprazole, a substituted benzimidazole available in i.v. formulation, it will become possible to acutely manage gastric acid secretion in the acute care setting of a hospital. This study was developed to monitor the safety and establish the efficacy of i.v. pantoprazole as an alternative to oral proton pump inhibitors for the control of gastric acid hypersecretion in patients with ZES. METHODS: The efficacy of replacing oral PPI therapy with i.v. pantoprazole was evaluated in 14 ZES patients. After study enrollment, patients taking their current doses of oral PPI (omeprazole or lansoprazole) were switched to pantoprazole i.v. for 6 days during an 8-day inpatient period in the clinical research center. Effective control was defined as an acid output (AO) of < 10 mEq/h (<5 mEq/h in patients with prior gastric acid-reducing surgery). RESULTS: The mean age of the 14 patients enrolled in the study was 52.4 yr (range = 38-67). Mean basal AO was 0.55 +/- 0.32 mEq/h and mean fasting gastrin was 1089 pg/ml (range = 36-3720). Four patients were also diagnosed with the multiple endocrine neoplasia type I syndrome, nine were male, and two had previously undergone acid-reducing surgery. Before study enrollment, gastric acid hypersecretion was controlled in nine of 14 patients with omeprazole (20-200 mg daily) and five of 14 with lansoprazole (30-210 mg daily). In the oral phase of the study all patients had adequate control of gastric acid secretion, with a mean AO of 0.55 0.32 mEq/h (mean SEM). Thereafter, 80 mg of i.v. pantoprazole was administered b.i.d. for 7 days by a brief (15 min) infusion and the dose was titrated upward to a predetermined maximum of 240 mg/24 h to control AO. A dose of 80 mg b.i.d. of i.v. pantoprazole controlled AO in 13 of 14 of the patients (93%) for the duration of the study (p > 0.05 compared to baseline values for all timepoints). One sporadic ZES patient (oral control value = 0.65 mEq/h on 100 mg of omeprazole b.i.d. p.o.) was not controlled with 80 mg of i.v. pantoprazole b.i.d. and dosage was titrated upward to 120 mg b.i.d. after day 2. CONCLUSIONS: There were no serious adverse events observed. Intravenous pantoprazole provides gastric acid secretory control that is equivalent to the acid suppression observed with oral proton pump inhibitors. Most ZES patients (93%) maintained effective control of AO previously established with oral PPIs when switched to 80 mg of i.v. pantoprazole b.i.d; however, for difficult-to-control patients, doses > 80 mg b.i.d. may be required. (C) 2001 by Am. Coll. of Gastroenterology. C1 Univ Penn, Med Ctr, Dept Med, Div Gastroenterol,GI Physiol Lab, Philadelphia, PA 19104 USA. Univ Calif Los Angeles, CURE, Digest Dis Res Ctr, Div Digest Dis,Dept Med,VA Greater Los Angeles He, Los Angeles, CA USA. Univ Florida, Div Gastroenterol, Gainesville, FL USA. Wyeth Ayerst Res, Clin Res & Dev, Radnor, PA USA. RP Pisegna, JR (reprint author), VA Greater Los Angeles Healthcare Syst 111C, Div Gastroenterol & Hepatol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCRR NIH HHS [M01-RR00000, M01-RR00040] NR 20 TC 23 Z9 24 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD DEC PY 2001 VL 96 IS 12 BP 3274 EP 3280 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502WV UT WOS:000172766500009 PM 11774936 ER PT J AU Chang, L Lee, OY Naliboff, B Mayer, EA AF Chang, L Lee, OY Naliboff, B Mayer, EA TI Sensation of bloating and visible abdominal distension in patients with irritable bowel syndrome SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID INTESTINAL GAS; UNITED-STATES; DISORDERS; SYMPTOMS; IMPACT; PAIN; FERMENTATION; PREVALENCE; PERCEPTION AB OBJECTIVES: Abdominal bloating and distension are common symptoms of irritable bowel syndrome (IBS). The postulated pathophysiological mechanisms underlying these symptoms include increased production, retention, or perception of gas or luminal contents. The aims of this study were to prospectively compare the prevalence of, and clinical factors related to, bloating and distension in an IBS patient population. METHODS: A total of 714 consecutive patients who met Rome I criteria for IBS were prospectively surveyed, and were classified as having bloating alone (B) or bloating and distension (B-I-D) based on a comprehensive bowel symptom questionnaire. GI, extraintestinal, and psychological symptoms, as well as health-related quality of life measures were also assessed using validated survey instruments. RESULTS: A total of 542 IBS patients (76%) who reported abdominal bloating were studied. Of these, 132 patients fulfilled criteria for the B group, whereas 410 patients fulfilled criteria for the B+D group. There was a significantly different gender distribution in the B and B+D groups (female:male ratios, 1.4:1 and 2.8:1, respectively p < 0.02). There was also a significantly different bowel habit subgroup distribution, with a greater predominance of constipation in B+D group and of diarrhea in the B group (p < 0.03). Both groups were similar in other clinical parameters, including progressive worsening of symptoms during the day, and relief by passing stool or gas. Both bloating and distension worsened when other abdominal symptoms worsened. Abdominal distension was associated with greater symptom severity and less diurnal variation in symptoms, and was less often perceived as associated with food intake. CONCLUSIONS: Bloating and visible abdominal distension may arise from two distinct but interrelated physiological processes. Although the sensation of bloating may be related to enhanced sensitivity to visceral afferent stimulation, abdominal distension in more severely affected patients may be related to triggering of a visceromotor reflex affecting the tone of abdominal wall muscles. (C) 2001 by Am. Coll. of Gastroenterology. C1 Univ Calif Los Angeles, CURE, Digest Dis Res Ctr, Neuroenter Dis Program,Dept Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Hanyang Univ, Coll Med, Dept Med, Seoul 133791, South Korea. Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Gastroenterol, Mexico City, DF, Mexico. RP Chang, L (reprint author), Univ Calif Los Angeles, CURE Clin Res Ctr, 924 Westwood Blvd, Los Angeles, CA 90024 USA. NR 30 TC 89 Z9 93 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD DEC PY 2001 VL 96 IS 12 BP 3341 EP 3347 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502WV UT WOS:000172766500020 PM 11774947 ER PT J AU Norton, LE Malloy, PF Salloway, S AF Norton, LE Malloy, PF Salloway, S TI The impact of behavioral symptoms on activities of daily living in patients with dementia SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID ALZHEIMERS-DISEASE; GERIATRIC DEPRESSION; RATING-SCALE; DYSFUNCTION; INVENTORY; HEALTH AB The authors examined whether scores on two recently developed measures of behavioral disturbance, the Frontal Lobe Personality Scale (FLOPS) and the Neuropsychiatric Inventory (NPI) are associated with functional impairments in patients with dementia. Caregivers of 30 dementia patients were administered the FLOPS Family Form, the NPI, and an Activities of Daily Living (ADL) scale. Findings indicated a relationship between behavioral changes and functional limitations inpatients with dementia. Moreover the FLOPS, an instrument designed to specifically measure behaviors subserved by frontal lobe systems, was more strongly related to failures in instrumental ALDs than was the NPI. The authors conclude that behavioral measures add information over and above that available from cognitive tests in determining ADL functioning. C1 Massachusetts Gen Hosp, Psychol Assessment Ctr, Boston, MA 02114 USA. Brown Univ, Sch Med, Butler Hosp, Providence, RI 02912 USA. RP Norton, LE (reprint author), Massachusetts Gen Hosp, Psychol Assessment Ctr, 5 Emerson Pl,Suite 105, Boston, MA 02114 USA. NR 29 TC 43 Z9 43 U1 0 U2 3 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 WIN PY 2001 VL 9 IS 1 BP 41 EP 48 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 392UF UT WOS:000166430400006 PM 11156751 ER PT J AU Huang, ES Meigs, JB Singer, DE AF Huang, ES Meigs, JB Singer, DE TI The effect of interventions to prevent cardiovascular disease in patients with type 2 diabetes mellitus SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; AVERAGE CHOLESTEROL LEVELS; RANDOMIZED TRIAL; MICROVASCULAR COMPLICATIONS; SYSTOLIC HYPERTENSION; VASCULAR-DISEASE; BLOOD-PRESSURE; THERAPY; EVENTS; MORTALITY AB PURPOSE: Cardiovascular complications account for over 50% of mortality among patients with type 2 diabetes mellitus. We quantify the cardiovascular benefit of lowering cholesterol, blood pressure, and glucose levels in these patients. METHODS: We conducted a meta-analysis of randomized controlled trials in type 2 diabetes or diabetes subgroups, comparing the cardiovascular effects of intensive medication control of risk factor levels in standard therapy or placebo. We identified trials by searching MEDLINE (1966 to 2000) and review articles. Treatment details, patient characteristics, and outcome events were obtained using a specified protocol. Data were pooled using fixed-effects models. RESULTS: Seven serum cholesterol-lowering trials, six blood pressure-lowering trials, and five blood glucose-lowering trials met eligibility criteria. For aggregate cardiac events (coronary heart disease death and nonfatal myocardial infarction), cholesterol lowering [rate ratio (RR) = 0.75; 95% confidence interval (Cl): 0.61 to 0.93) and blood pressure lowering (RR = 0.73; 95% Cl: 0.57 to 0.94) produced large, significant effects, whereas intensive glucose lowering reduced events without reaching statistical significance (RR = 0.87; 95% CI: 0.74 to 1.01). We observed this pattern for all individual cardiovascular outcomes. For cholesterol-lowering and blood pressure-lowering therapy, 69 to 300 person-years of treatment were needed to prevent one cardiovascular event. CONCLUSIONS: The evidence from these clinical trials demonstrates that lipid and blood pressure lowering in patients with type 2 diabetes is associated with substantial cardiovascular benefits. Intensive glucose lowering is essential for the prevention of microvascular disease, but improvements in cholesterol and blood pressure levels are central to reducing cardiovascular disease in these patients. C1 Univ Chicago, Div Gen Med, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Huang, ES (reprint author), Univ Chicago, Div Gen Med, 5841 S Maryland Ave,MC 2007, Chicago, IL 60637 USA. FU BHP HRSA HHS [PE-11001] NR 50 TC 106 Z9 111 U1 0 U2 3 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 DEC 1 PY 2001 VL 111 IS 8 BP 633 EP 642 DI 10.1016/S0002-9343(01)00978-0 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 539CA UT WOS:000174851100007 PM 11755507 ER PT J AU Economy, K Greenberg, J Ecker, J Barbieri, R AF Economy, K Greenberg, J Ecker, J Barbieri, R TI Gestational age as a risk factor for malpractice suits SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 86 BP S106 EP S106 DI 10.1016/S0002-9378(01)80121-6 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000088 ER PT J AU Sandler, L Wolf, M Hsu, K Munoz, K Thadhani, R Ecker, J AF Sandler, L Wolf, M Hsu, K Munoz, K Thadhani, R Ecker, J TI First trimester sex hormone binding globulin values predict later preeclampsia in lean women SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 336 BP S173 EP S173 DI 10.1016/S0002-9378(01)80367-7 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000333 ER PT J AU Shipp, T Zelop, C Cohen, A Repke, J Frigoletto, F Sachs, B Lieberman, E AF Shipp, T Zelop, C Cohen, A Repke, J Frigoletto, F Sachs, B Lieberman, E TI Prediction of the rate of uterine rupture using an obstetrical scoring system SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Connecticut, Ctr Hlth, Farmington, CT USA. Univ Nebraska, Ctr Med, Omaha, NE 68198 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Hosp, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 157 BP S124 EP S124 DI 10.1016/S0002-9378(01)80193-9 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000159 ER PT J AU Wu, J Viguera, A Riley, L Cohen, L Ecker, J AF Wu, J Viguera, A Riley, L Cohen, L Ecker, J TI Mood disturbance during pregnancy is not associated with mode of delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Program, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 359 BP S179 EP S179 DI 10.1016/S0002-9378(01)80390-2 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000356 ER PT J AU Merayo-Lloves, J Baltatzis, S Foster, CS AF Merayo-Lloves, J Baltatzis, S Foster, CS TI Epstein-Barr virus dacryoadenitis resulting in keratoconjunctivitis sicca in a child SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To describe a case of severe dry eye syndrome in a child. METHODS: Observational case report. The authors de. scribe a 10,year old male with severe dry eyes who was profoundly disabled by pain and photophobia despite aggressive conventional therapy. Lacrimal gland histology was consistent with the primary Sjogren syndrome, and serologic and immunohistologic evidence supported the hypothesis of Epstein-Barr virus causality. RESULTS: Treatment with systemic acyclovir and cyclosporin A resulted in dramatic and rapid reversal of the profound sicca syndrome and enabled the patient to resume his normal activities. CONCLUSION: Epstein-Barr virus dacryoadenitis should be considered in the differential diagnosis of keratocon, junctivitis sicca in children. Epstein-Barr virus can cause keratoconjunctivitis sicca, which can be treated success fully with acyclovir therapy in addition to suppression of the inflammatory response. (C) 2001 by Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. NR 1 TC 7 Z9 7 U1 0 U2 1 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 DEC PY 2001 VL 132 IS 6 BP 922 EP 923 DI 10.1016/S0002-9394(01)01182-5 PG 2 WC Ophthalmology SC Ophthalmology GA 498JT UT WOS:000172506900018 PM 11730660 ER PT J AU Miserocchi, E Waheed, NK Baltatzis, S Foster, CS AF Miserocchi, E Waheed, NK Baltatzis, S Foster, CS TI Chronic cicatrizing conjunctivitis in a patient with ocular cicatricial pemphigoid and fatal Wegener granulomatosis SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID IMMUNOSUPPRESSIVE THERAPY AB PURPOSE: To describe a case of chronic cicatrizing conjunctivitis in a patient with ocular cicatricial pemphigoid and Wegener granulomatosis. METHODS: Observational case report. A retrospective study. RESULTS: An 80-year-old man presented with chronic cicatrizing conjunctivitis, peripheral corneal thinning, and Wegener granulomatosis, which were diagnosed by his referring physician based on clinical (recurrent epi, staxis, sinus congestion) and histopathologic features of nasal mucosa (granulomatous inflammation, vasculitis). A conjunctival biopsy performed by us disclosed features of active Wegener granulomatosis and ocular cicatricial pemphigoid, which indicate lack of control of both diseases with methotrexate treatment. The patient died of pulmonary complications from Wegener granulomatosis 1 week after our evaluation. CONCLUSION: Ocular cicatricial pemphigoid and Wegener granulomatosis are both potentially fatal autoimmune diseases. Ocular involvement in Wegener granulomatosis indicates poor control of the underlying systemic condition and is a marker for active vasculitis, which indicates the need for treatment with cyclophosphamide. (C) 2001 by Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Immunol & Uveitis Serv, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. NR 6 TC 9 Z9 10 U1 1 U2 1 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 DEC PY 2001 VL 132 IS 6 BP 923 EP 924 DI 10.1016/S0002-9394(01)01194-1 PG 2 WC Ophthalmology SC Ophthalmology GA 498JT UT WOS:000172506900019 PM 11730661 ER PT J AU French, CA Miyoshi, I Aster, JC Kubonishi, I Kroll, TG Dal Cin, P Vargas, SO Perez-Atayde, AR Fletcher, JA AF French, CA Miyoshi, I Aster, JC Kubonishi, I Kroll, TG Dal Cin, P Vargas, SO Perez-Atayde, AR Fletcher, JA TI BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t(15;19) SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PAPILLARY THYROID-CARCINOMA; OLIGOMERIZATION DOMAIN; MYELOGENOUS LEUKEMIA; FUSION; LYMPHOMA; TUMORS; GIRL AB Translocation t(15;19)(q13;p13.1) defines a lethal midline carcinoma arising adjacent to respiratory tract in young people. To characterize molecular alterations responsible for the distinctly aggressive biological behavior of this cancer, we mapped the chromosome 15 and 19 translocation breakpoints by fluorescence in situ hybridization (FISH) and Southern blotting. To evaluate preliminarily the frequency, anatomical distribution, and histological features of t(15;19) cancer, we developed a FISH assay for paraffin sections. Our findings reveal a novel oncogenic mechanism in which the chromosome 19 translocation breakpoint interrupts the coding sequence of a bromodomain gene, BRD4. These studies implicate BRD4 as a potential partner in a t(15;19)-associated fusion oncogene. In addition, we localized the chromosome 15 breakpoint to a 9-kb region In each of two cases, thereby identifying several candidate oncogenes which might represent the BRD4 fusion partner. FISH evaluation of 13 pediatric carcinomas revealed t(15;19) in one of four sinonasal carcinomas, whereas this translocation was not detected in thymic (n = 3), mucoepidermoid (n = 3), laryngeal (n = 2), or nasopharyngeal (n = 1) carcinomas. Our studies shed light on the oncogenic mechanism underlying t(15;19) and provide further evidence that this highly lethal cancer arises from respiratory mucosa. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Kochi Med Sch, Nankoku, Kochi, Japan. RP French, CA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [T32-HLO7627] NR 31 TC 102 Z9 105 U1 0 U2 8 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 2001 VL 159 IS 6 BP 1987 EP 1992 DI 10.1016/S0002-9440(10)63049-0 PG 6 WC Pathology SC Pathology GA 497LR UT WOS:000172457400003 PM 11733348 ER PT J AU Giri, D Ozen, M Ittmann, M AF Giri, D Ozen, M Ittmann, M TI Interleukin-6 is an autocrine growth factor in human prostate cancer SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CARCINOMA-CELLS; ANDROGEN RECEPTOR; MESSENGER-RNA; EXPRESSION; BENIGN; HYPERPLASIA; ACTIVATION; PARACRINE; PATHWAY; KINASE AB Prostate cancer is the most common cancer in American men and the second leading cause of cancer deaths in this group. We have found that interleukin (IL)-6 protein concentrations are increased similar to 18-fold in clinically localized prostate cancers when compared to normal prostate tissue. Normal and neoplastic prostatic epithelial cells in culture, with the exception of LNCaP cells, secrete IL-6. Addition of exogenous IL-6 to primary epithelial cells in culture or the LNCaP prostate cancer cell line leads to phosphorylation of Stat-3 and increases in net cell proliferation. The concentration of IL-6 receptor is increased eightfold in the prostate cancer tissues and is increased in the cancer cells by immunohistochemistry. The increased expression of IL-6 receptor is correlated with increased proliferation of prostate cancer cells in vivo as assessed by Ki67 immunohistochemistry. These findings strongly support the hypothesis that IL-6 acts as a significant autocrine growth factor in vivo for primary, androgen-dependent prostate cancers. C1 Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Houston, TX USA. RP Ittmann, M (reprint author), VAMC, Res Serv 151, 2002 Holcombe Blvd, Houston, TX 77030 USA. FU NIDDK NIH HHS [R01 DK054170, R01 DK54170] NR 24 TC 216 Z9 218 U1 1 U2 5 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 2001 VL 159 IS 6 BP 2159 EP 2165 DI 10.1016/S0002-9440(10)63067-2 PG 7 WC Pathology SC Pathology GA 497LR UT WOS:000172457400021 PM 11733366 ER PT J AU Hinoi, T Tani, M Lucas, PC Caca, K Dunn, RL Macri, E Loda, M Appelman, HD Cho, KR Fearon, ER AF Hinoi, T Tani, M Lucas, PC Caca, K Dunn, RL Macri, E Loda, M Appelman, HD Cho, KR Fearon, ER TI Loss of CDX2 expression and microsatellite instability are prominent features of large cell minimally differentiated carcinomas of the colon SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID RAS GENE-MUTATIONS; COLORECTAL-CANCER; MISMATCH REPAIR; MOLECULAR CHARACTERISTICS; PROTEIN EXPRESSION; PROXIMAL COLON; BETA-CATENIN; ADENOCARCINOMA; TUMOR; IDENTIFICATION AB Most large bowel cancers are moderately to well-differentiated adenocarcinomas comprised chiefly or entirely of glands lined by tall columnar cells. We have identified a subset of poorly differentiated colon carcinomas with a distinctive histopathological appearance that we term large cell minimally differentiated carcinomas (LCMDCs). These tumors likely include a group of poorly differentiated carcinomas previously described by others as medullary adenocarcinomas. To better understand the pathogenesis of these uncommon neoplasms, we compared molecular features of 15 LCMDCs to those present in 25 differentiated adenocarcinomas (DACs) of the colon. Tumors were examined for alterations commonly seen in typical colorectal carcinomas, including increased p53 and beta -catenin immunoreactivity, K-ras gene mutations, microsatellite instability, and loss of heterozygosity of markers on chromosomes 5q, 17p, and 18q. In addition, tumors were evaluated by immunohistochemistry for CDX2, a homeobox protein whose expression in normal adult tissues is restricted to intestinal and colonic epithelium. Markedly reduced or absent CDX2 expression was noted in 13 of 15 (87%) LCMDCs, whereas only 1 of the 25 (4%) DACs showed reduced CDX2 expression (P < 0.001). Nine of 15 (60%) LCMDCs had the high-frequency microsatellite instability phenotype, but only 2 of 25 (8%) DACs had the high-frequency microsatellite instability phenotype (P = 0.002). Our findings provide support for the hypothesis that the molecular pathogenesis of LCMDCs is distinct from that of most DACs. CDX2 alterations and DNA mismatch repair defects have particularly prominent roles in the development of LCMDCs. C1 Univ Michigan, Dept Internal Med, Div Med Genet, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Canc, Ann Arbor, MI 48109 USA. Natl Canc Ctr, Res Inst, Div Biol, Chuo Ku, Tokyo 104, Japan. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Adult Oncol, Boston, MA USA. RP Fearon, ER (reprint author), Univ Michigan, Dept Internal Med, Div Med Genet, 4301 MSRB 3,150 W Med Ctr Dr, Ann Arbor, MI 48109 USA. FU NCI NIH HHS [R01 CA082223, R01CA82223] NR 39 TC 125 Z9 128 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 2001 VL 159 IS 6 BP 2239 EP 2248 DI 10.1016/S0002-9440(10)63074-X PG 10 WC Pathology SC Pathology GA 497LR UT WOS:000172457400028 PM 11733373 ER PT J AU Otto, MW Tuby, KS Gould, RA McLean, RYS Pollack, MH AF Otto, MW Tuby, KS Gould, RA McLean, RYS Pollack, MH TI An effect-size analysis of the relative efficacy and tolerability of serotonin selective reuptake inhibitors for panic disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Association-for-Advancement-of-Behavior-Therapy CY NOV 11-14, 1999 CL TORONTO, CANADA SP Assoc Advancement Behav Therapy ID RANDOMIZED CONTROLLED TRIAL; DOUBLE-BLIND; COGNITIVE THERAPY; MULTICENTER TRIAL; PLACEBO; METAANALYSIS; FLUVOXAMINE; PAROXETINE; IMIPRAMINE; SERTRALINE AB Objective: Serotonin selective reuptake inhibitors (SSRIs) are now considered the first-line pharmacotherapy for panic disorder. The preferential use and the presumption of greater tolerability of SSRIs relative to older agents, such as tricyclic antidepressants, occurred without direct comparisons between the two classes of medication. In this study the authors used an effect-size analysis to provide an initial comparison. Method: The authors conducted an effect-size analysis of 12 placebo-controlled, efficacy trials of SSRIs for panic disorder and compared these results to findings obtained in a recent meta-analysis of non-SSRI treatments for panic disorder. Results: The mean effect size for acute treatment outcome for SSRIs relative to placebo was 0.55, not significantly different from that for antidepressants in general (0.55) and for imipramine in particular (0.48). More recent studies of SSRIs, and studies using larger samples, were associated with lower effect sizes. No significant differences were found in dropout rates between those taking SSRIs and those taking older agents during acute treatment. Conclusions: An effect-size analysis of controlled studies of treatments for panic disorder revealed no significant differences between SSRIs and older antidepressants in terms of efficacy or tolerability in short-term trials. An inverse relationship was evident between sample size and effect size for SSRIs. Early studies of small samples may have led to initial overestimations of the efficacy of SSRIs for panic disorder. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Otto, MW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, WACC-812,15 Parkman St, Boston, MA 02114 USA. NR 29 TC 81 Z9 81 U1 1 U2 4 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 DEC PY 2001 VL 158 IS 12 BP 1989 EP 1992 DI 10.1176/appi.ajp.158.12.1989 PG 4 WC Psychiatry SC Psychiatry GA 497JQ UT WOS:000172452100008 PM 11729014 ER PT J AU Otto, MW Wilhelm, S Cohen, LS Harlow, BL AF Otto, MW Wilhelm, S Cohen, LS Harlow, BL TI Prevalence of body dysmorphic disorder in a community sample of women SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID IMAGINED UGLINESS; MAJOR DEPRESSION; ANXIETY DISORDERS; THERAPY; COMORBIDITY; TRIAL AB objective: In a large population-based study, the authors examined the prevalence and correlates of body dysmorphic disorder, a debilitating and chronic condition characterized by an imagined defect in appearance. Method: Rates and diagnostic correlates of body dysmorphic disorder were examined by using data from the Harvard Study of Moods and Cycles. This study used in-person structured clinical interviews to characterize the diagnostic status of a population-based, cross-sectional sample of 318 depressed and 658 nondepressed women between the ages of 36 and 44 who were selected from seven Boston metropolitan area communities. Results: The presence of body dysmorphic disorder was significantly associated with the presence of major depression and anxiety disorders. The authors estimated the overall point prevalence of body dysmorphic disorder as 0.7% in women in this age range in the community. Conclusions: The authors found that the presence of body dysmorphic disorder was linked to the presence of major depression and anxiety disorders, which is similar to findings in clinical studies. Their estimate of the point prevalence of body dysmorphic disorder is consistent with data from a community-based sample of Italian women and suggests a prevalence similar to that of other serious psychiatric disorders in women (e.g., schizophrenia and drug abuse and dependence). These prevalence data encourage the further development of treatment options for this debilitating condition. C1 Massachusetts Gen Hosp, Cognit Behav Therapy Program, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. RP Otto, MW (reprint author), Massachusetts Gen Hosp, Cognit Behav Therapy Program, Dept Psychiat, WACC-812, Boston, MA 02114 USA. FU NIMH NIH HHS [MH-50013] NR 23 TC 99 Z9 103 U1 3 U2 11 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 DEC PY 2001 VL 158 IS 12 BP 2061 EP 2063 DI 10.1176/appi.ajp.158.12.2061 PG 3 WC Psychiatry SC Psychiatry GA 497JQ UT WOS:000172452100020 PM 11729026 ER PT J AU Ozsunar, Y Unsal, A Akdilli, A Karaman, C Huisman, TAGM Sorensen, AG AF Ozsunar, Y Unsal, A Akdilli, A Karaman, C Huisman, TAGM Sorensen, AG TI Technology and archives in radiology research: A sampling analysis of articles published in the AJR and Radiology SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT 86th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America (RSNA) CY NOV 26-DEC 01, 2000 CL CHICAGO, ILLINOIS SP Radiol Soc N Amer ID JOURNALS AB OBJECTIVE. Our aim was to determine the use of advanced technology and archiving and the contribution of countries other than United States in the articles published in the American Journal of Roentgenology (AJR) and Radiology. We analyzed the association of these features with the type of research, the main technical features of the modalities used, and the countries of origin. MATERIALS AND METHODS. We determined the proportion of articles published in 18 randomly selected issues of the AJR and Radiology that required advanced imaging techniques and relied on the analysis of archived data. "Advanced technology" was defined as imaging techniques that serve a purpose other than simple anatomic imaging or that are not widely available because of the high cost of the technology, such as functional imaging and computer programming designed for an individual study or simulation studies. We analyzed the association of these features with the country of origin, the topic, and the methodology used. RESULTS. Sixteen percent of the studies required advanced technology. MR imaging, CT, and sonography were the most frequently used modalities (31 k, 27%, and 15% of studies, respectively). Archiving was used in 37% of the studies, and 67% of the original articles were prospective. The articles most commonly originated in North America (67%), Europe (20%), and Asia (12%). CONCLUSION. Only a small percentage of published research studies required advanced technology and approximately one third of the studies used archiving. These results may suggest that other criteria, such as the design of the study, its relevance for daily clinical use, and the originality of the paper, have a major impact on the acceptance of papers in clinically oriented radiology journals. C1 Adnan Menderes Univ, Sch Med, Dept Radiol, TR-09100 Aydin, Turkey. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, MGH NMR Ctr, Charlestown, MA 02129 USA. RP Ozsunar, Y (reprint author), Adnan Menderes Univ, Sch Med, Dept Radiol, TR-09100 Aydin, Turkey. NR 12 TC 14 Z9 14 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2001 VL 177 IS 6 BP 1281 EP 1284 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 495EG UT WOS:000172326800008 PM 11717066 ER PT J AU Wittram, C Fogg, J Farber, H AF Wittram, C Fogg, J Farber, H TI Radiologic-pathologic conferences of Boston University Medical Center - Immune restoration syndrome manifested by pulmonary sarcoidosis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID IMMUNODEFICIENCY C1 Massachusetts Gen Hosp, Dept Radiol, Sect Thorac Radiol, Boston, MA 02114 USA. Boston Univ, Med Ctr, Dept Radiol, Sect Thorac Radiol, Boston, MA 02118 USA. Dimock Community Hlth Ctr, Roxbury, MA 02119 USA. Boston Univ, Med Ctr, Ctr Pulm, Boston, MA 02118 USA. RP Wittram, C (reprint author), Massachusetts Gen Hosp, Dept Radiol, Sect Thorac Radiol, FND 202,55 Fruit St, Boston, MA 02114 USA. NR 4 TC 13 Z9 13 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2001 VL 177 IS 6 BP 1427 EP 1427 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 495EG UT WOS:000172326800035 PM 11717100 ER PT J AU Sanelli, PC Lev, MH Gonzalez, RG Schaefer, PW AF Sanelli, PC Lev, MH Gonzalez, RG Schaefer, PW TI Original report - Unique linear and nodular MR enhancement pattern in schistosomiasis of the central nervous system: Report of three patients SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CEREBRAL SCHISTOSOMIASIS; MANSONI AB OBJECTIVE. The purpose of this paper is to describe the unique MR imaging appearance of schistosomiasis of the central nervous system (CNS). CONCLUSION. Contrast-enhanced TI-weighted MR images in all three patients with CNS schistosomiasis revealed a central linear enhancement surrounded by multiple enhancing punctate nodules, forming an "arborized" appearance. Pathologically; this enhancement pattern correlated with a host granulomatous response to Schistosoma species ova. Although the pattern is not present in all cases of CNS schistosomiasis, when it is observed, a diagnosis of CNS schistosomiasis should be considered. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Sanelli, PC (reprint author), New York Presbyterian Hosp, Dept Radiol, New York Weill Cornell Med Ctr, 520 E 70th St,Starr Pavil,Starr 630, New York, NY 10021 USA. NR 12 TC 27 Z9 32 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2001 VL 177 IS 6 BP 1471 EP 1474 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 495EG UT WOS:000172326800042 PM 11717109 ER PT J AU Feig, BW Curley, S Lucci, A Hunt, KK Vauthey, JN Mansfield, PF Cleary, K Hamilton, S Ellis, V Brame, M Berger, DH AF Feig, BW Curley, S Lucci, A Hunt, KK Vauthey, JN Mansfield, PF Cleary, K Hamilton, S Ellis, V Brame, M Berger, DH TI A caution regarding lymphatic mapping in patients with colon cancer SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the Southwestern-Surgical-Congress CY APR 29-MAY 02, 2001 CL CANCUN, MEXICO SP SW Surg Congress DE colon cancer; lymphatic mapping; sentinel lymph node ID COLORECTAL-CANCER; NODE MICROMETASTASES; ADJUVANT THERAPY; CARCINOMA; FLUOROURACIL; IDENTIFICATION; LEVAMISOLE; RESECTION; MELANOMA; SURVIVAL AB Background: The value of lymphatic mapping and sentinel lymph node biopsy in the treatment of colon cancer is controversial. The purpose of this study was to determine the accuracy of lymphatic mapping in patients with colon cancer. Methods: Forty-eight patients with colon cancer underwent lymphatic mapping and sentinel lymph node biopsy using isosulfan blue dye followed by standard surgical resection. The sentinel lymph nodes underwent thin sectioning as will as immunohistochemical staining for cytokeratin, in addition to standard hematoxylin and eosin staining. Results: In 47 (98%) patients, a sentinel lymph node was identified. Sixteen patients had lymph nodes containing metastatic disease, and in 6 patients the sentinel lymph node was positive for disease. In no patient was the sentinel lymph node the only site of metastatic disease. In 10 patients the sentinel lymph node was negative for disease, whereas the nonsentinel lymph nodes contained metastatic disease (false negative rate = 38%) Conclusions: The role of lymphatic mapping and sentinel lymph node biopsy in colon cancer is not as clear as its role in other tumors. Further large prospective studies are needed to evaluate the accuracy and potential benefit of this procedure in patients with colon cancer. (C) 2002 Excerpta Medica, Inc. All rights reserved. C1 Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Feig, BW (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Box 444,1515 Holcombe Blvd, Houston, TX 77030 USA. EM bwfeig@mdanderson.org NR 25 TC 54 Z9 58 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD DEC PY 2001 VL 182 IS 6 BP 707 EP 712 DI 10.1016/S0002-9610(01)00803-0 PG 6 WC Surgery SC Surgery GA 522JZ UT WOS:000173894000031 PM 11839343 ER PT J AU McGregor, DK Khurana, KK Cao, C Tsao, CC Ayala, G Krishnan, B Ro, JY Lechago, J Truong, LD AF McGregor, DK Khurana, KK Cao, C Tsao, CC Ayala, G Krishnan, B Ro, JY Lechago, J Truong, LD TI Diagnosing primary and metastatic renal cell carcinoma - The use of the monoclonal antibody 'renal cell carcinoma marker' SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE primary renal cell carcinoma; metastatic renal cell carcinoma; immunostaining; monoclonal antibody; renal cell carcinoma marker ID IMMUNOHISTOCHEMICAL ANALYSIS; DIFFERENTIAL-DIAGNOSIS; EPITHELIAL NEOPLASMS; GRANULAR CYTOPLASM; INTERCALATED CELLS; SURFACE-ANTIGENS; TUMORS; ONCOCYTOMA; KIDNEY; CYTOKERATIN-7 AB The diagnosis of primary or metastatic renal cell carcinoma (RCC) can be difficult, especially in small biopsies, because of the wide variety of histologic appearances and clinical presentations that RCC can assume. An immunomarker specific for RCC is currently not available. We tested the relevant diagnostic use of the Renal Cell Carcinoma Marker (RCC Ma), a monoclonal antibody, against a normal human proximal tubular brush border antigen. immunostaining using RCC Ma and the avidin-biotin-peroxidase complex technique was performed on archival tissues from primary and metastatic tumors of renal or nonrenal origin. A total of 122 of 153 primary RCCs (79.7%) were positive (clear cell (84%), papillary (96%), chromophobe (45%), sarcomatoid (25%, and collecting duct (0%)], with greater than or equal to 10% of tumor cells stained in 93% of cases. None of the 64 primary renal tumors other than RCC, including 15 oncocytomas, was positive. Fifteen of 146 (10.2%) nonrenal primary tumors were positive (5 of 17 breast tumors, 8 of 8 parathyroid adenomas, and 2 of 7 embryonal carcinomas). Forty-two of 63 (67%) metastatic RCCs were positive with greater than or equal to 10% of cells being stained in 83% of them. Two of 108 (2%) metastases from tumors other than RCCs were positive, both of which were metastatic breast carcinomas; however, only 10% (2 of 19) of metastatic breast carcinomas were positive, RCC Ma is an excellent marker for primary RCC, which should facilitate its diagnosis in a small biopsy. Although RCC Ma remains highly specific (98%) for metastatic RCC, a negative result may not rule out metastatic RCC because of a rather low sensitivity and a focal staining pattern in some of the positive cases. RCC Ma may also facilitate the differential diagnosis between oncocytoma and other types of RCC when they are composed mostly of eosinophilic cells. C1 Methodist Hosp, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. VA Med Ctr, Dept Pathol, Houston, TX USA. MD Anderson Canc Ctr, Dept Pathol, Houston, TX USA. Upstate Med Univ, Syracuse, NY USA. RP Truong, LD (reprint author), Methodist Hosp, Dept Pathol, 6565 Fannin St,MS205, Houston, TX 77030 USA. NR 32 TC 119 Z9 122 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD DEC PY 2001 VL 25 IS 12 BP 1485 EP 1492 DI 10.1097/00000478-200112000-00003 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 496ZU UT WOS:000172428900003 PM 11717537 ER PT J AU Ochoa, ER Harris, NL Pilch, BZ AF Ochoa, ER Harris, NL Pilch, BZ TI Marginal zone B-cell lymphoma of the salivary gland arising in chronic sclerosing sialadenitis (Kuttner tumor) SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE extranodal marginal zone B-cell lymphoma; MALT lymphoma; chronic sclerosing sialadenitis; Kuttner tumor; lymphoepithelial sialadenitis; salivary gland ID MYOEPITHELIAL SIALADENITIS; HELICOBACTER-PYLORI; MALIGNANT-LYMPHOMA; GASTRIC LYMPHOMA; TISSUE AB We report a case of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type of the salivary gland arising in a background of chronic sclerosing sialadenitis. Chronic sclerosing sialadenitis is a common fibrosing chronic inflammatory lesion of the submandibular gland, which is thought to be the result of sialolithiasis, and is not associated with a systemic autoimmune disease. Salivary MALT lymphomas are typically associated with lymphoepithelial sialadenitis (LESA) in a patient with or without Sjogren's syndrome. Our case of salivary MALT lymphoma was neither preceded by Sjogren's syndrome nor accompanied by LESA. This case suggests that chronic inflammatory processes other than Sjogren's syndrome may provide a substrate for the development of MALT lymphoma. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Pilch, BZ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Warren 2,14 Fruit St, Boston, MA 02114 USA. NR 15 TC 36 Z9 40 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD DEC PY 2001 VL 25 IS 12 BP 1546 EP 1550 DI 10.1097/00000478-200112000-00012 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA 496ZU UT WOS:000172428900012 PM 11717546 ER PT J AU Huerta, S Heber, D Sawicki, MP Liu, CD Arthur, D Alexander, P Yip, I Li, ZP Livingston, EH AF Huerta, S Heber, D Sawicki, MP Liu, CD Arthur, D Alexander, P Yip, I Li, ZP Livingston, EH TI Reduced length of stay by implementation of a clinical pathway for bariatric surgery in an academic health care center SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT Annual Meeting of the Southern-California-Chapter-of-the-American-College-of-Surgeons CY JAN 19-21, 2001 CL SANTA BARBARA, CALIFORNIA SP American Coll Surgeons, S California Chapter ID VERTICAL BANDED GASTROPLASTY; MORBID-OBESITY; PRACTICE GUIDELINES; GASTRIC BYPASS; MANAGED CARE; MEDICINE; REALITY AB Bariatric surgery is being performed in increasing numbers in an era when reimbursements are being reduced. Academic health centers bear the responsibility for training surgeons to perform these operations yet must keep costs to a minimum and retain high quality. The UCLA Bariatric Surgery Program developed a clinical pathway for the pre- and postoperative management for gastric bypass patients to achieve these goals. Medical records for 182 consecutive gastric bypass patients were retrospectively reviewed before implementation of the pathway (Group I) during the fiscal year of 1998/1999. Data on average length of stay, average intensive care unit length of stay, average standard variable cost, percentage readmission rate, and percentage return to the operating room were collected. This information was compared with the data collected prospectively from 182 patients after implementation of the pathway in July of 1999 (Group II) during the fiscal year of 1999/2000. Hospital cost per admission was reduced by 40 per cent in Group II compared with Group I (P < 0.02). The average length of stay was reduced from 4.05 days in Group I to 3.17 days in Group II (P < 0.033). Overall readmission rate was decreased from 4.2 per cent in Group I to 3.2 per cent in Group II (P < 0.05). There were no differences in morbidities between both groups. The pathway reduced costs by reducing the hospital length of stay, intensive care unit utilization, and readmission rates. Quality was maintained as evidenced by a similar pattern of postoperative morbidities yet readmission rates were reduced. Our results indicate that implementation of a clinical pathway for bariatric surgery reduces cost and improves quality of care in an academic institution. C1 VA Greater Los Angeles Hlth Care Syst, Dept Surg 10H2, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Ctr Human Nutr, Los Angeles, CA USA. RP Livingston, EH (reprint author), VA Greater Los Angeles Hlth Care Syst, Dept Surg 10H2, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 23 TC 27 Z9 27 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD DEC PY 2001 VL 67 IS 12 BP 1128 EP 1135 PG 8 WC Surgery SC Surgery GA 501HA UT WOS:000172678200003 PM 11768815 ER PT J AU Rebeck, GW Grabowski, TJ Cho, HS Melchor, JP Van Nostrand, WE Greenberg, SM AF Rebeck, GW Grabowski, TJ Cho, HS Melchor, JP Van Nostrand, WE Greenberg, SM TI A mutation in AB associated with cerebral amyloid angiopathy and dementia SO AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Alzheimers Res Unit, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP PI LANCASTER PA RICHMOND HOUSE, WHITE CROSS, SOUTH ROAD, LANCASTER LA1 4XQ, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-J. Protein Fold. Disord. PD DEC PY 2001 VL 8 SU 2 BP 183 EP 183 PG 1 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 509ED UT WOS:000173132100194 ER PT J AU Wexler, HM Molitoris, D Finegold, SM AF Wexler, HM Molitoris, D Finegold, SM TI In vitro activity of gatifloxacin against 238 strains of anaerobic bacteria SO ANAEROBE LA English DT Article DE anaerobic bacteria; quinolone; gatifloxacin; susceptibility; resistance ID UNITED-STATES; QUINOLONES AB The activity of gatifloxacin, a new 8-methoxy-fluoroquinolone, was tested against 208 pulmonary pathogens and against an additional 30 isolates of the Bacteroides fragilis group. Pulmonary isolates were from patients with documented anaerobic pleuropulmonary infections and were obtained by appropriate sampling methods. MICs were determined using the NCCLS-approved Wadsworth brucella laked blood agar method and compared to those of clindamycin, imipenem, metronidazole and trovafloxacin. Breakpoints used to define susceptible and [resistant] categories were (in mug/ml): Clindamycin-2, imipenem-4, metronidazole 8 and trovafloxacin. No breakpoint has been defined for gatifloxacin. Gatifloxacin inhibited 99% of all anaerobes tested at 4 mug/ml and 97% of all strains at 2 mug/ml. One strain of B. fragilis was resistant to gatifloxacin at 4 mug/ml; all strains of other B. fragilis group species were susceptible. One strain of Peptostreptococclis sp. was resistant to both gatifloxacin and trovafloxacin (MIC > 4 pg/ml). All other strains were susceptible to all agents at less than or equal to2 mug/ml. All of the non-sporeforming Gram-positive rods were susceptible to gatifloxacin at less than or equal to4 mug/ml (three strains had an MIC of 4 mug/ml). Trovafloxacin had MICs of 4 mug/ml for two strains, and an MIC of 8 pg/ml for one strain. Five percent of B. fragilis, 21% of other B. fragilis group species and 20% of Clostridium species (other than C. difficile, C. perfringens or C. ramosum) were resistant to clindamycin. No imipenem resistant isolates were found in this study Gatifloxacin appears to have excellent hi vitro activity against pulmonary isolates of anaerobes and very good activity against strains of the B. fragilis group. (C) 2001 Academic Press. C1 VA Greater Los Angeles Healthcare Syst, Med Serv, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Res Serv, 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 Microbiol & Immunol, Los Angeles, CA 90024 USA. RP Wexler, HM (reprint author), Microbial Dis Res Lab, Bldg 304,Room E3-224,VAGLAHS 691-151J, Los Angeles, CA 90073 USA. NR 11 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1075-9964 J9 ANAEROBE JI Anaerobe PD DEC PY 2001 VL 7 IS 6 BP 285 EP 289 DI 10.1006/anae.2001.0395 PG 5 WC Microbiology SC Microbiology GA 523XX UT WOS:000173983800001 ER PT J AU Paiste, J Bjerke, RJ Williams, JP Zenati, MA Nagy, GE AF Paiste, J Bjerke, RJ Williams, JP Zenati, MA Nagy, GE TI Minimally invasive direct coronary artery bypass surgery under high thoracic epidural SO ANESTHESIA AND ANALGESIA LA English DT Article ID ANESTHESIA; ANALGESIA; PATIENT; DISEASE C1 Univ Pittsburgh, Sch Med, Dept Anesthesiol & Crit Care Med, Pittsburgh, PA 15260 USA. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. RP Paiste, J (reprint author), Univ Pittsburgh, VA Med Ctr, Univ Dr C, Pittsburgh, PA 15240 USA. NR 12 TC 12 Z9 13 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 DEC PY 2001 VL 93 IS 6 BP 1486 EP 1488 DI 10.1097/00000539-200112000-00028 PG 3 WC Anesthesiology SC Anesthesiology GA 495WU UT WOS:000172364000022 PM 11726428 ER PT J AU Anawalt, BD Amory, JK AF Anawalt, BD Amory, JK TI Advances in male hormonal contraception SO ANNALS OF MEDICINE LA English DT Article DE androgen; gonadotropins; gonadotropin-releasing hormone antagonists; male contraception; progestin; spermatogenesis; testosterone ID EFFECTIVELY SUPPRESSES SPERMATOGENESIS; INJECTABLE TESTOSTERONE UNDECANOATE; HEALTHY-MEN; ORAL LEVONORGESTREL; CYPROTERONE-ACETATE; HYPOGONADAL MEN; CLINICAL-TRIAL; ENANTHATE; GONADOTROPIN; ANDROGEN AB New male contraceptive options are urgently needed. Safe, effective and fully reversible methods of male contraception would be useful for monogamous couples who are trying to regulate their family size. In addition, an effective male hormonal contraceptive that could be implanted or injected as a long-acting formulation every 3-6 months would be useful in countries where limiting population growth has become a public policy imperative. Male hormonal contraception is based on the same principles as traditional oestrogen-progestin female oral contraceptives. Both spermatogenesis and ovulation are dependent upon normal secretion of the pituitary gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH). Exogenous gonadotropin-releasing hormone (GnRH) analogues and sex steroid hormones such as testosterone (T) and progestins suppress gonadotropins and spermatogenesis. Two large multicentre trials demonstrated that weekly administration of high-dosage T was very effective in suppressing gonadotropins and spermatogenesis and conferred an overall contraceptive efficacy comparable to female oral contraceptives. Studies of combination regimens of lower-dosage T plus a progestin or a GnRH analogue have demonstrated greater suppression of spermatogenesis than the World Health Organization trials of high-dosage T. Most of these male hormonal contraceptives have been associated with modest weight gain and suppression of serum high-density cholesterol (HDL) levels. In this article, we review the new developments in male hormonal contraception. C1 Univ Washington, Dept Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Anawalt, BD (reprint author), Univ Washington, Dept Med, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 57 TC 15 Z9 15 U1 1 U2 2 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 DEC PY 2001 VL 33 IS 9 BP 587 EP 595 DI 10.3109/07853890109002104 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 512DB UT WOS:000173304900004 PM 11817653 ER PT J AU Sharma, AG Capaccioli, K Hart, L Dubois, J Arroyo, JG AF Sharma, AG Capaccioli, K Hart, L Dubois, J Arroyo, JG TI Spontaneous rupture of the posterior lens capsule with improved vision SO ANNALS OF OPHTHALMOLOGY LA English DT Article AB A traumatic cataract developed in a 17-year-old boy after he sustained penetrating trauma and underwent treatment of endophthalmitis. B-scan ultrasonography revealed a swollen lens and an accumulation of echoes on the posterior capsule. Two months later this patient experienced sudden visual improvement, from hand motions to 20/25, associated with spontaneous rupture of the posterior capsule. This unusual,occurrence may he due to increased intralenticular pressure or weakness in the lens capsule. C1 Massachusetts Eye & Ear Infirm, Retina Serv, Dept Ophthalmol, Boston, MA 02114 USA. Wayne State Univ, Sch Med, Detroit, MI USA. RP Arroyo, JG (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, Dept Ophthalmol, 12th Floor, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CONTEMPORARY OPHTHALMOLOGY PI CHICAGO PA 820 N ORLEANS, STE 208, CHICAGO, IL 60610 USA SN 1530-4086 J9 ANN OPHTHALMOL JI Ann. Ophthalmol. PD WIN PY 2001 VL 33 IS 4 BP 335 EP 336 DI 10.1007/s12009-001-0051-8 PG 2 WC Ophthalmology SC Ophthalmology GA 506PB UT WOS:000172980000013 ER PT J AU Hartnick, CJ Hartley, BEJ Lacy, PD Liu, J Willging, JP Myer, CM Cotton, RT AF Hartnick, CJ Hartley, BEJ Lacy, PD Liu, J Willging, JP Myer, CM Cotton, RT TI Surgery for pediatric subglottic stenosis: Disease-specific outcomes SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Broncho-Esophagological-Association CY MAY 14-16, 2001 CL PALM DESERT, CALIFORNIA SP Amer Broncho Esophagol Assoc DE laryngotracheal reconstruction; outcome; subglottic stenosis ID STAGE LARYNGOTRACHEAL RECONSTRUCTION; PARTIAL CRICOTRACHEAL RESECTION; EXPERIENCE; UPDATE AB To set the foundation to develop a disease-based, operation-specific model to predict the outcome of pediatric airway reconstruction surgery, we performed a retrospective database review of children operated on at a single, tertiary-care children's hospital. Over the 12-year period 1988 to 2000, a total of 1,296 airway reconstruction procedures were per-formed. Out of these, charts were identified for 199 children who underwent laryngotracheal reconstruction for a sole diagnosis of subglottic stenosis. Children were excluded from the study if their disorder included supraglottic, glottic, or upper tracheal disease. The main outcome measures were Myer-Cotton grade-specific decannulation and extubation rates, including both operation-specific and overall results. There were 101 children who underwent double-stage laryngotracheal reconstruction. The operation-specific decannulation rates for Myer-Cotton grades 2, 3, and 4 were 85% (18/21), 37% (23/61), and 50% (7/14) (chi (2) analysis, p =.0007). The overall decannulation rates were 95% (20/21), 74% (45/61), and 86% (12/14) (chi (2) analysis, p =.04). There were 98 children who underwent single-stage laryngotracheal reconstruction. The operation - specific extubation rates for Myer-Cotton grades 2, 3, and 4 were 82% (37/45), 79% (34/ 43), and 67% (2/3) (chi (2) analysis p =.63). The overall extubation rates were 100% (45/45), 86% (37/43), and 100% (3/3) (chi (2) analysis, p =.03). Logistic regression analysis showed no effect of age (less than or greater than 2 years of age) on operation-specific or overall outcome parameters. We conclude that laryngotracheal reconstruction for pediatric subglottic stenosis remains a challenging set of procedures in which multiple operations may be required to achieve eventual extubation or decannulation. Children with Myer-Cotton grade 3 or 4 disease continue to represent a significant challenge, and refinements of techniques are being examined to address this subset of children. Disease-based, operation-specific outcome statistics are the first step in the development of a meaningful predictive model. C1 Childrens Hosp, Med Ctr, Dept Pediat Otolaryngol, Cincinnati, OH 45229 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 15 TC 42 Z9 42 U1 0 U2 2 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD DEC PY 2001 VL 110 IS 12 BP 1109 EP 1113 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 502MZ UT WOS:000172748500004 PM 11768698 ER PT J AU Bhatt, KA Liberman, MC Nadol, JB AF Bhatt, KA Liberman, MC Nadol, JB TI Morphometric analysis of age-related changes in the human basilar membrane SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Otolaryngology CY FEB 14-18, 1999 CL ST PETERSBURGH BEACH, FLORIDA SP Assoc Res Otolaryngol DE basilar membrane; cochlea; histopathology; human; inner ear; presbycusis; tympanic mesothelial cell ID INNER-EAR; IMMUNOHISTOCHEMICAL LOCALIZATION; COCHLEA; FIBRONECTIN; GERBIL; TECTORIAL; PROTEIN; RATS AB The histopathologic correlates of presbycusis suggest several categories, including degeneration of sensory cells, neurons, or the stria vascularis. Lack of clear-cut histopathologic changes in some cases has suggested an "indeterminate category"; however, several studies have suggested that a disorder of the basilar membrane (BM) may underlie indeterminate presbycusis. The objective of the present study was to quantify age-related changes in the human BM and correlate them with audiometric patterns. Under high-resolution light microscopy, BM thickness was calculated, and the number of tympanic mesothelial cells (TMCs) lining the BM was counted, at 4 cochlear locations in 92 temporal bones. The control group (n = 80) included subjects from 10 decades of age with normal hearing and/or histopathologic findings. The indeterminate group (n = 12) consisted of elderly patients (ages 64 to 91 years) with hearing loss and no apparent histopathologic changes. Age-related BM thickening was seen in both groups. but only in the most basal cochlear region. The BM thickness in the indeterminate group was not significantly different from that of age-matched controls. Counts of TMCs showed age-related decreases in all cochlear regions in both groups; however, TMC counts in the indeterminate group were not different from those of age-matched controls. The results suggest that BM histopathology is not a common cause of presbycusis. Although age-related BM thickening. seen in both groups. could contribute to hearing loss. the extreme basal region, to which the thickening was confined, is not tested in routine audiometry. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Nadol, JB (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC-0188, P30 DC005209, R01 DC-00152] NR 30 TC 19 Z9 19 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD DEC PY 2001 VL 110 IS 12 BP 1147 EP 1153 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 502MZ UT WOS:000172748500012 PM 11768706 ER PT J AU Vander Zanden, JA Valuck, RJ Bunch, CL Perlman, JI Anderson, C Wortman, GI AF Vander Zanden, JA Valuck, RJ Bunch, CL Perlman, JI Anderson, C Wortman, GI TI Systemic adverse effects of ophthalmic beta-blockers SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE beta-adrenergic antagonists; adverse effects; ophthalmic solutions ID OPEN-ANGLE GLAUCOMA; MEDICAL LITERATURE; EYE DROPS; OCULAR HYPERTENSION; RESPIRATORY ARREST; ASTHMATIC SUBJECTS; TOPICAL TIMOLOL; BETAXOLOL; DRUG; CARTEOLOL AB OBJECTIVE: To review published clinical information on the systemic adverse effects of ophthalmic beta -blockers for the purpose of developing a pilot contraindication/warning system for active prescriptions in the Veterans Affairs dispensing database. DATA SOURCES: Articles were identified by searching MEDLINE (1966-October 2000) and International Pharmaceutical Abstracts (1970-October 2000). STUDY SELECTION AND DATA EXTRACTION: Article relevance was determined by review of titles, abstracts, and key words. DATA SYNTHESIS: The preponderance of the evidence suggests that ophthalmic beta -blockers may be associated with bronchospasm and adverse cardiovascular effects including bradycardia. Depression and other central nervous system effects are reported less commonly. Data are inadequate to suggest that ophthalmic beta -blocker use is routinely associated with adverse metabolic effects. CONCLUSIONS: The strongest level of evidence (grade A1) supports a contraindication for use of ophthalmic beta -blockers for respiratory disease, with a moderate level of evidence (grade B1) for cardiovascular disease. Data are insufficient to support or refute contraindications for other disease states. The search technique and classification scheme described in this article provide a methodology for evaluating, grading, and applying evidence on potential adverse effects of drug therapy. C1 Univ Colorado, Hlth Sci Ctr, Sch Pharm, Dept Pharm Practice, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Sch Pharm, Dept Pharm Practice, Greenwood Village, CO USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ophthalmol Sect, Hines, IL 60141 USA. Pharmacia Corp, Global Hlth Outcomes Unit, Evergreen, CO USA. RP Valuck, RJ (reprint author), Univ Colorado, Hlth Sci Ctr, Sch Pharm, Dept Pharm Practice, 4200 E 9th Ave,Box C-238, Denver, CO 80262 USA. NR 43 TC 20 Z9 21 U1 1 U2 4 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD DEC PY 2001 VL 35 IS 12 BP 1633 EP 1637 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 505VP UT WOS:000172936500023 PM 11793633 ER PT J AU Vlahakes, GJ AF Vlahakes, GJ TI Esmolol and cardiopulmonary bypass during reperfusion reduce myocardial infarct size in dogs - Invited commentary SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Vlahakes, GJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER 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 DEC PY 2001 VL 72 IS 6 BP 1969 EP 1969 DI 10.1016/S0003-4975(01)03276-3 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 499RQ UT WOS:000172584500030 ER PT J AU Shahian, DM Normand, SL Torchiana, DF Lewis, SM Pastore, JO Kuntz, RE Dreyer, PI AF Shahian, DM Normand, SL Torchiana, DF Lewis, SM Pastore, JO Kuntz, RE Dreyer, PI TI Cardiac surgery report cards: Comprehensive review and statistical critique SO ANNALS OF THORACIC SURGERY LA English DT Review ID BYPASS GRAFT-SURGERY; NEW-YORK-STATE; COOPERATIVE CARDIOVASCULAR PROJECT; HIERARCHICAL LOGISTIC-REGRESSION; IMPROVE CLINICAL-PRACTICE; RISK-ADJUSTED OUTCOMES; HEALTH-CARE; NATIONAL-DATABASE; MORTALITY-RATES; QUALITY IMPROVEMENT AB Public report cards and confidential, collaborative peer education represent distinctly different approaches to cardiac surgery quality assessment and improvement. This review discusses the controversies regarding their methodology and relative effectiveness. Report cards have been the more commonly used approach, typically as a result of state legislation. They are based on the presumption that publication of outcomes effectively motivates providers, and that market forces will reward higher quality. Numerous studies have challenged the validity of these hypotheses. Furthermore, although states with report cards have reported significant decreases in risk-adjusted mortality, it is unclear whether this improvement resulted from public disclosure or, rather, from the development of internal quality programs by hospitals. An additional confounding factor is the nationwide decline in heart surgery mortality, including states without quality monitoring. Finally, report cards may engender negative behaviors such as high-risk case avoidance and "gaming" of the reporting system, especially if individual surgeon results are published. The alternative approach, continuous quality improvement, may provide an opportunity to enhance performance and reduce interprovider variability while avoiding the unintended negative consequences of report cards. This collaborative method, which uses exchange visits between programs and determination of best practice, has been highly effective in northern New England and in the Veterans Affairs Administration. However, despite their potential advantages, quality programs based solely on confidential continuous quality improvement do not address the issue of public accountability. For this reason, some states may continue to mandate report cards. In such instances, it is imperative that appropriate statistical techniques and report formats are used, and that professional organizations simultaneously implement continuous quality improvement programs. The statistical methodology underlying current report cards is flawed, and does not justify the degree of accuracy presented to the public. All existing risk-adjustment methods have substantial inherent imprecision, and this is compounded when the results of such patient-level models are aggregated and used inappropriately to assess provider performance. Specific problems include sample size differences, clustering of observations, multiple comparisons, and failure to account for the random component of interprovider variability. We advocate the use of hierarchical or multilevel statistical models to address these concerns, as well as report formats that emphasize the statistical uncertainty of the results. (C) 2001 by The Society of Thoracic Surgeons. C1 Lahey Clin Fdn, Dept Thorac & Cardiovasc Surg, Burlington, MA 01805 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA USA. Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Cardiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Cardiol, Boston, MA 02115 USA. Cardiovasc Data Anal Ctr, Boston, MA 02115 USA. Massachusetts Dept Publ Hlth, Div Hlth Care Qual, Boston, MA USA. RP Shahian, DM (reprint author), Lahey Clin Fdn, Dept Thorac & Cardiovasc Surg, 41 Mall Rd, Burlington, MA 01805 USA. NR 134 TC 154 Z9 158 U1 1 U2 13 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 DEC PY 2001 VL 72 IS 6 BP 2155 EP 2168 DI 10.1016/S0003-4975(01)03222-2 PG 14 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 499RQ UT WOS:000172584500086 PM 11789828 ER PT J AU Al-Tabbaa, A Gonzalez, RM Lee, D AF Al-Tabbaa, A Gonzalez, RM Lee, D TI The role of state-of-the-art echocardiography in the assessment of myocardial injury during and following cardiac surgery SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT Symposium on Monitoring and Improving Patient Safety During and Following Cardiac Surgery CY MAY 05, 2001 CL SAN DIEGO, CALIFORNIA ID INTRAOPERATIVE TRANSESOPHAGEAL ECHOCARDIOGRAPHY; TRANS-ESOPHAGEAL ECHOCARDIOGRAPHY; TWO-DIMENSIONAL ECHOCARDIOGRAPHY; VENTRICULAR EJECTION FRACTION; ANESTHESIOLOGISTS TASK-FORCE; BYPASS GRAFT-SURGERY; REGIONAL WALL-MOTION; REVASCULARIZATION; INFARCTION; GUIDELINES AB Use of intraoperative echocardiography during open heart surgery, transesophageal probes, high-frequency transducers, and color Doppler imaging provide important diagnostic information to surgeons and anesthesiologists. Early detection of myocardial ischemia, assessment of valvular disorders, and the ability to monitor for intracardiac air are among the most important roles of intraoperative transesophageal echocardiography. Large prospective studies are necessary to evaluate whether these changes affect the outcome of patients undergoing coronary artery bypass grafting in terms of morbidity, mortality, hospital length of stay, and functional recovery. The application of new techniques such as contrast-enhanced transesophageal echocardiography helps to assess the adequacy of cardioplegia distribution and, thus, myocardial protection during cardiopulmonary bypass, which has a significant influence on outcomes as well. (C) 2001 by The Society of Thoracic Surgeons. C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Al-Tabbaa, A (reprint author), VA Boston Healthcare Syst, Dept Surg 112, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. NR 29 TC 5 Z9 5 U1 0 U2 4 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 DEC PY 2001 VL 72 IS 6 BP S2214 EP S2218 DI 10.1016/S0003-4975(01)03300-8 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 499RQ UT WOS:000172584500111 PM 11789844 ER PT J AU Birjiniuk, V AF Birjiniuk, V TI Patient outcomes in the assessment of myocardial injury following cardiac surgery SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT Symposium on Monitoring and Improving Patient Safety During and Following Cardiac Surgery CY MAY 05, 2001 CL SAN DIEGO, CALIFORNIA ID ARTERY BYPASS-SURGERY; INTRAMYOCARDIAL PH; HEART-SURGERY; 1ST REPORT; RISK; MORTALITY; STRATIFICATION; MORBIDITY; SCORE; INFARCTION AB In the absence of online methods for the intraoperative assessment of the adequacy of myocardial protection, patient outcomes remain the gold standard for determining whether a patient has sustained injury in the course of a cardiac operation. Properly risk-adjusted 30-day postoperative mortality and myocardial infarction are the most definitive indicators of perioperative injury. The definition and clinical assessment of irreversible ischemic myocardial injury continues to be problematic postoperatively. In most instances, deterioration in postoperative cardiac function and performance is indicative of intraoperative injury. Late postoperative mortality and long-term survival may be affected by intraoperative myocardial injury. Likewise, long-term graft patency may be affected by intraoperative injury to the conduit vascular endothelium. Proper assessment of outcomes, although it may not change the intraoperative course of an operation, can be useful in the comparative assessment of the efficacy of various operations, methods, and techniques. (C) 2001 by The Society of Thoracic Surgeons. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg,VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Birjiniuk, V (reprint author), VA Boston Healthcare Syst, Surg Serv 112, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. NR 33 TC 8 Z9 8 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 DEC PY 2001 VL 72 IS 6 BP S2208 EP S2212 DI 10.1016/S0003-4975(01)03288-X PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 499RQ UT WOS:000172584500109 PM 11789843 ER PT J AU Crittenden, MD AF Crittenden, MD TI Intraoperative metabolic monitoring of the heart: I. Clinical assessment of coronary sinus metabolites SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT Symposium on Monitoring and Improving Patient Safety During and Following Cardiac Surgery CY MAY 05, 2001 CL SAN DIEGO, CALIFORNIA ID WARM BLOOD CARDIOPLEGIA; FATTY-ACID OXIDATION; RETROGRADE CARDIOPLEGIA; MYOCARDIAL PROTECTION; REPERFUSION INJURY; CARDIAC OPERATIONS; VALVE REPLACEMENT; ARTERY SURGERY; RELEASE; ISCHEMIA AB Numerous clinical studies have corroborated the ability of intraoperative sampling of coronary sinus blood to measure changes in myocardial metabolism induced by ischemia and reperfusion. Among other changes, cardiac arrest induces a period of obligate myocardial lactate production that persists for an indeterminate amount of time after reperfusion. Coronary sinus lactate assays have been established as a standard method to compare various myocardial protection strategies. Current methodology requires detailed sample processing, precluding realtime feedback in the operating room. Newer devices hold promise in allowing the online assessment of myocardial metabolism; however, these methods await precise validation. (C) 2001 by The Society of Thoracic Surgeons. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg,VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Crittenden, MD (reprint author), VA Boston Healthcare Syst, Surg Serv 112, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. NR 79 TC 12 Z9 12 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 DEC PY 2001 VL 72 IS 6 BP S2220 EP S2226 DI 10.1016/S0003-4975(01)03296-9 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 499RQ UT WOS:000172584500113 PM 11789845 ER PT J AU Dearani, JA Axford, TC Patel, MA Healey, NA Lavin, PT Khuri, SF AF Dearani, JA Axford, TC Patel, MA Healey, NA Lavin, PT Khuri, SF TI Role of myocardial temperature measurement in monitoring the adequacy of myocardial protection during cardiac surgery SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT Symposium on Monitoring and Improving Patient Safety During and Following Cardiac Surgery CY MAY 05, 2001 CL SAN DIEGO, CALIFORNIA ID WARM BLOOD CARDIOPLEGIA; INTRAMYOCARDIAL PH; CELL INJURY; 1ST REPORT; PRESERVATION; HYPOTHERMIA; ARREST; COLD; ISCHEMIA; DISEASE AB Inadequate myocardial protection continues to be encountered despite improved methods of cardioplegia delivery. Although myocardial temperature is commonly monitored to assess the adequacy of cardioplegia delivery, its relationship to the metabolic status of the myocardium has not been investigated. We prospectively reviewed patients who underwent valvular heart surgery with blood (n = 47) or crystalloid (n = 48) cardioplegia and continuous measurement of intraoperative myocardial tissue pH and temperature. We previously demonstrated a high correlation (r = 0.99) between extracellular myocardial pH, levels of intracellular hydrogen ion concentration, and a lowering of tissue ATP during coronary occlusion. Clinically, optimal metabolic protection was defined as the absence of myocardial tissue acidosis during the period of aortic occlusion as quantified by a temperature-corrected integrated mean pH of 6.8 or greater, which has been shown to be predictive of a favorable postoperative outcome. Age, bypass time, myocardial temperature, myocardial tissue pH at the onset of aortic occlusion, cross-clamp time, and volume of cardioplegia were not significantly different between blood and crystalloid groups. Linear regression analysis demonstrated no significant correlation between mean myocardial tissue pH and the corresponding mean myocardial temperature in either group during aortic occlusion. There was also no correlation between the mean myocardial tissue pH and volume of cardioplegia delivered in both groups. These data demonstrate wide intercardiac and intracardiac variability in the degree of regional tissue acidosis encountered during of hypothermic cardioplegia. Cardioplegia delivery guided by measurement of myocardial temperature or by standardized protocol did not prevent the occurrence of tissue acidosis and thus, did not ensure optimal metabolic protection of the heart. In 95 patients undergoing valvular heart surgery with cold blood or crystalloid cardioplegia, there was no correlation between myocardial tissue pH and mycardial temperature or between myocardial tissue pH and volume of cardioplegia administered. Temperature is a poor indicator of the metabolic state of the myocardium. (C) 2001 by The Society of Thoracic Surgeons. C1 Mayo Clin & Mayo Fdn, Div Cardiovasc Surg, Rochester, MN 55905 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst,Dept Surg, Boston, MA 02115 USA. Boston Biostat Res Fdn, Newton, MA USA. RP Khuri, SF (reprint author), VA Boston Healthcare Syst, Surg Serv 112, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. NR 40 TC 9 Z9 11 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 DEC PY 2001 VL 72 IS 6 BP S2235 EP S2243 DI 10.1016/S0003-4975(01)03320-3 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 499RQ UT WOS:000172584500117 PM 11789847 ER PT J AU Khuri, SF AF Khuri, SF TI Evidence, sources, and assessment of injury during and following cardiac surgery SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT Symposium on Monitoring and Improving Patient Safety During and Following Cardiac Surgery CY MAY 05, 2001 CL SAN DIEGO, CALIFORNIA ID MORTALITY C1 VA Boston Healthcare Syst, W Roxbury, MA 02132 USA. RP Khuri, SF (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. NR 21 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 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2001 VL 72 IS 6 BP S2205 EP S2207 DI 10.1016/S0003-4975(01)03294-5 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 499RQ UT WOS:000172584500108 PM 11789842 ER PT J AU Khuri, SF AF Khuri, SF TI Intraoperative metabolic monitoring of the heart: II. Online measurement of myocardial tissue pH - Discussion SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 VA Boston Healthcare Syst, Surg Serv, W Roxbury, MA 02132 USA. RP Khuri, SF (reprint author), VA Boston Healthcare Syst, Surg Serv, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. NR 0 TC 2 Z9 2 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 DEC PY 2001 VL 72 IS 6 BP S2233 EP S2234 DI 10.1016/S0003-4975(01)03285-4 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 499RQ UT WOS:000172584500116 ER PT J AU Thatte, HS Khuri, SF AF Thatte, HS Khuri, SF TI The coronary artery bypass conduit: I. Intraoperative endothelial injury and its implication on graft patency SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT Symposium on Monitoring and Improving Patient Safety During and Following Cardiac Surgery CY MAY 05, 2001 CL SAN DIEGO, CALIFORNIA ID FLUORESCENCE MICROSCOPY; NITRIC-OXIDE; VEIN; PATHOPHYSIOLOGY; DYSFUNCTION; FAILURE; DISEASE AB Prevention of intraoperative injury to the vascular endothelium is of primary importance in maintaining viability and patency of the aorto-coronary saphenous vein graft. Surgical manipulation, ischemia, storage conditions, and distension before anastomosis can abnormally alter the antithrombogenic property of the endothelium leading to vasospasms, thrombogenesis, occlusive intimal hyperplasia, and stenosis. Endothelial injury can also form an initiation site for the formation of later-stage atheromas and graft failure. A multifactorial strategy aimed at prevention of endothelial injury and graft failure should include improved surgical techniques, optimal preservation conditions, avoidance of nonphysiologic distension pressures, and use of specific pharmacologic agents as the primary form of intervention. The successful application of this strategy, and the development of newer and more efficacious strategies that may impact on long-term graft patency, can now be aided by assessment of the structural and functional integrity of bypass conduits using multiphoton imaging techniques. (C) 2001 by The Society of Thoracic Surgeons. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg,VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Thatte, HS (reprint author), VA Boston Healthcare Syst, Surg Serv 112, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. NR 24 TC 50 Z9 51 U1 0 U2 2 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 DEC PY 2001 VL 72 IS 6 BP S2245 EP S2252 DI 10.1016/S0003-4975(01)03272-6 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 499RQ UT WOS:000172584500119 PM 11789848 ER PT J AU Nelson, RG Rosowsky, A AF Nelson, RG Rosowsky, A TI Dicyclic and tricyclic diaminopyrimidine derivatives as potent inhibitors of Cryptosporidium parvum dihydrofolate reductase: Structure-activity and structure-selectivity correlations SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ISOSPORA-BELLI INFECTION; STRUCTURE-BASED DESIGN; PNEUMOCYSTIS-CARINII; TOXOPLASMA-GONDII; ANTITUMOR AGENTS; IN-VITRO; BIOLOGICAL-ACTIVITIES; TRIMETHOPRIM-SULFAMETHOXAZOLE; OPPORTUNISTIC INFECTIONS; ANTIFOLATE ACTIVITY AB A structurally diverse library of 93 lipophilic di- and tricyclic diaminopyrimidine derivatives was tested for the ability to inhibit recombinant dihydrofolate reductase (DHFR) cloned from human and bovine isolates of Cryptosporidium parvum (J. R. Vasquez et al., Mol. Biochem. Parasitol. 79:153-165, 1996). In parallel, the library was also tested against human DHFR and, for comparison, the enzyme from Escherichia coli. Fifty percent inhibitory concentrations (IC(50)s) were determined by means of a standard spectrophotometric assay of DHFR activity with dihydrofolate and NADPH as the cosubstrates. Of the compounds tested, 25 had IC(50)s in the 1 to 10 muM range against one or both C. parvum enzymes and thus were not substantially different from trimethoprim (IC(50)s, ca. 4 muM). Another 25 compounds had IC(50)s of < 1.0 muM, and 9 of these had IC(50)s of < 0.1 muM and thus were at least 40 times more potent than trimethoprim. The remaining 42 compounds were weak inhibitors (IC(50)s, > 10 muM) and thus were not considered to be of interest as drugs useful against this organism. A good correlation was generally obtained between the results of the spectrophotometric enzyme inhibition assays and those obtained recently in a yeast complementation assay (V. H. Brophy et al., Antimicrob. Agents Chemother. 44:1019-1028, 2000; H. Lau et al., Antimicrob. Agents Chemother. 45:187-195, 2001). Although many of the compounds in the library were more potent than trimethoprim, none had the degree of selectivity of trimethoprim for C. parvum versus human DHFR. Collectively, the results of these assays comprise the largest available database of lipophilic antifolates as potential anticryptosporidial agents. The compounds in the library were also tested as inhibitors of the proliferation of intracellular C. parvum oocysts in canine kidney epithelial cells cultured in folate-free medium containing thymidine (10 muM) and hypoxanthine (100 muM). After 72 h of drug exposure, the number of parasites inside the cells was quantitated by indirect immunofluorescence microscopy. Sixteen compounds had IC(50)s of < 3 muM, and five of these had IC(50)s of < 0.3 muM and thus were comparable in potency to trimetrexate. The finding that submicromolar concentrations of several of the compounds in the library could inhibit in vitro growth of C. parvum in host cells in the presence of thymidine (dThd) and hypoxanthine (Hx) suggests that lipophilic DHFR inhibitors, in combination with leucovorin, may find use in the treatment of intractable C. parvum infections. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA 94143 USA. RP Rosowsky, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [N01-AI35171, R0-AI29904, R01 AI029904, UO1-AI40319] NR 79 TC 25 Z9 26 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 2001 VL 45 IS 12 BP 3293 EP 3303 DI 10.1128/AAC.45.12.3293-3303.2001 PG 11 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 494UT UT WOS:000172304800003 PM 11709300 ER PT J AU McKee, GT Tambouret, RH Finkelstein, D AF McKee, GT Tambouret, RH Finkelstein, D TI A reliable method of demonstrating HER-2/neu, estrogen receptors, and progesterone receptors on routinely processed cytologic material SO APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY LA English DT Article; Proceedings Paper CT 89th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 23-31, 2000 CL NEW ORLEANS, LOUISIANA SP US & Canadian Acad Pathol DE cytology; estrogen receptor; fluorescence in situ hybridization; HER-2/neu; immunohistochemistry; progesterone receptor ID SITU HYBRIDIZATION FISH; BREAST-CANCER PATIENTS; IMMUNOCYTOCHEMICAL DETERMINATION; PROGNOSTIC FACTORS; FROZEN-SECTIONS; TISSUE-SECTIONS; SPECIMENS; CARCINOMA; ASSAY; AMPLIFICATION AB Estrogen (ER) and progesterone receptors (PR) and HER-2/neu (c-erbB-2) protein overexpression are important prognostic factors for breast carcinoma. This study describes a simple, rapid method that demonstrates the applicability of these tests to cytology smears. Smears were made from scrape samples of fresh breast tumors and were fixed in 95% alcohol for immunohistochemical staining for ER and PR and HER-2/neu protein overexpression. Scraped material was suspended in phosphate-buffered saline, and cytospin slides were prepared from the suspension and air dried for fluorescence in situ hybridization (FISH). The results for ER performed on cytology compared with the gold standard (immunohistochemistry on histology) showed 94% accuracy (95% confidence bounds (0.8432 0.9823)); PR results showed 71% accuracy (95% confidence bounds (0.5805 0.8180)) and HER-2/neu results showed 77% accuracy (95% confidence bounds (0.6500 0.8709)). Using HER-2/neu gene overamplification detected by FISH as the gold standard, immunohistochemistry for HER-2/neu protein overexpression showed sensitivity, specificity, and a positive predictive value of 88.8%, 77.7%, and 80% for histology, respectively, and 69%, 87%, and 90% for cytology, respectively. This study showed that fixation and storage of smears in 95% alcohol were effective for receptor studies, whereas air-dried cytospin smears were well suited to FISH. C1 Massachusetts Gen Hosp, Dept Cytopathol, Boston, MA 02493 USA. Massachusetts Gen Hosp, Ctr Canc, Dept Biostat, Boston, MA USA. RP McKee, GT (reprint author), Massachusetts Gen Hosp, Dept Cytopathol, 55 Fruit St,WRN 2, Boston, MA 02493 USA. NR 31 TC 7 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-3345 J9 APPL IMMUNOHISTO M M JI Appl. Immunohistochem. PD DEC PY 2001 VL 9 IS 4 BP 352 EP 357 DI 10.1097/00022744-200112000-00011 PG 6 WC Anatomy & Morphology; Medical Laboratory Technology; Pathology SC Anatomy & Morphology; Medical Laboratory Technology; Pathology GA 494JA UT WOS:000172277700011 PM 11759063 ER PT J AU Habinowski, SA Hirshman, M Sakamoto, K Kemp, BE Gould, SJ Goodyear, LJ Witters, LA AF Habinowski, SA Hirshman, M Sakamoto, K Kemp, BE Gould, SJ Goodyear, LJ Witters, LA TI Malonyl-CoA decarboxylase is not a substrate of AMP-activated protein kinase in rat fast-twitch skeletal muscle or an islet cell line SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE malonyl-CoA; acetyl-CoA carboxylase; malonyl-CoA decarboxylase; AMP-activated protein kinase; phosphorylation ID PANCREATIC BETA-CELLS; GLUCOSE-TRANSPORT; INSULIN-SECRETION; CARBOXYLASE; CONTRACTION; CARNITINE; STIMULATION; SUBUNIT; CLONING; TISSUES AB The AMP-activated protein kinase (AMPK) plays an important role in fuel metabolism in exercising skeletal muscle and possibly in the islet cell with respect to insulin secretion. Some of these effects are due to AMPK-mediated regulation of cellular malonyl-CoA content, ascribed to the ability of AMPK to phosphorylate and inactivate acetyl-CoA carboxylase (ACC), reducing malonyl-CoA formation. It has been suggested that AMPK may also regulate malonyl-CoA content by activation of malonyl-CoA decarboxylase (MCD). We have investigated the potential regulation of MCD by AMPK in exercising skeletal muscle, in an islet cell line, and in vitro. Three rat fast-twitch muscle types were studied using two different contraction methods or after exposure to the AMPK activator AICAR. Although all muscle treatments resulted in activation of AMPK and phosphorylation of ACC, no stimulus had any effect on MCD activity. In 832/13 INS-1 rat islet cells, two treatments that result in the activation of AMPK, namely low glucose and AICAR, also had no discernable effect on MCD activity. Last, AMPK did not phosphorylate in vitro either recombinant MCD or MCD immunoprecipitated from skeletal muscle or heart. We conclude that MCD is not a substrate for AMPK in fast-twitch muscle or the 832/13 INS-1 islet cell line and that the principal mechanism by which AMPK regulates malonyl-CoA content is through its regulation of ACC. (C) 2001 Elsevier Science. C1 Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Med, Hanover, NH 03755 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Biochem, Hanover, NH 03755 USA. Joslin Diabet Ctr, Metab Sect, Boston, MA 02215 USA. St Vincents Hosp, St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia. Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA. RP Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Med, Remsen 322,N Coll St, Hanover, NH 03755 USA. EM lee.a.witters@dartmouth.edu RI Kemp, Bruce/L-2633-2014 OI Kemp, Bruce/0000-0001-6735-5082 FU NIDDK NIH HHS [DK35712] NR 31 TC 43 Z9 43 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 EI 1096-0384 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD DEC 1 PY 2001 VL 396 IS 1 BP 71 EP 79 DI 10.1006/abbi.2001.2589 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 499PD UT WOS:000172578800010 PM 11716464 ER PT J AU North, PE Waner, M James, CA Mizeracki, A Frieden, IJ Mihm, MC AF North, PE Waner, M James, CA Mizeracki, A Frieden, IJ Mihm, MC TI Congenital nonprogressive hemangioma - A distinct clinicopathologic entity unlike infantile hemangioma SO ARCHIVES OF DERMATOLOGY LA English DT Article ID PAPILLARY ENDOTHELIAL HYPERPLASIA; INTRAVENOUS PYOGENIC GRANULOMA; LOBULAR CAPILLARY HEMANGIOMA; REACTIVE ANGIOENDOTHELIOMATOSIS; HEMANGIOENDOTHELIOMA; INFANCY AB Background: Infantile hemangiomas are common tumors, distinctive for their perinatal presentation, rapid growth during the first year of life, and subsequent involution-and for their expression of a unique immunophenotype shared by placental microvessels. Occasional "hemangiomas" differ from the classic form in presenting fully formed at birth, then following a static or rapidly involuting course. These congenitally fully developed lesions have generally been assumed to be clinical variants of more typical, postnatally developing hemangiomas. This assumption has not been tested by rigorous histologic and immunophenotypic comparisons. Objective: To compare the histologic and immunohistochemical features of congenital nonprogressive hemangiomas with those of typical, postnatally proliferating, hemangiomas. Design: All cellular vascular tumors resected from infants younger than 4 months at Arkansas Children's Hospital, Little Rock, over the past 20 years (43 lesions from 36 patients) were first characterized histologically and immunohistochemically, then clinically by chart review. Setting: A university-affiliated pediatric hospital. Main Outcome Measures: Histologic appearance, immunoreactivity for the infantile hemangioma-associated antigens GLUT1 and LeY, and clinical behavior, Results: Congenital nonprogressive hemangiomas differed from postnatally proliferating infantile hemangiomas in histologic appearance and immunohistochemical profile. Distinguishing pathologic features of these tumors were lobules of capillaries set within densely fibrotic stroma containing hemosiderin deposits; focal lobular thrombosis and sclerosis; frequent association with multiple thin-walled vessels; absence of "intermingling" of the neovasculature with normal tissue elements; and lack of immunoreactivity for GLUT1 and LeY. Conclusion: Congenital nonprogressive hemangiomas are histologically and immunophenotypically distinct from classically presenting hemangiomas of infancy, unlikely to be related to the latter in pathogenesis. C1 Arkansas Childrens Hosp, Dept Pediat Pathol, Little Rock, AR 72202 USA. Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Head & Neck Surg, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Otolaryngol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Radiol, Little Rock, AR 72205 USA. Univ Calif San Francisco, Med Ctr, Dept Pediat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Med Ctr, Dept Dermatol, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP North, PE (reprint author), Arkansas Childrens Hosp, Dept Pediat Pathol, 800 Marshall St, Little Rock, AR 72202 USA. OI Frieden, Ilona/0000-0001-7305-5940 NR 28 TC 88 Z9 101 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD DEC PY 2001 VL 137 IS 12 BP 1607 EP 1620 PG 14 WC Dermatology SC Dermatology GA 503HH UT WOS:000172792700006 PM 11735711 ER PT J AU Hind, JA Nicosia, MA Roecker, EB Carnes, ML Robbins, J AF Hind, JA Nicosia, MA Roecker, EB Carnes, ML Robbins, J TI Comparison of effortful and noneffortful swallows in healthy middle-aged and older adults SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE deglutition disorders; geriatrics; rehabilitation; therapeutics ID CLEARANCE; PRESSURE; VOLUME AB Objective: To assess the effects of effortful swallowing, a common compensatory strategy for dysphagia, on the bolus and swallowing mechanism of middle-aged and older men and women. Design: Case-controlled design in which subjects completed both the intervention technique and the control behavior. Setting: A university hospital. Participants: Sixty-four healthy men and women between 45 and 93 years of age from the community. Interventions: Participants swallowed 3-mL thin liquid boluses both normally and using the effortful swallow strategy. Main Outcomes Measures: The biomechanics and bolus flow patterns of swallows were analyzed from videofluoroscopic and simultaneous oral pressure data. Results: Subjects at all ages generated significantly increased oral pressures at each sensor location using the effortful swallow (p = .0001), with the pressure increase greater for the middle-aged subjects compared with older subjects. Several durational measures were significantly longer with the effortful swallow including: hyoid maximum anterior excursion (p < .04), laryngeal vestibule closure (p < .0001), and duration of the upper esophageal sphincter opening (p =.0001). The hyoid bone moved further in the superior direction with the effortful swallow (p = .002). There was a trend of decreased oral residue with the effortful swallow (p = .06). Conclusion: Biomechanical and bolus flow aspects of swallowing changed when healthy individuals performed effortful swallows with 3-mL boluses. C1 William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Madison, WI USA. Univ Wisconsin, Inst Aging, Madison, WI USA. Univ Wisconsin, Dept Biostat, Madison, WI USA. RP Robbins, J (reprint author), William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, 2500 Overlook Ter GRECC 11G, Madison, WI 53705 USA. FU NINDS NIH HHS [R01 NS24427] NR 20 TC 108 Z9 111 U1 0 U2 10 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 DEC PY 2001 VL 82 IS 12 BP 1661 EP 1665 DI 10.1053/apmr.2001.28006 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 499DR UT WOS:000172556200005 PM 11733879 ER PT J AU Luo, H Dearolf, CR AF Luo, H Dearolf, CR TI The JAK/STAT pathway and Drosophila development SO BIOESSAYS LA English DT Review ID PROTEIN-TYROSINE KINASE; JAK-STAT PATHWAYS; INTERFERON-ALPHA/BETA; SIGNALING PATHWAY; PSEUDOKINASE DOMAIN; 4-JOINTED GENE; EYE; POLARITY; RECEPTOR; LEUKEMIA AB The JAK/STAT signal transduction pathway plays a critical role in mammalian cells, particularly in hematopoiesis and immune responses. Several components of this pathway have been identified and characterized in Drosophila. Mutational analyses of these components have revealed a number of interesting developmental roles, and provide a mechanism to identify other interacting molecules and pathways. Hence, the JAK/STAT pathway in Drosophila serves as an attractive model for in vivo functional analyses of JAK/STAT signaling. (C) 2001 John Wiley & Sons, Inc. C1 Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Texas A&M Univ, Coll Med, Syst Hlth Sci Ctr, Div Mol Cardiol,Cardiovasc Res Inst, Temple, TX 76508 USA. RP Luo, H (reprint author), Massachusetts Gen Hosp, Dept Pediat, Jackson 1402,55 Fruit St, Boston, MA 02114 USA. NR 69 TC 44 Z9 44 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 0265-9247 J9 BIOESSAYS JI Bioessays PD DEC PY 2001 VL 23 IS 12 BP 1138 EP 1147 DI 10.1002/bies.10016 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 499FY UT WOS:000172561500009 PM 11746233 ER PT J AU Shen, Y Wu, DF Zelen, M AF Shen, Y Wu, DF Zelen, M TI Testing the independence of two diagnostic tests SO BIOMETRICS LA English DT Article DE breast cancer; clinical breast exams; diagnostic tests; likelihood ratio tests; mammograms; Wald tests ID BREAST-CANCER DETECTION; DEATH RATES; DISEASE; ACCURACY; MODELS AB Consider two diagnostic procedures having binary outcomes. If one of the tests results in a positive finding, a more definitive diagnostic procedure will be administered to establish the presence or absence of a disease. The use of both tests will improve the overall screening sensitivity when the two tests are independent, compared with employing two tests that are positively correlated. We estimate the correlation coefficient of the two tests and derive statistical methods for testing the independence of the two diagnostic procedures conditional on disease status. The statistical tests are used to investigate the independence of mammography and clinical breast exams aimed at establishing the benefit of early detection of breast cancer. The data used in the analysis are obtained from periodic screening examinations of three randomized clinical trials of breast cancer screening. Analysis of each of these trials confirms the independence of the clinical breast and mammography examinations. Based on these three large clinical trials, we conclude that a clinical breast exam considerably increases the overall sensitivity relative to screening with mammography alone and should be routinely included in early breast cancer detection programs. C1 Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shen, Y (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. OI Shen, Yu/0000-0002-3899-7868 FU NCI NIH HHS [CA-79466, CA-78607, CA-88270] NR 18 TC 13 Z9 13 U1 1 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 DEC PY 2001 VL 57 IS 4 BP 1009 EP 1017 DI 10.1111/j.0006-341X.2001.01009.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 540XU UT WOS:000174956800003 PM 11764239 ER PT J AU Ho, VT Soiffer, RJ AF Ho, VT Soiffer, RJ TI The history and future of T-cell depletion as graft-versus-host disease prophylaxis for allogeneic hematopoietic stem cell transplantation SO BLOOD LA English DT Review ID BONE-MARROW TRANSPLANTATION; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; NON-HODGKINS-LYMPHOMA; HLA-IDENTICAL SIBLINGS; COUNTERFLOW CENTRIFUGAL ELUTRIATION; SEVERE COMBINED IMMUNODEFICIENCY; DONOR LEUKOCYTE INFUSIONS; MONOCLONAL-ANTIBODY OKT3; BLOOD PROGENITOR CELLS C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Adult Oncol, Boston, MA 02115 USA. RP Soiffer, RJ (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Adult Oncol, 44 Binney St,D1B58, Boston, MA 02115 USA. FU NIAID NIH HHS [AI29530] NR 238 TC 245 Z9 260 U1 2 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 DEC 1 PY 2001 VL 98 IS 12 BP 3192 EP 3204 DI 10.1182/blood.V98.12.3192 PG 13 WC Hematology SC Hematology GA 495BV UT WOS:000172321100007 PM 11719354 ER PT J AU Lee, SJ Klein, JP Anasetti, C Antin, JH Loberiza, FR Bowell, BJ LeMaistre, CF Litzow, MR Marks, D Waller, EK Matlack, M Giralt, S Horowitz, MM AF Lee, SJ Klein, JP Anasetti, C Antin, JH Loberiza, FR Bowell, BJ LeMaistre, CF Litzow, MR Marks, D Waller, EK Matlack, M Giralt, S Horowitz, MM TI The effect of pretransplant interferon therapy on the outcome of unrelated donor hematopoietic stem cell transplantation for patients with chronic myelogenous leukemia in first chronic phase SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; CHRONIC MYELOID-LEUKEMIA; CHRONIC GRANULOCYTIC-LEUKEMIA; PROGNOSTIC DISCRIMINATION; CYTOGENETIC RESPONSE; ADVERSELY AFFECT; ALPHA; SURVIVAL; BUSULFAN; TRIAL AB Various therapeutic options are available for patients with chronic myelogenous leukemia. Allogeneic stem cell transplantation, though often curative, is associated with high nonrelapse mortality and long-term morbidity, particularly when cells from unrelated donors are used. Many physicians and patients opt for a trial of interferon-alpha (IFN)-based therapy first, reserving transplantation for patients with inadequate response or intolerance to IFN. Data were analyzed on 740 patients receiving unrelated donor transplants for chronic myelogenous leukemia in first chronic phase provided by the International Bone Marrow Transplant Registry and the National Marrow Donor Program to see whether IFN pretreatment compromised transplantation outcome. A total of 489 (66%) had received IFN prior to transplantation; 251 (34%) had not. Disease characteristics in the 2 groups were similar at diagnosis but at the time of transplantation, hematologic parameters and weight were lower in IFN patients and the interval between diagnosis and transplantation was longer. After adjustment for baseline covariates, no effect of IFN exposure was found on overall survival, leukemia-free survival, nonrelapse, mortality, engraftment, relapse, or acute or chronic graft-versus-host disease. Evaluation of effects based on duration of therapy and time off IFN prior to transplantation was limited by missing data and confounding with IFN intolerance and disease responsiveness. In conclusion, no evidence was found for an independent adverse effect of IFN pretreatment on the outcome of subsequent unrelated donor transplantation. (Blood. 2001;98:3205-3211) (C) 2001 by The American Society of Hematology. C1 Med Coll Wisconsin, Hlth Policy Inst, Int Bone Marrow Transplant Registry, Chron Leukemia Working Comm,Stat Ctr, Milwaukee, WI 53226 USA. Natl Marrow Donor Program, Coordinating Ctr, Minneapolis, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. S Texas Canc Inst, San Antonio, TX USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Bristol Childrens Hosp, Bristol, Avon, England. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Horowitz, MM (reprint author), Med Coll Wisconsin, Hlth Policy Inst, Int Bone Marrow Transplant Registry, Chron Leukemia Working Comm,Stat Ctr, 8701 Watertown Plank Rd,POB 26509, Milwaukee, WI 53226 USA. FU NCI NIH HHS [CA75267-03, U24-CA76518] NR 32 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2001 VL 98 IS 12 BP 3205 EP 3211 DI 10.1182/blood.V98.12.3205 PG 7 WC Hematology SC Hematology GA 495BV UT WOS:000172321100008 PM 11719355 ER PT J AU Li, JZ Yang, C Xia, YP Bertino, A Glaspy, J Roberts, M Kuter, DJ AF Li, JZ Yang, C Xia, YP Bertino, A Glaspy, J Roberts, M Kuter, DJ TI Thrombocytopenia caused by the development of antibodies to thrombopoietin SO BLOOD LA English DT Article ID RECOMBINANT HUMAN THROMBOPOIETIN; HUMAN MEGAKARYOCYTE GROWTH; MPL-DEFICIENT MICE; RED-CELL APLASIA; PLATELET PRODUCTION; ERYTHROPOIETIN; AUTOANTIBODIES; PATIENT; CANCER; INDUCTION AB Thrombocytopenia developed in some individuals treated with a recombinant thrombopoletin (TPO), pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF). Three of the subjects who developed severe thrombocytopenia were analyzed in detail to determine the cause of their thrombocytopenia. Except for easy bruising and heavy menses, none of these subjects had major bleeding episodes; none responded to intravenous immunoglobulin or prednisone. Bone marrow examination revealed a marked reduction in megakaryocytes. All 3 thrombocytopenic subjects had antibody to PEG-rHuMGDF that cross-reacted with endogenous TPO and neutralized its biological activity. All anti-TPO antibodies were immunoglobulin G (IgG), with increased amounts of IgG4; no IgM antibodies to TPO were detected at any time. A quantitative assay for IgG antibody to TPO was developed and showed that the antibody concentration varied inversely with the platelet count. Anti-TPO antibody recognized epitopes located in the first 163 amino acids of TPO and prevented TPO from binding to its receptor. In 2 subjects, endogenous TPO levels were elevated, but the TPO circulated as a biologically inactive immune complex with anti-TPO IgG; the endogenous TPO in these complexes had an apparent molecular weight of 95 000, slightly larger than the full-length recombinant TPO. None of the subjects had atypical HLA or platelet antigens, and the TPO cDNA was normal in both that were sequenced. Treatment of one subject with cyclosporine eliminated the antibody and normalized the platelet count. These data demonstrate a new mechanism for thrombocytopenia in which antibody develops to TPO; because endogenous TPO is produced constitutively, thrombocytopenia ensues. (Blood. 2001;98:3241-3248) (C) 2001 by The American Society of Hematology. C1 Massachusetts Gen Hosp, Hematol Unit, Boston, MA 02114 USA. Univ Calif Los Angeles, Ctr Canc, Los Angeles, CA USA. Hematol & Oncol Associates, Phoenix, AZ USA. RP Kuter, DJ (reprint author), Massachusetts Gen Hosp, Hematol Oncol Unit, COX 640, 100 Blossom St, Boston, MA 02114 USA. NR 33 TC 348 Z9 368 U1 4 U2 10 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2001 VL 98 IS 12 BP 3241 EP 3248 DI 10.1182/blood.V98.12.3241 PG 8 WC Hematology SC Hematology GA 495BV UT WOS:000172321100013 PM 11719360 ER PT J AU Yang, Y Kuang, YN De Oca, RM Hays, T Moreau, L Lu, NF Seed, B D'Andrea, AD AF Yang, Y Kuang, YN De Oca, RM Hays, T Moreau, L Lu, NF Seed, B D'Andrea, AD TI Targeted disruption of the murine Fanconi anemia gene, Fancg/Xrcc9 SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; IN-VIVO SELECTION; GROUP-C; NUCLEAR-COMPLEX; COMPLEMENTATION ANALYSIS; CHROMOSOMAL INSTABILITY; ATAXIA-TELANGIECTASIA; POSITIONAL CLONING; DEFICIENT MICE; GROUP-A AB Fanconi anemia (FA) is a human autosomal recessive cancer susceptibility disorder characterized by cellular sensitivity to mitomycin C and ionizing radiation. Six FA genes (corresponding to subtypes A, C, D2, E, F, and G) have been cloned, and the encoded FA proteins interact in a common cellular pathway. To further understand the in vivo role of one of these human genes (FANCG), we generated a targeted disruption of murine Fancg and bred mice homozygous for the targeted allele. Similar to the phenotype of the previously described Fancc(-/-) and Fanca(-/-) mice, the Fancg(-/-) mice had normal viability and no gross developmental abnormalities. Primary splenic lymphocytes, bone marrow progenitor cells, and murine embryo fibroblasts from the Fancg(-/-) mice demonstrated spontaneous chromosome breakage and increased sensitivity to mitomycin C and, to a lesser extent, ionizing radiation. Fancg(-/-) lymphocytes had a defect in the FA pathway, based on their failure to activate the monoubliquitination of the downstream Fancd2 protein in response to IR. Finally, Fancg(-/-) mice had decreased fertility and abnormal gonadal histology. In conclusion, disruption of the Fancg gene confirms the role of Fancg in the FA pathway. The Fancg(-/-) mouse may be useful as an animal model for future gene therapy and cancer susceptibility studies. (Blood. 2001;98:3435-3440) (C) 2001 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [P01-HL54785-04, R01-HL52725-04, UO1-HL66678]; NIAID NIH HHS [R01-AI27849]; NIDDK NIH HHS [R01-DK43889-09] NR 40 TC 87 Z9 87 U1 1 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 DEC 1 PY 2001 VL 98 IS 12 BP 3435 EP 3440 DI 10.1182/blood.V98.12.3435 PG 6 WC Hematology SC Hematology GA 495BV UT WOS:000172321100038 PM 11719385 ER PT J AU Reuter, U Bolay, H Jansen-Olesen, I Chiarugi, A del Rio, MS Letourneau, R Theoharides, TC Waeber, C Moskowitz, MA AF Reuter, U Bolay, H Jansen-Olesen, I Chiarugi, A del Rio, MS Letourneau, R Theoharides, TC Waeber, C Moskowitz, MA TI Delayed inflammation in rat meninges: implications for migraine pathophysiology SO BRAIN LA English DT Article DE migraine; nitroglycerin; inflammation; nitric oxide; macrophages ID NITRIC-OXIDE SYNTHASE; GENE-RELATED PEPTIDE; TRIGEMINAL NUCLEUS CAUDALIS; FACTOR-KAPPA-B; SUPERIOR SAGITTAL SINUS; C-FOS EXPRESSION; DURA-MATER; GLYCERYL TRINITRATE; CHEMICAL-STIMULATION; INDUCED ARTHRITIS AB Nitric oxide (NO) has been implicated in migraine pathogenesis based on the delayed development of typical migraine headache 4-6 h after infusing the NO donor nitroglycerin [glyceryl trinitrate (GTN)] to migraineurs. Furthermore, inhibiting the synthesis of NO by treatment with a NO synthase (NOS) inhibitor attenuates spontaneous migraine headaches in 67% of subjects. Because NO has been linked to inflammation and cytokine expression, we investigated the delayed consequences of brief GTN infusion (30 min) on the development of meningeal inflammation in a rat model using doses relevant to the human model. We found dose-dependent Type II NOS [inducible NOS (iNOS)] mRNA upregulation in dura mater beginning at 2 h and an increase in the corresponding protein expression at 4, 6 and 10 h after infusion. Type II NOS immunoreactivity was expressed chiefly within resident meningeal macrophages. Consistent with development of a delayed inflammatory response, we detected induction of interleukin 1 beta in dura mater at 2 and 6 h and increased interleukin 6 in dural macrophages and in rat cerebrospinal. fluid at 6 h after GTN infusion. Myeloperoxidase-positive cells were rarely found. Leakage of plasma proteins from dural blood vessels was first detected 4 h after GTN infusion, and this was suppressed by administering a specific Type II NOS inhibitor [L-N(6)-(1-iminoethyl)-lysine (L-NIL)]. In addition to cytokine induction, macrophage iNOS upregulation and oedema formation after GTN infusion, dural mast cells exhibited granular changes consistent with secretion at 4 and 6 h. Because iNOS was expressed in dural macrophages following topical GTN, and in the spleen after intravenous injection, the data suggest that the inflammatory response is mediated by direct actions on the dura and does not develop secondary to events within the brain. Our findings point to the importance of new gene expression and cytokine expression as fundamental to the delayed response following GTN infusion, and support the hypothesis that a similar response develops in human meninges after GTN challenge. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. Tufts Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02111 USA. RP Moskowitz, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, 149 13th St,Room 6403, Charlestown, MA 02129 USA. RI Theoharides, Theoharis/E-5596-2010; Moskowitz, Michael/D-9916-2011; Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 FU NINDS NIH HHS [5P01 NS35611] NR 71 TC 162 Z9 173 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD DEC PY 2001 VL 124 BP 2490 EP 2502 DI 10.1093/brain/124.12.2490 PN 12 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 503MZ UT WOS:000172803400014 PM 11701602 ER PT J AU Lo, EH Singhal, AB Torchilin, VP Abbott, NJ AF Lo, EH Singhal, AB Torchilin, VP Abbott, NJ TI Drug delivery to damaged brain SO BRAIN RESEARCH REVIEWS LA English DT Review DE neuroprotection; stroke; traumatic brain injury; drug delivery ID FOCAL CEREBRAL-ISCHEMIA; ARTERY OCCLUSION; INTRACEREBRAL HEMORRHAGE; NERVOUS-SYSTEM; BLOOD-FLOW; RAT-BRAIN; IN-VIVO; MATRIX METALLOPROTEINASES; BARRIER PERMEABILITY; SERINE PROTEASES AB Drug delivery to the brain poses unique challenges. Specialized anatomic and physiological features of the cerebrovasculature and cerebral tissue fluids result in barriers which significantly restrict delivery of a wide range of possible therapeutic agents. In addition to these normal restrictions to brain drug delivery, pathophysiological features and sequelae of acute brain injury will also impact upon the efficiency of drug delivery. This review is focused on acutely damaged brain that occurs after stroke and trauma. Pathophysiological events that may influence drug delivery include blood-brain barrier disruptions, blood flow alterations, edema and increased intracranial pressure, metabolic perturbations, and altered profiles of gene expression and protein synthesis. Careful consideration of these obstacles will provide a framework for further research into the optimization of drug delivery strategies into damaged brain. Without a rigorous assessment of these issues, it may not be possible to translate our mechanistic understanding of acute brain injury into successful clinical therapies. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Neuroprotect Res Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. Northeastern Univ, Dept Pharmaceut Sci, Boston, MA 02115 USA. Univ London Kings Coll, GKT Sch Biomed Sci, Neurosci Res Ctr, BBB Grp, London WC2R 2LS, England. RP Lo, EH (reprint author), Harvard Univ, Sch Med, Neuroprotect Res Lab, MGH East 149-2322, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [R01-HL55519]; NIGMS NIH HHS [R01-GM60200]; NINDS NIH HHS [R01-NS37074, R01-NS38731, R01-NS40529] NR 85 TC 69 Z9 69 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 J9 BRAIN RES REV JI Brain Res. Rev. PD DEC PY 2001 VL 38 IS 1-2 BP 140 EP 148 AR PII S0165-0173(01)00083-2 DI 10.1016/S0165-0173(01)00083-2 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 521RJ UT WOS:000173855100007 PM 11750930 ER PT J AU Husson, H Carideo, EG Cardoso, AA Lugli, SM Neuberg, D Munoz, O de Leval, L Schultze, J Freedman, AS AF Husson, H Carideo, EG Cardoso, AA Lugli, SM Neuberg, D Munoz, O de Leval, L Schultze, J Freedman, AS TI MCP-1 modulates chemotaxis by follicular lymphoma cells SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE chemokine; MCP-1; B cell; lymphoma; follicular dendritic cell ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; CHRONIC LYMPHOCYTIC-LEUKEMIA; GROWTH-STIMULATING FACTOR; CHEMOKINE RECEPTOR CXCR3; MALIGNANT B-CELLS; DENDRITIC CELLS; GERMINAL CENTER; MONOCLONAL-ANTIBODY; MOLECULAR-CLONING; LYMPHOTOXIN-BETA AB The localization and establishment of follicular lymphoma (FL) cells in distinct anatomic sites probably involves chemokine and adhesion receptors on the neoplastic cells and appropriate chemokines and adhesion receptor ligands in the microenvironment. Several chemokines play an important role in normal B-cell trafficking and differentiation. Monocyte chemoattractant protein-1 (MCP-1) is a C-C chemokine that induces chemotaxis of a variety of lymphoid cells through its receptor CCR2. CCR2 is also expressed on B cells, and MCP-1 induces chemotaxis of normal B cells. In this report, we investigated expression and function of CCR2 on FL cells. We found FL cells as well as the t(14; 18)(+) B-cell lymphoma line H2 expressed CCR2. MCP-1 potentiated SDF-1-induced chemotaxis of Fl, cells and H2 cells, but MCP-1 alone did not induce chemotaxis. The specificity of the effects of MCP-1 and SDF-1 was demonstrated by antibody blocking studies, Because FL cells are generally associated with follicular dendritic cells (FDCs), FDCs may be an important source of chemokines. We found that cultured FDCs produced MCP-1, and this production was enhanced by tumour necrosis factor. These data implicate MCP-1 in the migration and localization of FL cells. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Freedman, AS (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 [CA66996] NR 67 TC 20 Z9 20 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2001 VL 115 IS 3 BP 554 EP 562 DI 10.1046/j.1365-2141.2001.03145.x PG 9 WC Hematology SC Hematology GA 503NQ UT WOS:000172804900009 PM 11736935 ER PT J AU Vlahakes, GJ AF Vlahakes, GJ TI Haemoglobin solutions in surgery SO BRITISH JOURNAL OF SURGERY LA English DT Editorial Material ID BOVINE HEMOGLOBIN; SUBSTITUTES; EFFICACY; MODEL C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Vlahakes, GJ (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,BUL119, Boston, MA 02114 USA. NR 10 TC 1 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1323 J9 BRIT J SURG JI Br. J. Surg. PD DEC PY 2001 VL 88 IS 12 BP 1553 EP 1555 DI 10.1046/j.0007-1323.2001.01954.x PG 3 WC Surgery SC Surgery GA 500KY UT WOS:000172627400001 PM 11736963 ER PT J AU Jenike, MA AF Jenike, MA TI An update on obsessive-compulsive disorder SO BULLETIN OF THE MENNINGER CLINIC LA English DT Article; Proceedings Paper CT 22nd Annual Menninger Winter Psychiatry Conference CY MAR 05-10, 2000 CL PARK CITY, UTAH ID FLUOXETINE-TREATED PATIENTS; GLUCOSE METABOLIC-RATE; DOUBLE-BLIND; CONTROLLED TRIAL; FLUVOXAMINE; CLOMIPRAMINE; EFFICACY; AUGMENTATION; INHIBITORS; BUSPIRONE AB Tt is now recognized that obsessive-compulsive disorder (OCD) affects almost 3 % of the world's population and is a major worldwide health problem. Much has been learned in the past 2 decades about the treatment of these disorders. Recent developments in neuroimaging techniques have led to a better understanding of the biology of OCD and the brain circuits that may be involved in the production of symptoms. The most effective treatment approaches, based on controlled data, are behavior therapy consisting of exposure and response prevention and specific medications. Although controversial, more invasive neurosurgical and neurostimulation approaches may hold some promise for severely disabled patients. Despite impressive research efforts, a small minority of patients remain refractory to treatment. Future clinical research should focus on this refractory group. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Jenike, MA (reprint author), Massachusetts Gen Hosp, CNY-9,Bldg 149-13th St, Charlestown, MA 02129 USA. NR 61 TC 27 Z9 27 U1 2 U2 3 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0025-9284 J9 B MENNINGER CLIN JI Bull. Menninger Clin. PD WIN PY 2001 VL 65 IS 1 BP 4 EP 25 DI 10.1521/bumc.65.1.4.18714 PG 22 WC Psychiatry; Psychology, Psychoanalysis SC Psychiatry; Psychology GA 414AG UT WOS:000167643300002 PM 11280957 ER PT J AU Tramontina, S Martins, S Michalowski, MB Ketzer, CR Eizirik, M Biederman, J Rohde, LA AF Tramontina, S Martins, S Michalowski, MB Ketzer, CR Eizirik, M Biederman, J Rohde, LA TI School dropout and conduct disorder in Brazilian elementary school students SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Article DE school dropout; conduct disorder; absenteeism ID ADOLESCENTS; CHILDREN; RISK; SAMPLE; ADHD AB Objectives: To evaluate the association between DSM-IV conduct disorder (CD) and school dropout in a sample of students from the third and fourth elementary grades at state schools in the capital of the southermost state of Brazil. Methods: In this case-control study, students that dropped out of schools (h = 44) and a control group who continued attending schools (n = 44) were assessed for CD and other prevalent mental disorders, using the Schedule for Affective Disorders and Schizophrenia for School Age Children, Epidemiological Version (K-SADS-E). Results: The prevalence of DSM-IV CD was significantly higher in the school-dropout group than in control subjects (P < 0.001), both in the entire sample and in a subsample including only subjects under age 12 years (P = 0.001). Also, the odds ratio (OR)for school dropout was significantly higher in the presence of DSM-IV CD, even after controlling for potential confounding factors (age, estimated IQ, school repetition, family, structure, and income) (P < 0. 01). Conclusion: Our results extend to children and young adolescents previous findings from studies of older adolescents, suggesting an association between school dropout and CD. C1 Hosp Clin Porto Alegre, Serv Psiquiatria Infancia & Adolescencia, BR-90035003 Porto Alegre, RS, Brazil. Univ Fed Rio Grande Sul, Porto Alegre, RS, Brazil. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Unit, Boston, MA USA. RP Tramontina, S (reprint author), Hosp Clin Porto Alegre, Serv Psiquiatria Infancia & Adolescencia, Rua Ramiro Barcelos 2350, BR-90035003 Porto Alegre, RS, Brazil. RI Rohde, Luis Augusto/A-6426-2008; Michalowski, Mariana/D-5546-2014 OI Rohde, Luis Augusto/0000-0002-4552-4188; Michalowski, Mariana/0000-0002-9482-0776 NR 28 TC 21 Z9 24 U1 1 U2 3 PU CANADIAN PSYCHIATRIC ASSOC PI OTTAWA PA 260-441 MACLAREN ST, OTTAWA, ONTARIO K2H 2P3, CANADA SN 0706-7437 J9 CAN J PSYCHIAT JI Can. J. Psychiat.-Rev. Can. Psychiat. PD DEC PY 2001 VL 46 IS 10 BP 941 EP 947 PG 7 WC Psychiatry SC Psychiatry GA 508QH UT WOS:000173099800006 PM 11816315 ER PT J AU Vonderheide, RH Schultze, JL Anderson, KS Maecker, B Butler, MO Xia, ZN Kuroda, MJ von Bergwelt-Baildon, MS Bedor, MM Hoar, KM Schnipper, DR Brooks, MW Letvin, NL Stephans, KF Wucherpfennig, KW Hahn, WC Nadler, LM AF Vonderheide, RH Schultze, JL Anderson, KS Maecker, B Butler, MO Xia, ZN Kuroda, MJ von Bergwelt-Baildon, MS Bedor, MM Hoar, KM Schnipper, DR Brooks, MW Letvin, NL Stephans, KF Wucherpfennig, KW Hahn, WC Nadler, LM TI Equivalent induction of telomerase-specific cytotoxic T lymphocytes from tumor-bearing patients and healthy individuals SO CANCER RESEARCH LA English DT Article ID REVERSE-TRANSCRIPTASE; DENDRITIC CELLS; HUMAN CANCER; MELANOMA; INHIBITION; EXPRESSION; RESPONSES; IMMUNITY; TISSUES; VIVO AB Although high frequencies of T lymphocytes specific for certain tumor-associated antigens have been detected in some cancer patients, increasing evidence suggests that these T cells may be functionally defective in vivo and fail to induce meaningful clinical responses. One strategy to overcome this limitation is to target novel antigens that are ignored during the natural antitumor immune response but are nevertheless capable of triggering effector T-cell responses against tumors after optimal presentation by antigen-presenting cells. Here, we show that the telomerase catalytic subunit (hTERT)-a nearly universal tumor antigen identified by epitope deduction rather than from patient immune responses-is immunologically ignored by patients despite progressive tumor burden. Nevertheless, HLA-A2-restricted CTLs against hTERT are equivalently induced ex vivo from patients and healthy individuals and efficiently kill human tumor cell lines and primary tumors. Thus, telomerase-specific T cells from cancer patients are spared functional inactivation because of immunological ignorance. These findings support clinical efforts to target the hTERT as a tumor antigen with broad therapeutic potential. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Vonderheide, RH (reprint author), Univ Penn, Sch Med, Abramson Family Canc Res Inst, 551 BRB II-III,421 Curie Blvd, Philadelphia, PA 19104 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 FU NCI NIH HHS [P01-CA-66996]; NIAID NIH HHS [AI-20729] NR 18 TC 74 Z9 80 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 DEC 1 PY 2001 VL 61 IS 23 BP 8366 EP 8370 PG 5 WC Oncology SC Oncology GA 499WX UT WOS:000172594600003 PM 11731409 ER PT J AU Wilson, JB Johnson, MA Stuckert, AP Trueman, KL May, S Bryant, PE Meyn, RE D'Andrea, AD Jones, NJ AF Wilson, JB Johnson, MA Stuckert, AP Trueman, KL May, S Bryant, PE Meyn, RE D'Andrea, AD Jones, NJ TI The Chinese hamster FANCG/XRCC9 mutant NM3 fails to express the monoubiquitinated form of the FANCD2 protein, is hypersensitive to a range of DNA damaging agents and exhibits a normal level of spontaneous sister chromatid exchange SO CARCINOGENESIS LA English DT Article ID FANCONI-ANEMIA PROTEIN; RAY-SENSITIVE MUTANTS; DOUBLE-STRAND BREAKS; GROUP-G GENE; COMPLEMENTATION GROUP; CELL MUTANTS; MITOMYCIN-C; IONIZING-RADIATION; CHROMOSOMAL INSTABILITY; ATAXIA-TELANGIECTASIA AB Fanconi anemia (FA) is a human autosomal disorder characterized by cancer susceptibility and cellular sensitivity to DNA crosslinking agents such as mitomycin C and diepoxybutane. Six FA genes have been cloned including a gene designated XRCC9 (for X-ray Repair Cross Complementing), isolated using a mitomycin C-hypersensitive Chinese hamster cell mutant termed UV40, and subsequently found to be identical to FANCG. A nuclear complex containing the FANCA, FANCC, FANCE, FANCF and FANCG proteins is needed for the activation of a sixth FA protein FANCD2. When monoubiquitinated, the FANCD2 protein co-localizes with the breast cancer susceptibility protein BRCA1 in DNA damage induced foci. In this study, we have assigned NM3, a nitrogen mustard-hypersensitive Chinese hamster mutant to the same genetic complementation group as UV40. NM3, like human FA cell lines (but unlike UV40) exhibits a normal spontaneous level of sister chromatid exchange. We show that both NM3 and UV40 are also hypersensitive to other DNA crosslinking agents (including diepoxybutane and chlorambucil) and to non-crosslinking DNA damaging agents (including bleomycin, streptonigrin and EMS), and that all these sensitivities are all corrected upon transfection of the human FANCG/XRCC9 cDNA. Using immunoblotting, NM3 and UV40 were found not to express the active monoubiquitinated isoform of the FANCD2 protein, although expression of the FANCD-L isoform was restored in the FANCG cDNA transformants, correlating with the correction of mutagen-sensitivity. These data indicate that cellular resistance to these DNA damaging agents requires FANCG and that the FA gene pathway, via its activation of FANCD2 and that protein's subsequent interaction with BRCA1, is involved in maintaining genomic stability in response not only to DNA interstrand crosslinks but also a range of other DNA damages including DNA strand breaks. NM3 and other `FA-like' Chinese hamster mutants should provide an important resource for the study of these processes in mammalian cells. C1 Univ Liverpool, Sch Biol Sci, Donnan Labs, Mammalian DNA Repair Lab, Liverpool L69 7ZD, Merseyside, England. Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ St Andrews, Sch Biomed Sci, St Andrews KY16 9TS, Fife, Scotland. Univ Texas, MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA. RP Jones, NJ (reprint author), Univ Liverpool, Sch Biol Sci, Donnan Labs, Mammalian DNA Repair Lab, Liverpool L69 7ZD, Merseyside, England. RI Jones, Nigel/D-1997-2010 NR 63 TC 32 Z9 32 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 2001 VL 22 IS 12 BP 1939 EP 1946 DI 10.1093/carcin/22.12.1939 PG 8 WC Oncology SC Oncology GA 510NX UT WOS:000173215100004 PM 11751423 ER PT J AU Juarranz, MG Bolanos, O Gutierrez-Canas, I Lerner, EA Robberecht, P Carmena, MJ Prieto, JC Rodriguez-Henche, N AF Juarranz, MG Bolanos, O Gutierrez-Canas, I Lerner, EA Robberecht, P Carmena, MJ Prieto, JC Rodriguez-Henche, N TI Neuroendocrine differentiation of the LNCaP prostate cancer cell line maintains the expression and function of VIP and PACAP receptors SO CELLULAR SIGNALLING LA English DT Article DE neuroendocrine cells; transdifferentiation; prostate cancer; cAMP; VIP receptors; PACAP receptors ID CYCLASE-ACTIVATING POLYPEPTIDE; VASOACTIVE-INTESTINAL-PEPTIDE; RAT VENTRAL PROSTATE; BENIGN HYPERPLASTIC PROSTATE; ISOLATED EPITHELIAL-CELLS; ADENYLATE-CYCLASE; MOLECULAR-CLONING; SPLICE VARIANTS; SIGNAL-TRANSDUCTION; CARCINOMA-CELLS AB The molecular mechanisms involved in differentiation of prostate cancer cells to a neuroendocrine (NE) cell phenotype are not well understood. Here we used the androgen-dependent human prostate cancer cell line LNCaP to perform a systematic and broad analysis of the expression, pharmacology, and functionality of vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating peptide (PACAP) receptors. Reverse transcription polymerase chain reaction experiments, together with pharmacological approaches with a set of specific agonists and antagonists, demonstrated the presence of the three VIP/PACAP receptor subtypes (PAC(1), VPAC(1). and VPAC(2)) with a major role for VPAC(1), acting through adenylate cyclase (AC) stimulation. An essentially similar pattern was observed by NE differentiated cells (4 days after serum deprivation) in spite of the important morphological changes observed. However, the expression of the prostate-specific antigen (PSA) decreased in NE cells (and increased again by dihydrotestosterone, DHT, treatment). The present demonstration of the induction of NE transdifferentiation in LNCaP cells by increasing concentrations of VIP adds value to previous observations on the role of cAMP in this process, an interesting topic in the comprehension of the molecular changes that are involved in the progression of prostate cancer to androgen independence. (C) 2001 Elsevier Science Inc. Ail rights reserved. C1 Univ Alcala de Henares, Dept Biochem & Mol Biol, E-28871 Alcala De Henares, Spain. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Charlestown, MA 02129 USA. Free Univ Brussels, Sch Med, Dept Biochem & Nutr, B-1070 Brussels, Belgium. RP Prieto, JC (reprint author), Univ Alcala de Henares, Dept Biochem & Mol Biol, E-28871 Alcala De Henares, Spain. RI Carmena, Maria Jose/I-3198-2015; Gutierrez-Canas, Irene/H-8754-2016 OI Carmena, Maria Jose/0000-0002-5602-0014; Gutierrez-Canas, Irene/0000-0003-0678-3619 NR 49 TC 30 Z9 30 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD DEC PY 2001 VL 13 IS 12 BP 887 EP 894 DI 10.1016/S0898-6568(01)00199-1 PG 8 WC Cell Biology SC Cell Biology GA 495UX UT WOS:000172359700004 PM 11728828 ER PT J AU Hess, D AF Hess, D TI Ventilator modes used in weaning SO CHEST LA English DT Article DE mechanical ventilation; noninvasive positive pressure ventilation; pressure support ventilation; spontaneous breathing trial; synchronized intermittent mandatory ventilation; weaning ID INTERMITTENT MECHANICAL VENTILATION; PRESSURE-SUPPORT VENTILATION; RESPIRATORY-FAILURE; MOISTURE EXCHANGERS; TRIAL; HEAT; EXTUBATION; DURATION; OUTPUT; TUBE AB Weaning techniques include spontaneous breathing trials (SBTs), pressure-support ventilation (PSV), and synchronized intermittent mandatory ventilation (SIMV). SBTs can be conducted using one of several approaches, including T-piece breathing, low-level continuous positive airway pressure, low-level PSV, or setting the ventilator to flow-triggering with no pressure applied to the airway. The SBT can be used as a method to identify extubation readiness or as a weaning technique in which the duration of the trial is gradually increased over time. With pressure-support weaning, the level of pressure support is gradually reduced over time. With weaning using SIMV, the mandatory, rate setting on the ventilator is gradually reduced. Randomized controlled trials have reported the poorest weaning outcomes using SIMV. Although new ventilator modes have been introduced to facilitate weaning, to date there is no evidence to support the use of these modes. Noninvasive positive-pressure ventilation also has been reported to facilitate weaning, but the ability to generalize these findings remains to be determined. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hess, D (reprint author), Massachusetts Gen Hosp, Ellison 401,55 Fruit St, Boston, MA 02114 USA. NR 20 TC 14 Z9 22 U1 1 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 2001 VL 120 IS 6 SU S BP 474S EP 476S DI 10.1378/chest.120.6_suppl.474S PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 506KQ UT WOS:000172970100010 PM 11742968 ER PT J AU Khodadadyan-Klostermann, C Kandziora, F Schnake, KJ Lewandrowski, KU Wise, D Weiler, A Haas, NP AF Khodadadyan-Klostermann, C Kandziora, F Schnake, KJ Lewandrowski, KU Wise, D Weiler, A Haas, NP TI Biomechanical comparison of biodegradable lumbar interbody fusion cages SO CHIRURG LA German DT Article DE spine; lumbar spine; biomechanics; cages; biodegradable cages; biodegradable materials; PDLLA; intervertebral implant ID POLYLACTIC ACID; SPINAL-FUSION; SYSTEM; DEGRADATION; INSTABILITY; FIXATION; IMPLANTS; PLATE AB Introduction: A biodegradable interbody cage for lumbar spine fusion would be able to solve several problems associated with the use of metallic cages. In a biomechanical in vitro study using human lumbar spines three different biodegradable poly(L-lactide-co-D,L-lacitide)(PLDLLA) cages were compared to metallic cages of the same design. Material and method: 40 human cadaver lumbar specimens (L3-S1) were tested in flexion, extension, rotation, and bending with a non-destructive flexibility method using a nonconstrained testing apparatus. Seven different groups were examined: (1) control group (intact) (n = 40); (2) unstable group (after discectomy L4/5) (n = 40), (3) autologous iliac crest bone graft (n = 8), (4) BAK-Cage (n = 8), (5) BIO-Cage 1 (PLDLLA) (n = 8), (6) BIO-Cage 2 (PLDLLA/hydroxylapatite-buffer) (n = 8) and (7) BIO-Cage 3 (PLDLLA /hydroxylapatite particles of different size) (n = 8). Additionally, destructive compression tests of all implants were performed. Results: In comparison to the intact motion segment all cages showed significantly lower range of motion (ROM) in all test modes (P < 0.01). There was no significant difference in stiffness values and ROM between BIO-Cages and metallic cages. Axial compression stiffness and failure load were significantly highest for metallic BAK-cages (P < 0.05). No significant difference for failure load was observed between BIO-cage 1 and the intact motion segment. However, in comparison to the intact motion segment failure load was significantly lower for BIO-cage 2 and 3 (P < 0,05). Conclusion: The results of this study are encouraging, because the biodegradable cages were able to limit lumbar spine motion similar to the metallic cages. Especially, the biodegradable PLDLLA cage consisting of pure polymer (BIO-Cage 1) showed adequate initial compression strength. However, further in vivo animal experiments are essential prior to the clinical application of biodegradable lumbar interbody fusion cages. C1 Humboldt Univ, Univ Klinikum, Charite, D-13353 Berlin, Germany. Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA USA. RP Khodadadyan-Klostermann, C (reprint author), Humboldt Univ, Univ Klinikum, Charite, Augustenburgerpl 1,Campus Virchow Klinkum, D-13353 Berlin, Germany. NR 38 TC 5 Z9 5 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0009-4722 J9 CHIRURG JI Chirurg PD DEC PY 2001 VL 72 IS 12 BP 1431 EP 1438 PG 8 WC Surgery SC Surgery GA 506CW UT WOS:000172953200007 PM 11824028 ER PT J AU Weber, GF Cantor, H AF Weber, GF Cantor, H TI Differential roles of osteopontin/Eta-1 in early and late lpr disease SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE lymphoproliferation; immunoglobulin; osteopontin; knockout mase ID MRL-LPR/LPR MICE; NERVOUS-SYSTEM DISEASE; AUTOIMMUNE-DISEASE; MRL/LPR MICE; ETA-1; GENE; CYTOKINE; AUTOANTIBODIES; LYMPHOCYTES; EXPRESSION AB The cytokine osteopontin (Eta-1) leads to macrophage-dependent polyclonal B-cell activation and is induced early in autoimmune prone mice with the lpr mutation, suggesting a significant pathogenic role for this molecule. Indeed, C57BL/6-Fas(lpr/lpr) mice crossed with osteopontin(-/-) mice display delayed onset of polyclonal B-cell activation, as judged by serum immunoglobulin levels. In contrast, they are subject to normal onset, but late exacerbation of lymphoproliferation and evidence of kidney disease. These observations define two stages of Fas(lpr/lpr) disease with respect to osteopontin-dependent pathogenesis that should be taken into account in the design of therapeutic approaches to the clinical disease. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Weber, GF (reprint author), Tufts Univ New England Med Ctr, Dept Radiat Oncol, 750 Washington St,NEMC 824, Boston, MA 02111 USA. FU NCI NIH HHS [CA76176, R29 CA076176]; PHS HHS [A137833] NR 22 TC 24 Z9 24 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD DEC PY 2001 VL 126 IS 3 BP 578 EP 583 DI 10.1046/j.1365-2249.2001.01702.x PG 6 WC Immunology SC Immunology GA 549GY UT WOS:000175437200031 PM 11737079 ER PT J AU DeFrate, LE Li, G Zayontz, SJ Herndon, JH AF DeFrate, LE Li, G Zayontz, SJ Herndon, JH TI A minimally invasive method for the determination of force in the interosseous ligament SO CLINICAL BIOMECHANICS LA English DT Article ID FOREARM; MEMBRANE AB Objective. The objective was to develop and utilize a minimally invasive testing system to determine the force in the interosseous ligament under axial compressive loads across the range of motion of the human forearm. Design. Eleven fresh frozen human cadaveric forearms were used (51-72 years). Background. Current studies investigating interosseous ligament forces altered the structure of the forearm by implanting load cells into the radius and ulna. This may affect load transfer through the forearm. Little information was available on interosseous ligament function over the entire flexion range of the elbow. Methods. A robotic joint testing system was used to apply a 100 N compressive load to the forearm and measure the resulting displacement. Each forearm was tested with no disruption of the bones and soft tissues or the forearm. The principle of superposition was used to calculate the forces in the interosseous ligament and was indirectly validated using fluoroscopy. Results. The force in the interosseous ligament ranged from a minimum of 8 N in neutral forearm rotation at full extension to a maximum of 43 N in supination at 30 degrees of flexion. The largest force was found in supination at all flexion angles. Conclusions. The interosseous ligament is an important structure in the stability of the forearm. The force in the interosseous ligament depends on the elbow flexion angle and forearm rotation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Orthopaed Biomech Lab, Beth Israel Deaconess Med Ctr, Boston, MA USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Orthopaed Biomech Lab, Beth Israel Deaconess Med Ctr, Boston, MA USA. NR 17 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0268-0033 J9 CLIN BIOMECH JI Clin. Biomech. PD DEC PY 2001 VL 16 IS 10 BP 895 EP 900 DI 10.1016/S0268-0033(01)00092-4 PG 6 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA 497UV UT WOS:000172474600005 PM 11733127 ER PT J AU Fidias, P Supko, JG Martins, R Boral, A Carey, R Grossbard, M Shapiro, G Ostler, P Lucca, J Johnson, BE Skarin, A Lynch, TJ AF Fidias, P Supko, JG Martins, R Boral, A Carey, R Grossbard, M Shapiro, G Ostler, P Lucca, J Johnson, BE Skarin, A Lynch, TJ TI A phase II study of weekly paclitaxel in elderly patients with advanced non-small cell lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID LIQUID-CHROMATOGRAPHIC ASSAY; TRIAL COMPARING CISPLATIN; METASTATIC BREAST-CANCER; SOUTHWEST-ONCOLOGY-GROUP; PLUS VINORELBINE; OVARIAN-CANCER; HUMAN-PLASMA; GEMCITABINE; CHEMOTHERAPY; PHARMACOKINETICS AB Purpose: Our aim was to evaluate the efficacy, toxicity, and pharmacokinetic behavior of single-agent paclitaxel given weekly to elderly patients with lung cancer. Experimental Design: Previously untreated patients with stage IIIB/IV non-small cell lung cancer were eligible for the study if they were at least 70 years of age and had preserved organ function. Paclitaxel was administered over 1 h at a dose of 90 mg/m(2) for 6 consecutive weeks on an 8-week cycle. The pharmacokinetics of paclitaxel were assessed during the first and sixth week of therapy in a subgroup of eight patients. Results: A total of 35 patients (median age, 76 years; range, 70-85) were enrolled. The overall response rate was 23%. Median time to failure was 5.2 months, whereas the median survival time was 10.3 months. Survival rates after 1 and 2 years were 45 and 22%, respectively. Grade 3/4 toxicities included neutropenia (5.8%), hyperglycemia (17.6%), neuropathy (5.8%), and infection (8.8%). Two patients died from treatment-related toxicity. There was no significant difference (P = 0.18) between the total body clearance of paclitaxel on the first (17.4 +/- 2.9 liters/h/m(2), mean +/- SD) and sixth (15.8 +/- 4.1 liters/h/m(2)) week of therapy. Conclusion: Paclitaxel administered as a weekly 1-h infusion at a dose of 90 mg/m(2) is a safe and effective therapy for elderly patients with advanced non-small cell lung cancer. Its pharmacokinetics in elderly patients do not appear to differ from historical data for younger patients, and there was no suggestion of a change in drug clearance after repeated weekly dosing. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Dept Adult Oncol,Dana Farber Canc Inst, Boston, MA 02114 USA. RP Fidias, P (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 100 Blossom St,Cox 201, Boston, MA 02114 USA. NR 53 TC 76 Z9 81 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 DEC PY 2001 VL 7 IS 12 BP 3942 EP 3949 PG 8 WC Oncology SC Oncology GA 505UK UT WOS:000172933800013 PM 11751486 ER PT J AU Coghlan, ME Sommadossi, JP Jhala, NC Many, WJ Saag, MS Johnson, VA AF Coghlan, ME Sommadossi, JP Jhala, NC Many, WJ Saag, MS Johnson, VA TI Symptomatic lactic acidosis in hospitalized antiretroviral-treated patients with human immunodeficiency virus infection: A report of 12 cases SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the Infectious-Diseases-Society-of-America CY SEP 07-10, 2000 CL NEW ORLEANS, LOUISIANA SP Infect Dis Soc Amer ID REVERSE-TRANSCRIPTASE INHIBITORS; MITOCHONDRIAL-DNA; NUCLEOSIDE ANALOG; HEPATIC STEATOSIS; TOXICITY; ZIDOVUDINE; CELLS; DEPLETION; STAVUDINE; FAILURE AB We retrospectively investigated the clinical and histopathologic features of hospitalized patients infected with human immunodeficiency virus who had symptomatic lactic acidosis syndrome at a university teaching hospital during 1995-2000. Twelve patients were identified, 11 during 1998-2000; of these, 5 died with rapid progression to otherwise unexplained multiple-organ failure. All had extensive prior exposure to nucleoside analog reverse-transcriptase inhibitors (NRTIs). At presentation, the most commonly identified NRTI component of antiretroviral regimens was stavudine plus didanosine. Eleven patients presented with abdominal pain, nausea, and/or emesis. Eight patients had prior acute weight loss (mean [+/- SD],12 +/- 5.3 kg). Median venous plasma lactate levels were greater than or equal to2-fold greater than the upper limit of normal (2.1 mmol/L). Serum transaminase levels were near normal limits at presentation. Histopathologic studies confirmed hepatic macrovesicular and microvesicular steatosis in 6 patients. Concurrent chemical pancreatitis was identified in 6 patients. The increasing number of cases identified during the study period suggests that physicians better recognize symptomatic lactic acidosis and/or that cumulative NRTI exposure may increase the risk for this syndrome. C1 Univ Alabama, Sch Med, Div Infect Dis, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Sch Med, Dept Pharmacol & Toxicol, Birmingham, AL USA. Univ Alabama, Sch Med, Dept Anat Pathol, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Johnson, VA (reprint author), Univ Alabama, Sch Med, Div Infect Dis, Dept Med, THT 229,1530 3rd Ave S, Birmingham, AL 35294 USA. FU NHLBI NIH HHS [SK30 HL04146-03]; NIAID NIH HHS [1-RO1-AI40876, 5P30 AI27767-14, 1-RO1-AI33239] NR 26 TC 72 Z9 74 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 1 PY 2001 VL 33 IS 11 BP 1914 EP 1921 DI 10.1086/323783 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 489NX UT WOS:000171998800018 PM 11692304 ER PT J AU Harris, WH AF Harris, WH TI Wear and periprosthetic osteolysis - The problem SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT 7th Open Meeting of the Hip-Society/American-Association-of-Hip-and-Knee-Surgeons CY MAR 03, 2001 CL SAN FRANCISCO, CA SP Hip Soc, Amer Assoc Hip & Knee Surg ID CEMENTING TECHNIQUES; FEMORAL COMPONENT; HIP-ARTHROPLASTY; REPLACEMENT AB The dominant long-term problem in total hip replacement surgery, and an important problem in total knee replacement surgery, is wear of the polyethylene and its resulting periprosthetic osteolysis. Several of the key features of this unique disease are presented focusing on the importance of periprosthetic osteolysis, comprehension of the general progressive nature of periprosthetic osteolysis, understanding of the diverse radiographic evidence of this disease, and the consequences that can occur from the disease. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. NR 25 TC 208 Z9 222 U1 3 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 2001 IS 393 BP 66 EP 70 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 498CZ UT WOS:000172493400008 PM 11764372 ER PT J AU Raisch, DW Troutman, WG Sather, MR Fudala, PJ AF Raisch, DW Troutman, WG Sather, MR Fudala, PJ TI Variability in the assessment of adverse events in a multicenter clinical trial SO CLINICAL THERAPEUTICS LA English DT Article DE adverse events; clinical investigations; research ID DRUG-REACTIONS; JUDGMENTS AB Background: Consistent documentation, characterization, and evaluation of adverse events (AEs) are needed during multicenter clinical trials to ensure accuracy of data reported to the US Food and Drug Administration and in the medical literature. Objective: The purpose of this study was to identify and characterize variations in the assessment of AEs by clinical trial personnel. Methods: During the annual meeting of personnel from a multicenter, controlled clinical trial of an investigational new drug treatment for opioid dependence, an oral presentation of procedures for AE data collection was given to 25 principal investigators and ancillary study personnel who assessed AEs for the study. A post-test using 3 hypothetical AE cases in which AEs were categorized by type of reaction, relatedness to study drug, severity, action taken, and outcome was completed by study participants. Cases and expected responses were reviewed for content and validity by clinical research pharmacists who were not involved with the study. The level of agreement with expected responses was assessed using McNemar symmetry chi-square tests. Results: Assessments of type of AE, relatedness to study drug, and severity were less frequently aligned with expected responses than were action taken and outcome (P < 0.013). Less consistency with expected responses was found in 1 case than in the other 2, suggesting that certain types of AEs may be more difficult to assess. Conclusions: There was considerable variability in categorization of AEs in an exercise following training for AE data collection. Type of report, relatedness, and severity were found to have more variability in reporting than did action taken or outcome. The results suggest that unless data are gathered to verify reliability of reporting, subcategorization of AE data should be undertaken cautiously. Further research is needed regarding methods for improving consistency in reporting of AEs. C1 Dept Vet Affairs, Cooperat Studies Program, Clin Res Pharm Coordinating Ctr, Albuquerque, NM 87106 USA. Univ New Mexico, Coll Pharm, Albuquerque, NM 87131 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Raisch, DW (reprint author), Dept Vet Affairs, Cooperat Studies Program, Clin Res Pharm Coordinating Ctr, 2401 Ctr SE, Albuquerque, NM 87106 USA. NR 19 TC 18 Z9 18 U1 2 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD DEC PY 2001 VL 23 IS 12 BP 2011 EP 2020 DI 10.1016/S0149-2918(01)80153-3 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 509KA UT WOS:000173145900008 PM 11813935 ER PT J AU Moskowitz, MA Reuter, U Waeber, C AF Moskowitz, MA Reuter, U Waeber, C TI Emerging concepts in migraine pathophysiology SO CONFINIA CEPHALALGICA LA English DT Article; Proceedings Paper CT 10th Congress of the International-Headache-Society (IHC 2001) CY JUN 29-JUL 02, 2001 CL NEW YORK, NEW YORK SP Int Headache Soc DE cortical spreading depression; imaging; migraine pathophysiology; sensitization; serotonin receptors ID PLASMA-PROTEIN EXTRAVASATION; HUMAN CORONARY-ARTERIES; CUTANEOUS ALLODYNIA; TRIGEMINAL NEURONS; ERGOT ALKALOIDS; DURA MATER; RAT; STIMULATION; RECEPTOR; SUMATRIPTAN AB This review briefly focuses on recent developments in migraine research with emphasis on new imaging techniques including Blood Oxygenation Level-Dependent (BOLD) functional MR and Laser Speckle Imaging. The importance of cortical spreading depression and sensitization will also be addressed as will the importance of serotonin receptors in acute migraine treatment. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RI Moskowitz, Michael/D-9916-2011; Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 NR 32 TC 0 Z9 0 U1 0 U2 0 PU MASSON DIVISIONE PERIODICI PI MILAN PA VIA FRATELLI BRESSAN 2, 20126 MILAN, ITALY SN 1122-0279 J9 CONFIN CEPHALALGICA JI Confin. Cephalalgica PD DEC PY 2001 VL 10 IS 4 BP 171 EP 176 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 539TR UT WOS:000174887500004 ER PT J AU Robertson, CL Bell, MJ Kochanek, PM Adelson, PD Ruppel, RA Carcillo, JA Wisniewski, SR Mi, ZC Janesko, KL Clark, RSB Marion, DW Graham, SH Jackson, EK AF Robertson, CL Bell, MJ Kochanek, PM Adelson, PD Ruppel, RA Carcillo, JA Wisniewski, SR Mi, ZC Janesko, KL Clark, RSB Marion, DW Graham, SH Jackson, EK TI Increased adenosine in cerebrospinal fluid after severe traumatic brain injury in infants and children: Association with severity of injury and excitotoxicity SO CRITICAL CARE MEDICINE LA English DT Article DE head injury; purine; pediatrics; Glasgow Coma Scale; glutamate; shaken baby syndrome; child abuse ID CEREBRAL-BLOOD-FLOW; SEVERE HEAD-INJURY; AMINO-ACID RELEASE; GLUTAMATE-EVOKED RELEASE; ENDOGENOUS ADENOSINE; INTERSTITIAL ADENOSINE; RECEPTOR STIMULATION; NMDA RECEPTORS; FOCAL ISCHEMIA; RAT STRIATUM AB Objectives. To measure adenosine concentration in the cerebrospinal fluid of infants and children after severe traumatic brain injury and to evaluate the contribution of patient age, Glasgow Coma Scale score, mechanism of injury, Glasgow Outcome Score, and time after injury to cerebrospinal fluid adenosine concentrations. To evaluate the relationship between cerebrospinal fluid adenosine and glutamate concentrations in this population. Design. Prospective survey. Setting. Pediatric intensive care unit in a university-based children's hospital. Patients: Twenty-seven critically ill infants and children who had severe traumatic brain injury (Glasgow Coma Scale <8), who required placement of an intraventricular catheter and drainage of cerebrospinal fluid as part of their neurointensive care. Interventions. None. Measurements and Main Results: Patients ranged in age from 2 months to 14 yrs. Cerebrospinal fluid samples (n = 304) were collected from 27 patients during the first 7 days after traumatic brain injury. Control cerebrospinal fluid samples were obtained from lumbar puncture on 21 infants and children without traumatic brain injury or meningitis. Adenosine concentration was measured by using high-pressure liquid chromatography. Adenosine concentration was increased markedly in cerebrospinal fluid of children after traumatic brain injury vs. controls (p < .001). The increase in cerebrospinal fluid adenosine was independently associated with Glasgow Coma Scale less than or equal to4 vs. >4 and time after injury (both p < .005). Cerebrospinal fluid adenosine concentration was not independently associated with either age (less than or equal to4 vs. >4 yrs), mechanism of injury (abuse vs. other), or Glasgow Outcome Score (good/moderately disabled vs. severely disabled, vegetative, or dead). Of the 27 patients studied, 18 had cerebrospinal fluid glutamate concentration previously quantified by high-pressure liquid chromatography. There was a strong association between increases in cerebrospinal fluid adenosine and glutamate concentrations (p < .005) after injury. Conclusions: Cerebrospinal fluid adenosine concentration is increased in a time- and severity-dependent manner in infants and children after severe head injury. The association between cerebrospinal fluid adenosine and glutamate concentrations may reflect an endogenous attempt at neuroprotection against excitotoxicity after severe traumatic brain injury. C1 Univ Pittsburgh, Safar Ctr Resuscitat Res, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Anesthesiol & Crit Care Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Pediat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Publ Hlth, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Ctr Clin Pharmacol, Pittsburgh, PA 15260 USA. Univ Maryland, Dept Pediat, Baltimore, MD 21201 USA. Childrens Natl Med Ctr, Dept Crit Care Med, Washington, DC 20010 USA. Va Pittsburgh Hlth Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. Childrens Hosp Pittsburgh, Gen Clin Res Ctr, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Ctr Injury Control & Res, Pittsburgh, PA USA. RP Kochanek, PM (reprint author), Univ Pittsburgh, Safar Ctr Resuscitat Res, 3434 5th Ave, Pittsburgh, PA 15260 USA. EM kochanekpm@anes.upmc.edu RI Kochanek, Patrick/D-2371-2015; OI Kochanek, Patrick/0000-0002-2627-913X; Wisniewski, Stephen/0000-0002-3877-9860 FU NINDS NIH HHS [NS38087] NR 67 TC 32 Z9 34 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 DEC PY 2001 VL 29 IS 12 BP 2287 EP 2293 DI 10.1097/00003246-200112000-00009 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 505HN UT WOS:000172907500009 PM 11801827 ER PT J AU Dela Rosa, RS Kacmarek, R Matthews, B Haver, K Shubina, M Irving, C Noviski, N AF Dela Rosa, RS Kacmarek, R Matthews, B Haver, K Shubina, M Irving, C Noviski, N TI Correlation of automatic wheeze detection findings with clinical observations in the pediatric intensive care unit SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Karmel Med Technol, Illiit, Israel. 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2001 VL 29 IS 12 SU S MA 368 BP A112 EP A112 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 505PJ UT WOS:000172920900368 ER PT J AU Shahroor-Karni, S Chang, YC Noviski, N AF Shahroor-Karni, S Chang, YC Noviski, N TI Infants with respiratory syncytial virus (RSV) in the pediatric intensive care unit: Predictive factors of four severe outcomes SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2001 VL 29 IS 12 SU S MA 472 BP A143 EP A143 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 505PJ UT WOS:000172920900470 ER PT J AU Todres, ID Catlin, E Thiel, MM Kessler, C AF Todres, ID Catlin, E Thiel, MM Kessler, C TI The intensivist in a spiritual care training program: A clinical pastoral educational fellowship (CPE) SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2001 VL 29 IS 12 SU S MA 249 BP A77 EP A77 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 505PJ UT WOS:000172920900250 ER PT J AU Lassar, AB Orkin, S AF Lassar, AB Orkin, S TI Cell differentiation - Plasticity and commitment - developmental decisions in the life of a cell - Editorial overview SO CURRENT OPINION IN CELL BIOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Lassar, AB (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 240 Longwood Ave, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD DEC PY 2001 VL 13 IS 6 BP 659 EP 661 DI 10.1016/S0955-0674(00)00267-2 PG 3 WC Cell Biology SC Cell Biology GA 491GM UT WOS:000172100700001 ER PT J AU Huynh, KD Lee, JT AF Huynh, KD Lee, JT TI Imprinted X inactivation in eutherians: a model of gametic execution and zygotic relaxation SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID PREIMPLANTATION MOUSE EMBRYOS; CHROMOSOME INACTIVATION; PARENTAL ORIGIN; GENE-EXPRESSION; LACZ TRANSGENE; XIST GENE; YOLK-SAC; SPERMATOGENESIS; RNA; TSIX AB In mammals, X-chromosome inactivation (XCl) ensures equal expression of X-linked genes in XX and XY individuals by transcriptionally silencing one X-chromosome in female cells. In this review, we discuss an imprinted form of X-inactivation in which the paternal X (Xp) is preferentially silenced. Believed to be the ancestral mechanism of dosage compensation in mammals, imprinted X-inactivation can still be observed in modern-day marsupials and in the extraembryonic tissues of some eutherians such as the mouse. Recent experiments have addressed the nature of the gametic imprint and focused on the regulatory interaction between the noncoding RNA gene, Xist, and its antisense partner, Tsix. Our review of the literature has inspired an unconventional view of imprinted XCl in mice. First, the evidence strongly argues that imprinted Cl is inabsolute, so that a stochastic number of extraembryonic cells escape imprinting. Second, contrary to conventional thinking, we would like to consider the possibility that the paternal X might actually be transmitted to the zygote as a pre-inactivated chromosome. In this model, the gamete initiates and establishes imprinted XCl, while the zygote maintains the pre-established pattern of gametic inactivation. Finally, we hypothesize that the inabsolute nature of imprinting is caused by imperfect zygotic maintenance. We propose that the mouse represents a transitional stage in the evolution of random XCl from an absolutely imprinted mechanism. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst,Dept Mol Biol,Dept Genet, Boston, MA 02115 USA. RP Huynh, KD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst,Dept Mol Biol,Dept Genet, Boston, MA 02115 USA. NR 56 TC 60 Z9 62 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD DEC PY 2001 VL 13 IS 6 BP 690 EP 697 DI 10.1016/S0955-0674(00)00272-6 PG 8 WC Cell Biology SC Cell Biology GA 491GM UT WOS:000172100700006 PM 11698184 ER PT J AU Tapon, N Moberg, KH Hariharan, IK AF Tapon, N Moberg, KH Hariharan, IK TI The coupling of cell growth to the cell cycle SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID C-MYC; TRANSLATIONAL CONTROL; RIBOSOME BIOGENESIS; GENETIC-CONTROL; SIZE CONTROL; DROSOPHILA; PROGRESSION; EXPRESSION; TARGET; PROLIFERATION AB The development of a complex multicellular organism requires a coordination of growth and cell division under the control of patterning mechanisms. Studies in yeast have pioneered our understanding of the relationship between growth and cell division. In recent years, many of the pathways that regulate growth in multicellular eukaryotes have been identified. This work has revealed interesting and unexpected relationships between mechanisms that regulate growth and the cell cycle machinery. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Hariharan, IK (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NEI NIH HHS [EY11632]; NIGMS NIH HHS [GM61672]; NINDS NIH HHS [NS36084] NR 64 TC 62 Z9 64 U1 2 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD DEC PY 2001 VL 13 IS 6 BP 731 EP 737 DI 10.1016/S0955-0674(00)00284-2 PG 7 WC Cell Biology SC Cell Biology GA 491GM UT WOS:000172100700012 PM 11698190 ER PT J AU Wucherpfennig, KW AF Wucherpfennig, KW TI Insights into autoimmunity gained from structural analysis of MHC-peptide complexes SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID MYELIN BASIC-PROTEIN; MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-II MOLECULES; T-CELL REPERTOIRE; GLUTAMIC-ACID DECARBOXYLASE; MULTIPLE-SCLEROSIS PATIENTS; NONOBESE DIABETIC MICE; CELIAC-DISEASE; TISSUE TRANSGLUTAMINASE; RHEUMATOID-ARTHRITIS AB The structural and functional properties of HLA-DQ and -DR molecules that confer susceptibility to several common autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis and multiple sclerosis, have been defined. The relevant polymorphisms directly affect interaction with peptides, which provides strong support for the hypothesis that these diseases are peptide-antigen driven. Several studies indicate that structural modifications of peptides can affect MHC class II binding and/or TCR recognition and should be considered in the analysis of T cell responses in autoimmune diseases. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Room D1410,44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [R01 AI42316, P01 AI39619, P01 AI45757] NR 54 TC 35 Z9 38 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD DEC PY 2001 VL 13 IS 6 BP 650 EP 656 DI 10.1016/S0952-7915(01)00274-6 PG 7 WC Immunology SC Immunology GA 486BB UT WOS:000171797600004 PM 11677085 ER PT J AU Redding, SW AF Redding, SW TI The role of yeasts other than Candida albicans in oropharyngeal candidiasis SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review ID HIV-INFECTED INDIVIDUALS; ORAL CANDIDOSIS; ANTIFUNGAL AGENTS; IN-VITRO; DUBLINIENSIS; FLUCONAZOLE; GLABRATA; PATIENT; SUSCEPTIBILITIES; COLONIZATION AB Candida albicans has been recognized as the predominant infecting organism in oropharyngeal candidiasis. Yeasts other than C. albicans are commonly recognized as colonizing the oral cavity but have not been thought to be a significant cause of disease. This review will describe the emergence of yeasts other than C. albicans as causative pathogens in oropharyngeal candidiasis both as co-infecting organisms with C. albicans and as sole pathogens themselves. Diagnosis and treatment of these emerging infections will also be discussed. Curr Opin Infect Dis 14:673-677, (C) 2001 Lippincott Williams & Wilkins. C1 Univ Texas, Hlth Sci Ctr, S Texas Vet Healthcare Syst, Dept Gen Dent, San Antonio, TX 78229 USA. RP Redding, SW (reprint author), Univ Texas, Hlth Sci Ctr, S Texas Vet Healthcare Syst, Dept Gen Dent, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 31 TC 28 Z9 30 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD DEC PY 2001 VL 14 IS 6 BP 673 EP 677 PG 5 WC Infectious Diseases SC Infectious Diseases GA 501BM UT WOS:000172663200002 PM 11964883 ER PT J AU Yarm, F Sagot, I Pellman, D AF Yarm, F Sagot, I Pellman, D TI The social life of actin and microtubules: interaction versus cooperation SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID BUD-SITE SELECTION; SACCHAROMYCES-CEREVISIAE; FISSION YEAST; MITOTIC SPINDLE; POLARIZED GROWTH; BUDDING YEAST; CELL-DIVISION; PROTEIN; CYTOSKELETON; CYTOKINESIS AB The actin and microtubule cytoskeletons play key roles in cell polarity, spindle orientation and nuclear movement. Recent work in fungal systems has identified potential 'functional links' between these cytoskeletal systems. This review discusses molecular mechanisms through which these links may be established. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Yarm, F (reprint author), Dana Farber Canc Inst, Room M621A,44 Binney St, Boston, MA 02115 USA. NR 62 TC 31 Z9 31 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD DEC PY 2001 VL 4 IS 6 BP 696 EP 702 DI 10.1016/S1369-5274(01)00271-5 PG 7 WC Microbiology SC Microbiology GA 499DU UT WOS:000172556400012 PM 11731322 ER PT J AU Batchelor, T Stanley, K Andersen, J AF Batchelor, T Stanley, K Andersen, J TI Clinical trials in neuro-oncology SO CURRENT OPINION IN NEUROLOGY LA English DT Article ID RECURSIVE PARTITIONING ANALYSIS; BRAIN-TUMOR TRIALS; MALIGNANT GLIOMA; PROGNOSTIC FACTORS; RESPONSE CRITERIA; GRADE GLIOMA; PHASE-II; SURVIVAL; BIAS; OUTCOMES AB Clinical trials are prospective scientific studies involving human participants and form the basis for identifying new treatments for diseases like brain tumors. A clinical trial should be designed to provide definitive results for a study question. Therefore, investigators should understand the principles underlying the design, execution and analysis of clinical trials. In addition to the application of basic principles germane to the design of all clinical trials, studies in neuro-oncology also involve unique challenges in case definition, selection of endpoints and definition of response. This review begins with enumeration of the basic principles of clinical trial design including reduction of bias and variability, and concludes with a review of study design factors of particular relevance for neuro-oncology. Curr Opin Neurol 14:689-694. (C) 2001 Lippincott Williams Wilkins. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Batchelor, T (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, Dept Neurol, Cox 315,100 Blossom St, Boston, MA 02114 USA. NR 29 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD DEC PY 2001 VL 14 IS 6 BP 689 EP 694 DI 10.1097/00019052-200112000-00003 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 510NG UT WOS:000173213700003 PM 11723375 ER PT J AU Sims, KB AF Sims, KB TI Von Hippel-Lindau disease: gene to bedside SO CURRENT OPINION IN NEUROLOGY LA English DT Review ID TUMOR-SUPPRESSOR GENE; ENDOTHELIAL GROWTH-FACTOR; ENDOLYMPHATIC SAC TUMORS; CENTRAL-NERVOUS-SYSTEM; SPORADIC CEREBELLAR HEMANGIOBLASTOMAS; GENOTYPE-PHENOTYPE CORRELATIONS; MULTIPLE ENDOCRINE NEOPLASIA; BIOLOGICALLY-ACTIVE PRODUCT; HYPOXIA-INDUCIBLE FACTORS; UBIQUITIN LIGASE COMPLEX AB Von Hippel-Lindau is an autosomal dominant familial tumor syndrome with a risk of developing central nervous system and retinal hemangioblastomas, kidney cysts and clear cell carcinoma, cyst adenomas of other organs and pheochromocytoma. Despite continued elaboration of the neurobiologic role of the von Hippel-Lindau protein, the mainstay of management remains the definitive clinical diagnosis of von Hippel-Lindau syndrome (as distinct from sporadic cases of single von Hippel-Lindau-associated tumors), clinical monitoring and preemptive intervention by surgical or ablative therapy. Specific pharmacologic treatment awaits further biologic understanding of critical pathogenic components. Increasingly sensitive imaging and surgical techniques allow for optimum clinical management and intervention. This article will review von Hippel-Lindau molecular genetics, genotype-phenotype correlations and clinical classification, current understanding of the biology of the von Hippel-Lindau protein, its role in the pathophysiology of this disorder and the consequent implications for future therapeutic/interventional strategies. Central nervous system manifestations will be highlighted. Curr Opin Neurol 14:695-703. (C) 2001 Lippincott Williams Wilkins. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Sims, KB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. NR 138 TC 16 Z9 18 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD DEC PY 2001 VL 14 IS 6 BP 695 EP 703 DI 10.1097/00019052-200112000-00004 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 510NG UT WOS:000173213700004 PM 11723376 ER PT J AU Stoler, JM AF Stoler, JM TI Maternal antiepileptic drug use and effects on fetal development SO CURRENT OPINION IN PEDIATRICS LA English DT Review ID PRENATAL EXPOSURE; SPINA-BIFIDA; IN-UTERO; WOMEN; EPILEPSY; ANTICONVULSANTS; PREGNANCY; INFANTS; MALFORMATIONS; PHENYTOIN AB Many pregnant women take antiepileptic medications, and concern has arisen about the risks this poses to the fetus. It has been debated whether the causative agent is the medication or the underlying maternal disorder. Review of the recent literature indicates that the effects seem to be from the medications themselves. The frequency of malformations is about two to three-fold above the background rate and is dose-related for some of the medications. There seem to be effects on birth weight, length, and head circumference caused by at least some of the medications. The risks are greater when more than one medication is used. Cognitive effects from the medications have been shown, although these effects are of lower magnitude than previously reported. More investigation needs to be done to determine the exact risks of each individual medication, especially the newer ones. Studies on underlying mechanisms indicate potential genetic susceptibility and altered developmental gene expression patterns. (C) 2001 Lippincott Williams& Wilkins, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Teratol Unit, Boston, MA 02114 USA. RP Stoler, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Teratol Unit, 55 Fruit St,Warren 801, Boston, MA 02114 USA. NR 32 TC 5 Z9 5 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD DEC PY 2001 VL 13 IS 6 BP 566 EP 571 DI 10.1097/00008480-200112000-00013 PG 6 WC Pediatrics SC Pediatrics GA 505UP UT WOS:000172934200013 PM 11753108 ER PT J AU Dahlin, C AF Dahlin, C TI Crossing over: Narratives of palliative care SO DEATH STUDIES LA English DT Book Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dahlin, C (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 USA SN 0748-1187 J9 DEATH STUD JI Death Stud. PD DEC PY 2001 VL 25 IS 8 BP 709 EP 715 PG 7 WC Psychology, Multidisciplinary; Social Issues; Social Sciences, Biomedical SC Psychology; Social Issues; Biomedical Social Sciences GA 494XP UT WOS:000172311400005 ER PT J AU Hemler, ME AF Hemler, ME TI Retooling of the beta 4 integrin in tumor cells - Ligands lost and kinase gained SO DEVELOPMENTAL CELL LA English DT Editorial Material ID ALPHA-6-BETA-4 INTEGRIN; GROWTH-FACTOR; INVASION; HEMIDESMOSOMES; RECEPTOR; DOMAIN C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 9 TC 3 Z9 3 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD DEC PY 2001 VL 1 IS 6 BP 728 EP 730 DI 10.1016/S1534-5807(01)00102-2 PG 3 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 546XN UT WOS:000175301800003 PM 11740933 ER PT J AU Laviola, L Belsanti, G Davalli, AM Napoli, R Perrini, S Weir, GC Giorgino, R Giorgino, F AF Laviola, L Belsanti, G Davalli, AM Napoli, R Perrini, S Weir, GC Giorgino, R Giorgino, F TI Effects of streptozocin diabetes and diabetes treatment by islet transplantation on in vivo insulin signaling in rat heart SO DIABETES LA English DT Article ID PROTEIN-KINASE-B; GLYCOGEN-SYNTHASE KINASE-3; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; GLUCOSE-TRANSPORT SYSTEM; SKELETAL-MUSCLE; RECEPTOR SUBSTRATE-1; FEASIBILITY TRIAL; GLYCEMIC CONTROL; DOCKING PROTEIN; VA CSDM AB The insulin signaling cascade was investigated in rat myocardium in vivo in the presence of streptozocin (STZ)-induced diabetes and after diabetes treatment by islet transplantation under the kidney capsule. The levels of insulin-stimulated tyrosine phosphorylation of the insulin receptor beta -subunit, insulin receptor substrate (IRS)-2, and p52(Shc) were increased in diabetic compared with control heart, whereas tyrosine phosphorylation of IRS-1 was unchanged. The amount of the p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase) and the level of PI 3-kinase activity associated with IRS-2 were also elevated in diabetes, whereas no changes in IRS-1-associated PI 3-kinase were observed. Insulin-induced phosphorylation of Akt on Thr-308 was increased fivefold in diabetic heart, whereas Akt phosphorylation on Ser-473 was normal. In contrast with Akt phosphorylation, insulin-induced phosphorylation of glycogen synthase kinase (GSK)-3, a major cellular substrate of Akt, was markedly reduced in diabetes. In islet-transplanted rats, the majority of the alterations in insulin-signaling proteins found in diabetic rats were normalized, but insulin stimulation of IRS-2 tyrosine phosphorylation and association with PI 3-kinase was blunted. In conclusion, in the diabetic heart, 1) IRS-1, IRS-2, and p52(Shc) are differently altered, 2) the levels of Akt phosphorylation on Ser-473 and Thr-308, respectively, are not coordinately regulated, and 3) the increased activity of proximal-signaling proteins (i.e., IRS-2 and PI 3-kinase) is not propagated distally to GSK-3. Islet transplantation under the kidney capsule is a potentially effective therapy to correct several diabetes-induced abnormalities of insulin signaling in cardiac muscle but does not restore the responsiveness of all signaling reactions to insulin. C1 Univ Bari, Dept Emergency & Organ Transplantat, I-70124 Bari, Italy. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Giorgino, F (reprint author), Univ Bari, Dept Emergency & Organ Transplantat, Piazza Giulio Cesare 11, I-70124 Bari, Italy. RI Giorgino, Francesco/K-7262-2016; OI Giorgino, Francesco/0000-0001-7372-2678; Perrini, Sebastio/0000-0002-2728-7721; NAPOLI, Raffaele/0000-0002-3366-2321; Laviola, Luigi/0000-0001-8860-5845 NR 58 TC 45 Z9 48 U1 1 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2001 VL 50 IS 12 BP 2709 EP 2720 DI 10.2337/diabetes.50.12.2709 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 507CT UT WOS:000173009900010 PM 11723053 ER PT J AU Scott, LJ Warram, JH Hanna, LS Laffel, LMB Ryan, L Krolewski, AS AF Scott, LJ Warram, JH Hanna, LS Laffel, LMB Ryan, L Krolewski, AS TI A nonlinear effect of hyperglycemia and current cigarette smoking are major determinants of the onset of microalbuminuria in type I diabetes SO DIABETES LA English DT Article ID MICROVASCULAR COMPLICATIONS; RISK-FACTORS; NEPHROPATHY; MELLITUS; PROGRESSION; PROTEINURIA; RETINOPATHY; PREDICTORS; EXCRETION; ALBUMIN AB Cigarette smoking and poor glycemic control are risk factors for diabetic nephropathy in type 1 diabetes. However, the specifics of the relation of these risk factors to the onset of this complication have not been elucidated. To investigate these issues, we followed for 4 years 943 Joslin Clinic patients aged 15-44 years with type I diabetes who had normoalbuminuria during the 2-year baseline period. Microalbuminuria developed in 109 of the 943 individuals, giving an incidence rate of 3.3/100 person-years. The risk of onset of microalbuminuria was predicted somewhat more precisely by the measurements during the 1st and 2nd years preceding onset than by all the measurements during the longer (4-year) interval, suggesting attenuation of the impact of past hyperglycemia over time. Point estimates of the incidence rate (per 100 person-years) according to quartiles of HbA(1c) during the 1st and 2nd years preceding the outcome were 1.3 in the 1st, 1.5 in the 2nd, 3.1 in the 3rd, and 6.9 in the 4th (P=1.3 x 10(-9)). Point estimates of the incidence rate (per 100 person-years) according to smoking status were 7.9 for current smokers, 1.8 for past smokers, and 2.2 for those who had never smoked (P=2.0 x 10(-7)). In a multiple logistic model, the independent effects of HbA(1c) level and cigarette smoking remained highly significant, but their magnitudes were reduced. Using the same covariates in a generalized additive model, we examined the shape of the relationship between HbA(1c) and onset of microalbuminuria and found significant nonlinearity in the logarithm of odds scale (P=0.04). The slope was steeper with HbA(1c) >8% than <8%. Furthermore, the change in the slope was magnified among current smokers. In conclusion, patients with type I diabetes who smoke and have an HbA(1c) > 8% have the highest risk of onset of microalbuminuria. C1 Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, Boston, MA 02215 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, Sch Med, Dept Med, Boston, MA USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. EM andrzej.krolewski@joslin.harvard.edu RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NIDDK NIH HHS [R01-DK41526, T32 DK07260-21/22] NR 37 TC 64 Z9 64 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD DEC PY 2001 VL 50 IS 12 BP 2842 EP 2849 DI 10.2337/diabetes.50.12.2842 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 507CT UT WOS:000173009900026 PM 11723069 ER PT J AU Way, KJ Katai, N King, GL AF Way, KJ Katai, N King, GL TI Protein kinase C and the development of diabetic vascular complications SO DIABETIC MEDICINE LA English DT Review DE protein kinase C (PKC); diabetes mellitus; PKC isoforms; PKC beta; LY333531; vitamin E ID GLOMERULAR MESANGIAL CELLS; RETINAL BLOOD-FLOW; ENDOTHELIAL GROWTH-FACTOR; ELEVATED GLUCOSE-LEVELS; PKC-BETA INHIBITOR; SODIUM-POTASSIUM-ATPASE; NITRIC-OXIDE SYNTHASE; CARDIAC TROPONIN-I; D-ALPHA-TOCOPHEROL; VITAMIN-E AB Hyperglycemic control in diabetes is key to preventing the development and progression of vascular complications such as retinopathy, nephropathy and neuropathy. Increased activation of the diacylglycerol (DAG)-protein kinase C (PKC) signal transduction pathway has been identified in vascular tissues from diabetic animals, and in vascular cells exposed to elevated glucose. Vascular abnormalities associated with glucose-induced PKC activation leading to increased synthesis of DAG include altered vascular blood flow, extracellular matrix deposition, basement membrane thickening, increased permeability and neovascularization. Preferential activation of the PKC beta isoform by elevated glucose is reported to occur in a variety of vascular tissues. This has lead to the development of LY333531, a PKC beta isoform specific inhibitor, which has shown potential in animal models to be an orally effective and nontoxic therapy able to produce significant improvements in diabetic retinopathy, nephropathy, neuropathy and cardiac dysfunction. Additionally, the antioxidant vitamin E has been identified as an inhibitor of the DAG-PKC pathway, and shows promise in reducing vascular complications in animal models of diabetes. Given the overwhelming evidence indicating a role for PKC activation in contributing to the development of diabetic vascular complications, pharmacological therapies that can modulate this pathway, particularly with PKC isoform. selectivity, show great promise for treatment of vascular complications, even in the presence of hyperglycemia. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NEI NIH HHS [EY5110, EY9178] NR 167 TC 197 Z9 201 U1 1 U2 8 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD DEC PY 2001 VL 18 IS 12 BP 945 EP 959 DI 10.1046/j.0742-3071.2001.00638.x PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 504BJ UT WOS:000172836700001 PM 11903393 ER PT J AU Fan, HX Schichman, SA Swinnen, LJ Nicholls, JM Eagan, PA Luther, M Gulley, ML AF Fan, HX Schichman, SA Swinnen, LJ Nicholls, JM Eagan, PA Luther, M Gulley, ML TI Analytic validation of a competitive polymerase chain reaction assay for measuring Epstein-Barr viral load SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE Epstein-Barr virus; viral load; competitive polymerase chain reaction; analytic test validation ID POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE; PEDIATRIC TRANSPLANT PATIENTS; URACIL-DNA GLYCOSYLASE; CYTOTOXIC T-CELLS; NASOPHARYNGEAL CARCINOMA; VIRUS DNA; QUANTITATIVE-ANALYSIS; HODGKINS-DISEASE; PERIPHERAL-BLOOD; PLASMA AB Epstein-Barr virus (EBV) is associated with several benign and malignant diseases, and blood tests for EBV viral load show promise as markers of disease burden in affected patients. A commercial quantitative PCR method (BioSource International) was recently introduced to facilitate measuring viral load. It relies on coamplification of EBV DNA and a spiked competitor in plasma or serum, followed by semiautomated product detection on enzyme-linked immunosorbent assay (ELISA) plates. In the current study, analytic performance characteristics were assessed, and the authors describe several methodologic improvements to facilitate laboratory implementation. Rapid DNA extraction was accomplished using commercial silica spin columns, heat-labile uracil-N-glycosylase was used to inhibit amplicon contamination, and inexpensive agarose gels were used to screen for polymerase chain reaction products requiring ELISA plate quantitation. Accuracy and precision were verified using EBV DNA standards derived from two cell lines and plasmid containing viral sequences. The assay was sensitive to as few as five template copies per polymerase chain reaction and was linear across four orders of magnitude (correlation coefficient 0.995). When applied to matched plasma and serum samples from 15 patients with nasopharyngeal carcinoma, both sample types yielded similar viral load results. This commercial EBV viral load assay provides sensitive and quantitative detection of EBV DNA using equipment already available in many molecular diagnostic laboratories. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. JL McClellan Vet Affairs Med Ctr, Little Rock, AR USA. Loyola Univ, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. SW Oncol Grp, San Antonio, TX USA. RP Gulley, ML (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NCI NIH HHS [U10 CA32102] NR 25 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD DEC PY 2001 VL 10 IS 4 BP 255 EP 264 DI 10.1097/00019606-200112000-00008 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA 496GY UT WOS:000172388900008 PM 11763317 ER PT J AU Schlozman, SC AF Schlozman, SC TI The jitters SO EDUCATIONAL LEADERSHIP LA English DT Article C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. RP Schlozman, SC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ASSOC SUPERVISION CURRICULUM DEVELOPMENT PI ALEXANDRIA PA 1703 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0013-1784 J9 EDUC LEADERSHIP JI Educ. Leadership PD DEC PY 2001 VL 59 IS 4 BP 82 EP 83 PG 2 WC Education & Educational Research SC Education & Educational Research GA 521TF UT WOS:000173857100024 ER PT J AU Soegiarto, DW Kiachopoulos, S Schipani, E Juppner, H Erben, RG Lanske, B AF Soegiarto, DW Kiachopoulos, S Schipani, E Juppner, H Erben, RG Lanske, B TI Partial rescue of PTH/PTHrP receptor knockout mice by targeted expression of the Jansen transgene SO ENDOCRINOLOGY LA English DT Article ID HORMONE-RELATED PEPTIDE; COMPLETE NUCLEOTIDE-SEQUENCE; ENDOCHONDRAL BONE-FORMATION; PARATHYROID-HORMONE; METAPHYSEAL CHONDRODYSPLASIA; INDIAN HEDGEHOG; SIGNALING PATHWAY; BLOMSTRAND-CHONDRODYSPLASIA; INACTIVATING MUTATION; SKELETAL DEVELOPMENT AB The homozygous ablation of the gene encoding the PTH/PTHrP receptor (PPR-/-) leads to early lethality and limited developmental defects, including an acceleration of chondrocyte differentiation. In contrast to the findings in homozygous PTHrp-ablated (PTHrP(-/-)) animals, these PPR-/- mice show an increase in cortical bone, a decrease in trabecular bone, and a defect in bone mineralization. Opposite observations are made in Jansen's metaphyseal chondrodysplasia, a disorder caused by constitutively active PPR mutants, and in transgenic animals expressing one of these receptor mutants (HKrk-H223R) under control of the type alpha1(I) collagen promoter. Expression of the Jansen transgene under the control of the type cel (II) collagen promoter was, furthermore, shown to delay chondrocyte differentiation and to prevent the dramatic acceleration of chondrocyte differentiation in PTHrP(-/-) mice, thus rescuing the early lethality of these animals. In the present study we demonstrated that the type alpha1(II) collagen promoter Jansen transgene restored most of the bone abnormalities in PPR-/- mice, but did not prevent their perinatal lethality. These findings suggested that factors other than impaired gas exchange due to an abnormal rib cage contribute to the early death of PPR-/- mice. C1 Max Planck Inst Biochem, D-85152 Martinsried, Germany. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Endocrine Unit, Boston, MA 02114 USA. Univ Munich, Inst Anim Physiol, D-80539 Munich, Germany. RP Lanske, B (reprint author), Forsyth Inst, Harvard Forsyth Dept Oral Biol, 140 Fenway, Boston, MA 02115 USA. EM blanske@forsyth.org NR 41 TC 16 Z9 16 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2001 VL 142 IS 12 BP 5303 EP 5310 DI 10.1210/en.142.12.5303 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 497JX UT WOS:000172452700035 PM 11713230 ER PT J AU Chen, CH Sakai, Y Demay, MB AF Chen, CH Sakai, Y Demay, MB TI Targeting expression of the human vitamin D receptor to the keratinocytes of vitamin D receptor null mice prevents alopecia. SO ENDOCRINOLOGY LA English DT Article ID D-DEPENDENT RICKETS; 1,25-DIHYDROXYVITAMIN D-3; TRANSGENIC MICE; DIFFERENTIATION; PROLIFERATION; FOLLICLE; CALCIUM; GROWTH; SKIN; MODEL AB Vitamin D receptor (VDR) null mice develop hypocalcemia, hyperparathyroidism, rickets, osteomalacia and alopecia. Normalization of mineral ion homeostasis prevents all of these abnormalities except alopecia. Hair reconstitution assays, performed in athymic nude mice, demonstrate that the lack of VDR in keratinocytes leads to a defect in anagen initiation, similar to that observed in VDR null mice. Although these studies demonstrate that expression of the VDR in keratinocytes is necessary, they do not prove that it is sufficient, for maintenance of the normal hair cycle. To address this hypothesis, we generated transgenic mice expressing the human VDR under the control of the keratin 14 (K14) promoter. Two highly expressing transgenic lines were mated with VDR null mice to obtain VDR null mice expressing the human VDR transgene (hVDR+/mVDR-). Expression of the transgene in the VDR null mice prevented alopecia. Furthermore, when subjected to anagen initiation, the hair follicle keratinocytes of the hVDR+/mVDR- mice demonstrated an enhanced proliferative response compared to those of control littermates. Restoration of VDR expression in the keratinocytes of VDR null mice, prevents the hair cycle defect that leads to the development of alopecia. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Demay, MB (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK46974] NR 23 TC 66 Z9 67 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2001 VL 142 IS 12 BP 5386 EP 5389 DI 10.1210/en.142.12.5386 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 497JX UT WOS:000172452700045 PM 11713240 ER PT J AU Hamdy, O Goodyear, LJ Horton, ES AF Hamdy, O Goodyear, LJ Horton, ES TI Diet and exercise in type 2 diabetes mellitus SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Review ID RAT SKELETAL-MUSCLE; ACTIVATED PROTEIN-KINASE; ACETYL-COA CARBOXYLASE; NITRIC-OXIDE SYNTHASE; ENDOTHELIUM-DEPENDENT VASODILATION; STIMULATED GLUCOSE-TRANSPORT; PHYSICAL-ACTIVITY; INSULIN ACTION; INDUCED INCREASE; PLASMA-MEMBRANE AB It is now clear that regular physical exercise plays an important role in both the prevention and treatment of type 2 diabetes mellitus. Additionally, exercise combined with dietary restriction leads to decreased body fat, increased insulin sensitivity, improved long-term glycemic control, improved lipid profiles, lower blood pressure, and increased cardiovascular fitness. The biochemical mechanisms by which acute exercise and physical training regulate glucose transport and metabolism in skeletal muscle and improve insulin sensitivity are being defined now, and recent developments in this area are discussed. In addition, guidelines are presented for the development of an exercise program and for the evaluation of patients with type 2 diabetes mellitus before starting such a program. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Horton, ES (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM edward.horton@joslin.harvard.edu NR 132 TC 58 Z9 62 U1 0 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD DEC PY 2001 VL 30 IS 4 BP 883 EP + DI 10.1016/S0889-8529(05)70220-6 PG 26 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 493HQ UT WOS:000172216900007 PM 11727404 ER PT J AU Sassower, KC Rollinson, DC Duchowny, M AF Sassower, KC Rollinson, DC Duchowny, M TI Outcome of corpus callosotomy and other pediatric epilepsy surgery: parental perceptions SO EPILEPTIC DISORDERS LA English DT Article DE pediatric epilepsy surgery; parental opinions; intractable epilepsy; quality of life; surgical outcome ID QUALITY-OF-LIFE; EARLY-CHILDHOOD; INTRACTABLE EPILEPSY; TEMPORAL LOBECTOMY; FOLLOW-UP; SEIZURE; CHILDREN; ANTERIOR; MUTISM AB Purpose: Parental perceptions regarding the outcome of epilepsy surgery in their children were assessed preoperatively via telephone survey. Methods: Twenty-seven parents - sixteen mothers (MO), eleven fathers (FA) of sixteen children (nine boys, seven girls; ages 6 months-18 years) with intractable epilepsy (refractory to greater than or equal to 3 anticonvulsants) were interviewed. Twenty-four questions were posed during single, 20-minute sessions to both parents. Results: A majority of parents (63% MO, 82% FA) would consider epilepsy surgery successful if it achieved greater than or equal to 75% seizure reduction. Incomplete seizure control would even be acceptable if the overall number of seizures were reduced (69% MO, 18% FA). In order to gain seizure remissions, behavioral deterioration would be accepted (57% MO, 50% FA). Less than total seizure control would be accepted if surgery produced behavioral improvement (57% MO, 51% FA, Kappa > 0.6). For seizure reduction, parents would accept: visual field deficits (82% MO, 67% FA), short-term memory deficits (33% MO, 75% FA), and speech problems (56% MO, 17% FA). Conclusion: Parents of children with medically-resistant seizures perceive adverse physical and behavioral consequences of epilepsy surgery to be acceptable if there is adequate seizure control. Their acceptance of postoperative deficits underscores the magnitude of the handicap produced by chronic childhood epilepsy. C1 Massachusetts Gen Hosp, Dept Neurol, Div Clin Neurophysiol, Boston, MA 02114 USA. Tufts Univ New England Med Ctr, Dept Emergency Med, Boston, MA 02111 USA. Miami Childrens Hosp, Comprehens Epilepsy Ctr, Miami, FL USA. RP Sassower, KC (reprint author), Massachusetts Gen Hosp, Dept Neurol, Div Clin Neurophysiol, Bigelow 12,55 Fruit St, Boston, MA 02114 USA. NR 30 TC 4 Z9 6 U1 1 U2 1 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1294-9361 J9 EPILEPTIC DISORD JI Epileptic Disord. PD DEC PY 2001 VL 3 IS 4 BP 197 EP 202 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 527HG UT WOS:000174180200004 PM 11844714 ER PT J AU Fagerlie, S Lensch, MW Pang, QS Bagby, GC AF Fagerlie, S Lensch, MW Pang, QS Bagby, GC TI The Fanconi anemia group C gene product: Signaling functions in hematopoietic cells SO EXPERIMENTAL HEMATOLOGY LA English DT Review ID DEPENDENT PROTEIN-KINASE; COMPLEMENTATION GROUP-C; NECROSIS-FACTOR-ALPHA; EUKARYOTIC TRANSLATION INITIATION-FACTOR-2; INDUCED APOPTOTIC RESPONSES; MITOMYCIN-C; APLASTIC-ANEMIA; NUCLEAR-COMPLEX; CYTOPLASMIC LOCALIZATION; TARGETED DISRUPTION C1 Oregon Hlth Sci Univ, Inst Canc, Dept Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Inst Canc, Dept Med & Mol Genet, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. RP Bagby, GC (reprint author), Oregon Hlth Sci Univ, Inst Canc, Dept Med, 3181 SW Sam Jackson Pk Rd,Mail Code CR145, Portland, OR 97201 USA. FU NHLBI NIH HHS [HL48546] NR 99 TC 27 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD DEC PY 2001 VL 29 IS 12 BP 1371 EP 1381 DI 10.1016/S0301-472X(01)00755-X PG 11 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 506BB UT WOS:000172949100003 PM 11750095 ER PT J AU Jubinsky, PT Messer, A Bender, J Morris, RE Ciraolo, GM Witte, DP Hawley, RG Short, MK AF Jubinsky, PT Messer, A Bender, J Morris, RE Ciraolo, GM Witte, DP Hawley, RG Short, MK TI Identification and characterization of Magmas, a novel mitochondria-associated protein involved in granulocyte-macrophage colony-stimulating factor signal transduction SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID ADHERENT HUMAN-NEUTROPHILS; ZINC FINGER GENE; GM-CSF RECEPTOR; BETA-SUBUNIT; TYROSINE PHOSPHORYLATION; ALPHA-SUBUNIT; CELL-LINE; IN-VIVO; INTERLEUKIN-3; CHAIN AB Objective. The aim of this studs was to identify granulocyte-macrophage colony-stimulating factor (GM-CSF) responsive genes. Materials and Methods. Potential GM-CSF responsive genes were identified by comparing the mRNA expression pattern of the murine myeloid cell line PGMDI grown in either interleukin-3 (IL-3) or GM-CSF by differential display. Human and murine cDNA clones of one of the bands having increased expression in GM-CSF were isolated. mRNA expression of the gene was examined by Northern blot. Immunohistochemistry and studies with a green fluorescent fusion protein were used to determine its intracellular location. Growth factor-stimulated proliferation of PGMDI cells transfected with constitutively expressed sense and anti-sense cDNA constructs of the gene was measured by H-3-thymidine incorporation. Results. A gene, named Magmas (mitochondria-associated granulocyte macrophage CSF signaling molecule), was shown to be rapidly induced when cells were switched from IL-3 to GM-CSF. Analysis of the amino acid sequence of Magmas showed it contained a mitochondrial signal peptide, but not any other known functional domains. The human and murine clones encode nearly identical 13-kDa proteins that localized to the mitochondria. Magmas mRNA expression was observed in all tissues examined. PGMDI cells that overexpressed Magmas proliferated similarly to untransfected cells when cultured in IL-3 or GM-CSF. In contrast, cells with reduced protein levels grew normally in IL-3, but had impaired proliferation in GM-CSF. Conclusion. Magmas is a mitochondrial protein involved in GM-CSF signal transduction. (C) 2001 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 Childrens Hosp, Res Fdn, Med Ctr, Div Hematol Oncol, Cincinnati, OH 45229 USA. Childrens Hosp, Res Fdn, Div Pathol, Cincinnati, OH 45229 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Cincinnati, Coll Med, Dept Cell Biol Neurobiol & Anat, Cincinnati, OH USA. Amer Red Cross, Hematoiesis Dept, Rockville, MD USA. RP Jubinsky, PT (reprint author), Childrens Hosp, Res Fdn, Med Ctr, Div Hematol Oncol, 3333 Burnet Ave, Cincinnati, OH 45229 USA. NR 54 TC 18 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD DEC PY 2001 VL 29 IS 12 BP 1392 EP 1402 DI 10.1016/S0301-472X(01)00749-4 PG 11 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 506BB UT WOS:000172949100005 PM 11750097 ER PT J AU Siddique, MA Nakanishi, K Taniguchi, T Grompe, M D'Andrea, AD AF Siddique, MA Nakanishi, K Taniguchi, T Grompe, M D'Andrea, AD TI Function of the Fanconi anemia pathway in Fanconi anemia complementation group F and D1 cells SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID NUCLEAR-COMPLEX; GENE; FANCG/XRCC9; DIAGNOSIS; PROTEIN; REPAIR AB Objective. Fanconi anemia (FA) is a human autosomal-recessive cancer susceptibility disorder characterized by multiple congenital abnormalities, progressive bone marrow failure, and cellular sensitivity to mitomycin C (MMC). FA has at least eight complementation groups (A, B. C, D1, D2, E, F, G), and six or the FA genes have been cloned. Several FA proteins, including FANCA, FANCC, FANCF, and FANCG, interact in a nuclear complex, and this complex is required for the activation (monoubiquitination) of the downstream FANCD2 protein. Activation of FANCD2 results in the assembly of FANCD2/BRCA1 foci. The aim of this study Nas to analyze the FA pathway, in several FA patient-derived cell lines. Materials and Methods. We generated an antibody to FANCF and analyzed FANCF expression in human lymphoblasts corresponding to all known FA subtypes. We systematically analyzed the FA pathway (FANCD2 monoubiquitination and assembly of FANCD2 nuclear foci) in patient-derived FA-F and FA-DI cell lines. Results. FANCF protein expression is normal in cells derived from all FA complementation groups except FA-F and does not vary, during cell cycle progression. FANCF, but not FANCD2, is a component of the nuclear FA protein complex and appears to stabilize other subunits of the complex. FANCF is required for the monoubiquitination of the FANCD2 protein following ionizing radiation. FANCD2 is monoubiquitinated in FA-D1 cells. even though these cells are highly sensitive to MMC. Conclusions. The recently cloned FANCF protein is required for FANCD2 activation, and the yet uncloned FANCD1 protein functions further downstream or independently of the FA pathway. (C) 2001 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 Harvard Univ, Sch Med, Div Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. 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, Div Pediat Oncol, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL54785, HL52725] NR 30 TC 32 Z9 32 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD DEC PY 2001 VL 29 IS 12 BP 1448 EP 1455 DI 10.1016/S0301-472X(01)00754-8 PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 506BB UT WOS:000172949100012 PM 11750104 ER PT J AU Birbes, H El Bawab, S Hannun, YA Obeid, LM AF Birbes, H El Bawab, S Hannun, YA Obeid, LM TI Selective hydrolysis of a mitochondrial pool of sphingomyelin induces apoptosis SO FASEB JOURNAL LA English DT Article DE targeting; ceramide; mitochondria; apoptosis; Bcl-2; cytochrome c ID PERMEABILITY TRANSITION PORE; CERAMIDE-INDUCED APOPTOSIS; TUMOR-NECROSIS-FACTOR; CYTOCHROME-C RELEASE; DISTINCT POOL; CELL-SURFACE; BCL-2; ACTIVATION; MEMBRANES; DEATH AB Our previous results have indicated that the major cellular pool of sphingomyelin present on the outer leaflet of the plasma membrane is not involved in the ceramide pathway of apoptosis. Thus, in this study we aimed at defining which intracellular pools of sphingomyelin and ceramide are involved in cell death. The bacterial sphingomyelinase (SMase) gene fused with green fluorescent protein was subcloned into mammalian vectors containing sequences that target the fusion proteins to cytoplasm, plasma membrane, mitochondria, Golgi apparatus, endoplasmic reticulum, or nucleus. Transfection of MCF7 breast cancer cells showed for all constructs an increase in SMase activity ranging from 2- to 60-fold, concomitant with an increase in total cellular ceramide levels (10-100%) as compared with vector-transfected cells. Next, the effect of overexpression of the SMase on cell death was examined. Results demonstrate that only when bacterial SMase was targeted to mitochondria did cells undergo apoptosis; its targeting to the other intracellular compartments was ineffective. Further, the results show that apoptosis induced by mitochondrial targeting of bacterial SMase requires SMase catalytic activity, is prevented by the overexpression of Bcl-2, and is mediated by inducing cytochrome c release. These results demonstrate that ceramide induces cell death specifically when generated in mitochondria. The results highlight the significance of compartment-specific lipid-mediated cell regulation, and they offer a novel general approach for these studies. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm, Charleston, SC 29425 USA. RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, 114 Doughty St,Strom Thurmond Bldg,Room 605, Charleston, SC 29425 USA. EM obeidl@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NIA NIH HHS [AG16583]; NIGMS NIH HHS [GM43825] NR 60 TC 166 Z9 170 U1 0 U2 3 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 DEC PY 2001 VL 15 IS 14 BP 2669 EP 2679 DI 10.1096/fj.01-0539com PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 506HT UT WOS:000172964800037 PM 11726543 ER PT J AU Faigel, DO Gopal, D Weeks, DA Corless, C AF Faigel, DO Gopal, D Weeks, DA Corless, C TI Cap-assisted endoscopic submucosal resection of a pancreatic rest SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID ECTOPIC PANCREAS; ADENOMYOMA; STOMACH C1 Oregon Hlth Sci Univ, Portland VA Med Ctr, Dept Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Portland VA Med Ctr, Dept Pathol, Portland, OR 97201 USA. RP Faigel, DO (reprint author), Oregon Hlth Sci Univ, Portland VA Med Ctr, Dept Med, P3GI,3710 US Vet Hosp Rd, Portland, OR 97201 USA. NR 12 TC 12 Z9 12 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD DEC PY 2001 VL 54 IS 6 BP 782 EP 784 DI 10.1067/mge.2001.116620 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 499HJ UT WOS:000172565500024 PM 11726863 ER PT J AU Querido, E Blanchette, P Yan, Q Kamura, T Morrison, M Boivin, D Kaelin, WG Conaway, RC Conaway, JW Branton, PE AF Querido, E Blanchette, P Yan, Q Kamura, T Morrison, M Boivin, D Kaelin, WG Conaway, RC Conaway, JW Branton, PE TI Degradation of p53 by adenovirus E4orf6 and E1B55K proteins occurs via a novel mechanism, involving a Cullin-containing complex SO GENES & DEVELOPMENT LA English DT Article DE p53 adenovirus; protein degradation; Cullin complexes; ubiquitination; elongin B; elongin C; NEDD8 ID TUMOR-SUPPRESSOR PROTEIN; UBIQUITIN-LIKE PROTEIN; ELONGIN BC COMPLEX; SOCS-BOX MOTIF; NUCLEAR EXPORT; INFECTED-CELLS; TRANSCRIPTIONAL ACTIVATION; 55-KILODALTON PROTEIN; DEPENDENT PROTEOLYSIS; LIGASE ACTIVITY AB Although MDM2 plays a major role in regulating the stability of the p53 tumor suppressor protein, other poorly understood MDM2-independent pathways also exist. Human adenoviruses have evolved strategies to regulate p53 function and stability to permit efficient viral replication. One mechanism involves adenovirus E1B55K and E4orf6 proteins, which collaborate to target p53 for, degradation. To determine the mechanism of this process, a multiprotein E4orf6-associated complex was purified and shown to contain a novel Cullin-containing E3 ubiquitin ligase that is (1) composed of Cullin family member Cul5, Elongins B and C, and the RING-H2 finger protein Rbx1(ROC1); (2) remarkably similar to the von Hippel-Lindau tumor suppressor and SCF (Skp1-Cul1/Cdc53-F-box) E3 ubiquitin ligase complexes; and (3) capable of stimulating ubiquitination of p53 in vitro in the presence of E1/E2 ubiquitin-activating and -conjugating enzymes. Cullins are activated by NEDD8 modification; therefore, to determine whether Cullin complexes are required for adenovirus-induced p53 degradation, studies were conducted in ts41 Chinese hamster ovary cells that are temperature sensitive for the NEDD8 pathway. E4orf6/E1B55K failed to induce the degradation of p53 at the nonpermissive temperature. Thus, our results identify a novel role for the Cullin-based machinery in regulation of p53. C1 McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada. McGill Univ, McGill Canc Ctr, Montreal, PQ H3G 1Y6, Canada. Stowers Inst Med Res, Kansas City, MO 64110 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73190 USA. Kyushu Univ, Med Inst Bioregulat, Dept Mol & Cellular Biol, Kawaguchi, Saitama 332012, Japan. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Kansas, Med Ctr, Dept Biochem & Mol Biol, Kansas City, KS 66160 USA. RP Branton, PE (reprint author), McGill Univ, Dept Biochem, 3655 Drummond St, Montreal, PQ H3G 1Y6, Canada. RI Yan, Qin/E-8893-2012; OI Yan, Qin/0000-0003-4077-453X; Conaway, Joan/0000-0002-2786-0663 FU NIGMS NIH HHS [R37 GM041628, GM41628, R01 GM041628] NR 87 TC 321 Z9 326 U1 2 U2 17 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 DEC 1 PY 2001 VL 15 IS 23 BP 3104 EP 3117 DI 10.1101/gad.926401 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 499YP UT WOS:000172598800004 PM 11731475 ER PT J AU Robins, JM Smoller, JW Lunetta, KL AF Robins, JM Smoller, JW Lunetta, KL TI On the validity of the TDT test in the presence of comorbidity and ascertainment bias SO GENETIC EPIDEMIOLOGY LA English DT Article DE ascertainment bias; causal directed acyclic graphs; comorbidity; transmission/disequilibrium test ID CAUSAL DIAGRAMS; SOCIAL PHOBIA; SIBSHIP TEST; ASSOCIATION; LINKAGE; DISEQUILIBRIUM AB Comorbidity, the association of two disorders, occurs commonly with complex diseases. In this paper. we investigate the effects of both true (within-family) comorbidity and spurious comorbidity due to ascertainment bias on the validity of both the parental and sibling control transmission/disequilibrium test. Specifically. we consider settings in which a candidate gene is unlinked to the target phenotype but is in linkage disequilibrium with a comorbid phenotype. We derive conditions under which the presence of true and/or spurious comorbidity will result in an artificial correlation between the target phenotype and the candidate gene. (C) 2001 Wiley-Liss. Inc. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. RP Robins, JM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [AI32475-09]; NIMH NIH HHS [MH59532-02] NR 20 TC 7 Z9 7 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD DEC PY 2001 VL 21 IS 4 BP 326 EP 336 DI 10.1002/gepi.1038 PG 11 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 499HP UT WOS:000172566000005 PM 11754468 ER PT J AU Korey, CA Wilkie, G Davis, I Van Vactor, D AF Korey, CA Wilkie, G Davis, I Van Vactor, D TI small bristles is required for the morphogenesis of multiple tissues during Drosophila development SO GENETICS LA English DT Article ID MESSENGER-RNA EXPORT; CONSTITUTIVE TRANSPORT ELEMENT; FINE CYTOGENETICAL ANALYSIS; MELANOGASTER X-CHROMOSOME; GROWTH CONES; FLIGHTLESS MUTANTS; ADJOINING REGIONS; GENETIC-ANALYSIS; MUSCLE FUNCTION; NUCLEAR EXPORT AB We found that mutations in small bristles (sbr) affect several tissues during the development of the fruit fly. In sbr embryos, neurons have defects in pathfinding and the body wall muscles have defective morphology. As adults, sbr flies have smaller and thinner bristles With a reduced diameter, suggesting a defective cytoskeleton within, The phenotypes we observe are consistent with defects in cell morphogenesis. We identified DmNXF1, the Drosophila homolog of a mRNA export protein that has been characterized in human (NXF1/TAP) and yeast (Mex67p) as the protein encoded by the small bristles locus. Given that a global decrease in mRNA export in these mutants is likely, the phenotypes we observe suggest that certain tissues are acutely sensitive to lower levels of cytoplasmic mRNA and the resultant decrease in protein synthesis during key stages of cellular morphogenesis. C1 Harvard Univ, Sch Med, Dept Cell Biol, Neurosci Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc, Boston, MA 02115 USA. Univ Edinburgh, Inst Cell & Mol Biol, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland. RP Van Vactor, D (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Neurosci Program, 240 Longwood Ave,LHRRB Rm 401A, Boston, MA 02115 USA. RI Davis, Ilan/F-4975-2010; OI Davis, Ilan/0000-0002-5385-3053 FU NINDS NIH HHS [NS35909, NS40043] NR 53 TC 13 Z9 15 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD DEC PY 2001 VL 159 IS 4 BP 1659 EP 1670 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 508TZ UT WOS:000173106800024 PM 11779805 ER PT J AU Matthews, LR Vaglio, P Reboul, J Ge, H Davis, BP Garrels, J Vincent, S Vidal, M AF Matthews, LR Vaglio, P Reboul, J Ge, H Davis, BP Garrels, J Vincent, S Vidal, M TI Identification of potential interaction networks using sequence-based searches for conserved protein-protein interactions or "interologs" SO GENOME RESEARCH LA English DT Article ID INTERACTION MAP; GENOME; YEAST; SYSTEM; GENE AB Protein interaction maps have provided insight into the relationships among the predicted proteins of model organisms for which a genome sequence is available. These maps have been useful in generating potential interaction networks, which have confirmed the existence of known complexes and pathways and have suggested the existence of new complexes and or crosstalk between previously unlinked pathways. However, the generation of such maps is costly and labor intensive. Here, we investigate the extent to which a protein interaction map generated in one species can be used to predict interactions in another species. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM marc_vidal@dfci.harvard.edu RI Reboul, Jerome/P-9103-2016 OI Reboul, Jerome/0000-0002-5513-4546 FU NCI NIH HHS [P01CA80111-02, 7 R33 CA81658-02, P01 CA080111]; NHGRI NIH HHS [5R01HG01715, R01 HG001715] NR 26 TC 271 Z9 287 U1 1 U2 9 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD DEC PY 2001 VL 11 IS 12 BP 2120 EP 2126 DI 10.1101/gr.205301 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 497VF UT WOS:000172475600019 PM 11731503 ER PT J AU Abraczinskas, DR Ookubo, R Grace, ND Groszmann, RJ Bosch, J Garcia-Tsao, G Richardson, CR Matloff, DS Rodes, J Conn, HO AF Abraczinskas, DR Ookubo, R Grace, ND Groszmann, RJ Bosch, J Garcia-Tsao, G Richardson, CR Matloff, DS Rodes, J Conn, HO TI Propranolol for the prevention of first esophageal variceal hemorrhage: A lifetime commitment? SO HEPATOLOGY LA English DT Article ID RANDOMIZED TRIAL; CIRRHOSIS; SURVIVAL; PLACEBO; NADOLOL AB Although beta blockers have had significant impact in the treatment of portal hypertension, the question of how long they should be continued for prevention of variceal hemorrhage remains unknown. Prospective studies on beta blockers to prevent variceal hemorrhage lack long-term follow-up, and indefinite administration of beta blockers for primary prevention of variceal bleeding has become standard practice. The aim of this study was to determine the outcomes of patients in whom beta blocker therapy was discontinued. Patients completing a prospective, randomized, double-blind, placebo-controlled trial of propranolol for the primary prevention of variceal hemorrhage were tapered off of propranolol and placebo and followed prospectively for subsequent events. Of the 49 patients in the follow-up study (25 former propranolol, 24 former placebo), 9 experienced variceal hemorrhage (6 former propranolol, 3 former placebo). Following withdrawal of propranolol, the freedom from variceal bleeding was not significantly different between these 2 groups of patients, suggesting that the protective effect of propranolol against variceal hemorrhage, noted previously, was no longer present. Seventeen patients died (12 former propranolol, 5 former placebo) during the follow-up study. Cumulative survival was longer in the placebo group. These trends for EVH and survival were opposite to those observed in the original study population while patients were taking medication. When propranolol is withdrawn, the risk of variceal hemorrhage returns to what would be expected in an untreated population. Patients who discontinue beta blockers experience increased mortality compared with an untreated population. These observations support the current practice of indefinite prophylactic therapy. C1 Faulkner Hosp, Dept Gastroenterol, Boston, MA 02130 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Yale W Haven VA Med Ctr, Dept Gastroenterol, West Haven, CT USA. Hosp Clin Barcelona, Dept Hepatol, Hepat Hemodynam Lab, Barcelona, Spain. Univ Michigan Hlth Syst, Dept Family Med, Ann Arbor, MI USA. RP Grace, ND (reprint author), Faulkner Hosp, Dept Gastroenterol, 1153 Centre St, Boston, MA 02130 USA. FU NIDDK NIH HHS [T32DK07191] NR 22 TC 71 Z9 74 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 2001 VL 34 IS 6 BP 1096 EP 1102 DI 10.1053/jhep.2001.29305 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 498TN UT WOS:000172526700005 PM 11731997 ER PT J AU Dumke, CL Wetter, AC Arias, EB Kahn, CR Cartee, GD AF Dumke, CL Wetter, AC Arias, EB Kahn, CR Cartee, GD TI Absence of insulin receptor substrate-1 expression does not alter GLUT1 or GLUT4 abundance or contraction-stimulated glucose uptake by mouse skeletal muscle SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE exercise; glucose transport; insulin signaling; contractile activity; glycogen ID TRANSPORT ACTIVITY; RAT MUSCLE; MICE; SENSITIVITY; EXERCISE AB The purpose of this study was to determine the influence of insulin receptor substrate-1 (IRS-1) expression on GLUT1 and GLUT4 glucose transporter protein abundance, contraction-stimulated glucose uptake, and contraction-induced glycogen depletion by skeletal muscle. Mice (6 months old) from three genotypes were studied: wild-type (IRS-1(+/+)), heterozygous (IRS-1(+/-)) for the null allele, and IRS-1 knockouts (IRS-1(-/-)) lacking a functional IRS-1 gene. In situ muscle contraction was induced (electrical stimulation of sciatic nerve) in one hindlimb using contralateral muscles as controls. Soleus and extensor digitorum longus were dissected and 2-deoxyglucose uptake was measured in vitro. 2-Deoxyglucose uptake was higher in basal muscles (no contractions) from IRS-1(-/-) vs. both other genotypes. Contraction-stimulated 2-deoxyglucose uptake and glycogen depletion did not differ among genotypes. Muscle IRS-1 protein was undetectable for IRS-1(-/-) mice, and values were approximately 40% lower in IRS-1(+/-) than in IRS-1(+/+) mice. No difference was found in IRS-1(+/+) compared to IRS-1(-/-) groups regarding muscle abundance of GLUT1 and GLUT4. Substantial reduction or elimination of IRS-1 did not alter the hallmark effects of contractions on muscle carbohydrate metabolism - activation of glucose uptake and glycogen depletion. C1 Univ Wisconsin, Dept Kinesiol, Biodynam Lab, Madison, WI 53706 USA. Univ Wisconsin, Dept Nutr Sci, Biodynam Lab, Madison, WI USA. Harvard Univ, Sch Med, Res Div, Joslin Diabetes Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Cartee, GD (reprint author), Univ Wisconsin, Dept Kinesiol, Biodynam Lab, Madison, WI 53706 USA. OI Cartee, Gregory/0000-0001-5311-1722 FU NIA NIH HHS [AG 10026]; NIDDK NIH HHS [DK 33201] NR 20 TC 3 Z9 3 U1 0 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD DEC PY 2001 VL 33 IS 12 BP 696 EP 700 DI 10.1055/s-2001-19141 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 510FV UT WOS:000173198800002 PM 11753753 ER PT J AU Liu, XZ Xia, XJ Adams, J Chen, ZY Welch, KO Tekin, M Ouyang, XM Kristiansen, A Pandya, A Balkany, T Arnos, KS Nance, WE AF Liu, XZ Xia, XJ Adams, J Chen, ZY Welch, KO Tekin, M Ouyang, XM Kristiansen, A Pandya, A Balkany, T Arnos, KS Nance, WE TI Mutations in GJA1(connexin 43) are associated with non-syndromic autosomal recessive deafness SO HUMAN MOLECULAR GENETICS LA English DT Article ID MARIE-TOOTH DISEASE; GAP; CONNEXINS; FREQUENCY AB Mutations in four members of the connexin gene family have been shown to underlie distinct genetic forms of deafness, including GJB2 [connexin 26 (Cx26)], GJB3(Cx31), GJB6(Cx30) and GJB1 (Cx32). We have found that alterations in a fifth member of this family, GJA1 (Cx43), appear to cause a common form of deafness in African Americans. We identified two different GJA1mutations in four of 26 African American probands. Three were homozygous for a Leu --> Phe substitution in the absolutely conserved codon 11, whereas the other was homozygous for a Val --> Ala transversion at the highly conserved codon 24. Neither mutation was detected in DNA from 100 control subjects without deafness. Cx43 is expressed in the cochlea, as is demonstrated by PCR amplification from human fetal cochlear cDNA and by RT-PCR of mouse cochlear tissues. Immunohistochemical staining of mouse cochlear preparations showed immunostaining for Cx43 in non-sensory epithelial cells and in fibrocytes of the spiral ligament and the spiral limbus. To our knowledge this is the first alpha connexin gene to be associated with non-syndromic deafness. Cx43 must also play a critical role in the physiology of hearing, presumably by participating in the recycling of potassium to the cochlear endolymph. C1 Virginia Commonwealth Univ, Med Coll Virginia, Dept Human Genet, Richmond, VA 23298 USA. Univ Miami, Dept Otolaryngol, Miami, FL 33136 USA. Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02114 USA. Gallaudet Univ, Dept Biol, Washington, DC 20002 USA. RP Liu, XZ (reprint author), Univ Miami, Dept Otolaryngol D48, 1666 NW 12th Ave, Miami, FL 33136 USA. FU NIDCD NIH HHS [DC 04293, DC 02530, DC 03929, DC 04530, DC 04546, DC 05575] NR 24 TC 86 Z9 100 U1 0 U2 6 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 DEC 1 PY 2001 VL 10 IS 25 BP 2945 EP 2951 DI 10.1093/hmg/10.25.2945 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 504QW UT WOS:000172868200010 PM 11741837 ER PT J AU Meier, M King, GL Clermont, A Perez, A Hayashi, M Feener, EP AF Meier, M King, GL Clermont, A Perez, A Hayashi, M Feener, EP TI Angiotensin AT(1) receptor stimulates heat shock protein 27 phosphorylation in vitro and in vivo SO HYPERTENSION LA English DT Article DE angiotensin II; aorta; heat shock proteins; phosphorylation; protein kinases; receptors, angiotensin II ID VASCULAR SMOOTH-MUSCLE; P38 MAP KINASE; GROWTH-FACTOR; CELLS; PATHWAY; HSP27; INVOLVEMENT; ACTIVATION; MODULATION; ALPHA AB The angiotensin type I receptor (AT,) exerts a variety of its signaling and cellular actions through its effects on protein phosphorylation. Phosphoproteomic analysis of angiotensin (Ang) II-stimulated aortic smooth muscle cells revealed that heat shock protein 27 (HSP27) represents a major protein phosphorylation target of the AT, signaling pathway. Stimulation of cells with Ang II resulted in 1.7-fold (P<0.05) and 5.5-fold (P<0.001) increases in HSP27 phosphoisoforms at pI 5.7 and pI 5.4, respectively. This was accompanied by a 54% (P<0.01) decrease in the nonphosphorylated HSP27 isoform, located at pI 6.4. Treatment of samples with alkaline phosphatase reversed this redistribution of HSP27 phosphoisoforms. Ang II-stimulated HSP27 phosphorylation was completely blocked by pretreatment of cells with the AT I antagonist CV11974. Phosphoamino acid analysis demonstrated that Ang II-induced phosphorylation of both HSP27 phosphoisoforms occurred exclusively on serine. Protein kinase C inhibition completely blocked phorbol ester-induced HSP27 phosphorylation but did not impair Ang II-stimulated phosphorylation of HSP27, suggesting that AT, increased HSP27 phosphorylation by a protein kinase C-independent pathway. Intrajugular infusion of Ang II in rats increased HSP27 in aorta by 1.7-fold (P<0.02), and this response was inhibited by CV11974. These results suggest that Ang II-induced HSP27 phosphorylation is a physiologically relevant AT, signaling event. Because serine phosphorylation of HSP27 blocks its ability to cap F-actin, Ang II/AT(1)-induced HSP27 phosphorylation may play a key role in actin filament remodeling required for smooth muscle cell migration and contraction. C1 Harvard Univ, Div Res, Joslin Diabet Ctr, Sch Med, Boston, MA 02215 USA. RP Feener, EP (reprint author), Harvard Univ, Div Res, Joslin Diabet Ctr, Sch Med, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [P30 DK036836, DK53105, DK48358, DK36836] NR 27 TC 18 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD DEC PY 2001 VL 38 IS 6 BP 1260 EP 1265 DI 10.1161/hy1201.096573 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 509HT UT WOS:000173141500007 PM 11751700 ER PT J AU Mitchell, GF Tardif, JC Arnold, JMO Marchiori, G O'Brien, TX Dunlap, ME Pfeffer, MA AF Mitchell, GF Tardif, JC Arnold, JMO Marchiori, G O'Brien, TX Dunlap, ME Pfeffer, MA TI Pulsatile Hemodynamics in congestive heart failure SO HYPERTENSION LA English DT Article; Proceedings Paper CT 4th International Workshop on Structure and Function on Large Arteries CY APR 27-28, 2001 CL PARIS, FRANCE DE heart failure; hemodynamics; aorta; pulse pressure; vascular stiffness ID AORTIC INPUT IMPEDANCE; LEFT-VENTRICULAR DYSFUNCTION; PULSE PRESSURE; MYOCARDIAL-INFARCTION; ARTERIAL COMPLIANCE; HYDRAULIC LOAD; EXPRESSION; SUPEROXIDE; ACTIVATION; SYNTHASE AB Pulse pressure, an indirect measure of vascular stiffness and pulsatile load, predicts clinical events in congestive heart failure (CHF), suggesting that abnormal pulsatile load may contribute to CHF. This study was designed to assess more direct measures of central pulsatile load in CHF. Noninvasive hemodynamic evaluations were performed in 28 subjects with CHF and 40 controls using calibrated tonometry of the brachial, radial, femoral, and carotid arteries along with echocardiographic assessment of left ventricular outflow tract (LVOT) diameter and Doppler flow. Characteristic impedance (Z(c)) was calculated as the ratio of DeltaP (carotid) and DeltaQ (LVOT flow) in early systole. Carotid-radial (CR-PWV) and carotid-femoral (CF-PWV) pulse wave velocities were calculated from tonometry. Augmentation index was assessed from the carotid waveform. Total arterial compliance (TAC) was calculated using the area method. Brachial pulse pressure was elevated (62 16 versus 53+/-15 mm Hg, P=0.015) in CHF because of lower diastolic pressure (66 10 versus 73 9 mm Hg, P=0.003). CHF had higher Zc (225+/-76 versus 184+/-66 dyne . sec . cm(-5), P=0.020). CF-PWV did not differ (9.7+/-2.7 versus 9.2+/-2.0, P=0.337), whereas CR-PWV was lower in CHF (8.6+/-1.4 versus 9.4+/-1.5, P=0.038). There was no difference in TAC (1.4+/-0.5 versus 1.4+/-0.6 mL/mmHg, P=0.685), and augmentation index was lower in CHF (8 17 versus 21+/-13%, P=0.001). CHF subjects have elevated central pulsatile load (Z(c)), which is not apparent in global measures such as augmentation index or TAC, possibly because of contrasting changes in central and peripheral conduit vessels. This increased pulsatile load represents an important therapeutic target in CHF. C1 Cardiovasc Engn Inc, Holliston, MA 01746 USA. Montreal Heart Inst, Montreal, PQ, Canada. London Sci Ctr, London, ON, Canada. Ralph H Johnson VA Med Ctr, Charleston, SC USA. Louis Stokes VA Med Ctr, Cleveland, OH USA. Brigham & Womens Hosp, Boston, MA USA. RP Mitchell, GF (reprint author), Cardiovasc Engn Inc, 327 Fiske St, Holliston, MA 01746 USA. NR 29 TC 123 Z9 126 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD DEC PY 2001 VL 38 IS 6 BP 1433 EP 1439 DI 10.1161/hy1201.098298 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 509HT UT WOS:000173141500038 PM 11751731 ER PT J AU Riese, RJ Shi, GP Villadangos, J Stetson, D Driessen, C Lennon-Dumenil, AM CHu, CL Naumov, Y Behar, SM Ploegh, H Locksley, R Chapman, HA AF Riese, RJ Shi, GP Villadangos, J Stetson, D Driessen, C Lennon-Dumenil, AM CHu, CL Naumov, Y Behar, SM Ploegh, H Locksley, R Chapman, HA TI Regulation of CD1 function and NK1.1(+) T cell selection and maturation by cathepsin S SO IMMUNITY LA English DT Article ID COMPLEX CLASS-II; MHC CLASS-II; ANTIGEN-PRESENTING MOLECULES; INVARIANT CHAIN; DENDRITIC CELLS; MOUSE CD1; NKT CELLS; MICE; PEPTIDE; TRAFFICKING AB NK1.1(+) T cells develop and function through interactions with cell surface CD1 complexes. In I-A(B) mice lacking the invariant chain (Ii) processing enzyme, cathepsin S, NK1.1(+) T cell selection and function are impaired. In vitro, thymic dendritic cells (DCs) from cathepsin S=/- mice exhibit defective presentation of the CD1restricted antigen, a-galactosylceramide (alpha -GalCer). CD1 dysfunction is secondary to defective trafficking of CD1, which colocalizes with Ii fragments and accumulates within endocytic compartments of cathepsin S-/- DCs. [-A(k), cathepsin S-/- mice do not accumulate class [II-associated Ii fragments and accordingly do not display CD1 abnormalities. Thus, function of CD1 is critically linked to processing of li, revealing MHC class II haplotype and cathepsin S activity as regulators of NK T cells. C1 Univ Calif San Francisco, Dept Med, San Francisco, CA 94943 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Chapman, HA (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94943 USA. RI driessen, christoph/F-7061-2016; Lennon-Dumenil, Ana-Maria/I-6716-2016; OI driessen, christoph/0000-0002-1124-7303; Chu, Ching-Liang/0000-0002-8463-526X FU NHLBI NIH HHS [HL48716]; NIAID NIH HHS [AI01555] NR 46 TC 62 Z9 65 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 2001 VL 15 IS 6 BP 909 EP 919 DI 10.1016/S1074-7613(01)00247-3 PG 11 WC Immunology SC Immunology GA 506GK UT WOS:000172961400006 PM 11754813 ER PT J AU Raab, M Pfister, S Rudd, CE AF Raab, M Pfister, S Rudd, CE TI CD28 signaling via VAV/SLP-76 adaptors: Regulation of cytokine transcription independent of TCR ligation SO IMMUNITY LA English DT Article ID T-CELL RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; MOLECULAR-CLONING; PROMOTER ACTIVITY; PROTEIN SLP-76; ACTIVATION; VAV; COSTIMULATION; PROLIFERATION; BINDING AB Since CD28 provides cosignals in T cell responses, a key question is whether the coreceptor operates exclusively via TCR zeta /CD3 or also operates as an independent signaling unit. In this study, we show that CD28 can cooperate with VAV/SLP-76 adaptors to upregulate interleukin 2/4 transcription independently of TCR ligation. CD28 signaling is dependent on VAV/ SLP-76 complex formation and induces membrane localization of these complexes. CD28-VAV/SLP-76 also functions in nonlymphoid cells to promote nuclear entry of NFAT, indicating that these adaptors are the only lymphoid components needed for this pathway. Further downstream, CD28-VAV/SLP-76 synergizes with Rac1 and causes F-actin remodelling proximal to receptor. Autonomous CD28 signaling may account for the distinct nature of the second signal and in trans amplification of T cell responses. C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ London Imperial Coll Sci Technol & Med, Dept Haematol, London W12 0NN, England. RP Rudd, CE (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Pfister, Stefan/F-6860-2013 OI Pfister, Stefan/0000-0002-5447-5322 FU PHS HHS [A139021] NR 61 TC 74 Z9 75 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 2001 VL 15 IS 6 BP 921 EP 933 DI 10.1016/S1074-7613(01)00248-5 PG 13 WC Immunology SC Immunology GA 506GK UT WOS:000172961400007 PM 11754814 ER PT J AU Murga, M Fernandez-Capetillo, O Field, SJ Moreno, B Borlado, LR Fujiwara, Y Balomenos, D Vicario, A Carrera, AC Orkin, SH Greenberg, ME Zubiaga, AM AF Murga, M Fernandez-Capetillo, O Field, SJ Moreno, B Borlado, LR Fujiwara, Y Balomenos, D Vicario, A Carrera, AC Orkin, SH Greenberg, ME Zubiaga, AM TI Mutation of E2F2 in mice causes enhanced T lymphocyte proliferation, leading to the development of autoimmunity SO IMMUNITY LA English DT Article ID THYMIC NEGATIVE SELECTION; RECEPTOR TRANSGENIC MICE; S-PHASE ENTRY; TRANSCRIPTION FACTOR; RETINOBLASTOMA PROTEIN; CELL-PROLIFERATION; SUSCEPTIBILITY GENES; IN-VIVO; EXPRESSION; GROWTH AB E2Fs are important regulators of proliferation, differentiation, and apoptosis. Here we characterize the phenotype of mice deficient in E2F2. We show that E2F2 is required for immunologic self-tolerance. E2F2(-/-) mice develop late-onset autoimmune features, characterized by widespread inflammatory infiltrates, glomerular immunocomplex deposition, and anti-nuclear antibodies. E2F2-deficient T lymphocytes exhibit enhanced TCR-stimulated proliferation and a lower activation threshold, leading to the accumulation of a population of autoreactive effector/memory T lymphocytes, which appear to be responsible for causing autoimmunity in E2F2-deficient mice. Finally, we provide support for a model to explain E2F2's unexpected role as a suppressor of T lymphocyte proliferation. Rather than functioning as a transcriptional activator, E2F2 appears to function as a transcriptional repressor of genes required for normal S phase entry, particularly E2F1. C1 Univ Basque Country, Fac Sci, Dept Anim Biol & Genet, E-48080 Bilbao, Spain. Harvard Univ, Sch Med, Childrens Hosp, Div Neurosci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Basque Inst Agr Res & Dev, NEIKER, E-48160 Derio, Spain. Univ Autonoma Madrid, Ctr Nacl Biotecnol, CSIC, Dept Immunol & Oncol, E-28049 Madrid, Spain. Childrens Hosp, Howard Hughes Med Inst, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zubiaga, AM (reprint author), Univ Basque Country, Fac Sci, Dept Anim Biol & Genet, E-48080 Bilbao, Spain. RI Fernandez-Capetillo, Oscar/H-3508-2015; Balomenos, Dimitrios/I-3850-2015; OI Fernandez-Capetillo, Oscar/0000-0002-2690-6885; Carrera, Ana/0000-0002-3999-5434 FU NCI NIH HHS [CA43855] NR 49 TC 107 Z9 110 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 2001 VL 15 IS 6 BP 959 EP 970 DI 10.1016/S1074-7613(01)00254-0 PG 12 WC Immunology SC Immunology GA 506GK UT WOS:000172961400010 PM 11754817 ER PT J AU Ramet, M Pearson, A Manfruelli, P Li, XH Koziel, H Gobel, V Chung, E Krieger, M Ezekowitz, RAB AF Ramet, M Pearson, A Manfruelli, P Li, XH Koziel, H Gobel, V Chung, E Krieger, M Ezekowitz, RAB TI Drosophila scavenger receptor Cl is a pattern recognition receptor for bacteria SO IMMUNITY LA English DT Article ID HOST-DEFENSE; BINDING PROTEIN; BOMBYX-MORI; APOPTOTIC CELLS; INNATE IMMUNITY; LIGAND-BINDING; CLONING; GENE; PHAGOCYTOSIS; MELANOGASTER AB One hallmark of innate immunity apparently conserved from primitive life forms through to humans is the ability of the host to recognize pathogen-associated molecular patterns (PAMPs). Since macrophage pattern recognition receptors are not well defined in Drosophila, we set out to identify such receptors. Our findings reveal that Drosophila macrophages express multiple pattern recognition receptors and that the Drosophila scavenger receptor, dSR-CI, is one such receptor capable of recognizing both gram-negative and gram-positive bacteria, but not yeast. Our data indicate that scavenger receptor bacteria[ recognition is conserved from insects to humans and may represent one of the most primitive forms of microbial recognition. C1 Harvard Univ, Sch Med, Dept Pediat, MassGen Hosp Children,Lab Dev Immunol, Boston, MA 02114 USA. MIT, Dept Biol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Pulm & Crit Care Med, Dept Med, Boston, MA 02115 USA. RP Ramet, M (reprint author), Harvard Univ, Sch Med, Dept Pediat, MassGen Hosp Children,Lab Dev Immunol, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL41484, HL52212]; PHS HHS [P01 A144220-03] NR 57 TC 166 Z9 174 U1 0 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 2001 VL 15 IS 6 BP 1027 EP 1038 DI 10.1016/S1074-7613(01)00249-7 PG 12 WC Immunology SC Immunology GA 506GK UT WOS:000172961400015 PM 11754822 ER PT J AU Tian, W Boggs, DA Ding, WZ Chen, DF Fraser, PA AF Tian, W Boggs, DA Ding, WZ Chen, DF Fraser, PA TI MICA genetic polymorphism and linkage disequilibrium with HLA-B in 29 African-American families SO IMMUNOGENETICS LA English DT Article DE HLA; MICA; PCR/SSOP; linkage disequilibrium; African-Americans ID CLASS-I; CELLS; DIVERSITY; SEQUENCE AB The human major histocompatibility complex (MHC) class I chain-related gene A (MICA) is located 46 kb upstream of HLA-B and encodes a stress-inducible protein which displays a restricted pattern of tissue expression. MICA molecules interact with NKG2D, augmenting the activation of natural killer cells, CD8+ alphabeta T cells, and gammadelta T cells. MICA allelic variation is thought to be associated with disease susceptibility and immune response to transplants. We investigated MICA allelic variations and linkage disequilibrium with HLA-A, B, and DRB1 loci on 110 parental haplotypes from 29 African-American families. PCR/sequence-specific oligonucleotide probing (SSOP) was used to define MICA polymorphisms in exons 2, 3, and 4. Ambiguous allelic combinations were resolved by sequencing exons 2, 3, and 4. Exon 5 polymorphisms were analyzed by size sequencing. For HLA-A, B and DRB1 typing, low-resolution PCR/SSOP and allelic PCR/sequence-specific priming techniques were used. Twelve MICA alleles were observed, the most frequent of which were MICA*008, MICA*004, and MICA*002, with gene frequencies of 28.2, 26.4, and 25.5%, respectively. Thirty-eight HLA-B-MICA haplotypic combinations were uncovered, 22 of which have not been reported in the HLA homozygous typing cell lines from the 10th International Histocompatibility Workshop. Significant positive linkage disequilibria were found in 8 HLA-B-MICA haplotypes. Furthermore, haplotypes bearing HLA-B*1503, *1801, *4901, *5201, *5301, and *5703 were found to segregate with at least two different MICA alleles. Our results provide new data about MICA genetic polymorphisms in African-Americans, which will form the basis for future studies of MICA alleles in allogeneic stem cell transplantation outcome. C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Fraser, PA (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. NR 19 TC 20 Z9 24 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD DEC PY 2001 VL 53 IS 9 BP 724 EP 728 DI 10.1007/s00251-001-0392-x PG 5 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 528CD UT WOS:000174225500002 PM 11862403 ER PT J AU Soares, MP Brouard, S Smith, RN Bach, FH AF Soares, MP Brouard, S Smith, RN Bach, FH TI Heme oxygenase-1, a protective gene that prevents the rejection of transplanted organs SO IMMUNOLOGICAL REVIEWS LA English DT Review ID NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; ENDOTHELIAL-CELL ACTIVATION; DELAYED XENOGRAFT REJECTION; LONG-TERM SURVIVAL; ALPHA-INDUCED APOPTOSIS; CARBON-MONOXIDE; PROTEIN-KINASE; T-CELL; SUPEROXIDE-DISMUTASE AB Endothelial cells (EC) play a pivotal role in regulating inflammatory reactions such as those involved in the rejection of transplanted organs. This occurs through the expression of a series of pro- and anti-inflammatory genes that are associated with the activation of these cells, Presumably, the expression of pro-inflammatory genes promotes events that lead to graft rejection, while expression of anti-inflammatory (protective) genes suppresses those events and thus contributes in sustaining graft survival. Understanding how the expression of these genes is regulated and their mechanism of action are important issues for the development of new therapeutic strategies to suppress graft rejection. We have studied this phenomenon using experimental models of transplantation in rats. We discuss here data that supports the concept that grafts can express anti-inflammatory (protective) genes that mitigate inflammatory reactions leading to graft rejection. The data reviewed focus on the role of one of such genes, the stress responsive gene heme oxygenase-1, and of its byproduct carbon monoxide, which can suppress graft rejection and lead to long-term graft survival. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Immunobiol Res Ctr,Dept Surg, Boston, MA 02215 USA. Gulbenkian Inst Sci, Oeiras, Portugal. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RP Soares, MP (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Immunobiol Res Ctr,Dept Surg, 99 Brookline Ave, Boston, MA 02215 USA. RI brouard, sophie/Q-1285-2016; OI Soares, Miguel/0000-0002-9314-4833 FU NHLBI NIH HHS [HL58688, HL67040] NR 92 TC 67 Z9 73 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD DEC PY 2001 VL 184 BP 275 EP 285 DI 10.1034/j.1600-065x.2001.1840124.x PG 11 WC Immunology SC Immunology GA 519RH UT WOS:000173738900023 PM 12086318 ER PT J AU Gruber, A Lell, CP Speth, C Stoiber, H Lass-Florl, C Sonneborn, A Ernst, JF Dierich, MP Wurzner, R AF Gruber, A Lell, CP Speth, C Stoiber, H Lass-Florl, C Sonneborn, A Ernst, JF Dierich, MP Wurzner, R TI Human immunodeficiency virus type 1 Tat binds to Candida albicans, inducing hyphae but augmenting phagocytosis in vitro SO IMMUNOLOGY LA English DT Article; Proceedings Paper CT 15th Spring Meeting of the German-Society-of-Immunology CY MAR 01-04, 2000 CL COLOGNE, GERMANY SP German Soc Immunol ID HIV-1 TAT; T-CELLS; IMMUNE ACTIVATION; DENDRITIC CELLS; AIDS PATIENTS; GROWTH-FACTOR; PROTEIN; INFECTION; INTEGRIN; EXPRESSION AB Tat, the human immunodeficiency virus type 1 (HIV-1) transactivating protein, binds through its RGD-motif to human integrin receptors. Candida albicans, the commonest cause of mucosal candidiasis in subjects infected with HIV-1, also possesses RGD-binding capacity. The present Study reveals that Tat binds to C. albicans but not to C. tropicalis. Tat binding was markedly reduced by laminin and to a lesser extent by a complement C3 peptide containing the RGD motif, but not by a control peptide. The outgrowth of C. albicans was accelerated following binding of Tat, but phagocytosis of opsonizcd C. albicans was also increased after Tat binding. Thus, Tat binding promotes fungal virulence by inducing hyphae but may also reduce it by augmenting phagocytosis. The net effect of Tat in vivo is difficult to judge but in view of the many disease-promoting effects of Tat we propose that accelerating the formation of hyphae dominates over the augmentation of phagocytosis. C1 Univ Innsbruck, Inst Hyg & Social Med, A-6020 Innsbruck, Austria. Ludwig Boltzmann Inst AIDS Res, Innsbruck, Austria. Univ Dusseldorf, Inst Microbiol, D-4000 Dusseldorf, Germany. RP Gruber, A (reprint author), Dana Farber Canc Inst, 44 Binney St,JFB-809, Boston, MA 02115 USA. EM andreas_gruber@dfci.harvard.edu NR 58 TC 7 Z9 7 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 2001 VL 104 IS 4 BP 455 EP 461 DI 10.1046/j.1365-2567.2001.01328.x PG 7 WC Immunology SC Immunology GA 500LH UT WOS:000172628500013 PM 11899432 ER PT J AU Lenze, EJ Miller, MD Dew, MA Martire, LM Mulsant, BH Begley, AE Schulz, R Frank, E Reynolds, CF AF Lenze, EJ Miller, MD Dew, MA Martire, LM Mulsant, BH Begley, AE Schulz, R Frank, E Reynolds, CF TI Subjective health measures and acute treatment outcomes in geriatric depression SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE self-rated health; geriatric depression; antidepressants; interpersonal psychotherapy ID SELF-RATED HEALTH; QUALITY-OF-LIFE; PERCEIVED HEALTH; ELDERLY PATIENTS; MORTALITY; COMMUNITY; RECURRENT; DISEASE; OLDER; NORTRIPTYLINE AB Background Prior research suggests that elderly patients are less likely to respond to antidepressant treatment if they have low self-rated health. However, successful treatment for depression ha's been associated with improvement in self-rated health and other health measures. Objectives To examine measures of self-rated health, physical disability, and social function as predictors of treatment response in late-life depression, and to assess these same health measures as treatment outcomes. We hypothesized that greater impairment in these measures would predict poorer treatment response, and that these measures would show significant improvements with recovery from depression. Method Subjects were enrolled in a depression intervention study for people aged 60 and older with recurrent unipolar major depression; they were assessed with measures of self-rated health, physical disability, and social functioning at baseline and at the end of treatment. Baseline measures were compared between the 88 remitters. I I non-remitters, and seven dropouts. Additionally, changes in the measures were examined in subjects who recovered from the index depressive episode. Results Subjects with poorer self-rated health at baseline were more likely both to drop out of treatment and to not respond to adequate treatment. This relationship was independent of demographic measures, severity of depression, physical and social functioning, medical illness, personality, hopelessness, overall medication use, and side effects or non-compliance with treatment. Conclusion Although this finding is preliminary because of the small number of dropouts and non-remitters, it suggests that lower self-rated health may independently predict premature discontinuation of treatment for depression. Additionally, subjects who recovered from depression showed significant improvements in self-rated health, physical disability, and social functioning. Copyright (C) 2001 John Wiley Sons, Ltd. C1 Univ Pittsburgh, Sch Med, Dept Psychiat, Intervent Res Ctr Late Life Mood Disorders, Pittsburgh, PA 15213 USA. VA Pittsburgh Hlth Care Syst, GRECC, Pittsburgh, PA USA. RP Lenze, EJ (reprint author), Western Psychiat Inst & Clin, 3811 OHara St,Room E1124, Pittsburgh, PA 15213 USA. FU NIMH NIH HHS [K05 MH00295, K01 MH01683, P30 MH52247, R01 MH37869, T32 MH19986] NR 36 TC 23 Z9 23 U1 1 U2 5 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD DEC PY 2001 VL 16 IS 12 BP 1149 EP 1155 DI 10.1002/gps.503 PG 7 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 508BU UT WOS:000173068000005 PM 11748774 ER PT J AU Mintzer, J Faison, W Street, JS Sutton, VK Breier, A AF Mintzer, J Faison, W Street, JS Sutton, VK Breier, A TI Olanzapine in the treatment of anxiety symptoms due to Alzheimer's disease: a post hoc analysis SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Management of Psychoses in Older People CY NOV, 2000 CL BARCELONA, SPAIN SP Eli Lilly DE Behavoral and Psychological Symptoms of Dementia (BPSD); Alzheimer's disease; anxiety; pharmacological treatment; atypical antipsycholics ID BEHAVIORAL SYMPTOMS; NEUROPSYCHIATRIC INVENTORY; ELDERLY PATIENTS; DOUBLE-BLIND; DEMENTIA; DISORDERS; PLACEBO; TRIAL; HALOPERIDOL; PSYCHOSIS AB Background Alzheimer's disease (AD) is associated with both cognitive and behavioral symptoms. Agitation, hallucinations, delusions, aggression, irritability, and anxiety are observed in up to 90% of patients with dementia. Although new information has emerged in recent years on the treatment of psychosis and agitation in dementia, very little information is available about the treatment of anxiety symptoms in this population. Objectives To assess the efficacy and tolerability of olanzapine in the treatment of significant anxiety symptoms in patients with AD. Methods A post hoc analysis of a previously published study was performed. Those post hoc analysis evaluated the response to treatment with olanzapine of a subgroup of AD patients presenting with significant symptoms of anxiety. Patients were considered to have significant symptoms or anxiety if their baseline in the Nursing home version of the Neuropsychiatric Instrument NPI/NH anxiety scores were greater than or equal to 2. The analysis included 120 patients. Results Patients receiving olanzapine 5 mg/d were statistically significantly improved on the NPI/NH Anxiety item compared to those receiving placebo (olanzapine, 5 mg/d: -3.72; placebo: -1.67; p = 0.034). In the group of patients with clinically significant anxiety, somnolence was the only treatment-emergent event that was statistically different in any olanzapine treatment group compared with placebo (olanzapine 5 mg/d: 9 patients [25%], p = 0.034 10 mg/d: 7 [23%], p = 0.054; 15 mg/d: 7 [26%], p = 0.050; placebo: 1 [3.7%]). When controlling for treatment-emergent somnolence, the improvement in anxiety in the olanzapine 5 mg/d group remained Statistically significant (p = 0.049). Conclusions These findings suggest that olanzapine could be a safe and effective treatment for anxiety in Alzheimer's disease. Copyright (C), 2001 John Wiley Sons, Ltd. C1 Med Univ S Carolina, Alzheimers Res & Clin Programs, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC USA. Ralph H Johnson VA Med Ctr, Div Publ Psychiat, Charleston, SC USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Mintzer, J (reprint author), Med Univ S Carolina, Alzheimers Res & Clin Programs, 5900 Core Rd,Suite 203, N Charleston, SC 29406 USA. NR 33 TC 18 Z9 19 U1 2 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD DEC PY 2001 VL 16 SU 1 BP S71 EP S77 DI 10.1002/1099-1166(200112)16:1+<::AID-GPS568>3.0.CO;2-M PG 7 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 509EC UT WOS:000173132000009 PM 11748790 ER PT J AU Li, JZ Kuter, DJ AF Li, JZ Kuter, DJ TI The end is just the beginning: Megakaryocyte apoptosis and platelet release SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article DE megakaryocyte; apoptosis; platelet production; thrombopoietin; proplatelet ID PROTEIN-KINASE-C; TRANSCRIPTION FACTOR NF-E2; THROMBOPOIETIN SIGNAL-TRANSDUCTION; LEUKEMIA-CELL LINES; IN-VITRO; MPL-LIGAND; MYELODYSPLASTIC SYNDROMES; PROPLATELET FORMATION; BCL-X; CYTOPLASMIC MATURATION AB Under influence of hematopoietic growth factors, particularly thrombopoietin (TPO), hematopoietic stem cells in the bone marrow go through a process of commitment, proliferation, differentiation, and maturation and become mature megakaryocytes. At this critical point, terminally differentiated megakaryocytes face a new fate: ending the old life as mature megakaryocytes by induction of apoptosis and beginning a new life as platelets by fragmentation of the large megakaryocyte cytoplasm. These events are as important as megakaryocyte commitment, proliferation, differentiation, and maturation, but the molecular mechanisms regulating these events are not well established. Although TPO drives megakaryocyte proliferation and differentiation and protects hematopoietic progenitor cells from death, it does not appear to promote platelet release from terminally differentiated megakaryocytes. Although mature megakaryocyte apoptosis is temporally associated with platelet formation, premature megakaryocyte death directly causes thrombocytopenia in cancer therapy and in diseases such as myelodysplastic syndromes and human immunodeficiency virus infection. Also, genetic studies have shown that accumulation of megakaryocytes in bone marrow is not necessarily sufficient to produce platelets. All of these findings suggest that platelet release from megakaryocytes is an important and regulated aspect of platelet production, in which megakaryocyte apoptosis may also play a role. This review summarizes recent research progress on megakaryocyte apoptosis and platelet release. Hematol. 2001 74:365-374. (C) 2001 The Japanese Society of Hematology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Oncol Unit, Boston, MA 02114 USA. RP Li, JZ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Oncol Unit, Jackson 1021, Boston, MA 02114 USA. NR 88 TC 33 Z9 34 U1 0 U2 2 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 DEC PY 2001 VL 74 IS 4 BP 365 EP 374 DI 10.1007/BF02982078 PG 10 WC Hematology SC Hematology GA 508CL UT WOS:000173069600001 PM 11794690 ER PT J AU De Andrade, E Otomo-Corgel, J Pucher, J Ranganath, KA St George, N AF De Andrade, E Otomo-Corgel, J Pucher, J Ranganath, KA St George, N TI The intraosseous course of the mandibular incisive nerve in the mandibular symphysis SO INTERNATIONAL JOURNAL OF PERIODONTICS & RESTORATIVE DENTISTRY LA English DT Article ID INFERIOR ALVEOLAR NERVE; BONE-GRAFTS; OSSEOINTEGRATED IMPLANTS; CHIN; JAW AB The use of the mandibular symphysis as a source of autogenous bone grafting material has been well documented. Currently, no references in the literature describe the intraosseous distribution of the neurovascular complex anterior to the mental nerve with respect to its position buccolingually and apicocoronally. The objective of this study was to evaluate the distribution of the incisive nerve and measure its location buccolingually and apicocoronally in the anterior mandible and determine its possible significance to clinical practice. According to macroscopic dissection, the mandibular incisive nerve is a normal structure that typically extends closer to the midline than previously reported. To reduce postoperative neurovascular morbidity, this should be considered when using the mandibular symphysis as a source of autogenous bone or during placement of implants in the anterior mandible. C1 VA Greater Los Angeles Hlth Care Syst, Dept Periodontol, Sch Dent, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Periodontol, Sch Dent, Los Angeles, CA 90024 USA. Private Practice Ltd Periodont, Los Angeles, CA USA. VA Greater Los Angeles Hlth Care Syst, Postdoctoral Periodont Residency Program, Los Angeles, CA USA. VA Greater Los Angeles Hlth Care Syst, Dept Pathol & Lab Med, Los Angeles, CA USA. RP De Andrade, E (reprint author), 529 Artola St, Las Vegas, NV 89144 USA. NR 22 TC 27 Z9 27 U1 0 U2 0 PU QUINTESSENCE PUBL CO INC PI CAROL STREAM PA 551 NORTH KIMBERLY DR, CAROL STREAM, IL 60188-1881 USA SN 0198-7569 J9 INT J PERIODONT REST JI Int. J. Periodontics Restor. Dent. PD DEC PY 2001 VL 21 IS 6 BP 591 EP 597 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 508UK UT WOS:000173107900007 PM 11794570 ER PT J AU D'Amico, AV Manola, J Loffredo, M Lopes, L Nissen, K O'Farrell, DA Gordon, L Tempany, CM Cormack, RA AF D'Amico, AV Manola, J Loffredo, M Lopes, L Nissen, K O'Farrell, DA Gordon, L Tempany, CM Cormack, RA TI A practical method to achieve prostate gland immobilization and target verification for daily treatment SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; immobilization; radiation therapy; dose escalation ID RADIOTHERAPY DOSE-ESCALATION; CONFORMAL TREATMENT; RADIATION-THERAPY; CANCER; COMPLICATIONS; MORBIDITY AB Purpose: A practical method to achieve prostate immobilization and daily target localization for external beam radiation treatment is described. Methods and Materials: Ten patients who underwent prostate brachytherapy using permanent radioactive source placement were selected for study. To quantify prostate motion both with and without the presence of a specially designed inflatable intrarectal balloon, the computerized tomography-based coordinates of all intraprostatic radioactive sources were compared over 3 consecutive measurements at 1-min intervals. Results: The placement and inflation of the intrarectal balloon were well tolerated by all patients. The mean (range) displacement of the prostate gland when the intrarectal balloon was present vs. absent was 1.3 (0-2.2) mm vs. 1.8 (0-9.1) mm (p = 0.03) at 2 min respectively. The maximum displacement in any direction (anterior-posterior, superior-inferior, or right-left) when the intrarectal balloon was inflated vs. absent was reduced to less than or equal to1 mm from 4 mm. Conclusions: Both prostate gland immobilization and target verification are possible using a specially designed in datable intrarectal balloon. Using this device, the posterior margin necessary on the lateral fields to ensure dosimetric coverage of the entire prostate gland could be safely reduced to 5 mm and treatment could be set up and verified using a lateral portal image. (C) 2001 Elsevier Science Inc. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP D'Amico, AV (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Therapy, 75 Francis St,L-2 Level, Boston, MA 02115 USA. OI Cormack, Robert/0000-0001-5553-9984 NR 16 TC 76 Z9 78 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 DEC 1 PY 2001 VL 51 IS 5 BP 1431 EP 1436 DI 10.1016/S0360-3016(01)02663-3 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 498DU UT WOS:000172495200030 PM 11728704 ER PT J AU Kim, SK Dohlman, CH AF Kim, SK Dohlman, CH TI Causes of enlarged corneal nerves SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Symposium on Neuro-Ophthalmology CY MAR 13, 1999 CL MASSACHUSETTS ID ENDOCRINE NEOPLASIA TYPE-2A; GENE-RELATED PEPTIDE; ANTERIOR EYE SEGMENT; ACANTHAMOEBA-KERATITIS; RET PROTOONCOGENE; SUBSTANCE-P; IMMUNOREACTIVE NERVES; A-DELTA; LEPROSY; FIBERS C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Kim, SK (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. NR 81 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 2001 VL 41 IS 1 BP 13 EP 23 DI 10.1097/00004397-200101000-00004 PG 11 WC Ophthalmology SC Ophthalmology GA 391JH UT WOS:000166352500003 PM 11198139 ER PT J AU Sippel, KC AF Sippel, KC TI Ocular findings in neurofibromatosis type 1 SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Symposium on Neuro-Ophthalmology CY MAR 13, 1999 CL MASSACHUSETTS ID ANTERIOR VISUAL PATHWAY; OPTIC-NERVE GLIOMA; TERM FOLLOW-UP; VONRECKLINGHAUSEN NEUROFIBROMATOSIS; NF1 GENE; NATURAL-HISTORY; LONG-TERM; BENIGN NEUROFIBROMAS; HYPOTHALAMIC GLIOMAS; MALIGNANT-MELANOMA C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Sippel, KC (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. NR 93 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 2001 VL 41 IS 1 BP 25 EP 40 DI 10.1097/00004397-200101000-00005 PG 16 WC Ophthalmology SC Ophthalmology GA 391JH UT WOS:000166352500004 PM 11198145 ER PT J AU Perez, VL Foster, CS AF Perez, VL Foster, CS TI Uveitis with neurological manifestations SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Symposium on Neuro-Ophthalmology CY MAR 13, 1999 CL MASSACHUSETTS ID MENINGOCOCCAL DISEASE; HERPES-ZOSTER; COMPLICATIONS; VASCULITIS; FORM C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Perez, VL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. NR 37 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 2001 VL 41 IS 1 BP 41 EP 59 DI 10.1097/00004397-200101000-00006 PG 19 WC Ophthalmology SC Ophthalmology GA 391JH UT WOS:000166352500005 PM 11198146 ER PT J AU Zacks, DN D'Amico, DJ AF Zacks, DN D'Amico, DJ TI Maculopathies that resemble optic neuropathies SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Symposium on Neuro-Ophthalmology CY MAR 13, 1999 CL MASSACHUSETTS ID CENTRAL SEROUS CHORIORETINOPATHY; INDOCYANINE GREEN ANGIOGRAPHY; RECOVERIN-ASSOCIATED RETINOPATHY; MULTIFOCAL CHOROIDITIS; DISEASE; RETINITIS C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Zacks, DN (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. RI Zacks, David/I-4394-2013; OI Zacks, David/0000-0001-8592-5165 NR 39 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 2001 VL 41 IS 1 BP 61 EP 71 DI 10.1097/00004397-200101000-00007 PG 11 WC Ophthalmology SC Ophthalmology GA 391JH UT WOS:000166352500006 PM 11198147 ER PT J AU Harris, EW AF Harris, EW TI Leber's congenital amaurosis and RPE65 SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Symposium on Neuro-Ophthalmology CY MAR 13, 1999 CL MASSACHUSETTS ID RETINAL-PIGMENT EPITHELIUM; JOUBERT SYNDROME; OPTIC-NERVE; RETINITIS PIGMENTOSA; MICROSOMAL PROTEIN; GENE; ASSOCIATION; KERATOCONUS; MUTATIONS; PHOTORECEPTOR C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Harris, EW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 84 TC 13 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 2001 VL 41 IS 1 BP 73 EP 82 DI 10.1097/00004397-200101000-00008 PG 10 WC Ophthalmology SC Ophthalmology GA 391JH UT WOS:000166352500007 PM 11198148 ER PT J AU Ray, S Gragoudas, E AF Ray, S Gragoudas, E TI Neuroretinitis SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Symposium on Neuro-Ophthalmology CY MAR 13, 1999 CL MASSACHUSETTS ID UNILATERAL SUBACUTE NEURORETINITIS; CAT-SCRATCH DISEASE; IDIOPATHIC STELLATE NEURORETINITIS; HUMAN-IMMUNODEFICIENCY-VIRUS; LYME BORRELIOSIS; OPTIC NEURITIS; MANIFESTATIONS; TOXOPLASMOSIS; BAYLISASCARIS; DIAGNOSIS C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Ray, S (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. NR 46 TC 25 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 2001 VL 41 IS 1 BP 83 EP 102 DI 10.1097/00004397-200101000-00009 PG 20 WC Ophthalmology SC Ophthalmology GA 391JH UT WOS:000166352500008 PM 11198149 ER PT J AU Grant, CA Barson, EL AF Grant, CA Barson, EL TI Treatable forms of retinitis pigmentosa associated with systemic neurological disorders SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Symposium on Neuro-Ophthalmology CY MAR 13, 1999 CL MASSACHUSETTS ID TOCOPHEROL TRANSFER PROTEIN; ACID STORAGE DISEASE; VITAMIN-E-DEFICIENCY; REFSUMS DISEASE; LIVER C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Grant, CA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. NR 33 TC 9 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 2001 VL 41 IS 1 BP 103 EP 110 DI 10.1097/00004397-200101000-00010 PG 8 WC Ophthalmology SC Ophthalmology GA 391JH UT WOS:000166352500009 PM 11198137 ER PT J AU Farkas, RH Grosskreutz, CL AF Farkas, RH Grosskreutz, CL TI Apoptosis, neuroprotection, and retinal ganglion cell death: An overview SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Symposium on Neuro-Ophthalmology CY MAR 13, 1999 CL MASSACHUSETTS ID OPEN-ANGLE GLAUCOMA; NERVE-FIBER LAYER; HUMAN OPTIC-NERVE; LOW-TENSION GLAUCOMA; SPINAL-CORD INJURY; CALCIUM-CHANNEL ANTAGONISTS; SCANNING LASER POLARIMETRY; NEURORETINAL RIM AREA; METHYL-D-ASPARTATE; NITRIC-OXIDE C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Farkas, RH (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 140 TC 55 Z9 59 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 2001 VL 41 IS 1 BP 111 EP 130 DI 10.1097/00004397-200101000-00011 PG 20 WC Ophthalmology SC Ophthalmology GA 391JH UT WOS:000166352500010 PM 11198138 ER PT J AU Lit, ES D'Amico, DJ AF Lit, ES D'Amico, DJ TI Retinal manifestations of morning glory disc syndrome SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Symposium on Neuro-Ophthalmology CY MAR 13, 1999 CL MASSACHUSETTS ID DETACHMENT; PATHOGENESIS C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Lit, ES (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 35 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 2001 VL 41 IS 1 BP 131 EP 138 DI 10.1097/00004397-200101000-00012 PG 8 WC Ophthalmology SC Ophthalmology GA 391JH UT WOS:000166352500011 PM 11198140 ER PT J AU Ambati, BK Rizzo, JF AF Ambati, BK Rizzo, JF TI Nonglaucomatous cupping of the optic disc SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Symposium on Neuro-Ophthalmology CY MAR 13, 1999 CL MASSACHUSETTS ID LOW-TENSION GLAUCOMA; NERVE DAMAGE; NEUROPATHY; ATROPHY; EYES; COMPRESSION; SIZE; PITS; HEAD C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Ambati, BK (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 57 TC 13 Z9 15 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 2001 VL 41 IS 1 BP 139 EP 149 DI 10.1097/00004397-200101000-00013 PG 11 WC Ophthalmology SC Ophthalmology GA 391JH UT WOS:000166352500012 PM 11198141 ER PT J AU Afshari, NA Afshari, MA Lessell, S AF Afshari, NA Afshari, MA Lessell, S TI Temporal arteritis SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Symposium on Neuro-Ophthalmology CY MAR 13, 1999 CL MASSACHUSETTS ID GIANT-CELL ARTERITIS; ERYTHROCYTE SEDIMENTATION-RATE; POLYMYALGIA RHEUMATICA; EPIDEMIOLOGY; BIOPSY; MINNESOTA; REGIMENS; COUNTY C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Afshari, NA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 36 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 2001 VL 41 IS 1 BP 151 EP 158 DI 10.1097/00004397-200101000-00014 PG 8 WC Ophthalmology SC Ophthalmology GA 391JH UT WOS:000166352500013 PM 11198142 ER PT J AU Afshari, MA Afshari, NA Fulton, AB AF Afshari, MA Afshari, NA Fulton, AB TI Cortical visual impairment in infants and children SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Symposium on Neuro-Ophthalmology CY MAR 13, 1999 CL MASSACHUSETTS ID CEREBRAL BLINDNESS; EVOKED-POTENTIALS; CHILDHOOD; PROGNOSIS; VISION; FIELD; BLINDSIGHT; ETIOLOGY C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Afshari, MA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. RI Osman, Sanha/B-4056-2012 NR 53 TC 13 Z9 13 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 2001 VL 41 IS 1 BP 159 EP 169 DI 10.1097/00004397-200101000-00015 PG 11 WC Ophthalmology SC Ophthalmology GA 391JH UT WOS:000166352500014 PM 11198143 ER PT J AU Shen, TT Sakai, O Curtin, HD Rizzo, JF AF Shen, TT Sakai, O Curtin, HD Rizzo, JF TI Magnetic resonance imaging of primary anterior visual pathway tumors SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Symposium on Neuro-Ophthalmology CY MAR 13, 1999 CL MASSACHUSETTS ID OPTIC-NERVE SHEATH; COMPUTED-TOMOGRAPHY; GLIOMA; NEUROFIBROMATOSIS; MENINGIOMA; ADULTHOOD; MR C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Shen, TT (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 33 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 2001 VL 41 IS 1 BP 171 EP 180 DI 10.1097/00004397-200101000-00016 PG 10 WC Ophthalmology SC Ophthalmology GA 391JH UT WOS:000166352500015 PM 11198144 ER PT J AU Sweet, RA Pollock, BG Sukonick, DL Mulsant, BH Rosen, J Klunk, WE Kastango, KB DeKosky, ST Ferrell, RE AF Sweet, RA Pollock, BG Sukonick, DL Mulsant, BH Rosen, J Klunk, WE Kastango, KB DeKosky, ST Ferrell, RE TI The 5-HTTPR polymorphism confers liability to a combined phenotype of psychotic and aggressive behavior in Alzheimer disease SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Article DE serotonin transporter; Alzheimer disease; genetic; polymorphism; psychosis ID SEROTONIN TRANSPORTER GENE; COGNITIVE DECLINE; SYMPTOMS; DEMENTIA; PREDICTORS; DELUSIONS; PROGRESSION; DEPRESSION; AGITATION; PROMOTER AB Background: Psychotic symptoms in subjects with Alzheimer disease (AD+psychosis, AD+P) are a marker for a distinct phenotype characterized by more rapid cognitive and functional decline and a liability to aggressive behaviors. We recently found that AD subjects homozygous for long alleles (1) of an insertion/deletion polymorphism in the promoter region of the serotonin transporter (5-HTTPR) had elevated rates of aggressive behavior. Objective: To examine whether the 5-HTTPR ll genotype confers an increased risk of AD+P, and of the combined AD+P/aggressive phenotype. Methods: The 5-HTTPR genotype was determined in 332 subjects diagnosed with possible or probable AD. All subjects received structured psychiatric assessments and were categorized with regard to their history of aggressive behaviors and psychotic symptoms. Results: Consistent with other reports, AD+P was associated with a significant increased risk for aggressive behavior. AD+P and aggression were both significantly associated with 5-HTTPR ll genotype and with an increased I allele frequency. Subjects with the combined behavioral phenotype (AD+P and aggressive behavior) had the highest rate of ll genotype and highest l allele frequency. Conclusion: The 5-HTTPR I allele appears to confer risk for the combined AD+P/aggressive phenotype. Confirmation of this association in a similar behaviorally well-characterized independent sample is needed. C1 Univ Pittsburgh, Grad Sch Publ Hlth, Dept Psychiat, Div Geriatr & Neuropsychiat, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Neurol, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Sch Med, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. VA Pittsburgh Hlth Care Syst, GRECC, Pittsburgh, PA USA. RP Sweet, RA (reprint author), Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA. OI Klunk, William/0000-0001-5512-0251 FU NIA NIH HHS [AG05133]; NIMH NIH HHS [MH52247, MH01509, MH01613, MH59666] NR 34 TC 72 Z9 73 U1 3 U2 8 PU SPRINGER PUBLISHING CO PI NEW YORK PA 536 BROADWAY, NEW YORK, NY 10012 USA SN 1041-6102 J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PD DEC PY 2001 VL 13 IS 4 BP 401 EP 409 DI 10.1017/S1041610201007827 PG 9 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA 541QP UT WOS:000174995500002 PM 12003247 ER PT J AU Asch, SM Gifford, AL Bozzette, SA Turner, B Mathews, WC Kuromiya, K Cunningham, W Andersen, R Shapiro, M Rastegar, A McCutchan, JA AF Asch, SM Gifford, AL Bozzette, SA Turner, B Mathews, WC Kuromiya, K Cunningham, W Andersen, R Shapiro, M Rastegar, A McCutchan, JA TI Underuse of primary Mycobacterium avium complex and Pneumocystis carinii prophylaxis in the United States SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 12th World AIDS Conference CY JUN 28-JUL 03, 1998 CL GENEVA, SWITZERLAND DE MAC prophylaxis; PCP prophylaxis; HIV guidelines; HIV-positive; HIV prevention ID HIV-INFECTED ADULTS; ANTIRETROVIRAL THERAPY; GUIDELINES; ADHERENCE; PREVENTION; DISEASE AB Background: Little is known about the rates of Mycobacterium avium complex (MAC) and Pneumocystis carinii (PCP) prophylaxis adherence to guidelines and how they have changed after introduction of effective antiretroviral therapy. Objective: To determine rates of primary prophylaxis for MAC and PCP and to evaluate the influence of sociodemographic characteristics. region, and provider experience. Design: National probability sample cohort of HIV patients in care. Setting: One hundred sixty HIV health care providers. Patients: A total of 2864 patients interviewed in 1996 to 1997 (68% response) and 2267 follow-up interviews, representing 65% of surviving sampled patients (median follow-up, 15.1 months). Measurements: Use of prophylactic drugs, most recent CD4 count, sociodemographics, and regional and total HIV patients/providers. Results: Of patients eligible for primary MAC prophylaxis (most recent CD4 count < 50/mm(3)), 41% at baseline and 40% at follow-up patients were treated. Of patients eligible for primary PCP prophylaxis (i.e., those with CD4 counts < 200/mm(3);). 64% and 72% were treated, respectively. MAC prophylaxis at baseline was less likely in African American (adjusted odds ratio [OR], 35; 95% confidence interval [CI], 0.20-0.59), Hispanic (OR, 27; 95% CI, 0.08-0.94) and less-educated (OR, 0.61; 95% Cl, 0.36-1.0) patients and more likely in U. S. geographic regions in the Pacific West (OR, 4.9; 95% Cl, 1.0-23) and Midwest (OR, 6.4; 95% Cl, 1.2-33) and in practices with more HIV patients. Conclusions: Most eligible patients did not receive MAC prophylaxis; PCP prophylaxis rates were better but still suboptimal. Our results support outreach efforts to African Americans, Hispanics, the less educated, and those in the northeastern United States and in practices with fewer HIV patients. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. San Diego Hlth Syst, San Diego, CA USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Univ Calif San Diego, San Diego, CA 92103 USA. RAND Hlth, Santa Monica, CA USA. Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. RP Asch, SM (reprint author), VA Greater Los Angeles Healthcare Syst, 111G,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Mathews, William/E-4451-2010 OI Mathews, William/0000-0002-2352-0725 FU AHRQ HHS [U-01HS08578] NR 11 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD DEC 1 PY 2001 VL 28 IS 4 BP 340 EP 344 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 494YH UT WOS:000172313100006 PM 11707670 ER PT J AU Bauer, MS Williford, WO Dawson, EE Akiskal, HS Altshuler, L Fye, C Gelenberg, A Glick, H Kinosian, B Sajatovic, M AF Bauer, MS Williford, WO Dawson, EE Akiskal, HS Altshuler, L Fye, C Gelenberg, A Glick, H Kinosian, B Sajatovic, M TI Principles of effectiveness trials and their implementation in VA cooperative study #430: 'Reducing the efficacy-effectiveness gap in bipolar disorder' SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE bipolar disorder; clinical trial; outcome assessment (health care); costs and cost analysis (cost-benefit analysis); United States Department of Veterans Affairs; National Institute of Mental Health ID MENTAL-HOSPITAL TREATMENT; LITHIUM CARBONATE PROPHYLAXIS; ASSERTIVE COMMUNITY TREATMENT; FOLLOW-UP; NATIONAL-INSTITUTE; CLINICAL-PRACTICE; MANIA; ILLNESS; READMISSIONS; CARE AB Despite the availability of efficacious treatments for bipolar disorder, their effectiveness in general clinical practice is greatly attenuated, resulting in what has been called an 'efficacy-effectiveness gap'. In designing VA Cooperative Studies Program (CSP) Study #430 to address this gap, nine principles for conducting an effectiveness (in contrast to an efficacy) study were identified. These principles are presented and discussed, with specific aspects of CSP #430 serving as illustrations of how they can be implemented in an actual study. CSP #430 hypothesizes that an integrated, clinic-based treatment delivery system that emphasizes ( I) algorithm-driven somatotherapy, (2) standardized patient education. and (3) easy access to a single primary mental health care provider to maximize continuity-of-care, will address the efficacy-effectiveness gap and improve disease. functional, and economic outcome. It is an 11-site, randomized controlled clinical trial of this multi-modal, clinic-based intervention versus usual VA care running from 1997 to 2003. The trial has enrolled 191 subjects in each arm. using minimal exclusion criteria to maximize the external validity of the study. Subjects are followed for 3 years. The intervention is highly specified in a series of operations manuals for each of the three components. Several continuous quality improvement (CQI) interventions, process measures, and statistical techniques deal with drift of care in both the intervention and usual care arms to ensure the internal validity of the study. CSP #430 is designed to have impact well beyond the VA, since it evaluates a basic health care operational principle: that augmenting ambulatory access for major mental illness will improve outcome and reduce overall treatment costs. If results are positive, this study will provide a reason to reconsider the prevailing trend toward limitation of ambulatory services that is characteristic of many managed care systems today. Published by Elsevier Science B.V. C1 Providence VA Med Ctr, Providence, RI USA. Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. VA Cooperat Studies Coordinating Ctr, Perry Point, MD USA. Univ Calif Los Angeles, San Diego, CA USA. W Los Angeles VA Med Ctr, Los Angeles, CA USA. VA Cooperat Studies Program Clin Res Pharm Coordi, Albuquerque, NM USA. Univ Arizona, Dept Psychiat, Tucson, AZ USA. Univ Penn, Sect Gen Med, Philadelphia, PA 19104 USA. Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. VA Med Ctr, Cleveland, OH USA. RP Bauer, MS (reprint author), Brown Univ, VAMC, 116R, Providence, RI 02908 USA. RI Sajatovic, Martha/I-8001-2014 NR 90 TC 60 Z9 60 U1 5 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD DEC PY 2001 VL 67 IS 1-3 BP 61 EP 78 AR PII S0165-0327(01)00440-2 DI 10.1016/S0165-0327(01)00440-2 PG 18 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 535FD UT WOS:000174633800006 PM 11869753 ER PT J AU Yerevanian, BI Koek, RJ Ramdev, S AF Yerevanian, BI Koek, RJ Ramdev, S TI Anxiety disorders comorbidity in mood disorder subgroups: data from a mood disorders clinic SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE bipolar disorder; mood disorders; epidemiology; comorbidity ID OBSESSIVE-COMPULSIVE DISORDER; PANIC DISORDER; BIPOLAR DISORDER; UNIPOLAR DEPRESSION; MAJOR DEPRESSION; FAMILY HISTORY; MANIA; CONNECTION; HYPOMANIA; PHOBIA AB Background: Previous research has identified a high rate of anxiety disorders comorbidity in patients with a primary mood disorder diagnosis. Discrepancies between studies in the comorbidity prevalence of specific anxiety disorders in mood disorders, and of anxiety disorders comorbidity between unipolar depression and bipolar mood disorder are in part due to differences in sampling and diagnostic assessment methodology. Method: The authors reviewed the charts of 138 patients who received the SCID-P for DSM-III on enrollment in a Mood Disorders Clinic during the period 1982 through 1988. The comorbidity of specific DSM-III Anxiety Disorders with specific mood disorders was determined and comparatively examined using non-parametric statistics. Results: There was high overall comorbidity of anxiety disorders that did not differ between bipolar and unipolar subjects. There were no differences in the comorbidity of individual anxiety disorder diagnoses in the unipolar vs. bipolar groups. However, in unipolar patients with, compared to those without an additional diagnosis of dysthymia, there was greater overall anxiety disorders comorbidity, with a particularly high prevalence of generalized anxiety disorder. Limitations: The subgroup of patients with bipolar I disorder was relatively small (N = 8). Conclusion: Mood and anxiety disorders comorbidity is complex and presents a continuing challenge for both clinicians and researchers. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. VA Greater Los Angeles Hlth Care Syst, Sepulveda Mood Disorders Clin, Sepulveda, CA USA. RP Yerevanian, BI (reprint author), 16111 Plummer St,116A-11, Sepulveda, CA 91343 USA. NR 36 TC 21 Z9 22 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD DEC PY 2001 VL 67 IS 1-3 BP 167 EP 173 AR PII S0165-0327(01)00448-7 DI 10.1016/S0165-0327(01)00448-7 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 535FD UT WOS:000174633800017 PM 11869764 ER PT J AU Nakamura, H Luster, AD Nakamura, T In, KH Sonna, LA Deykin, A Israel, E Drazen, JM Lilly, CM AF Nakamura, H Luster, AD Nakamura, T In, KH Sonna, LA Deykin, A Israel, E Drazen, JM Lilly, CM TI Variant eotaxin: Its effects on the asthma phenotype SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE eotaxin; single-nucleotide polymorphism; chemokines; human genetics; asthma ID MESSENGER-RNA; BRONCHOALVEOLAR LAVAGE; MOLECULAR-CLONING; RECEPTOR CCR3; EXPRESSION; LUNG; IDENTIFICATION; CHEMOKINE; CELLS; HYPERRESPONSIVENESS AB Background: Eotaxin, a CC chemokine expressed in the asthmatic lung, has been associated with impaired lung function. The role of its variant form is unknown. Objective: The purpose of this study was to detect the population frequency and effects of a known single-nucleotide polymorphism in the eotaxin gene in which a threonine residue (THR23) is substituted for the wild-type alanine (ALA(23)) at the 23rd amino acid at the terminus of the peptide leader sequence. Methods: We measured eotaxin protein secretion in 293 cells transfected with expression vectors and in PBMCs obtained from individuals bearing the alternative forms of the gene. A case-control study of plasma eotaxin levels and eosinophil counts, a comparison of baseline lung function by genotype in a population of 806 subjects with asthma, and a comparison of the allele frequency with a nonasthmatic population were performed. Results: Human 293 cells and PBMCs with THR23 variant eotaxin secreted significantly less eotaxin protein than did ALA(23)-bearing cells. In the case-control study, THR23-THR23 individuals had lower plasma levels of eotaxin (310 [240-350] vs 420 [270-700] pg/mL; P < .05) and eosinophil counts (120 [5-220] vs 190 [110-470] cells/L; P < .05) than ALA(23)-ALA(23) subjects; heterozygous subjects had intermediate levels. Higher levels of lung function were associated with THR23 eotaxin (percent of predicted FEV1, 65% 3.5% [THR23-THR23] VS 58% 0.9% [THR23-ALA(23)] and 56% +/- 0.5% [ALA(23)-ALA(23)]; P < .05). Conclusion: The THR23 variant is associated with both decreased eosinophil counts and higher levels of lung function in subjects with asthma. C1 Brigham & Womens Hosp, Dept Med, Div Resp, Combined Program Pulm & Crit Care Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Harvard Med Sch, Charlestown, MA USA. USA, Environm Med Res Inst, Natick, MA 01760 USA. RP Lilly, CM (reprint author), Brigham & Womens Hosp, Dept Med, Div Resp, Combined Program Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL/AI-64104]; NIAID NIH HHS [AI 40618] NR 27 TC 36 Z9 37 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 2001 VL 108 IS 6 BP 946 EP 953 DI 10.1067/mai.2001.120135 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 505WK UT WOS:000172938400010 PM 11742272 ER PT J AU Merriam, GR Barsness, S Buchner, D Kletke, M Larsen, LH Moe, KE Schwartz, RS Vitiello, MV AF Merriam, GR Barsness, S Buchner, D Kletke, M Larsen, LH Moe, KE Schwartz, RS Vitiello, MV TI Growth hormone releasing hormone treatment in normal aging SO JOURNAL OF ANTI-AGING MEDICINE LA English DT Article ID HEALTHY OLDER MEN; FACTOR-I; BODY-COMPOSITION; ELDERLY SUBJECTS; GH; AGE; ADULTS; SECRETION; PEPTIDE; SECRETAGOGUE AB Because the aging pituitary remains responsive to stimulation by growth hormone (GH) secret-agogues-GHRH, ghrelin, and their mimetics-these compounds could potentially be used instead of GH itself to increase GH secretion in aging. The factors contributing to the age-related decline in GH secretion are largely extrapituitary, and with repeated or continuous administration GHS's can significantly increase GH secretion and elevate levels of insulin-like growth factor-I (IGF-I) to the young adult normal range. Treatment with GHS's has both theoretical and practical potential advantages over GH-preserving feedback regulation by IGF-I to buffer against overtreatment, and yielding a more physiologic pulsatile pattern of GH secretion. Non-peptide GHS's can also be administered orally. This review focuses primarily on results using GHRH; studies with ghrelin agonists are reviewed in detail in other articles from this symposium. We and others have shown that GHRH stimulates the brisk release of GH in healthy seniors, and that repeated administration of GHRH elevates IGF-I in a dose-dependent manner. In two 6-month treatment studies in healthy older women and men, subcutaneous injections of GHRH(1-29)NH2, self-administered once nightly, chronically increased nighttime GH secretion and produced sustained elevations of IGF-I levels. IGF-I increases were greatest in men, averaging 30%. Women not taking estrogen showed somewhat lesser increases (23%), and women taking oral estrogen replacement had no significant increase despite the greatest increments in GH secretion. Lean body mass increased; body fat was reduced by an average of 5-8%, with greatest effect on abdominal visceral fat; and again this effect was blunted in estrogenized women. Effects on physical function varied by group. In nonestrogenized women, physical function deteriorated in those receiving placebo; some measures were stabilized in women receiving GHRH. These changes were not significant in estrogenized subjects. GHRH appeared to improve cognitive function, especially in domains sensitive to changes in processing speed. The formulation of GHRH used in these studies is short-acting, with effects ending within a few hours. Perhaps for this reason, late-night GH secretion decreased after the initial GHRH-stimulated surge, and sleep quality was not improved. Side effects were those of fluid retention and were generally mild. The duration of these studies do not allow inferences to be drawn on prevention of the onset of clinical features of frailty. Thus, 6-month treatment with once-daily GHRH can elevate GH secretion and IGF-I, and improve body composition in a manner similar to the effects of GH. Effects on physical function are equivocal. Effects on cognition are encouraging but preliminary. The current GHRH formulation is too short-acting to provide optimal effects. C1 Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Merriam, GR (reprint author), Univ Washington, VA Puget Sound HCS, 9600 Vet Dr SW,Res A-151,Bldg 18S,Room 5, Lakewood, WA 98493 USA. OI Vitiello, Michael/0000-0002-9776-0473 NR 52 TC 2 Z9 2 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1094-5458 J9 J ANTI-AGING MED JI J. Anti-Aging Med. PD WIN PY 2001 VL 4 IS 4 BP 331 EP 343 DI 10.1089/10945450152850650 PG 13 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 535DR UT WOS:000174630400005 ER PT J AU Harris, WH AF Harris, WH TI A Festschrift celebrating William H. Harris, MD SO JOURNAL OF ARTHROPLASTY LA English DT Biographical-Item C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Harris, WH (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD DEC PY 2001 VL 16 IS 8 SU 1 BP 1 EP 1 PG 1 WC Orthopedics SC Orthopedics GA 503ZQ UT WOS:000172831900001 ER PT J AU Harris, WH AF Harris, WH TI My first 50 years of orthopaedic surgery SO JOURNAL OF ARTHROPLASTY LA English DT Biographical-Item C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. RP Harris, WH (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Jackson 1126, Boston, MA 02114 USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD DEC PY 2001 VL 16 IS 8 SU 1 BP 2 EP 7 DI 10.1054/arth.2001.28357 PG 6 WC Orthopedics SC Orthopedics GA 503ZQ UT WOS:000172831900002 PM 11742443 ER PT J AU Muratoglu, OK Bragdon, CR O'Connor, D Perinchief, RS Estok, DM Jasty, M Harris, WH AF Muratoglu, OK Bragdon, CR O'Connor, D Perinchief, RS Estok, DM Jasty, M Harris, WH TI Larger diameter femoral heads used in conjunction with a highly cross-linked ultra-high molecular weight polyethylene - A new concept SO JOURNAL OF ARTHROPLASTY LA English DT Article DE highly cross-linked ultra-high; molecular weight polyethylene (UHMWPE); larger femoral head sizes; wear; range of motion; stability; dislocation ID WEAR AB The design of femoral and acetabular components of metal-on-polyethylene total hip arthroplasty implants has been dominated by the limitations of the wear properties of ultra-high molecular weight polyethylene (UHMWPE). As a result, the commonest femoral head diameters used range from 22 to 32 mm, the latter producing maximal volumetric wear. Cross-linking has been shown to improve significantly the wear resistance of acetabular components when tested in vitro against conventional femoral head sizes (22-32 mm). We expanded the study of the wear behavior of I type of electron-beam cross-linked UHMWPE with femoral head diameters ranging from 22 to 46 mm. The simulated gait studies showed that wear was independent of head size for the range of femoral head sizes studied. Even for the 46-mm femoral head, wear was reduced significantly using criteria of gravimetric and geometric measurements and morphologic appearance of the machining marks out to 11 million cycles of simulated gait. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. RP Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, GRJ 1206,55 Fruit St, Boston, MA 02114 USA. EM orhun@alum.mit.edu NR 23 TC 117 Z9 128 U1 0 U2 9 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD DEC PY 2001 VL 16 IS 8 SU 1 BP 24 EP 30 DI 10.1054/arth.2001.28376 PG 7 WC Orthopedics SC Orthopedics GA 503ZQ UT WOS:000172831900006 PM 11742447 ER PT J AU Burroughs, BR Golladay, GJ Hallstrom, B Harris, WH AF Burroughs, BR Golladay, GJ Hallstrom, B Harris, WH TI A novel constrained acetabular liner design with increased range of motion SO JOURNAL OF ARTHROPLASTY LA English DT Article DE constrained acetabular component; total hip dislocation ID TOTAL HIP-ARTHROPLASTY; COMPONENTS; REVISION; CUP AB One treatment strategy for recurrent dislocation after total hip arthroplasty is the use of a constrained acetabular component. A major drawback of currently available constrained components is the limited range of motion (ROM). We present a novel constrained component that employs a monopolar, highly cross-linked polyethylene liner with cutouts oriented to allow increased ROM, while maintaining constraint against dislocation. ROM and lever-out tests comparing this novel design with a conventional constrained component showed that the cutaway monopolar component allowed ROM substantially greater than a currently available design. The lever-out torque for the cutaway monopolar constrained component was 243% higher than the conventional constrained component. This novel constrained acetabular component offers promise for providing excellent constraint against dislocation, while maintaining a wide ROM. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. RP Harris, WH (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Jackson 1126, Boston, MA 02114 USA. NR 24 TC 23 Z9 23 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD DEC PY 2001 VL 16 IS 8 SU 1 BP 31 EP 36 DI 10.1054/arth.2001.28361 PG 6 WC Orthopedics SC Orthopedics GA 503ZQ UT WOS:000172831900007 PM 11742448 ER PT J AU Hauser, DL Wessinger, SJ Condon, RT Golladay, GJ Hoeffel, DP Gillis, DJ Merrill, DR Chaisson, D Freiberg, AA Estok, DM Rubash, HE Malchau, H Harris, WH AF Hauser, DL Wessinger, SJ Condon, RT Golladay, GJ Hoeffel, DP Gillis, DJ Merrill, DR Chaisson, D Freiberg, AA Estok, DM Rubash, HE Malchau, H Harris, WH TI An electronic database for outcome studies that includes digital radiographs SO JOURNAL OF ARTHROPLASTY LA English DT Article DE outcomes; total hip; arthroplasty; registry; digital radiology; internet ID TOTAL HIP-ARTHROPLASTY; REGISTER AB We report on acquisition of key data from the clinical medical record, surgical data, radiologic studies, and patient surveys for a novel digital total hip arthroplasty (THA) registry that includes electronic capture of digital radiographic ima-es into a database on an internet platform for query. We now have the ability to collect demographic and operative data, including the operative note, discharge summary, surgery data, and Digital Imaging Communications in Medicine (DICOM) radiology images. Steps are being completed to assemble office encounters, hospital procedural codes, and implant bar codes. Two examples include a THA surgery record and a THA outcome study with plain radiograph set. Analysis of such data could suggest ways to improve clinical practice. C1 Massachusetts Gen Hosp, Orthopaed Biomech Lab, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Harris, WH (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech Lab, Dept Orthopaed Surg, GRJ 1126,55 Fruit St, Boston, MA 02114 USA. NR 17 TC 5 Z9 5 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD DEC PY 2001 VL 16 IS 8 SU 1 BP 71 EP 75 DI 10.1054/arth.2001.28366 PG 5 WC Orthopedics SC Orthopedics GA 503ZQ UT WOS:000172831900013 PM 11742454 ER PT J AU Li, G Zayontz, S Most, E Otterberg, E Sabbag, K Rubash, HE AF Li, G Zayontz, S Most, E Otterberg, E Sabbag, K Rubash, HE TI Cruciate-retaining and cruciate-substituting total knee arthroplasty - An in vitro comparison of the kinematics under muscle loads SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total knee arthroplasty; posterior cruciate ligament (PCL); kinematics; cam-spine mechanism forces; robotics ID PROSTHESIS; BEARING; DESIGN; FORCES AB The kinematics of posterior cruciate ligament (PCL)-retaining (PCR) and PCL-substituting (PS) total knee arthroplasty (TKA) were compared directly in a robotic, in vitro study, and the forces in the PCL and cam-spine mechanism were measured from 0 degrees to 120 degrees of flexion. The forces in the PCL after PCR TKA and in cam-spine contact after PS TKA increased only at a flexion of greater than or equal to 90 degrees. Posterior translation of the lateral femoral condyle was significantly greater than translation of the medial femoral condyle in the intact knees, consistent with femoral rollback and internal tibial rotation. The PCR and PS TKAs partially restored these kinematics when the knee flexed > 60 degrees (ie, when the forces increased in the PCL and ca-m-spine mechanism), whereas the PCL-deficient TKA failed to do so. The results reflect the importance of the PCL and cam-spine mechanism after PCL retention and substitution in TKA and confirm the necessity for either one, if knee kinematics are to be restored even partially. C1 Harvard Univ, Sch Med, Orthopaed Biomech Lab, MGH,BIDMC, Boston, MA 02215 USA. RP Li, G (reprint author), Harvard Univ, Sch Med, Orthopaed Biomech Lab, MGH,BIDMC, 330 Brookline Ave,RN 115, Boston, MA 02215 USA. NR 20 TC 45 Z9 46 U1 0 U2 7 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD DEC PY 2001 VL 16 IS 8 SU 1 BP 150 EP 156 DI 10.1054/arth.2001.28367 PG 7 WC Orthopedics SC Orthopedics GA 503ZQ UT WOS:000172831900027 PM 11742468 ER PT J AU Hendrickson, EL Plotnikova, J Mahajan-Miklos, S Rahme, LG Ausubel, FM AF Hendrickson, EL Plotnikova, J Mahajan-Miklos, S Rahme, LG Ausubel, FM TI Differential roles of the Pseudomonas aeruginosa PA14 rpoN gene in pathogenicity in plants, nematodes, insects, and mice SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ALTERNATIVE SIGMA-FACTOR; SYRINGAE PV. MACULICOLA; VIRULENCE FACTORS; CAENORHABDITIS-ELEGANS; INNATE IMMUNITY; BACTERIAL PATHOGENESIS; EPITHELIAL-CELLS; RNA-POLYMERASE; SECRETION; PROTEIN AB We cloned the rpoN (ntrA, glnF) gene encoding the alternate sigma factor sigma (54) from the opportunistic multihost pathogen Pseudomonas aeruginosa strain PA14. A marker exchange protocol was used to construct the PA14 rpoN insertional mutation rpoN::Gen(r) PA14 rpoN::Gen(r) synthesized reduced levels of pyocyanin and displayed a variety of phenotypes typical of rpoN mutants, including a lack of motility and the failure to grow on nitrate, glutamate, or histidine as the sole nitrogen source. Compared to wild-type PA14, rpoN::Gen(r) was ca. 100-fold less virulent in a mouse thermal injury model and was significantly impaired in its ability to kill the nematode Caenorhabditis elegans. In an Arabidopsis thaliana leaf infectivity assay, although rpoN::Gen(r) exhibited significantly reduced attachment to trichomes, stomata, and the epidermal cell surface, did not attach perpendicularly to or perforate mesophyll cell walls, and proliferated less rapidly in Arabidopsis, leaves, it nevertheless elicited similar disease symptoms to wild-type P. aeruginosa PA14 at later stages of infection. rpoN.:Gen was not impaired in virulence in a Galleria mellonella (greater wax moth) pathogenicity model. These data indicate that rpoN does not regulate the expression of any genes that encode virulence factors universally required for P. aeruginosa pathogenicity in diverse hosts. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Shriners Burns Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Ausubel, FM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Wellman 10, Boston, MA 02114 USA. FU NIGMS NIH HHS [R01 GM048707, GM48707, R37 GM048707] NR 62 TC 77 Z9 85 U1 1 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 2001 VL 183 IS 24 BP 7126 EP 7134 DI 10.1128/JB.183.24.7126-7134.2001 PG 9 WC Microbiology SC Microbiology GA 496HQ UT WOS:000172390500019 PM 11717271 ER PT J AU Shearman, LP Weaver, DR AF Shearman, LP Weaver, DR TI Distinct pharmacological mechanisms leading to c-fos gene expression in the fetal suprachiasmatic nucleus SO JOURNAL OF BIOLOGICAL RHYTHMS LA English DT Article DE circadian rhythms; D-1-dopamine receptor; gene expression; entrainment; SKF 38393; caffeine; nicotine ID DOPAMINE AGONIST SKF-38393; RAT-BRAIN; RECEPTOR GENE; CHOLINERGIC ANTAGONIST; ADENOSINE RECEPTORS; CIRCADIAN PACEMAKER; PRENATAL INJECTIONS; LOCOMOTOR-ACTIVITY; PHOTIC REGULATION; COCAINE EXPOSURE AB Maternal treatment with cocaine or a D-1-dopamine receptor agonist induces c-fos gene expression in the fetal suprachiasmatic nuclei (SCN). Other treatments that induce c-fos expression in the fetal SCN include caffeine and nicotine. In the current article, the authors assessed whether these different pharmacological treatments activate c-fos expression by a common neurochemical mechanism. The results indicate the presence of at least two distinct pharmacological pathways to c-fos expression in the fetal rat SCN. Previous studies demonstrate that prenatal activation of dopamine receptors affects the developing circadian system. The present work shows that stimulant drugs influence the fetal brain through multiple transmitter systems and further suggests that there may be multiple pathways leading to entrainment of the fetal biological clock. C1 Massachusetts Gen Hosp, MassGen Hosp Children, Lab Dev Chronobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Weaver, DR (reprint author), Univ Massachusetts, Sch Med, Dept Neurobiol, 55 Lake Ave N, Worcester, MA 01655 USA. RI Jelinek, Milan/C-8515-2011 FU NHLBI NIH HHS [HL07901]; NICHD NIH HHS [HD14427, HD29470] NR 57 TC 8 Z9 8 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0748-7304 J9 J BIOL RHYTHM JI J. Biol. Rhythms PD DEC PY 2001 VL 16 IS 6 BP 531 EP 540 DI 10.1177/074873001129002222 PG 10 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 495PX UT WOS:000172350500004 PM 11760011 ER PT J AU Polanczyk, CA Newton, C Dec, GW Di Salvo, TG AF Polanczyk, CA Newton, C Dec, GW Di Salvo, TG TI Quality of care and hospital readmission in congestive heart failure: An explicit review process SO JOURNAL OF CARDIAC FAILURE LA English DT Review DE quality; heart failure; readmission ID ACUTE MYOCARDIAL-INFARCTION; PHYSICIAN SPECIALTY; UNITED-STATES; MANAGEMENT; OUTCOMES; CARDIOLOGISTS; GENERALIST; GUIDELINES; CRITERIA; MEDICINE AB Background: The effect of hospital quality of care on hospital readmission for patients with congestive heart failure (CHF) has not been widely studied. Methods and Results: We examined the effects of clinical factors, hospital quality of care, and cardiologist involvement on 3-month readmission rates in patients with CHF by using a 125-item explicit review instrument comprising 3 major domains: admission work-up, evaluation and treatment, and readiness for discharge. During the 3 months after discharge, 59 (30%) of 205 patients were readmitted for CHF. The average evaluation and treatment score was lower for readmitted patients (63% v 58%; P = .04). The specific quality criteria differing between patients readmitted or not readmitted included the performance of any diagnostic evaluation, performance of echocardiography in patients with unknown ejection fraction or suspected valvular disease, and therapy with an angiotensin-converting enzyme inhibitor on discharge. Patients with less than or equal to 50% of the evaluation and treatment criteria met were more likely to be readmitted (odds ratio, 2.5; 95% confidence interval, 1.1-5.3; P = .02). In a multivariate model including both clinical characteristics and quality criteria, a low evaluation and treatment score was an independent predictor of readmission. Cardiologist involvement was correlated with higher quality-of-care scores in the admission work-up (4.8% higher; P < .01) and evaluation and treatment (8.6% higher; P < .0001). Conclusions: Hospital quality of care for patients with CHF is independently associated with 3-month readmission rates, and cardiologist involvement during hospitalization is associated with overall quality of care. C1 Massachusetts Gen Hosp, MGH Heart Failure Ctr, Div Cardiol, Heart Failure & Cardiac Transplantat Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Di Salvo, TG (reprint author), Massachusetts Gen Hosp, MGH Heart Failure Ctr, Div Cardiol, Heart Failure & Cardiac Transplantat Unit, Bigelow 628,55 Fruit St, Boston, MA 02114 USA. RI Polanczyk, Carisi/D-6208-2013 NR 33 TC 31 Z9 31 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD DEC PY 2001 VL 7 IS 4 BP 289 EP 298 DI 10.1054/jcaf.2001.28931 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 504DX UT WOS:000172843000003 PM 11782850 ER PT J AU Braaten, EB Biederman, J DiMauro, A Mick, E Monuteaux, MC Muehl, K Faraone, SV AF Braaten, EB Biederman, J DiMauro, A Mick, E Monuteaux, MC Muehl, K Faraone, SV TI Methodological complexities in the diagnosis of major depression in youth: An analysis of mother and youth self-reports SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID CHILD; PARENT; INFORMANTS; DISORDERS; AGREEMENT; SYMPTOMS; PSYCHOPATHOLOGY; INTERVIEW; RISK AB Objective: Considering the well-documented low level of agreement between youth and parent reports on the diagnosis of major depressive disorder (MDD), uncertainties remain as to the informativeness of discrepant youth and parent reports in clinical studies. To this end we evaluated whether morbidity and functional correlates on the diagnosis of MDD in youth vary by informant source. Methods: The sample consisted of 186 pairs of independently assessed mother and youth self-reports on the diagnosis of MDD using structured diagnostic interviews ascertained in a large study of youth with and without attention deficit hyperactivity disorder of both genders. Subjects were also assessed on measures of interpersonal, school, and family functioning as well as prior treatment history. Results: The diagnosis of MDD endorsed by youth self-report only when compared with that reported by the mother was characterized by significantly: shorter duration episode, later age at onset, milder depression-associated impairment, less impairment in interpersonal functioning, lower rates of comorbid disorders, and decreased likelihood to receive any course of treatment for depression. The morbidity and dysfunction associated with MDD varied significantly by informant source, and followed a dose-response association with the highest morbidity associated with the concurrent reports of the youth and the mothers, followed by mother report alone, with the least morbidity and dysfunction when endorsed by youth alone. Conclusions: These findings suggest that exclusive reliance on youth self-reports may identify a mild form of depression associated with limited morbidity and disability compared with that identified by parental reports. C1 Massachusetts Gen Hosp, Pediat Psychopharmcol Unit ACC 725, Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmcol Unit ACC 725, Psychiat Serv, 15 Parkman St, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH41314-07] NR 24 TC 29 Z9 29 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD WIN PY 2001 VL 11 IS 4 BP 395 EP 407 DI 10.1089/104454601317261573 PG 13 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 518VU UT WOS:000173689200005 PM 11838822 ER PT J AU Cohen, LG Biederman, J AF Cohen, LG Biederman, J TI Treatment of risperidone-induced hyperprolactinemia with a dopamine agonist in children SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID SCHIZOPHRENIC-PATIENTS; CLINICAL PRESENTATION; PREMENOPAUSAL WOMEN; PROLACTIN LEVELS; ADOLESCENTS; CABERGOLINE; HALOPERIDOL; BROMOCRIPTINE; AMENORRHEA; SWITCH AB Background: Risperidone, a potent antagonist of both serotonergic (5HT(2A)) and dopaminergic D-2 receptors is associated with hyperprolactinemia in adults and children. Chronically elevated prolactin levels in children with prolactinomas may be associated with arrested growth and development resulting in either delayed puberty or short stature. These possibilities stress the importance of developing a safe and effective approach to drug-induced hyperprolactinemia in youth. We report the successful treatment of risperidone-induced hyperprolactinemia with cabergoline in youth. Methods: We undertook a retrospective case review of four children with risperidone-induced hyperprolactinemia treated with cabergoline. Results: Four males (age 6-11 years) with Diagnostic and Statistical Manual of Mental Disorders (fourth edition) bipolar disorder or psychoses, with risperidone-induced elevations in serum prolactin levels (57.5-129 ng/mL, normal 5-15 ng/mL), were treated with cabergoline (mean dose 2.13 +/- 0.09 mg/week). When serum prolactin levels normalized in all four subjects (mean 11.2 +/- 10.9 ng/mL), the cabergoline dose was reduced to 1 mg/week in three of four subjects. The mean duration of therapy with cabergoline was 523.5 +/- 129.7 days, and the mean duration of therapy with risperidone was 788.5 +/- 162.5 days. Cabergoline was well tolerated without adverse effects. Conclusions: Cabergoline may be useful for the treatment of risperidone-induced hyperprolactinemia in youth; however, further research is needed. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Psychiat Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Cohen, LG (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Psychiat Serv, 15 Parkham St,WACC 725, Boston, MA 02114 USA. NR 34 TC 29 Z9 31 U1 1 U2 5 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD WIN PY 2001 VL 11 IS 4 BP 435 EP 440 DI 10.1089/104454601317261618 PG 6 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 518VU UT WOS:000173689200009 PM 11838826 ER PT J AU Biederman, J Monuteaux, MC Greene, RW Braaten, E Doyle, AE Faraone, SV AF Biederman, J Monuteaux, MC Greene, RW Braaten, E Doyle, AE Faraone, SV TI Long-term stability of the child behavior checklist in a clinical sample of youth with attention deficit hyperactivity disorder SO JOURNAL OF CLINICAL CHILD PSYCHOLOGY LA English DT Article ID FOLLOW-UP; RISK-FACTORS; DEFICIT/HYPERACTIVITY DISORDER; PSYCHIATRIC DIAGNOSES; SOCIAL DISABILITY; CONDUCT DISORDER; FAMILIAL SUBTYPE; ADHD CHILDREN; COMORBIDITY; CONVERGENCE AB Evaluated the long-term stability of the Child Behavior Checklist (CBCL) in a longitudinal clinical sample of youth with attention deficit hyperactivity disorder (ADHD), testing the hypothesis that the CBCL scales will show stability over time. Participants were 105 Caucasian, non-Hispanic boys with ADHD between the ages of 6 and 17 assessed at baseline and at a 4-year follow-up. Stability of CBCL scales were computed for dimensional (intraclass correlation coefficients [ICCs], Pearson correlations) and dichotomized scale scores (kappa coefficients and odds ratios [ORs]). Evidence was found for stability of the categorical and dimensional types of scores, as demonstrated by statistically significant stability of the Pearson correlation coefficients, kappas, and ORs. The robust findings obtained from ICCs and kappa coefficients document substantial stability for CBCL scales over time within individuals with ADHD. These results support the informativeness of the CBCL as a use il measure of longitudinal course in clinical samples of youth with ADHD. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Unit ACC 725, Boston, MA 02114 USA. McLean Hosp, Belmont, MA 02178 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. RP Biederman, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Unit ACC 725, Fruit St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01MH-41314] NR 51 TC 37 Z9 38 U1 1 U2 7 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0047-228X J9 J CLIN CHILD PSYCHOL JI J. Clin. Child Psychol. PD DEC PY 2001 VL 30 IS 4 BP 492 EP 502 DI 10.1207/S15374424JCCP3004_06 PG 11 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 485MF UT WOS:000171757600005 PM 11708237 ER PT J AU Sesmilo, G Miller, KK Hayden, D Klibanski, A AF Sesmilo, G Miller, KK Hayden, D Klibanski, A TI Inflammatory cardiovascular risk markers in women with hypopituitarism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID C-REACTIVE PROTEIN; GROWTH-HORMONE DEFICIENCY; CORONARY HEART-DISEASE; INSULIN-RESISTANCE; ENDOTHELIAL DYSFUNCTION; ADIPOSE-TISSUE; GH TREATMENT; ADULTS; HEALTHY; INTERLEUKIN-6 AB Patients with hypopituitarism have increased cardiovascular mortality. A high prevalence of conventional cardiovascular risk factors, including obesity, central fat distribution, insulin resistance, and dyslipidemia, have been described in these patients. The inflammatory markers C-reactive protein (CRP) and IL-6 are predictors of cardiovascular events, and high levels of CRP have been reported in men with hypopituitarism is known about inflamma- and GH deficiency. However, little. tory cardiovascular risk markers in women with hypopituitarism. We therefore investigated whether inflammatory and traditional cardiovascular risk markers are elevated in women with hypopituitarism. Fifty-three women with hypopituitarism and Ill healthy control women were included in this cross-sectional study. Morning blood samples were drawn after an overnight fast. Serum was assayed for CRP, IL-6, glucose, insulin, IGF-I, triglycerides, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein (HDL) cholesterol, lipoprotein(a), E2, total testosterone (total T) and free testosterone (free T), and dehydroepiandrosterone sulfate. IL-6 and CRP levels were higher in women with hypopituitarism than in healthy controls (P < 0.0001 for comparison between groups). In a multivariate model, CRP levels depended on hypopituitarism, body mass index (BAH), and estrogen use. There was an interaction between the effect of BAH and hypopituitarism on CRP levels, such that the importance of hypopituitarism in determining CRP levels disappeared at high BMIs. In a similar multivariate model, IL-6 levels depended on hypopituitarism and BMI. Total cholesterol, the total to HDL cholesterol ratio, and triglycerides were higher in hypopituitary patients, but only triglycerides and the total to HDL cholesterol ratio depended on hypopituitarism when controlling for BMI. There was no significant difference in lipoprotein(a) levels between hypopituitary women and control subjects. However, when controlling for estrogen use, lipoprotein(a) levels showed a trend toward being lower in the hypopituitary group (P = 0.075). In patients with hypopituitarism, CRP correlated negatively with IGF-I (r = -0.35; P = 0.010), total T (r = -0.42; P = 0.0020), and free T (r = -0.30; P = 0.031). Similarly, IL-6 correlated negatively with total T (r = -0.39; P = 0.0040) and androstenedione (r = -0.27, P = 0.048) in hypopituitary patients. In conclusion, hypopituitary women have increased levels of IL-6 and CRP, both of which are inflammatory markers of atherosclerosis. GH deficiency and androgen deficiency may contribute to these findings. Chronic inflammation may contribute to the high cardiovascular risk seen in this population. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Hosp Clin Barcelona, E-08036 Barcelona, Spain. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM aklibanski@partners.org FU NCRR NIH HHS [M01-RR-01066] NR 37 TC 65 Z9 65 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 DEC PY 2001 VL 86 IS 12 BP 5774 EP 5781 DI 10.1210/jc.86.12.5774 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 502DJ UT WOS:000172728200021 PM 11739438 ER PT J AU Kahn, SE Montgomery, B Howell, W Ligueros-Saylan, M Hsu, CH Devineni, D McLeod, JF Horowitz, A Foley, JE AF Kahn, SE Montgomery, B Howell, W Ligueros-Saylan, M Hsu, CH Devineni, D McLeod, JF Horowitz, A Foley, JE TI Importance of early phase insulin secretion to intravenous glucose tolerance in subjects with type 2 diabetes mellitus SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BETA-CELL FUNCTION; RESISTANCE; HYPERGLYCEMIA; SENSITIVITY; CONTRIBUTE; CAPACITY AB Insulin secretion is impaired in type 2 diabetes with the early response being essentially absent. The loss of this early insulin secretion is hypothesized to be important in the deterioration of glucose tolerance. To determine whether enhancement of the early-phase insulin response can enhance, glucose tolerance, we administered 1) 120 mg nateglinide, an insulinotropic agent that enhances early insulin secretion; 2) 10 mg glyburide, which enhances the later. phases of insulin secretion; or 3) placebo in random order to 21 subjects with type 2 diabetes (14 males and 7 females; aged 59.2 +/- 2.1 yr, x +/- SEM; body mass index 29.7 +/- 1.0 kg/m(2); fasting plasma glucose 8.1 +/- 0.1 mM). beta -Cell function was quantified as the incremental area under the curve for different time periods for the 5 h following iv glucose administration and glucose tolerance as the glucose disappearance constant (Kg) from 10 to 60 min. Insulin release commenced immediately after nateglinide administration, even before glucose injection, but this was not observed with glyburide. Both nateglinide and glyburide enhanced glucose-induced insulin release, compared with placebo (area under the curve -15-300 min: nateglinide 23,595 +/- 11,212 pM/min, glyburide 54,556 +/- 15,253 pM/min, placebo 10,242 +/- 2,414 pM/min). The profiles of insulin release demonstrated significant enhancement of release between -15 and 30 min for nateglinide, compared with glyburide and between 60 and 300 min for glyburide over nateglinide. Kg increased by 15% with nateglinide (0.87 +/- 0.04/min), but it did not increase significantly with glyburide (0.79 +/- 0.04%/min), compared with placebo (0.76 +/- 0.04%/min). The enhancement of insulin release by glyburide resulted in a lower minimal glucose concentration with glyburide (3.8 +/- 0.2 mM), compared with nateglinide (5.0 +/- 0.2 mM) and placebo (5.9 +/- 0.2 mM). Thus, enhancement of the early phase of insulin secretion improves iv glucose tolerance, whereas delaying it by 30 min results in a slower rate of glucose disappearance for the first 2 h after iv glucose administration. Further, the differences in the kinetics of nateglinide and glyburide. action results in continued insulin release with glyburide despite the fact that glucose levels have returned to basal, thus resulting-iu a further reduction in glucose levels and a lower nadir. C1 VA Puget Sound Health Care Syst, Dept Med, Seattle, WA 98108 USA. VA Puget Sound Health Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Novartis Pharmaceut Corp, E Hanover, NJ 07936 USA. RP Kahn, SE (reprint author), VA Puget Sound Health Care Syst, Dept Med, 151,1660 S Columbian Way, Seattle, WA 98108 USA. EM skahn@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 FU NIDDK NIH HHS [DK-02654, DK-17047] NR 28 TC 57 Z9 67 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 DEC PY 2001 VL 86 IS 12 BP 5824 EP 5829 DI 10.1210/jc.86.12.5824 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 502DJ UT WOS:000172728200028 PM 11739446 ER PT J AU Rabeneck, L Menke, T Simberkoff, MS Hartigan, PM Dickinson, GM Jensen, PC George, WL Goetz, MB Wray, NP AF Rabeneck, L Menke, T Simberkoff, MS Hartigan, PM Dickinson, GM Jensen, PC George, WL Goetz, MB Wray, NP TI Using the national registry of HIV-infected veterans in research: Lessons for the development of disease registries SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE HIV infection; disease registry; health outcomes ID POPULATION; AIDS; CARE AB Disease-specific registries have many important applications in epidemiologic, clinical and health services research. Since 1989 the Department of Veterans Affairs has maintained a national HIV registry. VA's HIV registry is national in scope. it contains longitudinal data and detailed resource utilization and clinical information. To describe the structure, function, and limitations of VA's national HIV registry, and to test its accuracy and completeness. The VA's national HIV registry contains data that are electronically extracted from VA's computerized comprehensive clinical and administrative databases, called Veterans Integrated Health Systems Technology and Architecture (VISTA). We examined the number of AIDS patients and the number of new patients identified to the registry, by year, through December 1996. We verified data elements against information obtained from the medical records at five VA sites. By December 1996, 40.000 HIV-infected patients had been identified to the registry. We encountered missing data and problems with data classification. Missing data occurred for some elements related to the computer programming that creates the registry (e.g., pharmacy files), and for other elements because manual entry is required (e.g., ethnicity). Lack of a standardized data classification system was a problem. especially for the pharmacy and laboratory files. In using VA's national HIV registry we have learned important lessons, which, if taken into account in the future, could lead to the creation of model disease-specific registries. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Dept Vet Affairs VA Hlth Serv Res & Dev HSR&D, Ctr Excellence, Houston, TX USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Manhattan VA Med Ctr, New York, NY USA. NYU, New York, NY USA. VA Cooperat Studies Program Coordinating Ctr, West Haven, CT USA. VAMC, Miami, FL USA. Univ Miami, Miami, FL 33152 USA. VAMC, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. W Los Angeles VAMC, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Rabeneck, L (reprint author), VA Med Ctr 111D, 2002 Holcombe Blvd, Houston, TX 77030 USA. OI Goetz, Matthew/0000-0003-4542-992X NR 15 TC 19 Z9 20 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD DEC PY 2001 VL 54 IS 12 BP 1195 EP 1203 DI 10.1016/S0895-4356(01)00397-3 PG 9 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 501WF UT WOS:000172708500004 PM 11750188 ER PT J AU Danielson, ME Justice, AC AF Danielson, ME Justice, AC CA VACS Project Team TI Veterans aging cohort study (VACS) meeting summary SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE veterans; aging; cohort study AB The Veterans Aging Cohort Study (VACS) planning meeting vas the first of a series of organizational meetings and VA-sponsored conference calls designed to build the scientific foundation and methodological infrastructure for a multisite, longitudinal study of HI-V and chronic disease outcomes among aging veterans. More specifically, it served as a consensus conference to determine scientific priorities, develop hypotheses, and to assemble working groups and committees to outline the specific methodological approaches needed. Scientists, physicians from 20 VA clinical facilities in the United States, community members, and experts in the fields of immunology, cancer, sociology, aging, cognition, psychiatry and mental health, epidemiology, large database analysis, and health services research gathered for an intense, 2-day meeting held in Pittsburgh, PA, November 8-9, 2000. (C) 2001 Elsevier Science Inc. All rights reserved. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Re & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Div Gen Internal Med, VACS Ctr, Pittsburgh, PA USA. RP Justice, AC (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Re & Promot, Univ Dr C 111E0U,130-U, Pittsburgh, PA 15240 USA. FU NIA NIH HHS [K23 AG 00826-03] NR 12 TC 1 Z9 2 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD DEC PY 2001 VL 54 SU 1 BP S9 EP S11 DI 10.1016/S0895-4356(01)00441-3 PG 3 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 503QK UT WOS:000172811300003 PM 11750203 ER PT J AU Justice, AC Holmes, W Gifford, AL Rabeneck, L Zackin, R Sinclair, G Weissman, S Neidig, J Marcus, C Chesney, M Cohn, SE Wu, AW AF Justice, AC Holmes, W Gifford, AL Rabeneck, L Zackin, R Sinclair, G Weissman, S Neidig, J Marcus, C Chesney, M Cohn, SE Wu, AW CA Adult AIDS Clinical Trials Unit Ou TI Development and validation of a self-completed HIV symptom index SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE self-completed HIV symptom index; clinical management; adverse drug-event reporting ID QUALITY-OF-LIFE; HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; CLINICAL PREDICTORS; MEDICAL OUTCOMES; RELIABILITY; INFECTION; VALIDITY; DISEASE; AIDS AB Traditional, open-ended provider questions regarding patient symptoms are insensitive. Better methods are needed to measure symptoms for clinical management, patient-oriented research, and adverse drug-event reporting. Our objective was to develop and initially validate a brief, self-reported HIV symptom index tailored to patients exposed to multidrug antiretroviral therapies and protease inhibitors, and to compare the new index to existing symptom measures. The research design was a multistage design including quantitative review of existing literature, qualitative and quantitative analyses of pilot data, and quantitative analyses of a prospective sample, Statistical analyses include frequencies, chi-square tests for significance, linear and logistic regression. The subjects were from a multisite convenience sample (n = 73) within the AIDS Clinical Trials Group and a prospective sample from the Cleveland Veterans Affairs Medical Center (n = 115). Measures were patient-reported symptoms and health-related quality of life, physician-assessed disease severity, CD4 cell count, and HIV-1 RNA viral quantification. A 20-item, self-completed HIV symptom index was developed based upon prior reports of symptom frequency and bother and expert opinion. When compared with prior measures the index included more frequent and bothersome symptoms, yet was easier to use (self-report rather than provider interview). The index required less than 5 minutes to complete, achieved excellent completion rates, and was thought comprehensive and comprehensible in a convenience sample. It was further tested in a prospective sample of patients and demonstrated strong associations with physical and mental health summary scores and with disease severity. These associations were independent of CD4 cell count and HIV-1 RNA viral quantification. This 20-item HIV symptom index has demonstrated construct validity, and offers a simple and rational approach to measuring HIV symptoms for clinical management, patient-oriented research, and adverse drug reporting. (C) 2001 Elsevier Science Inc. All rights reserved. C1 VA Piitsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, VACS Ctr, Div Gen Med, Pittsburgh, PA USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Calif San Diego, San Diego, CA 92103 USA. VA San Diego Healthcare Syst, San Diego, CA USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Vet Affairs Hlth Serv Res & Dev Ctr Excellen, Houston, TX 77030 USA. Harvard Univ, Stat & Data Anal Ctr, Boston, MA 02115 USA. Parkland Hosp, Dallas, TX USA. Yale Univ, Sch Med, St Raphaels Hosp, New Haven, CT USA. Ohio State Univ, Columbus, OH 43210 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA. Univ Rochester, Med Ctr, Infect Dis Unit, Rochester, NY 14642 USA. Johns Hopkins Univ, Dept Hlth Policy & Management, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD 21218 USA. RP Justice, AC (reprint author), VA Piitsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C 11E-124 130-U, Pittsburgh, PA 15240 USA. FU NIA NIH HHS [K23 AG 00826-03]; NIAID NIH HHS [U01 AI38855, U01 AI38858] NR 33 TC 189 Z9 190 U1 3 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD DEC PY 2001 VL 54 SU 1 BP S77 EP S90 DI 10.1016/S0895-4356(01)00449-8 PG 14 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 503QK UT WOS:000172811300013 PM 11750213 ER PT J AU Justice, AC Landefeld, CS Asch, SM Gifford, AL Whalen, CC Covinsky, KE AF Justice, AC Landefeld, CS Asch, SM Gifford, AL Whalen, CC Covinsky, KE TI Justification for a new cohort study of people aging with and without HIV infection SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE cohort study; people aging; HIV-positive; HIV-negative ID HUMAN-IMMUNODEFICIENCY-VIRUS; RANDOMIZED CLINICAL-TRIALS; QUALITY-OF-LIFE; PRIMARY-CARE; HEPATITIS-C; HOSPITALIZED-PATIENTS; DIABETES-MELLITUS; ADVERSE EVENTS; AIDS; SURVIVAL AB This supplement contains a series of papers supporting the justification, design, and implementation of a longitudinal cohort study of an aging HIV-positive and HIV-negative veteran population called the Veterans Aging Cohort Study (VACS). Although the papers cover a wide range of topics and several papers address methodologic issues not unique to a study of aging-veterans, all are motivated by a unifying set of assumptions. Specifically: (a) HIV/AIDS is a chronic disease in an aging population; (b) conditions among HIV-positive and -negative patients in care have overlapping etiologies; (c) individuals with pre-existing organ injury are at increased risk for iatrogenic injury; (d) cohort studies are uniquely suited to the study of chronic disease complicated by aging, comorbid conditions, drug toxicities, and substance use/abuse; (e) VACS is well positioned to study HIN as a chronic disease in an aging population. (C) 2001 Elsevier-Science, Inc. All rights reserved. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, VACS Ctr, Div Gen Internal Med, Pittsburgh, PA USA. VA San Francisco Healthcare Syst, San Francisco, CA USA. Univ Calif San Francisco, Sch Med, Dept Geriatr, San Francisco, CA USA. VA Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Div Gen Internal Med, Los Angeles, CA USA. VA San Diego Healthcare Syst, San Diego, CA USA. Univ Calif San Diego, Sch Med, Div Gen Internal Med, San Diego, CA 92103 USA. Case Western Reserve Univ, Sch Med, Div Infect Dis, Cleveland, OH USA. Case Western Reserve Univ, Sch Med, Dept Epidemiol, Cleveland, OH USA. RP Justice, AC (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C 11E-124 130-U, Pittsburgh, PA 15240 USA. FU FIC NIH HHS [D43 TW000011]; NIA NIH HHS [K23 AG 00826-03] NR 72 TC 26 Z9 26 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD DEC PY 2001 VL 54 SU 1 BP S3 EP S8 DI 10.1016/S0895-4356(01)00440-1 PG 6 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 503QK UT WOS:000172811300002 PM 11750202 ER PT J AU Kilbourne, AM Justice, AC Rabeneck, L Rodriguez-Barradas, M Weissman, S AF Kilbourne, AM Justice, AC Rabeneck, L Rodriguez-Barradas, M Weissman, S CA VACS 3 Project Team TI General medical and psychiatric comorbidity among HIV-infected veterans in the post-HAART era SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE psychiatric comorbidity; HIV-infected veterans; post-HAART era ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IDENTIFICATION TEST AUDIT; ANTIRETROVIRAL THERAPY; VIRUS-INFECTION; PRIMARY-CARE; HEPATITIS-C; DISORDERS; DISEASE; AIDS; DEPRESSION AB We examined the prevalence of HIV, general medical, and psychiatric comorbidities by age based on a recent multisite cohort of HIV infected veterans receiving care: the Veterans with HIV/AlDS 3 Site Study (VACS 3). VACS 3 includes 881 adult patients with HIV infection enrolled between June 1999 and July 2000. Providers reported their patients' CDC-defined HIV comorbidities, general medical comorbidities (based on Duke and Charlson comorbidity scales), and psychiatric comorbidity. Mean age of participants was 49 years and 54% were African-American. The most common HIV comorbidities were oral candidiasis (21%), peripheral neuropathy (16%), and herpes zoster (16%). The most common general medical comorbidities included chemical hepatitis (53%), hypertension (24%), and hyperlipidemia (17%). The mean number of HIV and general medical-comorbidities experienced by patients were respectively 1.1 and 1.4 (P < .001). Older (greater than or equal to 50 years) HIV-infected patients experienced a greater number of general medical comorbidities than those < 50 years (respectively 1.7 versus 1.2, P < .001). There was no significant difference in mean HIV comorbidity number by age. Based on patient report, 46% had significant depressive symptoms (greater than or equal to 10 on 10-item CES-D) and 21% reported at-risk drinking (greater than or equal to8 on AUDIT). Providers reported 32% of patients had anxiety, 4% mania, 4% schizophrenia, and 11% cognitive impairment/dementia. General medical and psychiatric comorbidities constituted a higher disease burden for HIV-Infected veterans than HIV comorbidities. Whether these comorbidities are due to antiretroviral drug toxicity or are age or lifestyle-associated conditions, the substantial prevalence of these "non-HIV" comorbidities suggest an important role for general medical and psychiatric management of HIV-infected patients. (C) 2001 Elsevier Science Inc. All rights reserved. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, VACS Ctr, Div Gen Internal Med, Pittsburgh, PA USA. VA Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Yale Univ, Sch Med, Dept Internal Med, Infect Dis Sect, New Haven, CT 06510 USA. Hosp St Raphael, New Haven, CT USA. RP Justice, AC (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C 11E-124 130-U, Pittsburgh, PA 15240 USA. FU NIA NIH HHS [K23 AG 00826-03] NR 33 TC 75 Z9 76 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD DEC PY 2001 VL 54 SU 1 BP S22 EP S28 DI 10.1016/S0895-4356(01)00443-7 PG 7 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 503QK UT WOS:000172811300006 PM 11750206 ER PT J AU Landefeld, CS Justice, AC Covinsky, KE Gifford, AL Whalen, CC Asch, SM AF Landefeld, CS Justice, AC Covinsky, KE Gifford, AL Whalen, CC Asch, SM TI Introduction to the supplement SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Editorial Material C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Calif San Francisco, Sch Med, Div Geriatr, San Francisco, CA USA. VA San Francisco Healthcare Syst, San Francisco, CA USA. Univ Pittsburgh, Sch Med, Div Gen Internal Med, VACS Ctr, Pittsburgh, PA USA. VA San Diego Healthcare Syst, San Diego, CA USA. Univ Calif San Diego, Sch Med, Div Gen Internal Med, San Diego, CA 92103 USA. Case Western Reserve Univ, Sch Med, Div Infect Dis, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Epidemiol, Cleveland, OH 44106 USA. Univ Calif Los Angeles, Sch Med, Div Gen Internal Med, Los Angeles, CA USA. VA Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Justice, AC (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C 11E-124 130-U, Pittsburgh, PA 15240 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD DEC PY 2001 VL 54 SU 1 BP S1 EP S2 DI 10.1016/S0895-4356(01)00439-5 PG 2 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 503QK UT WOS:000172811300001 ER PT J AU Smola, S Justice, AC Wagner, J Rabeneck, L Weissman, S Rodriguez-Barradas, M AF Smola, S Justice, AC Wagner, J Rabeneck, L Weissman, S Rodriguez-Barradas, M CA VACS 3 Project Team TI Veterans aging cohort three-site study (VACS 3): overview and description SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE Veterans Aging Cohort Three-Site Study; middle-aged individuals; HIV infection; age-related differences ID DEPRESSION SCALE; NEGATIVE AFFECT; OLDER ADULTS; PRIMARY-CARE; SHORT-FORM; CES-D; VALIDITY; RELIABILITY; VALIDATION; ATTRIBUTES AB Outcomes for middle-aged and older individuals with HIN infection are poor, and are likely to be mediated by age-related differences in risks and resources (access to care, relationship with the provider, comorbid conditions, health habits, and changes brought about by aging). The goal of the Veterans Aging Cohort Three-Site Study (VACS 3) is to study the influence of age and mediating factors on outcomes with HIV in order to identify mutable mediators of poorer outcomes. VACS 3 is an observational, longitudinal study. Data sources include patient and provider surveys and electronic medical data collected at baseline and 12-month follow-up from the Infections Disease Clinics at three Veterans Affairs Medical Centers (Cleveland, OH, Houston, TX, and Manhattan, NY). Trained Survey Coordinators at each site determined which patients are HIV infected, obtained consent, and asked the patient to complete a questionnaire. The primary provider also completed a questionnaire. Twelve-month follow-up will be completed July 2001. Of all veterans with HIV seen in these clinics 85% (881) have consented and enrolled. Of the 881 corresponding provider surveys, 92% were completed. Mean age is 49; 55% are African-American; 38% of the sample were men who have sex with men; and less than 2% are women. Almost a third (32%) have been without a permanent address. Complimentary or alternative therapies are common as are the use of cigarettes, alcohol, and illicit drugs. The majority (87%) of the patients are taking multiple antiretroviral medications. The median CD4 count is 331 mm(3), and the median viral load was 714 copies/ml. There is substantial variation by site. Veterans with HIV infection have characteristics that will likely become more prevalent among HIN-infected persons in the United States: they are older, commonly suffer comorbid disease, and are members of minority populations. VACS 3 may help inform the design of future clinical interventions to improve outcomes for people aging with HIV. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Univ Pittsburgh, Sch Med, VACS Ctr, Div Gen Internal Med, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. RP Justice, AC (reprint author), Univ Pittsburgh, Sch Med, VACS Ctr, Div Gen Internal Med, Pittsburgh, PA 15260 USA. FU NIA NIH HHS [K23 AG 00826-03] NR 27 TC 24 Z9 26 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD DEC PY 2001 VL 54 SU 1 BP S61 EP S76 DI 10.1016/S0895-4356(01)00448-6 PG 16 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 503QK UT WOS:000172811300012 PM 11750212 ER PT J AU Wagner, JH Justice, AC Chesney, M Sinclair, G Weissman, S Rodriguez-Barradas, M AF Wagner, JH Justice, AC Chesney, M Sinclair, G Weissman, S Rodriguez-Barradas, M CA VACS 3 Project Team TI Patient- and provider-reported adherence: toward a clinically useful approach to measuring antiretroviral adherence SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE HIV; adherence; drug use; alcohol use; depressive symptoms; homelessness; HIV-1 viral load; AUDIT; CESD-10 ID HUMAN-IMMUNODEFICIENCY-VIRUS; IDENTIFICATION TEST AUDIT; PROTEASE INHIBITORS; DRUG-RESISTANCE; NATURAL-HISTORY; HIV-INFECTION; THERAPY; MEDICATION; TRIALS; DETERMINANTS AB We seek to develop a clinically useful measure of antiretroviral medication adherence. Because there is no gold standard for adherence, we will assess the clinical validity of patient- and provider-reported adherence by the strength of their expected associations with current viral load, depressive symptoms, alcohol and illicit drug use, and homelessness. The Veterans Aging Cohort 3 Site Study (VACS 3) is a multisite study of 881 patients at Cleveland, Houston, and Manhattan Veterans Affairs health care systems. Data was collected on adherence using patient report and provider assessment; depressive symptoms using the Center for Epidemiological Studies Depression (CESD) and provider assessment; alcohol use using the Alcohol Use Disorders Identification Test (AUDIT) and provider assessment; and homelessness using patient report only. Viral load was collected from electronic laboratory data. Although agreement between providers and patients about the patient's adherence was not better than chance (61%; weighted kappa = .07), both patient and provider-reported adherence were related to viral load (P < .001), current alcohol use (P < .01), current drug use (P < .01), and depressive symptoms (P < .001). Patient-reported adherence was also associated with homelessness (P < .05). In multivariate regression models, provider assessment of adherence demonstrated independent associations with viral load (P < .001), current alcohol use (P < .001), current drug use (P < .001), and depressive symptoms (P < .001) after adjustment for the patient's report of adherence (also significantly associated). The consistent and largely independent association between patient and provider reported adherence and a range of variables previously shown to be associated with adherence suggests that patient- and provider-reported adherence independently measure actual adherence. Future work will explore how patient- and provider-reported adherence might best be combined, and whether the measure may be further enhanced with pharmacy refill data. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Univ Pittsburgh, Sch Med, Div Gen Internal Med, VACS Ctr, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Calif San Francisco, Sch Med, AIDS Res Inst, San Francisco, CA USA. Univ Texas, SW Med Ctr, Dept Internal Med, Div Infect Dis, Dallas, TX USA. Yale Univ, Sch Med, St Raphael Hosp, New Haven, CT USA. VA Med Ctr, AIDS Unit, Houston, TX USA. RP Justice, AC (reprint author), Univ Pittsburgh, Sch Med, Div Gen Internal Med, VACS Ctr, Pittsburgh, PA 15260 USA. FU NIA NIH HHS [K23 AG 00826-03] NR 44 TC 76 Z9 77 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD DEC PY 2001 VL 54 SU 1 BP S91 EP S98 DI 10.1016/S0895-4356(01)00450-4 PG 8 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 503QK UT WOS:000172811300014 PM 11750214 ER PT J AU McCullough, LB Molinari, V Workman, RH AF McCullough, LB Molinari, V Workman, RH TI Implications of impaired executive control functions for patient autonomy and surrogate decision making SO JOURNAL OF CLINICAL ETHICS LA English DT Article ID CONSENT C1 Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX USA. Baylor Coll Med, Huffington Ctr Aging, Houston, TX USA. Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX USA. Houston Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP McCullough, LB (reprint author), Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX USA. NR 29 TC 5 Z9 5 U1 2 U2 2 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 17100 COLE RD #312, HAGERSTOWN, MD 21740-6901 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD WIN PY 2001 VL 12 IS 4 BP 397 EP 405 PG 9 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 551DB UT WOS:000175543300008 PM 12026746 ER PT J AU Akiba, Y Furukawa, O Guth, PH Engel, E Nastaskin, I Sassani, P Dukkipatis, R Pushkin, A Kurtz, I Kaunitz, JD AF Akiba, Y Furukawa, O Guth, PH Engel, E Nastaskin, I Sassani, P Dukkipatis, R Pushkin, A Kurtz, I Kaunitz, JD TI Cellular bicarbonate protects rat duodenal mucosa from acid-induced injury SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CYSTIC-FIBROSIS; ALKALINE SECRETION; HCO3 SECRETION; INTRACELLULAR PH; GASTROESOPHAGEAL REFLUX; NA+HCO3 COTRANSPORTER; HELICOBACTER-PYLORI; CL-/HCO3 EXCHANGE; EPITHELIAL-CELLS; NA+/H+ EXCHANGER AB Secretion of bicarbonate from epithelial cells is considered to be the primary mechanism by which the duodenal mucosa is protected from acid-related injury. Against this view is the Finding that patients with cystic fibrosis, who have impaired duodenal bicarbonate secretion, are paradoxically protected from developing duodenal ulcers. Therefore, we hypothesized that epithelial cell intracellular pH regulation, rather than secreted extracellular bicarbonate, was the principal means by which duodenal epithelial cells are protected from acidification and injury. Using a novel in vivo microscopic method, we have measured bicarbonate secretion and epithelial cell intracellular pH (pH(i)), and we have followed cell injury in the presence of the anion transport inhibitor DIDS and the Cl-channel inhibitor, 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB). DIDS and NPPB abolished the increase of duodenal bicarbonate secretion following luminal acid perfusion. DIDS decreased basal pHi, whereas NPPB increased pHi; DIDS further decreased pHi during acid challenge and abolished the pHi overshoot over baseline observed after acid challenge, whereas NPPB attenuated the fall of pHi and exaggerated the overshoot. Finally, acid-induced epithelial injury was enhanced by DIDS and decreased by NPPB. The results support the role of intracellular bicarbonate in the protection of duodenal epithelial cells from luminal gastric acid. C1 Univ Calif Los Angeles, CURE, Digest Dis Res Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Div Nephrol, Los Angeles, CA USA. Univ Calif Los Angeles, Coll Letters & Sci, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Div Digest Dis, Los Angeles, CA USA. Univ Calif Los Angeles, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,Bldg 114,Room 217, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK85863, R01-DK54221, R01 DK054221, T32 DK007789, DK07789] NR 62 TC 44 Z9 46 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2001 VL 108 IS 12 BP 1807 EP 1816 DI 10.1172/JCI12218 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 503WC UT WOS:000172823700012 PM 11748264 ER PT J AU Choi, SJ Oba, Y Gazitt, Y Alsina, M Cruz, J Anderson, J Roodman, GD AF Choi, SJ Oba, Y Gazitt, Y Alsina, M Cruz, J Anderson, J Roodman, GD TI Antisense inhibition of macrophage inflammatory protein 1-alpha blocks bone destruction in a model of myeloma bone disease SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID RESISTANCE CAM-DR; MULTIPLE-MYELOMA; CELL-LINES; ADHESION; MARROW; EXPRESSION; PROTEIN-1-ALPHA; IDENTIFICATION; RESORPTION; CHEMOKINES AB We recently identified macrophage inflammatory protein 1-alpha (MIP-1 alpha) as a factor produced by multiple myeloma (MM) cells that maybe responsible for the bone destruction in MM (1). To investigate the role of MIP-1 alpha in MM bone disease in vivo, the human MM-derived cell line ARH was stably transfected with an antisense construct to MIP-1 alpha (AS-ARH) and tested for its capacity to induce MM bone disease in SCID mice. Human MIP-1 alpha levels in marrow plasma from AS-ARH mice were markedly decreased compared with controls treated with ARH cells transfected with empty vector (EV-ARH). Mice treated with AS-ARH cells lived longer than controls and, unlike the controls, they showed no radiologically identifiable lytic lesions. Histomorphometric analysis demonstrated that osteoclasts (OCLs) per square millimeter of bone and OCLs per millimeter of bone surface of AS-ARH mice were significantly less than in EV-ARH mice, and the percentage of tumors per total bone area was also significantly decreased. AS-ARH cells demonstrated decreased adherence to marrow stromal cells, due to reduced expression of the alpha (5)beta (1) integrin and diminished homing capacity and survival. These data support an important role for MIP-1 alpha in cell homing, survival, and bone destruction in MM. C1 Univ Texas, Hlth Sci Ctr, Dept Med Hematol, San Antonio, TX USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP Roodman, GD (reprint author), Res 151, E-1152 BST,200 Lothrop St, Pittsburgh, PA 15213 USA. FU NCI NIH HHS [CA40035, P01 CA040035]; NIA NIH HHS [AG-13625, R01 AG013625]; NIAMS NIH HHS [AR-41336, AR-44603, R01 AR041336, R01 AR044603] NR 22 TC 153 Z9 155 U1 1 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2001 VL 108 IS 12 BP 1833 EP 1841 DI 10.1172/JCI13116 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 503WC UT WOS:000172823700015 PM 11748267 ER PT J AU Price, BH Baral, I Cosgrove, GR Rauch, SL Nierenberg, AA Jenike, MA Cassem, EH AF Price, BH Baral, I Cosgrove, GR Rauch, SL Nierenberg, AA Jenike, MA Cassem, EH TI Improvement in severe self-mutilation following limbic leucotomy: A series of 5 consecutive cases SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; LA-TOURETTE SYNDROME; INJURIOUS-BEHAVIOR; CINGULOTOMY; LEUKOTOMY; STIMULATION AB Background. The efficacy of neurosurgical intervention for self-mutilation behavior associated with severe, intractable psychiatric disorders remains undetermined. We report the effects of limbic leucotomy in 5 consecutive patients with severe self-mutilation behaviors. Method: After unsolicited referrals from their psychiatrists and careful consideration by the Massachusetts General Hospital Cingulotomy Assessment Committee (MGH-CAC), 5 patients were treated with limbic leucotomy. Their primary DSM-IV psychiatric diagnoses were either obsessive-compulsive disorder or schizoaffective disorder. Comorbid severe, treatment-refractory self-mutilation was an additional target symptom. Outcome was measured by an independent observer using the Clinical Global Improvement, Current Global Psychiatric-Social Status Rating, and DSM-IV Global Assessment of Functioning scales in addition to telephone interviews with patients, families, their psychiatrists, and treatment teams. The mean postoperative follow-up period was 31.5 months. Results: All measures indicated sustained improvement in 4 of 5 patients. In particular, there was a substantial decrease in self-mutilation behaviors. Postoperative complications were transient in nature, and postoperative compared with preoperative neuropsychological assessments revealed no clinically significant deficits. Conclusion: In carefully selected patients as described in this report, limbic leucotomy may be an appropriate therapeutic consideration for self-mutilation associated with severe, intractable psychiatric disorders. C1 McLean Hosp, Dept Neurol, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Istanbul, Sch Med, Dept Psychiat, TR-34459 Istanbul, Turkey. RP Price, BH (reprint author), McLean Hosp, Dept Neurol, 115 Mill St, Belmont, MA 02478 USA. NR 30 TC 20 Z9 20 U1 2 U2 3 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 DEC PY 2001 VL 62 IS 12 BP 925 EP + PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 505MA UT WOS:000172915500002 PM 11780871 ER PT J AU Kupfer, DJ Chengappa, KNR Gelenberg, AJ Hirschfeld, RMA Goldberg, JF Sachs, GS Grochocinski, VJ Houck, PR Kolar, AB AF Kupfer, DJ Chengappa, KNR Gelenberg, AJ Hirschfeld, RMA Goldberg, JF Sachs, GS Grochocinski, VJ Houck, PR Kolar, AB TI Citalopram as adjunctive therapy in bipolar depression SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 09-14, 2000 CL SAN JUAN, PUERTO RICO SP Amer Coll Neuropsychopharmacol ID MANIA; ANTIDEPRESSANTS AB Background. The treatment of bipolar depression remains a major clinical challenge. The effectiveness and safety of adjunctive citalopram were evaluated in DSM-IV-diagnosed bipolar depressed patients in a 5-site study. Method: The treatment strategy consisted of an open-label add-on design in which patients received 8 weeks of acute treatment with citalopram adjunctive to their ongoing treatment with mood stabilizers. Ongoing treatment with 1 anti-psychotic, 1 anxiolytic, and 1 hypnotic agent was permitted. Responders to the 8-week trial then received 16 weeks of additional treatment with citalopram. Results: Forty-five subjects entered the trial; 12 dropped out before the end of the acute treatment phase. Of the 33 patients who completed the acute treatment phase, 64% (N = 21) were responders and 36% (N = 12) were nonresponders. In the continuation phase of the study, 14 patients achieved sustained remission, 3 patients did not achieve remission before completing 16 weeks of continuation treatment, 2 patients experienced a relapse, and 2 patients dropped out of the study and did not have a chance to remit. In spite of the extensive concomitant medication usage allowed in this study, citalopram treatment was well tolerated and the level of reported adverse events (including headache, nausea, diarrhea, and sexual dysfunction) relatively low. Conclusion: The high response rate, the high rate of sustained remission, and the low rate of adverse events strongly support the use of citalopram as a treatment for bipolar I or II depression. These findings should stimulate a controlled double-blind trial to demonstrate even more clearly the usefulness of this drug in the therapeutic regimen for bipolar disorder. C1 Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. Arizona Hlth Sci Ctr, Dept Psychiat, Tucson, AZ 85724 USA. Univ Texas, Med Branch, Dept Psychiat & Behav Sci, Galveston, TX 77550 USA. Cornell Univ, Dept Psychiat, New York, NY 10021 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Kupfer, DJ (reprint author), Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, 3811 Ohara St, Pittsburgh, PA 15213 USA. NR 19 TC 40 Z9 43 U1 0 U2 1 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 DEC PY 2001 VL 62 IS 12 BP 985 EP 990 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 505MA UT WOS:000172915500012 PM 11780881 ER PT J AU Manne, S Nereo, N DuHamel, K Ostroff, J Parsons, S Martini, R Williams, S Mee, L Sexson, S Lewis, J Vickberg, SJ Redd, WH AF Manne, S Nereo, N DuHamel, K Ostroff, J Parsons, S Martini, R Williams, S Mee, L Sexson, S Lewis, J Vickberg, SJ Redd, WH TI Anxiety and depression in mothers of children undergoing bone marrow transplant: Symptom prevalence and use of the Beck depression and Beck Anxiety Inventories as screening instruments SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID STRUCTURED CLINICAL INTERVIEW; NATIONAL-COMORBIDITY-SURVEY; DSM-III; PSYCHOMETRIC PROPERTIES; PSYCHIATRIC OUTPATIENTS; RESEARCH METHODOLOGIES; SOCIAL-PSYCHOLOGY; PARENTS; STRESS; RELIABILITY AB This study examined anxiety and depressive symptoms among 115 mothers of children undergoing bone marrow transplant and evaluated the ability of the Beck Anxiety Inventory (BAI; A. T. Beck, N. Epstein, et al., 1988) and the Beck Depression Inventory (BDI; A. T. Beck, 1978) to serve as screening tools for assessing generalized anxiety disorder (GAD), panic disorder (PD), and major depressive disorder (MDD). Mothers with BAI or BDI scores greater than or equal to 14 were administered a structured clinical interview, An additional 20% was randomly selected for interview to determine whether the scale cutoff was an accurate screening method. Among the 64 mothers interviewed, 20% received at least 1 of the 3 diagnoses. Although the BAI did not demonstrate predictive accuracy in assessing GAD and PD, the BDI did in assessing MDD. The results suggest that a subset of mothers may have an anxiety or depressive disorder and that investigators should use caution before using the BAI as a screening instrument for anxiety disorder. C1 Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. Mt Sinai Sch Med, Ruttenberg Canc Ctr, New York, NY USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Sch Med, Childrens Mem Hosp, Evanston, IL 60208 USA. Stanford Univ, Packard Childrens Hosp, Sch Med, Stanford, CA 94305 USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. RP Manne, S (reprint author), Fox Chase Canc Ctr, Div Populat Sci, 7701 Burholme Ave,Suite P1100, Philadelphia, PA 19111 USA. OI Ostroff, Jamie/0000-0003-2671-5680 FU NIMH NIH HHS [MH 57738] NR 49 TC 39 Z9 39 U1 1 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD DEC PY 2001 VL 69 IS 6 BP 1037 EP 1047 DI 10.1037//0022-006X.69.6.1037 PG 11 WC Psychology, Clinical SC Psychology GA 504DF UT WOS:000172841500017 PM 11777107 ER PT J AU Steinman, MA Sands, LP Covinsky, KE AF Steinman, MA Sands, LP Covinsky, KE TI Self-restriction of medications due to cost in seniors without prescription coverage - A national survey SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 04, 2001 CL SAN DIEGO, CALIFORNIA SP Soc Gen Internal Med DE insurance, pharmaceutical services; health services accessibility; prescriptions, drug; fees, pharmaceutical; aged ID MEDICARE BENEFICIARIES; DRUG COVERAGE; CARDIOVASCULAR DRUGS; HEALTH; RECALL; CARE; VALIDITY; AGREEMENT; ADMISSION; BENEFITS AB OBJECTIVE: Little is known about patients who skip doses or otherwise avoid using their medications because of cost. We sought to identify which elderly patients are at highest risk of restricting their medications because of cost, and how prescription coverage modifies this risk. DESIGN AND PARTICIPANTS: Cross-sectional study from the 1995-1996 wave of the Survey of Asset and Health Dynamics Among the Oldest Old, a population-based survey of Americans age 70 years and older. MEASUREMENTS: Subjects were asked the extent of their prescription coverage, and whether they had taken less medicine than prescribed for them because of cost over the prior 2 years. We used bivariate and multivariate analyses to identify risk factors for medication restriction in subjects who lacked prescription coverage. Among these high-risk groups, we then examined the effect of prescription coverage on rates of medication restriction. MAIN RESULTS: Of 4,896 seniors who regularly used prescription medications, medication restriction because of cost was reported by 8% of subjects with no prescription coverage, 3% with partial coverage, and 2% with full coverage (P < .01 for trend). Among subjects with no prescription coverage, the strongest independent predictors of medication restriction were minority ethnicity (odds ratio [OR], 2.9 compared with white ethnicity; 95% confidence interval [95% CI], 2.0 to 4.2), annual income <$10,000 (OR, 3.8 compared with income greater than or equal to $20,000; 95% CI, 2.4 to 6.1), and out-of-pocket prescription drug costs >$100 per month (OR, 3.3 compared to costs less than or equal to $20; 95% CI, 1.5 to 7.2). The prevalence of medication restriction in members of these 3 risk groups was 21%, 16%, and 13%, respectively. Almost half (43%) of subjects with all 3 risk factors and no prescription coverage reported restricting their use of medications. After multivariable adjustment, highrisk subjects with no coverage had 3 to 15 times higher odds of medication restriction than subjects with partial or full coverage (P < .01). CONCLUSIONS: Medication restriction is common in seniors who lack prescription coverage, particularly among certain vulnerable groups. Seniors in these high-risk groups who have prescription coverage are much less likely to restrict their use of medications. C1 San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, VA Natl Qual Scholars Program, San Francisco, CA 94121 USA. RP Steinman, MA (reprint author), San Francisco VA Med Ctr, Div Geriatr, VA Box 181-G,4150 Clement St, San Francisco, CA 94121 USA. RI Sands, Laura/E-8919-2015 OI Sands, Laura/0000-0003-2446-4486 FU AHRQ HHS [K02 HS000006, K02HS00006-01] NR 42 TC 143 Z9 150 U1 1 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2001 VL 16 IS 12 BP 793 EP 799 DI 10.1046/j.1525-1497.2001.10412.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 504AY UT WOS:000172835700001 PM 11903757 ER PT J AU Fremont, AM Cleary, PD Hargraves, JL Rowe, RM Jacobson, NB Ayanian, JZ AF Fremont, AM Cleary, PD Hargraves, JL Rowe, RM Jacobson, NB Ayanian, JZ TI Patient-centered processes of care and long-term outcomes of myocardial infarction SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the Society-for-General-Internal Medicine CY MAY 02-06, 2000 CL BOSTON, MASSACHUSETTS SP Soc Gen Internal Med DE myocardial infarction; quality of care; patient-centered care; patient satisfaction; outcomes; health status; longitudinal study ID CORONARY-ARTERY DISEASE; COOPERATIVE CARDIOVASCULAR PROJECT; QUALITY-OF-LIFE; HEART-DISEASE; MEDICAL-CARE; PSYCHOSOCIAL FACTORS; SOCIOECONOMIC-STATUS; HEALTH; DEPRESSION; SATISFACTION AB OBJECTIVE: To examine whether patients' experiences with nontechnical aspects of care such as patient education and discharge planning are associated with long-term outcomes. DESIGN: Observational cohort study. SETTING: Twenty-three New Hampshire hospitals during 1996 and 1997. PARTICIPANTS: Acute myocardial infarction (AMI) patients (N = 2,272) enrolled prior to discharge. MEASUREMENTS: Surveys asking about problems with care and health were mailed to patients 1, 3, and 12 months after discharge. Patients were stratified into "worse" or "better" care groups on the basis of their hospital care problem score. Outcomes included self-reported overall health, physical health, mental health, chest pain, and shortness of breath. Other clinical measures were obtained from hospital discharge abstracts. MAIN RESULTS: The 1-, 3-, and 12-month surveys were returned by 1,346 (59.2%), 1,046 (46%), and 964 (42.4%) enrolled patients, respectively. The primary analytic cohort consisted of the 762 patients who completed both the 1- and 12-month surveys. After adjustment for postdischarge health status and other clinical factors, patients experiencing worse hospital care had lower ratings of overall health (48.4 vs 52.5 on 100-point scale; P = .02) and physical health (59.7 vs 68.4; P < .001), and were more likely to have chest pain (odds ratio [OR], 1.6; confidence interval [CI], 1.0 to 2.4; P = .04) 12 months after their AMI than other patients. However, differences in reports of chest pain were reduced if patients reporting worse hospital care had better experiences with subsequent ambulatory care. CONCLUSIONS: Patients' experiences with nontechnical processes of AMI hospital care are associated with long-term outcomes; however the association between a negative hospital experience and subsequent chest pain may be offset by more positive outpatient experiences. C1 RAND Corp, Hlth, Santa Monica, CA 90407 USA. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Brigham & Womens Hosp, Dept Med, Div Gen Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Ctr Studying Hlth Syst Change, Washington, DC USA. Fdn Healthy Communities, Concord, NH USA. HBS Int, Burlington, MA USA. RP Fremont, AM (reprint author), RAND Corp, Hlth, 1700 Main St,POB 2138, Santa Monica, CA 90407 USA. NR 56 TC 59 Z9 59 U1 3 U2 5 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2001 VL 16 IS 12 BP 800 EP 808 DI 10.1046/j.1525-1497.2001.10102.x PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 504AY UT WOS:000172835700002 PM 11903758 ER PT J AU Kiefe, CI AF Kiefe, CI TI Processes and outcomes in acute myocardial infarction - How technical should we get? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID QUALITY; CARE C1 Univ Alabama, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Kiefe, CI (reprint author), Univ Alabama, Birmingham, AL 35294 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2001 VL 16 IS 12 BP 868 EP 869 DI 10.1046/j.1525-1497.2001.11016.x PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 504AY UT WOS:000172835700013 PM 11903769 ER PT J AU Karlawish, JHT Casarett, D AF Karlawish, JHT Casarett, D TI Addressing the ethical challenges of clinical trials that involve patients with dementia SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; DEPRESSED-PATIENTS; INFORMED CONSENT; ELDERLY PATIENTS; DRUGS; PREFERENCES; COMPETENCE; EQUIPOISE; OUTCOMES; PROXY AB Research subjects face uncertainties, risks, burdens, and indignities, and research protocol requirements inhibit the physician's ability to make individualized treatment decisions. To address these problems, investigators and Institutional Review Boards (IRBs) should justify research risks using informed consent and the judgment that the risks of research are reasonable with respect to the potential benefits, if any, to subjects and to the expectation that the research will produce important knowledge. But clinical research in Alzheimer's disease (AD) presents investigators and IRBs with significant challenges to achieve these two requirements. Broadly, these challenges are the result of the impact of patients' cognitive impairment and the caregiving experience on decision making and the indeterminacy of defining clinically meaningful treatment benefits. In this article, we review the data that begin to answer whether and how patients' cognitive impairments and the caregiving experience impact on their decision making and what kinds of research results justify research risks. We will use these data to suggest changes to the design and conduct of clinical research in AD that can meet the challenge of justifying research risks. C1 Ctr Bioeth, Philadelphia, PA USA. Rush Alzheimers Dis Ctr, Philadelphia, PA USA. Univ Penn, Philadelphia Vet Affairs Med Ctr, Dept Med, Div Geriatr, Philadelphia, PA 19104 USA. RP Karlawish, JHT (reprint author), 3815 Chestnut St,Room 215, Philadelphia, PA 19104 USA. FU NIA NIH HHS [K01-AG00931, P30-AG01024] NR 40 TC 10 Z9 10 U1 2 U2 3 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 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD WIN PY 2001 VL 14 IS 4 BP 222 EP 228 DI 10.1177/089198870101400407 PG 7 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 498QE UT WOS:000172521500007 PM 11794450 ER PT J AU Teranishi, K Treter, S Alwayn, IPJ Buhler, L Awwad, M Cooper, DKC AF Teranishi, K Treter, S Alwayn, IPJ Buhler, L Awwad, M Cooper, DKC TI Assessment of methotrexate as a potential immunosuppressive agent in baboons SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID LOW-DOSE METHOTREXATE; RHEUMATOID-ARTHRITIS; SUPPRESSION; REJECTION; XENOGRAFT; SURVIVAL; ANTIBODY; THERAPY; PHARMACOKINETICS AB Methotrexate is an anti-proliferative agent that affects both T-cell and B-cell immunity, and therefore might be expected to suppress antibody,(Ab) production. Although it has been used in xenotransplantation studies to suppress anti-pig Ab production, it has always been used in combination with other immunosuppressants. The purpose of this study was to measure its effect as a single immunosuppressant on anti-G at Ab production in baboons (n=4). Pharmacokinetic studies showed that methotrexate was not detected in the blood when administered per os. Prolonged daily IV or IM administration (i) reduced T-cell and B-cell numbers by 50% to 70% and modestly reduced responsiveness on mixed lymphocyte reaction (but only at toxic doses) and (ii) did not result in lowered anti-Gal Ab levels, only marginally reducing the rate of return of Ab after extracorporeal immunoadsorption. Our observations would suggest that methotrexate will not contribute significantly to immunosuppressive regimens in the baboon at non-toxic doses. C1 Harvard Univ, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E,Sch Med, Boston, MA 02129 USA. Biotransplant Inc, Charlestown, MA USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E,Sch Med, Bldg 149-9019,13th St, Boston, MA 02129 USA. NR 19 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD DEC PY 2001 VL 20 IS 12 BP 1335 EP 1339 DI 10.1016/S1053-2498(01)00317-5 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 506JM UT WOS:000172966700013 PM 11744419 ER PT J AU Kweon, YO Goodman, ZD Dienstag, JL Schiff, ER Brown, NA Burkhardt, E Schoonhoven, R Brenner, DA Fried, MW AF Kweon, YO Goodman, ZD Dienstag, JL Schiff, ER Brown, NA Burkhardt, E Schoonhoven, R Brenner, DA Fried, MW TI Decreasing fibrogenesis: an immunohistochemical study of paired liver biopsies following lamivudine therapy for chronic hepatitis B SO JOURNAL OF HEPATOLOGY LA English DT Article DE hepatitis B; lamivudine; fibrosis; hepatic stellate cell; alpha-smooth muscle actin; C-terminal procollagen alpha 1(III) propeptide; immunohistochemistry ID CHRONIC VIRAL-HEPATITIS; FAT-STORING CELLS; INTERFERON THERAPY; STELLATE CELL; FIBROSIS PROGRESSION; RAT-LIVER; LIPOCYTES; PROLIFERATION; INTEROBSERVER; RESOLUTION AB Background: Activation of hepatic stellate cells is the earliest step in fibrogenesis. Alpha-smooth muscle actin (alpha -SMA), expressed by activated hepatic stellate cells, and C-terminal procollagen alpha1(III) propeptide (PIIICP) are early markers of fibrogenesis and should precede fibrosis. Aim: Determine if suppression of hepatitis B virus replication with lamivudine would decrease fibrogenesis as measured by immunohistochemical markers. Methods: Paired liver biopsies from patients with hepatitis B before and after therapy with lamivudine (n = 47) or placebo (n = 33) were studied. alpha -SMA and PIIICP were detected in paraffin-embedded tissue by immunohistochemistry and quantified in a blinded manner by video imaging analysis. Results: Liver biopsies from patients treated with lamivudine showed a significant decrease in ei-SMA expression (1.06 +/- 0.23 vs. 0.58 +/- 0.11, pre vs. post, P < 0.05). Placebo recipients had increased levels of a-SMA (0.82 +/- 0.14 vs. 1.32 +/- 0.21, P < 0.05). PIIICP was similarly decreased after lamivudine. Among subjects whose Histologic Activity Index fibrosis score was unchanged or worsened, the mean change in cz-SMA expression was significantly decreased in the lamivudine group compared with placebo. Conclusions: Lamivudine decreased markers of hepatic stellate cell activation and collagen synthesis. Immunohistochemical techniques are sensitive for assessing fibrogenesis and will be useful in trials of antiviral and antifibrotic agents. (C) 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved. C1 Univ N Carolina, Chapel Hill, NC 27599 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Miami, Miami, FL 33152 USA. GlaxoSmithKline, Res Triangle Pk, NC USA. Bayer Pharmaceut, Leverkusen, Germany. RP Fried, MW (reprint author), Univ N Carolina, CB 7080,Room 708,Burnett Womack Bldg, Chapel Hill, NC 27599 USA. FU NCRR NIH HHS [M01-RR01066]; NHLBI NIH HHS [R01-HL64817-1] NR 37 TC 103 Z9 110 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD DEC PY 2001 VL 35 IS 6 BP 749 EP 755 DI 10.1016/S0168-8278(01)00218-5 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 505VZ UT WOS:000172937400010 PM 11738102 ER PT J AU Taylor, E AF Taylor, E TI Positive psychology and humanistic psychology: A reply to Seligman SO JOURNAL OF HUMANISTIC PSYCHOLOGY LA English DT Editorial Material AB Arguments in the current debate between "positive psychology" and humanistic psychology are reviewed with particular emphasis on Martin Seligman's comment that humanistic psychologists do not represent "positive psychology" because they have generated no research tradition, are narcissistic, and are antiscientific. Each one of these claims is dispelled with specific references to the larger humanistic tradition in American psychology, which includes the psychology of William James; the personality-social psychologists of the 1930s and 1940s, such as Allport, Murray, and Murphy; and the humanistic psychologists, per se, of the 1950s and 1960s. Additional examples of how mainstream cognitive-behaviorism has continued to preempt humanistic and transpersonal psychology are also given. The conclusion, however, is that Seligman may be rushing to exclude on a priori grounds the very tradition his own theory represents. C1 Massachusetts Gen Hosp, Psychol Assessment Ctr, Boston, MA 02114 USA. RP Taylor, E (reprint author), Massachusetts Gen Hosp, Psychol Assessment Ctr, 5 Emerson Pl, Boston, MA 02114 USA. NR 37 TC 27 Z9 30 U1 1 U2 16 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-1678 J9 J HUMANIST PSYCHOL JI J. Humanist. Psychol. PD WIN PY 2001 VL 41 IS 1 BP 13 EP 29 DI 10.1177/0022167801411003 PG 17 WC Psychology, Multidisciplinary SC Psychology GA 383FP UT WOS:000165872700003 ER PT J AU Soejima, K Rollins, BJ AF Soejima, K Rollins, BJ TI A functional IFN-gamma-inducible protein-10/CXCL10-specific receptor expressed by epithelial and endothelial cells that is neither CXCR3 nor glycosaminoglycan SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; MEMORY T-CELLS; CHEMOKINE RECEPTOR; HOST-DEFENSE; MICE LACKING; HUMAN GENE; CHEMOATTRACTANT; ANGIOGENESIS; LYMPHOCYTES; ADHESION AB Interferon-gamma -inducible protein-10 (IP-10)/CXCL10 is a CXC chemokine that attracts T lymphocytes and NK cells through activation of CXCR3, the only chemokine receptor identified to date that binds IP-10/CXCL10. We have found that several nonhemopoietic cell types, including epithelial and endothelial cells, have abundant levels of a receptor that binds IP-10/CXCL10 with a K-d of 1-6 nM. Surprisingly, these cells expressed no detectable CXCR3 mRNA. Furthermore, no cell surface expression of CXCR3 was detectable by flow cytometry, and the binding of I-125-labeled IP-10/CXCL10 to these cells was not competed by the other high affinity ligands for CXCR3, monokine induced by IFN-gamma /CXCL9, and I-TAC/CXCL11. Although IP-10/CXCL10 binds to cell surface heparan sulfate glycosaminoglycan (GAG), the receptor expressed by these cells is not GAG, since the affinity of IP-10/CXCL10 for this receptor is much higher than it is for GAG, its binding is not competed by platelet factor 4/CXCL4, and it is present on cells that are genetically incapable of synthesizing GAG. Furthermore, in contrast to IP-10/CXCL10 binding to GAG, IP-10/CXCL10 binding to these cells induces new gene expression and chemotaxis, indicating the ability of this receptor to transduce a signal. These high affinity IP-10/CXCL10-specific receptors on epithelial cells may be involved in cell migration and, perhaps, in the spread of metastatic cells as they exit from the vasculature. (All of the lung cancer cells we examined also expressed CXCR4, which has been shown to play a role in breast cancer metastasis.) CXCR3-negative endothelial cells may also use this receptor to mediate the angiostatic activity of IP-10/CXCL10, which is also expressed by these cells in an autocrine manner. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Rollins, BJ (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA53091] NR 46 TC 72 Z9 75 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2001 VL 167 IS 11 BP 6576 EP 6582 PG 7 WC Immunology SC Immunology GA 494WU UT WOS:000172309500066 PM 11714827 ER PT J AU Lathey, JL Tierney, C Chang, SYP D'Aquila, RT Bettendorf, DM Alexander, HC Santini, CD Hughes, AM Barroga, CF Spector, SA Landes, JE Hammer, SM Katzenstein, DA AF Lathey, JL Tierney, C Chang, SYP D'Aquila, RT Bettendorf, DM Alexander, HC Santini, CD Hughes, AM Barroga, CF Spector, SA Landes, JE Hammer, SM Katzenstein, DA CA AIDS Clin Trials Grp 175 Virology TI Associations of CCR5, CCR2, and stromal cell-derived factor 1 genotypes with human immunodeficiency virus disease progression in patients receiving nucleoside therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CHEMOKINE GENE VARIANT; HIV-INFECTED ADULTS; CLINICAL COURSE; CUBIC MILLIMETER; TYPE-1 RNA; ALLELE; TRANSMISSION; POLYMORPHISM; PLASMA AB Genotype data for CCR5, CCR2, and stromal cell-derived factor 1 (SDF-1) were obtained from 354 human immunodeficiency virus type 1 (HIV-1)-positive subjects who were being treated with nucleosides. Associations with HIV-1 load, HIV syncytium-inducing (SI) phenotype, CD4 cell count, and disease progression were analyzed. No differences in HIV-1 load or CD4 cell count were observed between wild type (+) and variant genotypes. Changes from non-SI to SI viral phenotype were more frequent in heterozygotes with a 32-bp deletion (Delta 32) in the CCR5 gene than in + homozygotes (40% vs. 7%; P = .01). In a multivariate analysis, heterozygous CCR5 Delta 32 was associated with reduced hazard of progression (hazard ratio, 0.32; P = .02). Subjects homozygous for the SDF-1 3'A variant had more-rapid disease progression (P = .008). The SDF-1 homozygous 3'A variant was related to more-rapid disease progression, and CCR5 Delta 32 was associated with reduced rates of hazard for disease progression in nucleoside-treated subjects. C1 Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA. Roche Mol Syst, Alameda, CA USA. Stanford Univ, Dept Med, Palo Alto, CA 94304 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Columbia Presbyterian Med Ctr, Dept Med, New York, NY 10032 USA. RP Lathey, JL (reprint author), ZYCOS, 44 Hartwell Ave, Lexington, MA 02421 USA. FU NIAID NIH HHS [AI-27670, AI-29193, AI-38855, AI-36214, AI-139004, AI2-7659] NR 23 TC 18 Z9 18 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 1 PY 2001 VL 184 IS 11 BP 1402 EP 1411 DI 10.1086/324427 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 492BG UT WOS:000172145400006 PM 11709782 ER PT J AU Zonios, G Bykowski, J Kollias, N AF Zonios, G Bykowski, J Kollias, N TI Skin melanin, hemoglobin, and light scattering properties can be quantitatively assessed in vivo using diffuse reflectance spectroscopy SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE diffusion; hemoglobin; melanin; optical properties; reflectance; scattering ID NONINVASIVE DETERMINATION; OPTICAL-PROPERTIES; BIOLOGICAL TISSUE; IN-VIVO; INVIVO; PHOTOPROTECTION; OXYGENATION; ABSORPTION; MODEL AB Noninvasive and real-time analysis of skin properties is useful in a wide variety of applications. In particular, the quantitative assessment of skin in terms of hemoglobin and melanin content, as well as in terms of its light scattering properties, is a challenging problem in dermatology. We present here a technique for examining human skin, based on the in vivo measurement of diffuse reflectance spectra in the visible and near-infrared ranges of the electromagnetic spectrum. Spectra were measured by means of a fiber optic probe, and they were analyzed using an analytical model of light diffusion in the skin. The results of the analysis indicate that it is possible to obtain quantitative information about hemoglobin and melanin content, as well as basic information regarding the scattering properties of the skin. C1 Harvard Univ, Massachusetts Gen Hosp, Wellman Labs Photomed, Sch Med, Boston, MA 02115 USA. RP Kollias, N (reprint author), Johnson & Johnson Consumer Prod Worldwide, 199 Grandview Rd, Skillman, NJ 08558 USA. NR 32 TC 197 Z9 201 U1 5 U2 28 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 2001 VL 117 IS 6 BP 1452 EP 1457 DI 10.1046/j.0022-202x.2001.01577.x PG 6 WC Dermatology SC Dermatology GA 505FR UT WOS:000172903200017 PM 11886508 ER PT J AU Li, W Nadelman, C Henry, G Fan, JH Muellenhoff, M Medina, E Gratch, NS Chen, M Han, JH Woodley, D AF Li, W Nadelman, C Henry, G Fan, JH Muellenhoff, M Medina, E Gratch, NS Chen, M Han, JH Woodley, D TI The p38-MAPK/SAPK pathway is required for human keratinocyte migration on dermal collagen SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE extracellular matrix; keratinocytes; p38-MAPK; motility; signal transduction ID ACTIVATED PROTEIN-KINASE; SIGNAL-TRANSDUCTION PATHWAY; GROWTH-FACTOR EGF; P38 MAP KINASE; SELECTIVE ACTIVATION; CELL-MIGRATION; EXPRESSION; MOTILITY; HYPOXIA; PHOSPHORYLATION AB Human keratinocyte motility plays an important role in the re-epithelialization of human skin wounds. The wound bed over which human keratinocytes migrate is rich in extracellular matrices, such as fibrin, fibronectin, and collagen, and serum factors, such as platelet-derived growth factor and transforming growth factor beta1. Extracellular matrices and the serum factors bind to cell surface receptors and initiate a cascade of intracellular signaling events that regulate cell migration. In this study, we identified an intracellular signaling pathway that mediates collagen-driven motility of human keratinocytes. Pharmacologic inhibition of the activation of p38-alpha and p38-beta mitogen-activated protein kinase activation potently blocked collagen-driven human keratinocyte migration. Transfection of the same keratinocytes with the kinase-negative mutants of p38-alpha or p38-beta mitogen-activated protein kinase markedly inhibited keratinocyte migration on collagen. Attachment of keratinocytes to collagen activated p38 mitogen-activated protein kinase, as well as p44/p42 ERKs. Interestingly, activation of the p38 mitogen-activated protein kinase cascade by overexpressing the constitutively active MKK3 and MKK6, MKK3b(E) and MKK6b(E), could neither initiate migration in the absence of collagen nor enhance collagen-driven migration. This study provides evidence that the p38-MAPK/SAPK pathway is necessary, but insufficient, for mediating human keratinocyte migration on collagen. C1 Univ So Calif, Keck Sch Med, Dept Med, Div Dermatol, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Norris Canc Ctr, Los Angeles, CA 90033 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Greater Los Angeles Vet Adm Healthcare Syst, Los Angeles, CA USA. RP Woodley, D (reprint author), Univ So Calif, Keck Sch Med, Dept Med, Div Dermatol, 1303 N Mission Rd, Los Angeles, CA 90033 USA. RI Han, J/G-4671-2010 FU NIAMS NIH HHS [R01 AR46538-01] NR 56 TC 35 Z9 35 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 2001 VL 117 IS 6 BP 1601 EP 1611 DI 10.1046/j.0022-202x.2001.01608.x PG 11 WC Dermatology SC Dermatology GA 505FR UT WOS:000172903200038 PM 11886529 ER PT J AU Choi, CM Lerner, EA AF Choi, CM Lerner, EA TI Leishmaniasis as an emerging infection SO JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS LA English DT Article; Proceedings Paper CT 49th Montagna Annual Symposium on the Biology of Skin CY AUG 12-16, 2000 CL SNOWMASS, CO ID HUMAN-IMMUNODEFICIENCY-VIRUS; AMERICAN CUTANEOUS LEISHMANIASIS; AZAR DERMAL LEISHMANIASIS; SODIUM STIBOGLUCONATE PENTOSTAM; CONGENITAL KALA-AZAR; VISCERAL LEISHMANIASIS; IMMUNE-RESPONSE; HIV-INFECTION; TEGUMENTARY LEISHMANIASIS; IMMUNOCOMPETENT PATIENTS AB Leishmaniasis is a protozoan disease whose diverse clinical manifestations are dependent both on the infecting species of Leishmania and the immune response of the host. Transmission of the disease occurs by the bite of a sand fly infected with Leishmania parasites. Infection may be restricted to the skin in cutaneous leishmaniasis, limited to the mucous membranes in mucosal leishmaniasis, or spread internally in visceral leishmaniasis or kala azar. The overall prevalence of leishmaniasis is 12 million cases worldwide, and the global yearly incidence of all clinical forms approaches 2 million new cases (World Health Organization WHO/ LEISH/200.42, Leishinanial/IV Co-Infection in Southwestern Europe 1990-98: Retrospective Analysis of 965 Cases, 2000). In the last two decades, leishmaniasis, especially visceral leishmaniasis, has been recognized as an opportunistic disease in the immunocompromised, particularly in patients infected with human immunodeficiency virus. C1 Massachusetts Gen Hosp East, CBRC, Boston, MA 02129 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Lerner, EA (reprint author), Massachusetts Gen Hosp East, CBRC, Bldg 149,13th St, Boston, MA 02129 USA. EM ethan.lerner@cbrc2.mgh.harvard.edu NR 86 TC 50 Z9 54 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0024 EI 1529-1774 J9 J INVEST DERM SYMP P JI J. Invest. Dermatol. Symp. Proc. PD DEC PY 2001 VL 6 IS 3 BP 175 EP 182 DI 10.1046/j.0022-202x.2001.00038.x PG 8 WC Dermatology SC Dermatology GA 533FP UT WOS:000174519000004 PM 11924824 ER PT J AU Duda, RB Kang, SS Archer, SY Meng, SF Hodin, RA AF Duda, RB Kang, SS Archer, SY Meng, SF Hodin, RA TI American ginseng transcriptionally activates p21 mRNA in breast cancer cell lines SO JOURNAL OF KOREAN MEDICAL SCIENCE LA English DT Article; Proceedings Paper CT International Symposium on Cancer Prevention of Insam CY APR 20, 2001 CL SEOUL, SOUTH KOREA DE p21; American ginseng; breast neoplasms ID CYCLIN-DEPENDENT KINASES; P53-INDEPENDENT INDUCTION; MCF-7 CELLS; DNA-DAMAGE; GROWTH; EXPRESSION; APOPTOSIS; ESTROGEN; INHIBITOR; ARREST AB American ginseng (AG) has been demonstrated to inhibit breast cancer cell growth in vitro. p21 protein, a universal cell cycle inhibitor, binds cyclin-CDK complexes, an important mechanism in cell cycle regulation. The purpose of this investigation was to determine if AG induces p2l gene expression in hormone sensitive (MCF-7) and insensitive (MDA-MB-231) breast cancer cell lines. Cells grown in steroid stripped medium (SSM) were treated with AG, 17-beta-estradiol (E-2), genistein or cycloheximide (CHX). Northern blot analyses were performed using human p21Cip1 and 36134 cDNA probes. Cell lines were transiently transfected with select mouse p2l CAT reporter constructs, including those lacking a p53 binding site. Cell cycle analyses was performed by FACScan. The results revealed that AG induced p2l mRNA expression in MCF-7 and MDA-MB-231 cells (p=0.0004; pless than or equal to0.0001, respectively). Neither E-2 nor genistein alter p21 mRNA expression. CHX, a protein synthesis inhibitor, did not block p2l mRNA expression induced by AG, indicating that p2l is induced as an immediate early gene. AG activated p2l reporter constructs in transfected cells, independent of p53 binding sites, The cell cycle proliferative phase was significantly decreased by AG and increased by E-2 (pless than or equal to0.0001). AG may inhibit breast cancer cell growth by transcriptional activation of the p2l gene, independent of p53. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA USA. RP Duda, RB (reprint author), Beth Israel Deaconess Med Ctr Surg Oncol, RW 871,330 Brookline Ave, Boston, MA 02215 USA. NR 44 TC 13 Z9 14 U1 0 U2 1 PU KOREAN ACAD MEDICAL SCIENCES PI SEOUL PA 302 75 DONG DU ICHON, DONG YONGSAN KU, SEOUL 140 031, SOUTH KOREA SN 1011-8934 J9 J KOREAN MED SCI JI J. Korean Med. Sci. PD DEC PY 2001 VL 16 SU S BP S54 EP S60 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 508CZ UT WOS:000173071300009 PM 11748377 ER PT J AU Hoffmann, U Frank, H Stefenelli, T Kaiser, B Klaar, U Globits, S AF Hoffmann, U Frank, H Stefenelli, T Kaiser, B Klaar, U Globits, S TI Afterload reduction in severe aortic regurgitation SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE aortic regurgitation; magnetic resonance tomography; hydralazine; afterload reduction; left ventricular function ID IMPROVED CARDIAC-PERFORMANCE; LEFT-VENTRICULAR FUNCTION; ASYMPTOMATIC PATIENTS; NIFEDIPINE; INSUFFICIENCY; HYDRALAZINE; EXERCISE; THERAPY AB This study was designed to assess the effects of afterload reduction in asymptomatic patients with severe aortic regurgitation (AR) and maintained LV function by cine-MRI. We studied 13 patients at baseline and after 0.2 mg/kg Hydralazine (I.V.). Patients were stratified according to the volumetric IV response to acute afterload reduction: Group I comprised patients with improved IV response; Group H comprised patients with unchanged or deteriorated IV response. Baseline IV function and severity of AR were not significantly different between groups. However, regurgitant fraction decreased (50 +/- 12 vs. 36 +/- 9%; P < 0.03) and cardiac output increased (4.9 +/- 1.4 vs. 7.1 +/- 1.61/minute; P < 0.001) in Group I and remained unchanged in Group II (54 +/- 10 vs. 55 +/- 10%, P = n.s. and 5.5 +/- 1.4 vs. 6.6 +/- 0.91/minute; P = n.s.) during maximal vasodilation. Beat-to-beat analysis revealed a decrease of left ventricular endsystolic volume index in group 1 (48 +/- 13 vs. 37 +/- 9 ml/beat; P < 0.05) and no change in group II (61 +/- 20 vs. 62 +/- 20 ml/beat; P = n.s.). In the natural history of chronic AR, the absence of improved LV performance during acute vasodilation using beat-to-beat analysis by MRI may identify patients with more advanced cardiac adaptation to chronic volume overload. (C) 2001 Wiley-Liss, Inc. C1 Univ Hosp Vienna, Dept Radiol, Vienna, Austria. RP Hoffmann, U (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, 1st Fruit St 55,Bartlett 510, Boston, MA 02114 USA. NR 22 TC 5 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD DEC PY 2001 VL 14 IS 6 BP 693 EP 697 DI 10.1002/jmri.10015 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 537LE UT WOS:000174759300005 PM 11747025 ER PT J AU Proios, H Chialant, D Caplan, D AF Proios, H Chialant, D Caplan, D TI The multidisciplinary assessment of visual hemispatial neglect: A case report of a bilingual patient SO JOURNAL OF MEDICAL SPEECH-LANGUAGE PATHOLOGY LA English DT Article ID SPATIAL NEGLECT AB The authors present and discuss the assessment procedures used in a case of left-sided neglect in a bilingual Italian-English, right-hemisphere temporal craniotomy patient. Assessment was done by a speech-language pathologist, a neuropsychologist, and a neurologist. Assessment tools included common bedside tasks, such as picture description, line cancellation, search task, verbal and nonverbal cancellation and drawing from memory and copying. Additionally, the authors used a new research-based assessment tool that employs real and chimeric figures (created by joining two halves of different objects) for oral naming. The findings indicate a clear left-sided neglect in a number of motor response tasks and verbal response tasks. This pattern of performance indicates a deficit affecting processing after the first retino-topic level of visual processing, Performance profile is discussed as a coherent framework for establishing the foundations for an individual treatment program. C1 Spaulding Rehabil Hosp, Dept Speech & Language Pathol, Boston, MA USA. Harvard Univ, Dept Psychol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. RP Proios, H (reprint author), Univ Zurich Hosp, Dept Neuropsychol, CH-8092 Zurich, Switzerland. NR 21 TC 1 Z9 1 U1 0 U2 1 PU SINGULAR PUBLISHING GROUP INC PI CLIFTON PARK PA 5 MAXWELL DR, CLIFTON PARK, NY 12065 USA SN 1065-1438 J9 J MED SPEECH-LANG PA JI J. Med. Speech-Lang. Pathol. PD DEC PY 2001 VL 9 IS 4 BP 277 EP 289 PG 13 WC Audiology & Speech-Language Pathology; Clinical Neurology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology GA 502YW UT WOS:000172771200008 ER PT J AU Schultz, SG Leaf, A AF Schultz, SG Leaf, A TI Hans Ussing memorial issue: Epithelial membrane transport SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Biographical-Item C1 Univ Texas, Sch Med, Dept Integrat Biol & Pharmacol, Houston, TX USA. Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. RP Leaf, A (reprint author), Univ Texas, Sch Med, Dept Integrat Biol & Pharmacol, POB 20708, Houston, TX USA. NR 1 TC 4 Z9 4 U1 0 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD DEC 1 PY 2001 VL 184 IS 3 BP 199 EP 202 DI 10.1007/s00232-001-0087-0 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 507YZ UT WOS:000173060400001 ER PT J AU Leaf, A Xiao, YF AF Leaf, A Xiao, YF TI The modulation of ionic currents in excitable tissues by n-3 polyunsaturated fatty acids SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE heart; arrhythmias; brain; seizures ID RAT CARDIAC MYOCYTES; NA+ CHANNELS; VENTRICULAR-FIBRILLATION; GRAMICIDIN CHANNELS; BILAYER DEFORMATIONS; LOCAL-ANESTHETICS; LONG-CHAIN; PREVENTION; BLOCK; ARRHYTHMIAS C1 Massachusetts Gen Hosp, Dept Med, Cambridge, MA 02139 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Leaf, A (reprint author), Massachusetts Gen Hosp, Dept Med, Bldg 149,13th St, Cambridge, MA 02139 USA. FU NHLBI NIH HHS [HL62284]; NIDDK NIH HHS [DK38165] NR 29 TC 32 Z9 34 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD DEC 1 PY 2001 VL 184 IS 3 BP 263 EP 271 DI 10.1007/s00232-001-0095-0 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 507YZ UT WOS:000173060400010 PM 11891551 ER PT J AU Bogdanov, MB Andreassen, OA Dedeoglu, A Ferrante, RJ Beal, MF AF Bogdanov, MB Andreassen, OA Dedeoglu, A Ferrante, RJ Beal, MF TI Increased oxidative damage to DNA in a transgenic mouse model of Huntington's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE free radicals; Huntington's disease; 8-hydroxy-2-deoxyguanosine; oxidative damage; microdialysis; transgenic ID AMYOTROPHIC-LATERAL-SCLEROSIS; NEUROLOGICAL PHENOTYPE; ALZHEIMERS-DISEASE; MITOCHONDRIAL-DNA; BRAIN; MICE; 8-HYDROXY-2'-DEOXYGUANOSINE; DYSFUNCTION; GENE AB Mitochondrial dysfunction and oxidative damage may play a role in the pathogenesis of Huntington's disease (HD). We examined concentrations of 8-hydroxy-2-deoxyguanosine (OH(8)dG), a well-established marker of oxidative damage to DNA, in a transgenic mouse model of HD (R6/2). Increased concentrations of OH(8)dG were found in the urine, plasma and striatal microdialysates of the HD mice. Increased concentrations were also observed in isolated brain DNA at 12 and 14 weeks of age. Immunocytochemistry showed increased OH(8)dG staining in late stages of the illness. These results suggest that oxidative damage may play a role in the pathogenesis of neuronal degeneration in the R6/2 transgenic mouse model of HD. C1 Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Vet Adm 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. New York Presbyterian Hosp, New York, 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. FU NIA NIH HHS [AG12992, AG13846, AG14930]; NINDS NIH HHS [NS37102, NS35255, NS39258] NR 21 TC 165 Z9 169 U1 0 U2 7 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2001 VL 79 IS 6 BP 1246 EP 1249 DI 10.1046/j.1471-4159.2001.00689.x PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 505BE UT WOS:000172890500014 PM 11752065 ER PT J AU Brower, MC Price, BH AF Brower, MC Price, BH TI Neuropsychiatry of frontal lobe dysfunction in violent and criminal behaviour: a critical review SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Review DE frontal lobe dysfunction; aggression; violence ID POSITRON-EMISSION-TOMOGRAPHY; ANTISOCIAL PERSONALITY-DISORDER; AGGRESSIVE-BEHAVIOR; PSYCHIATRIC-PATIENTS; PREFRONTAL CORTEX; SUBSTANCE-ABUSE; FAMILY HISTORY; UNITED-STATES; MURDERERS; DAMAGE AB Objectives-To establish the link between frontal lobe dysfunction and violent and criminal behaviour, based on a review of relevant literature. Methods-Articles relating evidence of frontal lobe dysfunction with violence or crime were collected through a MEDLINE search using the keyword "frontal lobe" combined with the terms "aggression," "violence," "crime," "antisocial personality disorder," "psychopathy," "impulse control disorders", and "episodic dyscontrol." Reference lists were then searched for additional articles. Results-High rates of neuropsychiatric abnormalities reported in persons with violent and criminal behaviour suggest an association between aggressive dyscontrol and brain injury, especially involving the frontal lobes. The studies reviewed support an association between frontal lobe dysfunction and increased aggressive and antisocial behaviour. Focal orbitofrontal injury is specifically associated with increased aggression. Deficits in frontal executive function may increase the likelihood of future aggression, but no study has reliably demonstrated a characteristic pattern of frontal network dysfunction predictive of violent crime. Conclusions-Clinically significant focal frontal lobe dysfunction is associated with aggressive dyscontrol, but the increased risk of violence seems less than is widely presumed. Evidence is strongest for an association between focal prefrontal damage and an impulsive subtype of aggressive behaviour. C1 McLean Hosp, Dept Neurol, Belmont, MA 02478 USA. Taunton State Hosp, Secure Care Program, Dept Psychiat, Taunton, MA USA. Harvard Univ, Sch Med, Secure Care Program, Dept Psychiat, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Price, BH (reprint author), McLean Hosp, Dept Neurol, 115 Mill St, Belmont, MA 02478 USA. NR 69 TC 246 Z9 265 U1 34 U2 118 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD DEC PY 2001 VL 71 IS 6 BP 720 EP 726 DI 10.1136/jnnp.71.6.720 PG 7 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 497EK UT WOS:000172442300006 PM 11723190 ER PT J AU Laforet, GA Sapp, E Chase, K McIntyre, C Boyce, FM Campbell, M Cadigan, BA Warzecki, L Tagle, DA Reddy, PH Cepeda, C Calvert, CR Jokel, ES Klapstein, GJ Ariano, MA Levine, MS DiFiglia, M Aronin, N AF Laforet, GA Sapp, E Chase, K McIntyre, C Boyce, FM Campbell, M Cadigan, BA Warzecki, L Tagle, DA Reddy, PH Cepeda, C Calvert, CR Jokel, ES Klapstein, GJ Ariano, MA Levine, MS DiFiglia, M Aronin, N TI Changes in cortical and striatal neurons predict behavioral and electrophysiological abnormalities in a transgenic murine model of Huntington's disease SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cortex; Huntington's disease; NMDA; neuronal morphology; striatum; transgenic mice ID LENGTH HD CDNA; INTRANUCLEAR INCLUSIONS; MUTANT HUNTINGTIN; METABOLIC DYSFUNCTION; PYRAMIDAL NEURONS; MICE; EXPRESSION; BRAIN; NEUROPATHOLOGY; LOCALIZATION AB Neurons in Huntington's disease exhibit selective morphological and subcellular alterations in the striatum and cortex. The link between these neuronal changes and behavioral abnormalities is unclear. We investigated relationships between essential neuronal changes that predict motor impairment and possible involvement of the corticostriatal pathway in developing behavioral phenotypes. We therefore generated heterozygote mice expressing the N-terminal one-third of huntingtin with normal (CT18) or expanded (HD46, HD100) glutamine repeats. The HD mice exhibited motor deficits between 3 and 10 months. The age of onset depended on an expanded polyglutamine length; phenotype severity correlated with increasing age. Neuronal changes in the striatum (nuclear inclusions) preceded the onset of phenotype, whereas cortical changes, especially the accumulation of huntingtin in the nucleus and cytoplasm and the appearance of dysmorphic dendrites, predicted the onset and severity of behavioral deficits. Striatal neurons in the HD mice displayed altered responses to cortical stimulation and to activation by the excitotoxic agent NMDA. Application of NMDA increased intracellular Ca2+ levels in HD100 neurons compared with wild-type neurons. Results suggest that motor deficits in Huntington's disease arise from cumulative morphological and physiological changes in neurons that impair corticostriatal circuitry. C1 Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01655 USA. Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Natl Genome Res Inst, NIH, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Mental Retardat Res Ctr, Los Angeles, CA 90095 USA. Chicago Med Sch, Dept Neurosci, N Chicago, IL 60064 USA. RP Aronin, N (reprint author), Univ Massachusetts, Sch Med, Dept Med, 55 Lake Ave N, Worcester, MA 01655 USA. FU NIDDK NIH HHS [DK32520]; NINDS NIH HHS [NS 16367, NS 35711, NS 38194] NR 52 TC 186 Z9 188 U1 1 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 1 PY 2001 VL 21 IS 23 BP 9112 EP 9123 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 494BL UT WOS:000172258400007 PM 11717344 ER PT J AU Nagai, M Aoki, M Miyoshi, I Kato, M Pasinelli, P Kasai, N Brown, RH Itoyama, Y AF Nagai, M Aoki, M Miyoshi, I Kato, M Pasinelli, P Kasai, N Brown, RH Itoyama, Y TI Rats expressing human cytosolic copper-zinc superoxide dismutase transgenes with amyotrophic lateral sclerosis: Associated mutations develop motor neuron disease SO JOURNAL OF NEUROSCIENCE LA English DT Article DE familial amyotrophic lateral sclerosis; copper-zinc SOD; SOD1; transgenic rats; glutamate; caspase ID ANTERIOR HORN CELLS; AMINO-ACID LEVELS; FAMILIAL ALS; MODEL; GENE; MICE; SOD1; INCLUSIONS; DEATH; DEGENERATION AB Some cases of familial amyotrophic lateral sclerosis (ALS) are caused by mutations in the gene encoding cytosolic, copper-zinc superoxide dismutase (SOD1). We report here that rats that express a human SOD1 transgene with two different ALS-associated mutations (G93A and H46R) develop striking motor neuron degeneration and paralysis. As in the human disease and transgenic ALS mice, pathological analysis demonstrates selective loss of motor neurons in the spinal cords of these transgenic rats. In spinal cord tissues, this is accompanied by activation of apoptotic genes known to be activated by mutant SOD1 protein in vitro and in vivo. These animals provide additional support for the proposition that motor neuron death in SOD1-related ALS reflects one or more acquired, neurotoxic properties of the mutant SOD1 protein. The larger size of this rat model as compared with the ALS mice will facilitate studies involving manipulations of spinal fluid (implantation of intrathecal catheters for chronic therapeutic studies; CSF sampling) and spinal cord (e.g., direct administration of viral- and cell-mediated therapies). C1 Tohoku Univ, Grad Sch Med, Dept Neurosci, Div Neurol, Sendai, Miyagi 9808574, Japan. Massachusetts Gen Hosp, Day Neuromuscular Res Lab, Charlestown, MA 02129 USA. Tohoku Univ, Grad Sch Med, Inst Expt Anim, Sendai, Miyagi 9808574, Japan. RP Aoki, M (reprint author), Tohoku Univ, Grad Sch Med, Dept Neurosci, Div Neurol, 1-1 Seiryo Machi, Sendai, Miyagi 9808574, Japan. FU NINDS NIH HHS [P01NS31248, P01NS37912] NR 50 TC 219 Z9 230 U1 0 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 1 PY 2001 VL 21 IS 23 BP 9246 EP 9254 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 494BL UT WOS:000172258400021 PM 11717358 ER PT J AU Kass, J Jacob, TC Kim, P Kaplan, JM AF Kass, J Jacob, TC Kim, P Kaplan, JM TI The EGL-3 proprotein convertase regulates mechanosensory responses of Caenorhabditis elegans SO JOURNAL OF NEUROSCIENCE LA English DT Article DE mechanosensation; neuropeptide; synapse; proprotein convertase; egl-3; glr-1; glutamate receptor; C. elegans ID GLR-1 GLUTAMATE-RECEPTOR; C-ELEGANS; NEUROPEPTIDE GENE; MICE LACKING; NEURONS; HOMOLOG; LOCALIZATION; BEHAVIOR; CLONING; PEPTIDE AB Neuroactive peptides are packaged as proproteins into dense core vesicles or secretory granules, where they are cleaved at dibasic residues by copackaged proprotein convertases. We show here that the Caenorhabditis elegans egl-3 gene encodes a protein that is 57% identical to mouse proprotein convertase type 2 (PC2), and we provide evidence that this convertase regulates mechanosensory responses. Nose touch sensitivity (mediated by ASH sensory neurons) is defective in mutants lacking GLR-1 glutamate receptors (GluRs); however, mutations eliminating the egl-3 PC2 restored nose touch sensitivity to glr-1 GluR mutants. By contrast, body touch sensitivity (mediated by the touch cells) is greatly diminished in egl-3 PC2 mutants. Taken together, these results suggest that egl-3 PC2-processed peptides normally regulate the responsiveness of C. elegans to mechanical stimuli. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Kaplan, JM (reprint author), Univ Calif Berkeley, LSA 361, Dept Cell & Mol Biol, Berkeley, CA 94720 USA. EM Joshkap@socrates.berkeley.edu FU NINDS NIH HHS [NS32196] NR 46 TC 94 Z9 97 U1 1 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 1 PY 2001 VL 21 IS 23 BP 9265 EP 9272 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 494BL UT WOS:000172258400023 PM 11717360 ER PT J AU Kekelidze, T Khait, I Togliatti, A Benzecry, JM Wieringa, B Holtzman, D AF Kekelidze, T Khait, I Togliatti, A Benzecry, JM Wieringa, B Holtzman, D TI Altered brain phosphocreatine and ATP regulation when mitochondrial creatine kinase is absent SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the Society-for-Neuroscience CY NOV 07-12, 1998 CL LOS ANGELES, CALIFORNIA SP Soc Neurosci DE ATP; hypoxia; mitochondrial creatine kinase; phosphocreatine; seizures ID NUCLEAR-MAGNETIC-RESONANCE; CEREBRAL GRAY; WHITE-MATTER; MOUSE-BRAIN; IN-VIVO; METABOLISM; DEFICIENT; SEIZURES; CORTEX; MICE AB In cerebral gray matter, ATP concentration is closely maintained despite rapid, large increases in turnover and low substrate reserves. As seen in vivo by P-31 nuclear magnetic resonance (NMR) spectroscopy, brain ATP is stable early in seizures, a state of high energy demand, and in mild hypoxia, a state of substrate deficiency. Like other tissues with high and variable ATP turnover, cerebral gray matter has high phosphocreatine (PCr) concentration and both cytosolic and mitochondrial creatine kinase (UbMi-CK) isoenzymes. To understand the physiology of brain creatine kinases, we used P-31 NMR to study PCr and ATP regulation during seizures and hypoxia in mice with targeted deletion of the UbMi-CK gene. The baseline CK reaction rate constant (k) was higher in mutants than wild-types. During seizures, PCr and ATP decreased in mutants but not in wild-types. The k-value for the CK catalyzed reaction rate increased in wild-types but not in the mutants. Hypoxic mutants and wild-types showed similar PCr losses and stable ATP. During recovery from hypoxia, brain PCr and ATP concentrations returned to baseline in wild-types but were 20% higher than baseline in the mutants. We propose that UbMi-CK couples ATP turnover to the CK catalyzed reaction rate and regulates ATP concentration when synthesis is increased. (C) 2001 Wiley-Liss, Inc. C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Nijmegen, Med Ctr, Dept Cell Biol, NL-6526 ED Nijmegen, Netherlands. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Holtzman, D (reprint author), Massachusetts Gen Hosp East, Box 21,149 13th St, Boston, MA 02129 USA. RI Wieringa, Berend/A-5346-2011 OI Wieringa, Berend/0000-0001-9192-8020 FU NINDS NIH HHS [NS 26371]; PHS HHS [NX 10176] NR 26 TC 24 Z9 28 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD DEC 1 PY 2001 VL 66 IS 5 BP 866 EP 872 DI 10.1002/jnr.10060 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 499GF UT WOS:000172562200018 PM 11746413 ER PT J AU Bourdette, DN McCauley, LA Barkhuizen, A Johnston, W Wynn, M Joos, SK Storzbach, D Shuell, T Sticker, D AF Bourdette, DN McCauley, LA Barkhuizen, A Johnston, W Wynn, M Joos, SK Storzbach, D Shuell, T Sticker, D TI Symptom factor analysis, clinical findings, and functional status in a population-based case control study of Gulf War unexplained illness SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHRONIC FATIGUE SYNDROME; FIBROMYALGIA SYNDROME; GENERAL-POPULATION; COMMON SYMPTOMS; LYME-DISEASE; CIVIL-WAR; PREVALENCE; VETERANS; INFECTION AB Few epidemiological studies have been conducted that haze incorporated clinical evaluations of Gulf War veterans with unexplained health symptoms and healthy controls. We conducted a mail survey of 2022 Gulf War veterans residing in the northwest United States and clinical examinations on a subset of 443 responders who seemed to have unexplained health symptoms or were healthy. Few clinical differences were found between cases and controls. The most frequent unexplained symptoms were cognitive/psychological, but significant overlap existed with musculoskeletal and fatigue symptoms. Over half of, for the veterans with unexplained musculoskeletal pain met the criteria fibromyalgia, and a significant portion of the veterans with unexplained fatigue met the criteria. for chronic fatigue syndrome. Similarities were found in the clinical interpretation of unexplained illness in this population and statistical factor analysis performed by this study group and others. C1 Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Div Med Informat & Outcome Res, Portland, OR USA. RP Bourdette, DN (reprint author), Portland Vet Affairs Med Ctr, Serv Neurol, Mailcode P-3-NEURO,3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. NR 62 TC 40 Z9 40 U1 2 U2 3 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 DEC PY 2001 VL 43 IS 12 BP 1026 EP 1040 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 501TK UT WOS:000172702000005 PM 11765674 ER PT J AU Spencer, PS McCauley, LA Lapidus, JA Lasarev, M Joos, SK Storzbach, D AF Spencer, PS McCauley, LA Lapidus, JA Lasarev, M Joos, SK Storzbach, D TI Self-reported exposures and their association with unexplained illness in a population-based case-control study of Gulf War veterans SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID PYRIDOSTIGMINE BROMIDE; HEALTH SYMPTOMS; STRESS; PENETRATION; SERVICE; SYSTEM; STATES; BRAIN; DEET AB Many factors haze been considered as possible causes of the unexplained illness reported by veterans of the Gulf War (GW). In this study, we report an analysis of risk factors and unexplained illness in a population-based sample of GW veterans who underwent clinical evaluation. Multiple risk factors were compared in 241 veterans who met criteria for unexplained illness and 113 healthy controls. Results suggest that GW unexplained illness is most highly associated with combat conditions, heat stress, and hazing sought medical attention during the GW. When controlling for multiple simultaneous exposures during the GW, interactions around pyridostigmine bromide, insecticides and repellents, and stress were not significant. These results indicate that most unexplained illness in GW veterans cannot be explained by neurotoxic effects of exposures to chemicals that inhibit cholinesterase activity: C1 Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Spencer, PS (reprint author), Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, 3181 SW Sam Jackson Pk Rd,CROET Mailcode L606, Portland, OR 97201 USA. OI Lasarev, Michael R/0000-0002-1896-2705 NR 46 TC 26 Z9 26 U1 2 U2 2 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 DEC PY 2001 VL 43 IS 12 BP 1041 EP 1056 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 501TK UT WOS:000172702000006 PM 11765675 ER PT J AU Kales, SN Mendoza, PJ Hill, JM Christiani, DC AF Kales, SN Mendoza, PJ Hill, JM Christiani, DC TI Spirometric surveillance in hazardous materials firefighters: Does hazardous materials duty affect lung function? SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID MEDICAL SURVEILLANCE; PULMONARY-FUNCTION; WASTE WORKERS; FIRE FIGHTERS; EXPOSURE AB We analyzed spirometry results for 351 male hazardous materials firefighters from 1996 to 1999 who underwent one or more annual medical surveillance/fitness for duty examinations: 276 (79%) technicians and 75 (21%) support members. Support members had a very limited potential for hazardous materials exposure and served as referents. In cross-sectional comparisons, the technicians' average forced vital capacity and forced expiratory volume in 1 second were either statistically better or not significantly different from that of the support members at all four examinations. Longitudinally, no statistically significant differences were seen for forced vital capacity. The mean percent of predicted forced expiratory volume in 1 second decreased by support controls (P = 0.433), and 3% for technicians (P = 0.029), the total cohort (P = 0.014). Although respiratory irritants are the most common type of exposure in hazardous materials releases, the results suggest that hazardous materials technicians do not lose pulmonary function at a more accelerated rate than support team firefighters. C1 Cambridge Hosp, Dept Med, Cambridge, MA 02139 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Pulm Crit Care Unit, Boston, MA 02114 USA. Massachusetts Resp Hosp, Ctr Occupat & Environm, 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]; PHS HHS [0H03729] NR 31 TC 1 Z9 1 U1 0 U2 0 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 DEC PY 2001 VL 43 IS 12 BP 1114 EP 1120 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 501TK UT WOS:000172702000013 PM 11765682 ER PT J AU Troulis, MJ AF Troulis, MJ TI Influence of distraction rates on the temporomandibular joint position and cartilage morphology in a rabbit model of mandibular lengthening - Discussion SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Editorial Material ID OSTEOGENESIS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Troulis, MJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 12 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD DEC PY 2001 VL 59 IS 12 BP 1460 EP 1461 DI 10.1053/joms.2001.28283 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 498BP UT WOS:000172490200018 ER PT J AU Genuth, S Nathan, D Shamoon, H Duffy, H Engel, S Engel, H Dahms, W Mayer, L Pendegras, S Zegarra, H Miller, D Singerman, L Brillion, D Lackaye, M Heinemann, M Rahhal, F Reppuci, V Lee, T Whitehouse, F Kruger, D Carey, JD Bergenstal, R Johnson, M Kendall, D Spencer, M Noller, D Morgan, K Etzwiler, D Jacobson, A Golden, E Soroko, D Sharuk, G Arrigg, P Doyle, J Nathan, D Fritz, S Crowell, S Godine, J McKitrick, C Lou, P Service, J Ziegler, G Pach, J Colwell, J Wood, D Mayfield, R Hermayer, K Szpiech, M Lyons, T Parker, J Farr, A Elsing, S Thompson, T Molitch, M Schaefer, B Jampol, L Weinberg, D Lyon, A Kolterman, O Lorenzi, G Goldbaum, M Sivitz, W Bayless, M Zeither, R Weingeist, T Stone, E Boidt, HC Gehries, K Russell, S Counts, D Kowarski, A Ostrowski, D Donner, T Steidl, S Jones, B Herman, W Greene, D Martin, C Stevens, MJ Vine, AK Elner, S Bantle, J Rogness, B Olsen, T Steuer, E Kaushel, S Goldstein, D Hitt, S Giangiacomo, J Ormerod, LD Schade, D Canady, J Schluster, M Das, A Hornbeck, D Schwartz, S Maschak-Carey, BJ Baker, L Braunstein, S Brucker, A Orchard, T Silvers, N Songer, T Doft, B Olson, S Bergren, RL Fineman, M Malone, J Vacarro-Kish, J Berger, C Gstalder, R Pavan, PR Bryer-Ash, M Kitabchi, A Lambeth, H Murphy, MB Moser, S Meyer, D Iannacone, A Raskin, P Strowig, S Edwards, A Alappatt, J Wilson, C Park, S Zinman, B Barnie, A MacLean, S Devenyi, R Mandelcorn, M Brent, M Palmer, J Catton, S Kinyoun, J Van Ottingham, L Dupre, J Harth, J Canny, C Nicolle, D May, M Lorenz, R Lipps, J Survant, L Feman, S Tawansy, K Agarwal, A White, N Santiago, J Levandoski, L Boniuk, I Grand, G Thomas, M Burgess, D Joseph, D Blinder, K Tamborlane, W Gatcomb, P Stroessel, K Dahms, B Trail, R Quin, J Lachin, J Cleary, P Kenny, D Backlund, J Diminick, L Henry, A Klump, K Lamas, D Cowie, C Eastman, R Fradkin, J Davis, M Hubbard, L Geithman, P Brickbauer, J Kastorff, L Neider, M Badal, D Esser, B Miner, K Wabers, H Steffes, M Bucksa, J Chavers, B O'Leary, D Funk, I Crow, R O'Donnell, C Gloeb, B Thomas, S Weir, G Clark, C D'Agostino, R Espeland, M Klein, B Jacobson, H Manolio, T Rand, L Singer, D Stern, M Garvey, WT Lyons, TJ Jenkins, A Klein, R Lopes-Virella, M Virella, G Jaffa, AA Zheng, D Lackland, D McGee, D Mayfield, RK Boright, A Paterson, A Scherer, S Zinman, B Brunzell, J Hokanson, J Marcovina, S Purnell, J Sibley, S AF Genuth, S Nathan, D Shamoon, H Duffy, H Engel, S Engel, H Dahms, W Mayer, L Pendegras, S Zegarra, H Miller, D Singerman, L Brillion, D Lackaye, M Heinemann, M Rahhal, F Reppuci, V Lee, T Whitehouse, F Kruger, D Carey, JD Bergenstal, R Johnson, M Kendall, D Spencer, M Noller, D Morgan, K Etzwiler, D Jacobson, A Golden, E Soroko, D Sharuk, G Arrigg, P Doyle, J Nathan, D Fritz, S Crowell, S Godine, J McKitrick, C Lou, P Service, J Ziegler, G Pach, J Colwell, J Wood, D Mayfield, R Hermayer, K Szpiech, M Lyons, T Parker, J Farr, A Elsing, S Thompson, T Molitch, M Schaefer, B Jampol, L Weinberg, D Lyon, A Kolterman, O Lorenzi, G Goldbaum, M Sivitz, W Bayless, M Zeither, R Weingeist, T Stone, E Boidt, HC Gehries, K Russell, S Counts, D Kowarski, A Ostrowski, D Donner, T Steidl, S Jones, B Herman, W Greene, D Martin, C Stevens, MJ Vine, AK Elner, S Bantle, J Rogness, B Olsen, T Steuer, E Kaushel, S Goldstein, D Hitt, S Giangiacomo, J Ormerod, LD Schade, D Canady, J Schluster, M Das, A Hornbeck, D Schwartz, S Maschak-Carey, BJ Baker, L Braunstein, S Brucker, A Orchard, T Silvers, N Songer, T Doft, B Olson, S Bergren, RL Fineman, M Malone, J Vacarro-Kish, J Berger, C Gstalder, R Pavan, PR Bryer-Ash, M Kitabchi, A Lambeth, H Murphy, MB Moser, S Meyer, D Iannacone, A Raskin, P Strowig, S Edwards, A Alappatt, J Wilson, C Park, S Zinman, B Barnie, A MacLean, S Devenyi, R Mandelcorn, M Brent, M Palmer, J Catton, S Kinyoun, J Van Ottingham, L Dupre, J Harth, J Canny, C Nicolle, D May, M Lorenz, R Lipps, J Survant, L Feman, S Tawansy, K Agarwal, A White, N Santiago, J Levandoski, L Boniuk, I Grand, G Thomas, M Burgess, D Joseph, D Blinder, K Tamborlane, W Gatcomb, P Stroessel, K Dahms, B Trail, R Quin, J Lachin, J Cleary, P Kenny, D Backlund, J Diminick, L Henry, A Klump, K Lamas, D Cowie, C Eastman, R Fradkin, J Davis, M Hubbard, L Geithman, P Brickbauer, J Kastorff, L Neider, M Badal, D Esser, B Miner, K Wabers, H Steffes, M Bucksa, J Chavers, B O'Leary, D Funk, I Crow, R O'Donnell, C Gloeb, B Thomas, S Weir, G Clark, C D'Agostino, R Espeland, M Klein, B Jacobson, H Manolio, T Rand, L Singer, D Stern, M Garvey, WT Lyons, TJ Jenkins, A Klein, R Lopes-Virella, M Virella, G Jaffa, AA Zheng, D Lackland, D McGee, D Mayfield, RK Boright, A Paterson, A Scherer, S Zinman, B Brunzell, J Hokanson, J Marcovina, S Purnell, J Sibley, S CA Diabet Control Complications Trial Epidemiology Diabet Interventions TI Beneficial effects of intensive therapy of diabetes during adolescence: Outcomes after the conclusion of the Diabetes Control and Complications Trial (DCCT) SO JOURNAL OF PEDIATRICS LA English DT Article AB Objective: The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive therapy of type I diabetes mellitus reduces the risk of development and progression of microvascular complications. The Epidemiology, of Diabetes Interventions and Complications (EDIC) study assessed whether these benefits persisted after the end of DCCT. Results for the adolescent DCCT cohort are reported here. Study design: Of the DCCT adolescent cohort (n = 195), 175 participated in EDIC, 151 had fundus photography, and 156 had albumin excretion rate measured at year 3 or 4. The odds of progression of retinopathy and albuminuria from closeout of the DCCT until ED IC year 4 were assessed. Results: In contrast to the 7.4 years of the DCCT during which mean hemoglobin A,, levels were significantly lower with intensive therapy than conventional therapy (8.06% vs 9.76%; P < .0001), the subsequent first 4 years of EDIC had mean hemoglobin Alc levels that were similar between the former intensive and the former conventional groups (8.38% vs 8.45%). However, the prevalence of worsening of 3 steps or more in retinopathy and of progression to proliferative or severe nonproliferative retinopathy were reduced by 74% (P < .001) and 78% (P < .007), respectively, in the former intensive therapy group compared with the Former conventional group. Conclusions: These findings provide further support for the DCCT recommendation that most adolescents with type I diabetes receive intensive therapy aimed at achieving glycemic control as close to normal as possible to reduce the risk of microvascular complications. C1 Albert Einstein Coll Med, Bronx, NY USA. Case Western Reserve Univ, Clin Coordinating Ctr, Cleveland, OH 44106 USA. Cornell Univ, Med Ctr, Ithaca, NY 14853 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Northwestern Univ, Evanston, IL 60208 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Univ Iowa, Iowa City, IA 52242 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Univ Missouri, Columbia, MO 65211 USA. Univ New Mexico, Albuquerque, NM 87131 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ S Florida, Tampa, FL 33620 USA. Univ Tennessee, Knoxville, TN 37996 USA. Univ Texas, SW Med Ctr, Dallas, TX 75235 USA. Univ Toronto, Toronto, ON, Canada. Univ Washington, Lipoprot Distribut Grp, Seattle, WA 98195 USA. Univ Western Ontario, London, ON N6A 3K7, Canada. Vanderbilt Univ, Nashville, TN 37240 USA. Washington Univ, St Louis, MO 63130 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. George Washington Univ, Data Coordinating Ctr, Ctr Biostat, Washington, DC 20052 USA. NIDDKD, Program Off, Bethesda, MD USA. Univ Wisconsin, Cent Fundus Photograph Reading Ctr, Madison, WI 53706 USA. Univ Minnesota, Cent Biochem Lab, Minneapolis, MN 55455 USA. Univ Minnesota, Cent ECG Reading Unit, Minneapolis, MN 55455 USA. Med Univ S Carolina, Mol Risk Factors Program Project, Charleston, SC USA. Hosp Sick Children, Genet Studies Grp, Toronto, ON, Canada. RP Genuth, S (reprint author), Albert Einstein Coll Med, Bronx, NY USA. RI Paterson, Andrew/A-4088-2011; OI Paterson, Andrew/0000-0002-9169-118X; Shamoon, Harry/0000-0002-5014-5211 NR 20 TC 64 Z9 69 U1 0 U2 4 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 DEC PY 2001 VL 139 IS 6 BP 804 EP 812 DI 10.1067/mpd.2001.118887 PG 9 WC Pediatrics SC Pediatrics GA 505JA UT WOS:000172908600012 ER PT J AU Smith, SR Baity, MR Knowles, ESK Hilsenroth, MJ AF Smith, SR Baity, MR Knowles, ESK Hilsenroth, MJ TI Assessment of disordered thinking in children and adolescents: The Rorschach Perceptual-Thinking Index SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID DIAGNOSTIC EFFICIENCY; INKBLOT METHOD; SCHIZOPHRENIA; VALIDITY; MMPI; RELIABILITY; SYSTEM AB The new Rorschach Perceptual-Thinking Index (PTI; Exner, 2000a, 2000b) was designed to assess thought disorders more accurately than the Schizophrenia Index (SCZI; Exner, 1993). Using a sample of child and adolescent inpatients, we examined the relation of Rorschach variables (PTI, SCZI, M-, and X- %) to thought disorder indexes on a behavior rating scale (Behavior Assessment System for Children; Reynolds & Kamphaus, 1992) and a self-report measure (Personality Inventory for Youth; Lachar & Gruber, 1995). Results indicate that, when used in a categorical manner, the PTI differentiated between those patients with and without elevated thought disorder scores on the other measures. Of all Rorschach variables, M- was most related to the other measures, indicating that this variable may be a particularly robust indicator of thought disorder among children and adolescents. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Arkansas, Dept Psychol, Fayetteville, AR 72701 USA. Adelphi Univ, Derner Inst Adv Psychol Studies, Garden City, NY 11530 USA. RP Smith, SR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. NR 52 TC 24 Z9 25 U1 16 U2 18 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD DEC PY 2001 VL 77 IS 3 BP 447 EP 463 DI 10.1207/S15327752JPA7703_06 PG 17 WC Psychology, Clinical; Psychology, Social SC Psychology GA 506NL UT WOS:000172978600005 PM 11781032 ER PT J AU Starkebaum, G AF Starkebaum, G TI Rheumatoid arthritis, methotrexate, and lymphoma: Risk substitution, or cat and mouse with Epstein-Barr virus? SO JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material ID POSTTRANSPLANTATION LYMPHOPROLIFERATIVE DISORDERS; CANCER; INFECTION; NEOPLASMS; HODGKINS; THERAPY C1 Univ Washington, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Starkebaum, G (reprint author), Univ Washington, S-01 CMO,1660 S Columbian Way, Seattle, WA 98108 USA. NR 28 TC 22 Z9 22 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 DEC PY 2001 VL 28 IS 12 BP 2573 EP 2575 PG 3 WC Rheumatology SC Rheumatology GA 498NP UT WOS:000172517800002 PM 11764198 ER PT J AU Cooper, GS Dooley, MA Treadwell, EL St Clair, EW Gilkeson, GS AF Cooper, GS Dooley, MA Treadwell, EL St Clair, EW Gilkeson, GS TI Smoking and use of hair treatments in relation to risk of developing systemic lupus erythematosus SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE systemic lupus erythematosus; autoimmune disease; tobacco; aromatic amines ID REVISED CRITERIA; DISEASE; CLASSIFICATION AB Objective. To examine the association between smoking and hair treatments (dyes, permanents) and risk of developing systemic lupus erythematosus (SLE). Methods. Patients (n = 265) diagnosed between January 1, 1995, and July 31, 1999, were recruited through 4 university based and 30 community based rheumatology practices in eastern North Carolina and South Carolina. Controls (n = 355) were identified through driver's license records and were frequency matched to patients by age, sex, and state. Data collection included a 60 min in-person interview. Analyses were limited to experiences that occurred before age at diagnosis (patients) or reference age (controls). Because the prevalence of use of hair treatments among men was very low, the analyses of those exposures were limited to women. Results. There was no association with smoking history and risk of developing SLE when analyzed as status (current, former, or never-smoker) or measures of dose (duration or pack-years). Use of permanent hair dyes in women was associated with a small increased risk of developing SLE (OR 1.5, 95% CI 1.0, 2.2). This association increased with longer duration of use (compared with nonusers, OR 1.7, 95% CI 1.0, 2.7 for 6 or more years). There was little evidence of an association between SLE and use of temporary dyes or of permanents and straighteners. Conclusion. These results suggest at most a weak association between SLE risk and permanent hair dyes or smoking. Genetic variability in the metabolism of these products may be important to assess in future studies. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Div Rheumatol, Chapel Hill, NC USA. E Carolina Univ, Sch Med, Div Rheumatol, Greenville, NC USA. Duke Univ, Med Ctr, Div Rheumatol Allergy & Clin Immunol, Durham, NC USA. Ralph H Johnson Vet Adm Med Ctr, Med Res Serv, Charleston, SC USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch, A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. NR 15 TC 25 Z9 27 U1 0 U2 2 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 DEC PY 2001 VL 28 IS 12 BP 2653 EP 2656 PG 4 WC Rheumatology SC Rheumatology GA 498NP UT WOS:000172517800016 PM 11764212 ER PT J AU Livingston, EH Sebastian, JL Huerta, S Yip, I Heber, D AF Livingston, EH Sebastian, JL Huerta, S Yip, I Heber, D TI Biexponential model for predicting weight loss after gastric surgery for obesity SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE compartment modeling; biexponential models; obesity surgery; gastric bypass; weight loss; mathematical models; bioimpedance analysis ID BODY-MASS INDEX; BIOELECTRICAL-IMPEDANCE ANALYSIS; MORBID-OBESITY; REDUCTION; MORTALITY; SLEEP; TERM; ASSOCIATION; VALIDATION; BYPASS AB Background. Following gastric restrictive surgery, morbidly obese patients rarely achieve their ideal body weight defined by Metropolitan Life tables. The final body weight will depend on the initial body composition because there will be greater weight loss from fat than lean body mass. The purpose of this study was to develop a mathematical model that accurately estimates the rate and extent of weight loss following gastric bypass surgery. Methods. Patients underwent gastric bypass followed by intensive medical therapy and serial bioelectrical impedance analysis (BIA) body composition measurements. Differential equations were derived to model weight loss. Results. Weight loss in the fat and lean body compartments followed monoexponential decay kinetics with differing rate constants. Total body weight loss (W-T) at time t was W-T = k(f)/(k(f) - k(l)) (W(fo)e(-kft) + Wl(o)e(-klt)), where W-fo and W-lo are the initial fat and lean body masses determined by BIA and k(f) and k(l) are the rate constants for the fat and lean compartments, respectively. Following surgically induced weight loss, kf = 7.61 +/- 1.27 x 10(-2), and k(l) = -0.93 +/- 0.13 x 10(-2), with the ratio of residual sum of the squares to the total sum of the squares of 98.8%. Conclusion. Accurate prediction of weight loss depends on the initial fat and lean compartment mass since each of these loses weight at a different rate and to a different extent. When these effects are accounted for, the total body weight loss can be accurately predicted for any given time following surgery. (C) 2001 Elsevier Science. C1 VA Greater Los Angeles Hlth Care Syst, Dept Surg, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Ctr Human Nutr, Los Angeles, CA 90095 USA. RP Livingston, EH (reprint author), Univ Calif Los Angeles, Sch Med, Bariatr Surg Program, Box 95-6904, Los Angeles, CA 90095 USA. NR 35 TC 9 Z9 9 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 0022-4804 J9 J SURG RES JI J. Surg. Res. PD DEC PY 2001 VL 101 IS 2 BP 216 EP 224 DI 10.1006/jsre.2001.6286 PG 9 WC Surgery SC Surgery GA 510QN UT WOS:000173218900016 PM 11735279 ER PT J AU Saliba, D Elliott, M Rubenstein, LZ Solomon, DH Young, RT Kamberg, CJ Roth, C MacLean, CH Shekelle, PG Sloss, EM Wenger, NS AF Saliba, D Elliott, M Rubenstein, LZ Solomon, DH Young, RT Kamberg, CJ Roth, C MacLean, CH Shekelle, PG Sloss, EM Wenger, NS TI The vulnerable elders survey: A tool for identifying vulnerable older people in the community SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Geriatrics-Society CY MAY, 2000 CL NASHVILLE, TENNESSEE SP Amer Geriatr Soc DE function; mortality; frail; risk; survey ID HEALTH-STATUS; FUNCTIONAL STATUS; PREDICTING MORTALITY; PHYSICAL-DISABILITY; SELF-REPORT; FOLLOW-UP; CARE; ADULTS; RISK; HOSPITALIZATION AB OBJECTIVES: To develop a simple method for identifying community-dwelling vulnerable older people, defined as persons age 65 and older at increased risk of death or functional decline. To assess whether self-reported diagnoses and conditions add predictive ability to a function-based survey. DESIGN: Analysis of longitudinal survey data. SETTING: A nationally representative community-based survey. PARTICIPANTS: Six thousand two hundred five Medicare beneficiaries age 65 and older. MEASUREMENTS: Bivariate and multivariate analyses of the Medicare Current Beneficiary Survey; development and comparison of scoring systems that use age, function, and self-reported diagnoses to predict future death and functional decline. RESULTS: A multivariate model using function, self-rated health, and age to predict death or functional decline was only slightly improved when self-reported diagnoses and conditions were included as predictors and was significantly better than a model using age plus self-reported diagnoses alone. These analyses provide the basis for a 13-item function-based scoring system that considers age, self-rated health, limitation in physical function, and functional disabilities. A score of greater than or equal to3 targeted 32% of this nationally representative sample as vulnerable. This targeted group had 4.2 times the risk of death or functional decline over a 2-year period compared with those with scores <3. The receiver operating characteristics curve had an area of .78. An alternative scoring system that included self-reported diagnoses did not substantially improve predictive ability when compared with a function-based scoring system. CONCLUSIONS: A function-based targeting system effectively and efficiently identifies older people at risk of functional decline and death. Self-reported diagnoses and conditions, when added to the system, do not enhance predictive ability. The function-based targeting system relies on self-report and is easily transported across care settings. C1 RAND Corp, Santa Monica, CA USA. Greater Los Angeles Syst Vet Adm Med Ctr, Sepulveda Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA USA. RP Saliba, D (reprint author), RAND Corp, 1700 Main St, Santa Monica, CA USA. FU NIA NIH HHS [AG10415] NR 57 TC 355 Z9 361 U1 3 U2 15 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2001 VL 49 IS 12 BP 1691 EP 1699 DI 10.1046/j.1532-5415.2001.49281.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 505JH UT WOS:000172909300016 PM 11844005 ER PT J AU Hazzard, WR AF Hazzard, WR TI An open letter to every medical student who aspires to become a leader in academic geriatric medicine SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Hazzard, WR (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2001 VL 49 IS 12 BP 1733 EP 1734 DI 10.1046/j.1532-5415.2001.49288.x PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 505JH UT WOS:000172909300022 PM 11844011 ER PT J AU Wu, JH Billings, BJ Balkovetz, DF AF Wu, JH Billings, BJ Balkovetz, DF TI Hepatocyte growth factor alters renal epithelial cell susceptibility to uropathogenic Escherichia coli SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID E-CADHERIN; POLARITY; KIDNEY; MONOLAYERS; IDENTIFICATION; CYTOTOXICITY; GRANULOCYTES; REGENERATION; OBSTRUCTION; POLYPEPTIDE AB The urinary tract is frequently the source of Escherichia coli bacteremia. Bacteria from the urinary tract must cross an epithelial layer to enter the bloodstream. Hepatocyte growth factor (HGF) alters the polarity of Madin-Darby canine kidney (MDCK) epithelial cells. The role of cell polarity in determining renal epithelial resistance to Escherichia coli invasion is not well known. A model of polarized and HGF-treated MDCK epithelial cells grown on filters was used to study the role of epithelial cell polarity during the interaction of nonvirulent (XL1-Blue) and uropathogenic (J96) strains of Escherichia coli with renal epithelium. Basolateral. exposure of MDCK cells to J96, but not XL1-Blue, resulted in loss of transepithelial resistance (TER), which was due to epithelial cytotoxicity and not degradation of epithelial junctional proteins by bacterial proteases. Apical exposure to both J96 and XL1-Blue did not alter TER. Pretreatment of polarized MDCK cell monolayers with HGF renders the cells sensitive to loss of TER and cytotoxicity by apical exposure to J96. Analysis by confocal microscopy demonstrated that HGF treatment of MDCK cell monolayers also greatly enhances adherence of J96 to the apical surface of the cell monolayer. These data demonstrate that the basolateral surface of polarized epithelia is more susceptible to J96 cytotoxicity. The data also support the hypothesis that processes that alter epithelial cell polarity increase sensitivity of epithelia to bacterial injury and adherence from the apical compartment. C1 Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA. Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. RP Balkovetz, DF (reprint author), 668 LHRB,1530 3rd Ave S, Birmingham, AL 35294 USA. FU NIAID NIH HHS [T32 AI 07041] NR 45 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2001 VL 12 IS 12 BP 2543 EP 2553 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 496TM UT WOS:000172412900001 PM 11729222 ER PT J AU Coull, BA Hobert, JP Ryan, LM Holmes, LB AF Coull, BA Hobert, JP Ryan, LM Holmes, LB TI Crossed random effect models for multiple outcomes in a study of teratogenesis SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article; Proceedings Paper CT 160th Annual Meeting of the American-Statistical-Association CY FEB, 2000 CL BOSTON, MASSACHUSETTS SP Amer Statist Assoc DE generalized linear mixed model; lasso; logistic regression; Markov chain Monte Carlo; Monte Carlo EM algorithm; Monte Carlo Newton-Raphson ID LINEAR MIXED MODELS; LATENT VARIABLE MODELS; MONTE-CARLO EM; BINARY OUTCOMES; ANTICONVULSANT TERATOGENESIS; CLINICAL-TRIALS; BIRTH-DEFECTS; REGRESSION; ALGORITHM; DISCRETE AB Human teratogens often manifest themselves through a broad spectrum of adverse effects. Although often not serious when considered individually, such outcomes taken together may represent a syndrome that can lead to serious developmental problems. Accordingly, studies that investigate the effect of human teratogens on fetal development typically record the presence or absence of a multitude of abnormalities, resulting in the data of multivariate binary form for each infant. Such studies typically have three objectives: (1) estimate an overall effect of exposure across outcomes, (2) identify subjects having the syndrome, and (3) identify those outcomes that constitute the syndrome so that doctors know what to look for when diagnosing the syndrome in other exposed newborns. This article proposes the use of a logistic regression model with crossed random effect structure to address all three questions simultaneously. We use the proposed models to analyze data from a study investigating the effects of in utero antiepileptic drug exposure on fetal development. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Florida, Dept Stat, Gainesville, FL 32611 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Coull, BA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 665 Huntington Ave, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 48 TC 15 Z9 15 U1 0 U2 7 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 2001 VL 96 IS 456 BP 1194 EP 1204 DI 10.1198/016214501753381841 PG 11 WC Statistics & Probability SC Mathematics GA 502DG UT WOS:000172728000006 ER PT J AU D'Amico, AV Whittington, R Malkowicz, SB Weinstein, M Tomaszewski, JE Schultz, D Rhude, M Rocha, S Wein, A Richie, JP AF D'Amico, AV Whittington, R Malkowicz, SB Weinstein, M Tomaszewski, JE Schultz, D Rhude, M Rocha, S Wein, A Richie, JP TI Predicting prostate specific antigen outcome preoperatively in the prostate specific antigen era SO JOURNAL OF UROLOGY LA English DT Article; Proceedings Paper CT 96th Annual Meeting of the American-Urological-Association CY JUN 02-07, 2001 CL ANAHEIM, CALIFORNIA SP Amer Urol Assoc DE prostate; prostatic neoplasms; neoplasm staging; prostate-specific antigen ID EXTERNAL-BEAM RADIATION; RADICAL PROSTATECTOMY; DISEASE RECURRENCE; ADJUVANT THERAPY; FREE SURVIVAL; CANCER; CARCINOMA; STAGE; ADENOCARCINOMA; PROGRESSION AB Purpose: We evaluated the ability of previously defined risk groups to predict prostate specific antigen (PSA) outcome 10 years after radical prostatectomy in patients diagnosed with clinically localized prostate cancer during the PSA era. Materials and Methods: Between 1989 and 2000, 2,127 men with clinically localized prostate cancer underwent radical prostatectomy, including 1,027 at Hospital of the University of Pennsylvania (study cohort) and 1,100 at Brigham and Women's Hospital (validation cohort). Cox regression analysis was done to calculate the relative risk of PSA failure with the 95% confidence interval (CI) in patients at intermediate and high versus low risk. The Kaplan-Meier actuarial method was used to estimate PSA outcome 10 years after radical prostatectomy. Results: Compared with low risk patients (stages Tlc to 2a disease, PSA 10 ng./ml. or less and Gleason score 6 or less) the relative risk of PSA failure in those at intermediate (stage T2b disease or PSA greater than 10 to 20 ng./ml. or less, or Gleason score 7) and high (stage T2c disease, or PSA greater than 20 ng./ml. or Gleason score 8 or greater) risk was 3.8 (95% CI 2.6 to 5.7) and 9.6 (95% CI 6.6 to 13.9) in the study cohort, and 3.3 (95% CI 2.3 to 4.8) and 6.3 (95% CI 4.3 to 9.4) in the validation cohort. The 10-year PSA failure-free survival rate in the 1,020 patients in the low, 693 in the intermediate and 414 in the high risk groups was 83%, 46% and 29%, respectively (p <0.0001). Conclusions: Based on 10-year actuarial estimates of PSA outcome after radical prostatectomy 3 groups of patients were identified using preoperative PSA, biopsy Gleason score and 1992 clinical T category. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Urol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. Millersville Univ, Dept Math, Millersville, PA 17551 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. NR 24 TC 90 Z9 93 U1 0 U2 3 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 DEC PY 2001 VL 166 IS 6 BP 2185 EP 2188 DI 10.1016/S0022-5347(05)65531-0 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 491WW UT WOS:000172133900050 PM 11696732 ER PT J AU Clarke, P Meintzer, SM Widmann, C Johnson, GL Tyler, KL AF Clarke, P Meintzer, SM Widmann, C Johnson, GL Tyler, KL TI Reovirus infection activates JNK and the JNK-dependent transcription factor c-Jun SO JOURNAL OF VIROLOGY LA English DT Article ID NF-KAPPA-B; PROTEIN-KINASE PATHWAYS; INDUCED APOPTOSIS; TERMINAL KINASE; SIGNAL-TRANSDUCTION; MEDIATED APOPTOSIS; CHROMIUM RELEASE; M2 GENE; T-CELLS; DEATH AB Viral infection often perturbs host cell signaling pathways including those involving mitogen-activated protein kinases (MAPKs). We now show that reovirus infection results in the selective activation of c-Jun N-terminal kinase (JNK). Reovirus-induced JNK activation is associated with an increase in the phosphorylation of the JNK-dependent transcription factor c-Jun. Reovirus serotype 3 prototype strains Abney (T3A) and Dearing (T3D) induce significantly more JNK activation and c-Jun phosphorylation than does the serotype 1 prototypic strain Lang (TIL). T3D and T3A also induce more apoptosis in infected cells than TIL, and there was a significant correlation between the ability of these viruses to phosphorylate c-Jun and induce apoptosis. However, reovirus-induced apoptosis, but not reovirus-induced c-Jun phosphorylation, is inhibited by blocking TRAIL/receptor binding, suggesting that apoptosis and c-Jun phosphorylation involve parallel rather than identical pathways. Strain-specific differences in JNK activation are determined by the reovirus S1 and M2 gene segments, which encode viral outer capsid proteins (sigma1 and mu 1c) involved in receptor binding and host cell membrane penetration. These same gene segments also determine differences in the capacity of reovirus strains to induce apoptosis, and again a significant correlation between the capacity of T1L X T3D reassortant reoviruses to both activate JNK and phosphorylate c-Jun and to induce apoptosis was shown. The extracellular signal-related kinase (ERK) is also activated in a strain-specific manner following reovirus infection. Unlike JNK activation, ERK activation could not be mapped to specific reovirus gene segments, suggesting that ERK activation and JNK activation are triggered by different events during virus-host cell interaction. C1 Denver VA Med Ctr, Dept Neurol 127, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Microbiol & Immunol, Denver, CO 80262 USA. RP Tyler, KL (reprint author), Denver VA Med Ctr, Dept Neurol 127, 1055 Clermont St, Denver, CO 80220 USA. RI Widmann, Christian/N-9851-2013; OI Widmann, Christian/0000-0002-6881-0363; Tyler, Kenneth/0000-0003-3294-5888 FU NIA NIH HHS [1RO1AG14071]; NIGMS NIH HHS [GM30324, R01 GM030324, R37 GM030324] NR 63 TC 52 Z9 55 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 DEC PY 2001 VL 75 IS 23 BP 11275 EP 11283 DI 10.1128/JVI.75.23.11275-11283.2001 PG 9 WC Virology SC Virology GA 490CP UT WOS:000172033100002 PM 11689607 ER PT J AU Lai, LL Liu, HM Wu, XY Kappes, JC AF Lai, LL Liu, HM Wu, XY Kappes, JC TI Moloney murine leukemia virus integrase protein augments viral DNA synthesis in infected cells SO JOURNAL OF VIROLOGY LA English DT Article ID TYPE-1 INTEGRASE; NUCLEOCAPSID PROTEIN; CARBOXYL-TERMINUS; GENETIC-ANALYSIS; IN-VITRO; MUTATIONS; MUTANTS; POL; REPLICATION; EXPRESSION AB Mutations in the IN domain of retroviral DNA may affect multiple steps of the virus life cycle, suggesting that the IN protein may have other functions in addition to its integration function. We previously reported that the human immunodeficiency virus type 1 IN protein is required for efficient viral DNA synthesis and that this function requires specific interaction with other viral components but not enzyme (integration) activity. In this report, we characterized the structure and function of the Moloney murine leukemia virus (MLV) IN protein in viral DNA synthesis. Using an MLV vector containing green fluorescent protein as a sensitive reporter for virus infection, we found that mutations in either the catalytic triad (D184A) or the HHCC motif (H61A) reduced infectivity by approximately 1,000-fold. Mutations that deleted the entire IN (Delta IN) or 34 C-terminal amino acid residues (Delta 34) were more severely defective, with infectivity levels consistently reduced by 10,000-fold. Immunoblot analysis indicated that these mutants were similar to wild-type MLV with respect to virion production and proteolytic processing of the Gag and Pol precursor proteins. Using semiquantitative PCR to analyze viral cDNA synthesis in infected cells, we found the Delta 34 and Delta IN mutants to be markedly impaired while the D184A and H61A mutants synthesized cDNA at levels similar to the wild type. The DNA synthesis defect was rescued by complementing the Delta 34 and Delta IN mutants in trans with either wild-type IN or the D184A mutant IN, provided as a Gag-IN fusion protein. However, the DNA synthesis defect of Delta IN mutant virions could not be complemented with the Delta 34 IN mutant. Taken together, these analyses strongly suggested that the MLV IN protein itself is required for efficient viral DNA synthesis and that this function may be conserved among other retroviruses. C1 Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Res Serv, Birmingham, AL 35233 USA. RP Kappes, JC (reprint author), Univ Alabama, Dept Med, THT 513H,1530 3rd Ave, Birmingham, AL 35294 USA. FU NCI NIH HHS [CA73470]; NIAID NIH HHS [P30 AI027767, P30-AI-27767, R01 AI047714, AI47714] NR 34 TC 24 Z9 24 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 DEC PY 2001 VL 75 IS 23 BP 11365 EP 11372 DI 10.1128/JVI.75.23.11365-11372.2001 PG 8 WC Virology SC Virology GA 490CP UT WOS:000172033100012 PM 11689617 ER PT J AU Shera, KA Shera, CA McDougall, JK AF Shera, KA Shera, CA McDougall, JK TI Small tumor virus genomes are integrated near nuclear matrix attachment regions in transformed cells SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-PAPILLOMAVIRUS TYPE-16; HEPATITIS-B VIRUS; IMMUNOGLOBULIN-MU ENHANCER; CERVICAL-CARCINOMA; HEPATOCELLULAR-CARCINOMA; NUCLEOTIDE-SEQUENCE; MOLECULAR ANALYSIS; GENE-EXPRESSION; DNA INTEGRATION; SITES AB More than 15% of human cancers have a viral etiology. In benign lesions induced by the small DNA tumor viruses, viral genomes are typically maintained extrachromosomally. Malignant progression is often associated with viral integration into host cell chromatin. To study the role of viral integration in tumorigenesis, we analyzed the positions of integrated viral genomes in tumors and tumor cell lines induced by the small oncogenic viruses, including the high-risk human papillomaviruses, hepatitis B virus, simian virus 40, and human T-cell leukemia virus type 1. We show that viral integrations in tumor cells lie near cellular sequences identified as nuclear matrix attachment regions (MARs), while integrations in nonneoplastic cells show no significant correlation with these regions. In mammalian cells, the nuclear matrix functions in gene expression and DNA replication. MARs play varied but poorly understood roles in eukaryotic gene expression. Our results suggest that integrated tumor virus genomes are subject to MAR-mediated transcriptional regulation, providing insight into mechanisms of viral carcinogenesis. Furthermore, the viral oncoproteins serve as invaluable tools for the study of mechanisms controlling cellular growth. Similarly, our demonstration that integrated viral genomes may be subject to MAR-mediated transcriptional effects should facilitate elucidation of fundamental mechanisms regulating eukaryotic gene expression. C1 Fred Hutchinson Canc Res Ctr, Canc Biol Program, Seattle, WA 98109 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP McDougall, JK (reprint author), Fred Hutchinson Canc Res Ctr, Canc Biol Program, 1100 Fairview Ave N,C1-105, Seattle, WA 98109 USA. FU NCI NIH HHS [CA42792, P01 CA042792]; NIDCD NIH HHS [DC03687, R01 DC003687] NR 56 TC 25 Z9 28 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 DEC PY 2001 VL 75 IS 24 BP 12339 EP 12346 DI 10.1128/JVI.75.24.12339-12346.2001 PG 8 WC Virology SC Virology GA 495RZ UT WOS:000172355300041 PM 11711624 ER PT J AU Jarboe, JK Zeitels, SM Elias, B AF Jarboe, JK Zeitels, SM Elias, B TI Tonsillectomy and adenoidectomy in singers SO JOURNAL OF VOICE LA English DT Article C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Div Laryngol,Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Univ Groningen Hosp, Dept Otorhinolaryngol, Groningen, Netherlands. RP Zeitels, SM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 5 TC 4 Z9 5 U1 0 U2 2 PU SINGULAR PUBLISHING GROUP INC PI CLIFTON PARK PA 5 MAXWELL DR, CLIFTON PARK, NY 12065 USA SN 0892-1997 J9 J VOICE JI J. Voice PD DEC PY 2001 VL 15 IS 4 BP 561 EP 564 DI 10.1016/S0892-1997(01)00057-1 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 503MT UT WOS:000172802800012 PM 11792033 ER PT J AU Joffe, H Groninger, H Soares, C Nonacs, R Cohen, LS AF Joffe, H Groninger, H Soares, C Nonacs, R Cohen, LS TI An open trial of mirtazapine in menopausal women with depression unresponsive to estrogen replacement therapy SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE 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 DOUBLE-BLIND; MAJOR DEPRESSION; PERIMENOPAUSE; TOLERABILITY; SEROTONIN; SYMPTOMS; EFFICACY AB Treatment of major depression in menopausal women is controversial. Estrogen replacement therapy (ERT) treats mild depression but may not treat more severe depression in this population. Antidepressants are recommended as treatment for major depression in menopausal women, but the specific efficacy of antidepressants has not been examined in menopause-associated depression. Twenty-two perimenopausal and postmenopausal women aged 40-61 taking stable doses of ERT who met Structured Clinical Interview for DSM-IV (SCID-IV) criteria for major depression were accessioned into an open-label clinical trial of mirtazapine. Subjects were treated with 30-45 mg/day mirtazapine for 8 weeks and were assessed every 2 weeks with the Hamilton Depression Rating Scale-17 (HDRS-17), Beck Depression Inventory (BDI), and Clinical Global Impression (CGI) Scale. Remission of depression was defined as an HDRS-17 score:57 at the week 8 study visit. Sixteen (73%) of the enrolled subjects completed the 8-week study. The median HDRS-17 score declined from 20.5 (range 12-37) at baseline to 2 (range 0-9) at week 8 (Wilcoxon signed-rank test, p < 0.001). Remission of depression was achieved by 14 of 16 (87.5%) study completers. Subjects responded well to mirtazapine regardless of whether their depression preceded ERT use or developed after ERT was initiated. Therapeutic response also appeared independent of menopausal status (perimenopausal vs. postmenopausal), ERT preparation, and concomitant use of medroxyprogesterone. Mirtazapine is an effective treatment for major depression in perimenopausal and postmenopausal women whose depression precedes ERT use and does not respond to ERT or whose depression develops after ERT is initiated. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Psychiat, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. RP Joffe, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Psychiat, Perinatal & Reprod Psychiat Clin Res Program, 15 Parkman St,WACC815, Boston, MA 02114 USA. NR 17 TC 31 Z9 34 U1 0 U2 3 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 DEC PY 2001 VL 10 IS 10 BP 999 EP 1004 DI 10.1089/152460901317193576 PG 6 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 509FZ UT WOS:000173136800009 PM 11788110 ER PT J AU Perell, KL Nelson, A Goldman, RL Luther, SL Prieto-Lewis, N Rubenstein, LZ AF Perell, KL Nelson, A Goldman, RL Luther, SL Prieto-Lewis, N Rubenstein, LZ TI Fall risk assessment measures: An analytic review SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID ELDERLY PATIENTS; FUNCTIONAL ASSESSMENT; ASSESSMENT-TOOL; OLDER ADULTS; NURSING-HOME; PRIMARY-CARE; WILL FALL; PREVENTION; COMMUNITY; INDEX AB Background. Clinicians are often unaware of the many existing scales for identifying fall risk and are uncertain about how to select an appropriate one. Our purpose was to summarize existing fall risk assessment scales to enable more informed choices regarding their use. Methods. After a systematic literature search, 21 articles published from 1984 through 2000 describing 20 fall risk assessments were reviewed independently for content and validation by a panel of five reviewers using a standardized review form. Fourteen were institution-focused nursing assessment scales, and six were functional assessment scales. Results. The majority of the scales were developed for elderly populations. mainly in hospital or nursing home settings. The patient characteristics assessed were quite similar across the nursing assessment forms. The time to complete the form varied from less than I minute to 80 minutes. For those scales with reported diagnostic accuracy, sensitivity varied from 43% to 100% (median = 80%), and specificity varied from 38% to 96% (median = 75%). Several scales with superior diagnostic characteristics were identified. Conclusions. A substantial number of fall risk assessment tools are readily available and assess similar patient characteristics. Although their diagnostic accuracy and overall usefulness showed wide variability, there are several scales that can be used with confidence as part of an effective falls prevention program. Consequently, there should be little need for facilities to develop their own scales. To continue to develop fall risk assessments unique to individual facilities may be counterproductive because scores will not be comparable across facilities. C1 VA Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, Phys Med & Rehabil Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Mt St Marys Coll, Dept Phys Therapy, Los Angeles, CA USA. James A Haley Vet Adm Med Ctr, Vet Integrated Serv Network 8, Patient Safety Ctr Inquiry, Tampa, FL 33612 USA. Off Qual & Performance, VA Headquarters, Washington, DC USA. Gait & Balance Clin N Florida, S Georgia Vet Hlth Syst, Phys Med & Rehabil Serv, Gainesville, FL USA. VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Sepulveda Ambulatory Care Ctr, Sepulveda, CA USA. RP Perell, KL (reprint author), VA Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, Phys Med & Rehabil Serv, 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 44 TC 181 Z9 183 U1 12 U2 34 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 DEC PY 2001 VL 56 IS 12 BP M761 EP M766 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 498DT UT WOS:000172495100010 PM 11723150 ER PT J AU Simmons, SF Osterweil, D Schnelle, JF AF Simmons, SF Osterweil, D Schnelle, JF TI Improving food intake in nursing home residents with feeding assistance: A staffing analysis SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID PROTEIN-CALORIE UNDERNUTRITION; WEIGHT-LOSS; CARE; MEALTIME; PREDICTORS; MORTALITY; INDEX; RISK AB Background. Recommendations have been made to increase the number of nursing home (NH) staff available to provide feeding assistance during mealtime. There are. however, no specific data related to two critical variables necessary to estimate mealtime staffing needs: (1) How many residents are responsive to feeding assistance? (2) How much staff time is required to provide feeding assistance to these residents? The purpose of this study was to collect preliminary data relevant to these two issues. Methods. Seventy-four residents in three NHs received a 2-day. or six-meal. trial of one-on-one feeding assistance. Total percentage (0% to 100%) of food and fluid consumed during mealtime was estimated across 3 days during usual NH care and 2 days during the intervention. The amount of time that staff spent providing assistance and type of assistance (i.e,, frequency of verbal and physical prompts) was measured under each condition. Results. One half (50%) of the participants significantly increased their oral food and fluid intake during mealtime. The intervention required significantly more staff time to implement (average of 38 minutes per resident/meal vs 9 minutes rendered by NH staff). Conclusions. The time required to implement the feeding assistance intervention greatly exceeded the time the nursing staff spent assisting residents in usual mealtime care conditions. These data suggest that it will almost certainly be necessary to both increase staffing levels and to organize staff better to produce higher quality feeding assistance during mealtimes. C1 Univ Calif Los Angeles, Jewish Home Aging, Borun Ctr Gerontol Res, Reseda, CA 91335 USA. Univ Calif Los Angeles, Sch Med, Dept Geriatr, Borun Ctr Gerontol Res, Los Angeles, CA USA. Vet Adm Greater Los Angeles Healthcare Syt, Sepulveda Geriat Res Educ & Clin Ctr, Sepulveda, CA USA. RP Simmons, SF (reprint author), Univ Calif Los Angeles, Jewish Home Aging, Borun Ctr Gerontol Res, 7150 Tampa Ave, Reseda, CA 91335 USA. NR 32 TC 74 Z9 79 U1 1 U2 4 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 DEC PY 2001 VL 56 IS 12 BP M790 EP M794 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 498DT UT WOS:000172495100016 PM 11723156 ER PT J AU Gupta, D Treon, SP Shima, Y Hideshima, T Podar, K Tai, YT Lin, B Lentzsch, S Davies, FE Chauhan, D Schlossman, RL Richardson, P Ralph, P Wu, L Payvandi, F Muller, G Stirling, DI Anderson, KC AF Gupta, D Treon, SP Shima, Y Hideshima, T Podar, K Tai, YT Lin, B Lentzsch, S Davies, FE Chauhan, D Schlossman, RL Richardson, P Ralph, P Wu, L Payvandi, F Muller, G Stirling, DI Anderson, KC TI Adherence of multiple myeloma cells to bone marrow stromal cells upregulates vascular endothelial growth factor secretion: therapeutic applications SO LEUKEMIA LA English DT Article DE multiple myeloma; interleukin-6; vascular endothelial growth factor; thalidomide; immunomodulatory drug IMiD1-CC4047 ID TUMOR ANGIOGENESIS; PROGNOSTIC VALUE; TYROSINE KINASE; ELEVATED LEVELS; LUNG-CANCER; THALIDOMIDE; INTERLEUKIN-6; EXPRESSION; ACTIVATION; TRANSPLANTATION AB Increased angiogenesis has recently been recognized in active multiple myeloma (MM). Since vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are two key mediators of angiogenesis, we characterized the production of VEGF, b-FGF and interleukin-6 (IL-6) (a MM growth and survival factor) in MM cell lines and Epstein-Barr virus (EBV) transformed B cell lines from MM patients, patient MM cells, as well as bone marrow stromal cells (BMSCs) from normal healthy donors and MM patients. We detected secretion of VEGF, but no bFGF and IL-6, in MM cell lines (MM.1S, RPMI 8226 and U266); EBV transformed B cell lines from MM patients (IM-9, HS-Sultan and ARH77); MM cell lines resistant to doxorubicin (RPMI-DOX40), mitoxantrone (RPMI-MR20), melphalan (RPMI-LR5) and dexamethasone (MM.1R); and patient MM cells (MM1 and MM2). BMSCs from MM patients and normal donors secreted VEGF, b-FGF and IL-6. Importantly, when MM cells were adhered to BMSCs, there was a significant increase in VEGF (1.5- to 3.1-fold) and IL-6 (1.9- to 56-fold) secretion. In contrast, the bFGF decreased in co-cultures of BMSCs and MM cells. Paraformaldehyde fixation of BMSCs or MM cells prior to adhesion revealed that VEGF was produced both from BMSCs and MM cells, though it may come primarily from BMSCs in some cultures. IL-6 was produced exclusively in BMSCs, rather than MM cells. Moreover, when MM cells were placed in Transwell insert chambers to allow their juxtaposition to BMSCs without cell to cell contact, induction of VEGF and IL-6 secretion persisted, suggesting the importance of humoral factors. Addition of exogenous IL-6 (10 ng/ml) increased VEGF secretion by BMSCs. Conversely, VEGF (100 ng/ml) significantly increased IL-6 secretion by BMSCs. Moreover, anti-human VEGF (1 mug/ml) and anti-human IL-6 (10 mug/ml) neutralizing antibodies reduced IL-6 and VEGF secretion respectively, in cultures of BMSCs alone and co-cultures of BMSCs and MM cells. Finally, thalidomide (100 muM) and its immunomodulatory analog IMiD1-CC4047 (1 muM) decreased the upregulation of IL-6 and VEGF secretion in cultures of BMSCs, MM cells and co-cultures of BMSCs with MM cells. These data demonstrate the importance of stromal-MM cell interactions in regulating VEGF and IL-6 secretion, and suggest additional mechanisms whereby thalidomide and IMiD1-CC4047 act against MM cells in the BM millieu. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Genentech Inc, San Francisco, CA 94080 USA. Celgene Corp, Warren, NJ USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Mayer 557,44 Binney St, Boston, MA 02115 USA. FU PHS HHS [P0-1 78378] NR 56 TC 335 Z9 356 U1 5 U2 32 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD DEC PY 2001 VL 15 IS 12 BP 1950 EP 1961 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA 499VV UT WOS:000172591900019 PM 11753617 ER PT J AU Taylor, BJ Olson, DP Ivy, SP AF Taylor, BJ Olson, DP Ivy, SP TI Detection of P-glycoprotein in cell lines and leukemic blasts: failure of select monoclonal antibodies to detect clinically significant Pgp levels in primary cells SO LEUKEMIA RESEARCH LA English DT Article DE Pgp; p-glycoprotein; MDR1; multidrug resistance; pediatric leukemia; flow cytometry ID ACUTE MYELOID-LEUKEMIA; MULTIDRUG RESISTANCE GENE; CYCLOSPORINE-A; PERIPHERAL-BLOOD; IN-VITRO; EXPRESSION; VERAPAMIL; REVERSAL; MALIGNANCIES; TRANSPORTER AB Multidrug resistance (MDR) is a salient feature of chemotherapy failure in pediatric patients. One of the most common and well-studied mechanisms implicated in causing MDR is P-glycoprotein (Pgp), an ATP-dependent, transmembrane drug efflux. pump. Accurate and reproducible detection of this MDR protein is necessary as it may have important clinical implications. In this study comparing the directly conjugated anti-Pgp monoclonal antibodies UIC2-PE and 15D3-PE to the unconjugated anti-Pgp mAb MRK16, we analyzed cell lines, normal peripheral blood cells, and bone marrow cells from pediatric patients diagnosed with acute myeloid leukemia and acute lymphoblastic leukemia; all samples were also analyzed for Pgp function using rhodamine 123 in order to correlate results from antibody staining with functional activity. For all patient samples evaluated, only MRK16 correlated well with the rhodamine 123 assay. Both the directly conjugated antibodies UIC2-PE and 15D3-PE failed to detect Pgp in almost all cases. Pre-treatment of cells with neuraminidase did not provide a consistent enhancement of antigen detection. Based on these results, we suggest that while UIC2-PE and 15D3-PE may be able to detect the very high levels of Pgp expressing laboratory-cultured cell lines, they are not suitable for clinical application in their currently available conjugated form. When assaying patient samples for Pgp expression and function using flow cytometry, the rhodamine 123 functional assay should be performed in concert with staining with MRK16. Published by Elsevier Science Ltd. C1 Childrens Natl Med Ctr, Div Hematol & Oncol, Washington, DC 20010 USA. RP Olson, DP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, AIDS Res Ctr, Room 5246,149 13th St, Boston, MA 02129 USA. NR 43 TC 11 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD DEC PY 2001 VL 25 IS 12 BP 1127 EP 1135 DI 10.1016/S0145-2126(01)00085-6 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 492QU UT WOS:000172179700014 PM 11684287 ER PT J AU Stone, ME AF Stone, ME TI Women and pain: Why it hurts and what you can do. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp, Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp, Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD DEC PY 2001 VL 126 IS 20 BP 158 EP 158 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 501MP UT WOS:000172688700238 ER PT J AU Gurwitz, JH Guadagnoli, E Landrum, MB Silliman, RA Wolf, R Weeks, JC AF Gurwitz, JH Guadagnoli, E Landrum, MB Silliman, RA Wolf, R Weeks, JC TI The treating physician as active gatekeeper in the recruitment of research subjects SO MEDICAL CARE LA English DT Article DE health-services research; patient selection; selection bias; human; research methods ID BREAST-CANCER; CARE AB BACKGROUND. Institutional Review Boards vary in regard to the conditions imposed on investigators concerning contacting potential subjects to participate in health-services research studies. OBJECTIVE. The impact of more active involvement of the treating physician was examined in the approval process for recruiting study subjects. DESIGN. In recruiting subjects for a Massachusetts-based, multihospital (n = 17), health-services research study of treatment patterns for early stage breast cancer that required patient interviews, four hospitals stipulated that the treating surgeon provide written permission to the investigators to allow any contact with a potential study subject for the purpose of recruitment (active physician involvement group); the remaining 13 hospitals stipulated that the treating surgeon need only respond to the investigators if contact with a potential subject was forbidden (passive physician involvement group). SUBJECTS. Of the 1401 potential subjects treated for early stage breast cancer, 697 were in the active physician involvement group and 704 were in the passive physician involvement group. MEASURES. The percentages of patients for whom contact was allowed for recruitment purposes and who enrolled in the study were determined for the active physician involvement group and the passive physician involvement group, respectively. Logistic regression models were used to assess the independent effect of physician involvement on study enrollment. RESULTS. Of the 697 patients in the active physician involvement group, contact was approved by the treating surgeon for 72% (n = 505), compared with 91% (n = 638) of the passive physician involvement group (P < 0.001). After adjustment for a variety of patient, physician, and hospital-level variables, patients in the passive physician involvement group were found to be significantly more likely to be enrolled in the study (adjusted OR 2.61; 95% CI, 1.53-4.45). However, among those patients approved for investigator contact, there were no significant differences between patients who were enrolled and patients who were not enrolled in the study with regard to physician involvement in the recruitment process (adjusted OR 1.13; 95% CI, 0.70-1.81). CONCLUSION. Our findings demonstrate that more stringent IRB requirements on health services researchers to verify permission from the treating physician to access patients for recruitment purposes adversely impact on the enrollment of patients even in noninterventional research studies. Current procedures for involving the treating physician as a gatekeeper in the recruitment of research subjects may limit access to patient participation in research studies from the perspectives of both researchers and potential subjects. C1 Meyers Primary Care Inst, Worcester, MA 01605 USA. Fallon Healthcare Syst, Worcester, MA 01605 USA. Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Boston Med Ctr, Boston, MA USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Adult Oncol, Boston, MA USA. Harvard Univ, Sch Med, Ctr Outcomes & Policy Res, Boston, MA USA. RP Gurwitz, JH (reprint author), Meyers Primary Care Inst, 630 Plantat St, Worcester, MA 01605 USA. FU NCI NIH HHS [CA 59408] NR 8 TC 9 Z9 9 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 DEC PY 2001 VL 39 IS 12 BP 1339 EP 1344 DI 10.1097/00005650-200112000-00009 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 499PF UT WOS:000172579000008 PM 11717575 ER PT J AU Arva, J Fitzgerald, SG Cooper, RA Boninger, ML AF Arva, J Fitzgerald, SG Cooper, RA Boninger, ML TI Mechanical efficiency and user power requirement with a pushrim activated power assisted wheelchair SO MEDICAL ENGINEERING & PHYSICS LA English DT Article DE wheelchairs; human-machine power; metabolic energy; mechanical power ID FORCE APPLICATION; PROPULSION; PAIN AB The objective of this study was to quantify the difference in mechanical efficiency and user power generation between traditional manual wheelchairs and a pushrim activated power assisted wheelchair (PAPAW). Ten manual wheelchair users were evaluated in a repeated measures design trial with and without the PAPAW for propulsion efficiency. Subjects propelled a Quickie GP equipped with the PAPAW and their own chair on a computer controlled wheelchair dynamometer at five different resistance levels. Power output, user power with the PAPAW hubs, subjects' oxygen consumption per minute and mechanical efficiency were analyzed. Metabolic energy and user power were significantly lower (p<0.05), and mechanical efficiency significantly higher with the PAPAW than with subjects' own chairs. Subjects needed to generate on average 3.65 times more power when propelling their own wheelchairs as compared to PAPAW. Mean mechanical efficiency over all trials was 80.33% higher with the power assisted hubs. PAPAW provides on average 73% of the total power when subjects propel with power assistance. Significantly increased efficiency and reduced requirement of user power is achieved using the PAPAW. With use, the PAPAW may contribute to delaying secondary injuries of manual wheelchair users. In addition, it may be suitable for people who have (or at risk for) upper extremity joint degeneration, reduced exercise capacity, low strength or endurance who currently use electric powered wheelchairs. Published by Elsevier Science Ltd on behalf of IPEM. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs, VA Rehabil Res & Dev Ctr, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15261 USA. RP Fitzgerald, SG (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151R1, 7180 Highland Dr, Pittsburgh, PA 15206 USA. OI Boninger, Michael/0000-0001-6966-919X NR 21 TC 28 Z9 29 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1350-4533 J9 MED ENG PHYS JI Med. Eng. Phys. PD DEC PY 2001 VL 23 IS 10 BP 699 EP 705 DI 10.1016/S1350-4533(01)00054-6 PG 7 WC Engineering, Biomedical SC Engineering GA 516AN UT WOS:000173529300005 PM 11801411 ER PT J AU Bharatha, A Hirose, M Hata, N Warfield, SK Ferrant, M Zou, KH Suarez-Santana, E Ruiz-Alzola, J D'Amico, A Cormack, RA Kikinis, R Jolesz, FA Tempany, CMC AF Bharatha, A Hirose, M Hata, N Warfield, SK Ferrant, M Zou, KH Suarez-Santana, E Ruiz-Alzola, J D'Amico, A Cormack, RA Kikinis, R Jolesz, FA Tempany, CMC TI Evaluation of three-dimensional finite element-based deformable registration of pre- and intraoperative prostate imaging SO MEDICAL PHYSICS LA English DT Article DE prostate cancer; brachytherapy; magnetic resonance imaging; registration; image guided therapy ID MR-IMAGES; THERAPY; BRACHYTHERAPY; CANCER AB In this report we evaluate an image registration technique that can improve the information content of intraoperative image data by deformable matching of preoperative images. In this study, pretreatment 1.5 tesla (T) magnetic resonance (MR) images of the prostate are registered with 0.5 T intraoperative images. The method involves rigid and nonrigid registration using biomechanical finite element modeling. Preoperative 1.5 T MR imaging is conducted with the patient supine, using an endorectal coil, while intraoperatively. the patient is in the lithotomy position with a rectal obturator in place. We have previously observed that these changes in patient position and rectal filling produce a shape change in the prostate. The registration of 1.5 T preoperative images depicting the prostate substructure [namely central gland (CG) and peripheral zone (PZ)] to 0.5 T intraoperative MR images using this method can facilitate the segmentation of the substructure of the gland for radiation treatment planning. After creating and validating a dataset of manually segmented glands from images obtained in ten sequential MR-guided brachytherapy cases, we conducted a set of experiments to assess our hypothesis that the proposed registration system can significantly improve the quality of matching of the total gland (TG), CG, and PZ. The results showed that the method statistically-significantly improves the quality of match (compared to rigid registration), raising the Dice similarity coefficient (DSC) from prematched coefficients of 0.81, 0.78, and 0.59 for TG, CG, and PZ, respectively, to 0.94, 0.86, and 0.76. A point-based measure of registration agreement was also improved by the deformable registration. CG and PZ volumes are not changed by the registration, indicating that the method maintains the biomechanical topology of the prostate. Although this strategy was tested for MRI-guided brachytherapy, the preliminary results from these experiments suggest that it may be applied to other settings such as transrectal ultrasound-guided therapy, where the integration of preoperative MRI may have a significant impact upon treatment planning and guidance. (C) 2001 American Association of Physicists in Medicine. C1 Brigham & Womens Hosp, Dept Radiol, Surg Planning Lab, Div MRI,Harvard Med Sch, Boston, MA 02115 USA. Univ Toronto, Sch Med, Toronto, ON, Canada. Showa Univ, Sch Med, Dept Radiol, Tokyo 142, Japan. Catholic Univ Louvain, Telecommun Lab, B-3000 Louvain, Belgium. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Tempany, CMC (reprint author), Brigham & Womens Hosp, Dept Radiol, Surg Planning Lab, Div MRI,Harvard Med Sch, 75 Francis St,L1-050, Boston, MA 02115 USA. RI Warfield, Simon/B-3352-2009; Hata, Nobuhiko/L-5221-2014; OI Hata, Nobuhiko/0000-0002-6818-7700; Cormack, Robert/0000-0001-5553-9984; Warfield, Simon/0000-0002-7659-3880 FU NCI NIH HHS [P01 CA67165]; NCRR NIH HHS [P41 RR013218, R01 RR11747]; NIA NIH HHS [R01 AG 19513-01] NR 25 TC 130 Z9 134 U1 0 U2 17 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD DEC PY 2001 VL 28 IS 12 BP 2551 EP 2560 DI 10.1118/1.1414009 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 505DL UT WOS:000172896200021 PM 11797960 ER PT J AU Goldberg, MB AF Goldberg, MB TI Actin-based motility of intracellular microbial pathogens SO MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS LA English DT Review ID WISKOTT-ALDRICH-SYNDROME; LISTERIA-MONOCYTOGENES ACTA; VASODILATOR-STIMULATED PHOSPHOPROTEIN; TO-CELL SPREAD; HOST MICROFILAMENT PROTEINS; WASP-INTERACTING PROTEIN; FILAMENT BARBED ENDS; YEAST ARP2/3 COMPLEX; PROLINE-RICH REGION; SHIGELLA-FLEXNERI AB A diverse group of intracellular microorganisms, including Listeria monocytogenes, Shigella spp., Rickettsia spp., and vaccinia virus, utilize actin-based motility to move within and spread between mammalian host cells. These organisms have in common a pathogenic life cycle that involves a stage within the cytoplasm of mammalian host cells. Within the cytoplasm of host cells, these organisms activate components of the cellular actin assembly machinery to induce the formation of actin tails on the microbial surface. The assembly of these actin tails provides force that propels the organisms through the cell cytoplasm to the cell periphery or into adjacent cells. Each of these organisms utilizes preexisting mammalian pathways of actin rearrangement to induce its own actin-based motility. Particularly remarkable is that while all of these microbes use the same or overlapping pathways, each intercepts the pathway at a different step. In addition, the microbial molecules involved are each distinctly different from the others. Taken together, these observations suggest that each of these microbes separately and convergently evolved a mechanism to utilize the cellular actin assembly machinery. The current understanding of the molecular mechanisms of microbial actin-based motility is the subject of this review. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Goldberg, MB (reprint author), Massachusetts Gen Hosp, Univ Pk,65 Landsdowne St, Cambridge, MA 02139 USA. NR 201 TC 153 Z9 161 U1 0 U2 20 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1092-2172 J9 MICROBIOL MOL BIOL R JI Microbiol. Mol. Biol. Rev. PD DEC PY 2001 VL 65 IS 4 BP 595 EP + DI 10.1128/MMBR.65.4.595-626.2001 PG 33 WC Microbiology SC Microbiology GA 499YJ UT WOS:000172598200005 PM 11729265 ER PT J AU Schnitzler, GR Cheung, CL Hafner, JH Saurin, AJ Kingston, RE Lieber, CM AF Schnitzler, GR Cheung, CL Hafner, JH Saurin, AJ Kingston, RE Lieber, CM TI Direct imaging of human SWI/SNF-remodeled mono- and polynucleosomes by atomic force microscopy employing carbon nanotube tips SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HISTONE OCTAMER; SWI-SNF; NUCLEOSOME ARRAYS; DIRECT GROWTH; CHROMATIN; COMPLEX; DNA; TRANSCRIPTION; ACETYLATION; RESOLUTION AB Chromatin-remodeling complexes alter chromatin structure to facilitate, or in some cases repress, gene expression. Recent studies have suggested two potential pathways by which such regulation might occur. In the first, the remodeling complex repositions nucleosomes along DNA to open or occlude regulatory sites. In the second, the remodeling complex creates an altered dimeric form of the nucleosome that has altered accessibility to transcription factors. The extent of translational repositioning, the structure of the remodeled dimer, and the presence of dimers on remodeled polynucleosomes have been difficult to gauge by biochemical assays. To address these questions, ultrahigh-resolution carbon nanotube tip atomic force microscopy was used to examine the products of remodeling reactions carried out by the human SWI/SNF (hSWI/SNF) complex. We found that mononucleosome remodeling by hSWI/SNF resulted in a dimer of mononucleosomes in which 60 bp of DNA is more weakly bound than in control nucleosomes. Arrays of evenly spaced nucleosomes that were positioned by 5S rRNA gene sequences were disorganized by hSWI/SNF, and this resulted in long stretches of bare DNA, as well as clusters of nucleosomes. The formation of structurally altered nucleosomes on the array is suggested by a significant increase in the fraction of closely abutting nucleosome pairs and by a general destabilization of nucleosomes on the array. These results suggest that both the repositioning and structural alteration of nucleosomes are important aspects of hSWI/SNF action on polynucleosomes. C1 Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. RP Lieber, CM (reprint author), Tufts Univ, Sch Med, Dept Biochem, 136 Harrison Ave, Boston, MA 02111 USA. RI Cheung, Chin Li/B-8270-2013; Hafner, Jason/A-7959-2008 OI Hafner, Jason/0000-0002-6943-4232 FU NINDS NIH HHS [F32 NS010706, F32 NS 10706] NR 36 TC 67 Z9 69 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2001 VL 21 IS 24 BP 8504 EP 8511 DI 10.1128/MCB.21.24.8504-8511.2001 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 494ZM UT WOS:000172315800024 PM 11713285 ER PT J AU Zhu, JW Field, SJ Gore, L Thompson, M Yang, HD Fujiwara, Y Cardiff, RD Greenberg, M Orkin, SH DeGregori, J AF Zhu, JW Field, SJ Gore, L Thompson, M Yang, HD Fujiwara, Y Cardiff, RD Greenberg, M Orkin, SH DeGregori, J TI E2F1 and E2F2 determine thresholds for antigen-induced T-cell proliferation and suppress tumorigenesis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID THYMIC NEGATIVE SELECTION; DISTINCT ROLES; S-PHASE; APOPTOSIS; ACTIVATION; INDUCTION; CYCLE; MICE; PRB; P73 AB E2F activity is critical for the control of the G, to S phase transition. We show that the combined loss of E2F1 and E2F2 results in profound effects on hematopoietic cell proliferation and differentiation, as well as increased tumorigenesis and decreased lymphocyte tolerance. The loss of E2F1 and E2F2 impedes B-cell differentiation, and hematopoietic progenitor cells in the bone mar-row of mice lacking E2F1 and E2F2 exhibit increased cell cycling. Importantly, we show that E2F1 and E2F2 double-knockout T cells exhibit more rapid entry into S phase following antigenic stimulation. Furthermore, T cells lacking E2F1 and E2F2 proliferate much more extensively in response to subthreshold antigenic stimulation. Consistent with these observations, E2F1/E2F2 mutant mice are highly predisposed to the development of tumors, and some mice exhibit signs of autoimmunity. C1 Univ Colorado, Hlth Sci Ctr, Dept Biochem & Mol Genet, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Integrated Dept Immunol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Childrens Hosp, Div Neurosci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Davis, Sch Med, Ctr Comparat Med, Davis, CA 95616 USA. Univ Calif Davis, Sch Med, Dept Pathol, Davis, CA 95616 USA. RP DeGregori, J (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Biochem & Mol Genet, BRB802,4200 E 9th Ave, Denver, CO 80262 USA. FU NCI NIH HHS [2P30 CA 46934-09, P30 CA046934, R01 CA 43855, R01 CA 77314-01, R01 CA077314, R01 CA077314-02, R01 CA077314-03]; NICHD NIH HHS [P30 HD018655, P30-HD 18655]; PHS HHS [P30 DR 57516] NR 53 TC 71 Z9 72 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2001 VL 21 IS 24 BP 8547 EP 8564 DI 10.1128/MCB.21.24.8547-8564.2001 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 494ZM UT WOS:000172315800028 PM 11713289 ER PT J AU Tang, H Hornstein, E Stolovich, M Levy, G Livingstone, M Templeton, D Avruch, J Meyuhas, O AF Tang, H Hornstein, E Stolovich, M Levy, G Livingstone, M Templeton, D Avruch, J Meyuhas, O TI Amino acid-induced translation of TOP mRNAs is fully dependent on phosphatidylinositol 3-kinase-mediated signaling, is partially inhibited by rapamycin and is independent of S6K1 and rpS6 phosphorylation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RIBOSOMAL-PROTEIN S6; CIS-REGULATORY ELEMENT; KINASE C-ZETA; LYMPHOSARCOMA CELLS; MAMMALIAN TARGET; GENE-EXPRESSION; TUMOR-SUPPRESSOR; QUIESCENT CELLS; L6 MYOBLASTS; RAT-LIVER AB Vertebrate TOP mRNAs contain an oligopyrimidine tract at their 5' termini (5'TOP) and encode components of the translational machinery. Previously it has been shown that they are subject to selective translational repression upon growth arrest and that their translational behavior correlates with the activity of S6K1. We now show that the translation of TOP mRNAs is rapidly repressed by amino acid withdrawal and that this nutritional control depends strictly on the integrity of the 5'TOP motif. However, neither phosphorylation of ribosomal protein (rp) S6 nor activation of S6K1 per se is sufficient to relieve the translational repression of TOP mRNAs in amino acid-starved cells. Likewise, inhibition of S6K1 activity and rpS6 phosphorylation by overexpression of dominant-negative S6K1 mutants failed to suppress the translational activation of TOP mRNAs in amino acid-refed cells. Furthermore, TOP mRNAs were translationally regulated by amino acid sufficiency in embryonic stem cells lacking both alleles of the S6K1 gene. Inhibition of mTOR by rapamycin led to fast and complete repression of S6K1, as judged by rpS6 phosphorylation, but to only partial and delayed repression of translational activation of TOP mRNAs. In contrast, interference in the phosphatidylinositol 3-kinase (P13-kinase) -mediated pathway by chemical or genetic manipulations blocked rapidly and completely the translational activation of TOP mRNAs. It appears, therefore, that translational regulation of TOP mRNAs, at least by amino acids, (i) is fully dependent on P13-kinase, (ii) is partially sensitive to rapamycin, and (iii) requires neither S6K1 activity nor rpS6 phosphorylation. C1 Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem, IL-91120 Jerusalem, Israel. Cell Signaling Technol, Beverly, MA 01915 USA. Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA. Massachusetts Gen Hosp, Diabet Unit, Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Diabet Unit, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. RP Meyuhas, O (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem, POB 12272, IL-91120 Jerusalem, Israel. EM meyuhas@cc.huji.ac.il RI Templeton, Dennis/F-7695-2011; Livingstone, Mark/H-1709-2011; HORNSTEIN, ERAN/K-1340-2012; OI HORNSTEIN, ERAN/0000-0002-5534-1924; Livingstone, Mark/0000-0002-2757-7008 NR 73 TC 194 Z9 200 U1 2 U2 9 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 DEC PY 2001 VL 21 IS 24 BP 8671 EP 8683 DI 10.1128/MCB.21.24.8671-8683.2001 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 494ZM UT WOS:000172315800038 PM 11713299 ER PT J AU Angeloni, D Lee, JD Johnson, BE Teh, BT Dean, M Lerman, MI Sterneck, E AF Angeloni, D Lee, JD Johnson, BE Teh, BT Dean, M Lerman, MI Sterneck, E TI C306A single nucleotide polymorphism in the human CEBPD gene that maps at 8p11.1-p11.2 SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE CEBPD; single nucleotide polymorphism (SNP) ID C/EBP-DELTA; LUNG; EXPRESSION; PROTEIN; FAMILY C1 NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Van Andel Res Inst, Gran Rapids, MI 48503 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Regulat Cell Growth Lab, Frederick, MD 21702 USA. RP Angeloni, D (reprint author), NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. OI Dean, Michael/0000-0003-2234-0631 FU NCI NIH HHS [N01-CO-56000] NR 11 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD DEC PY 2001 VL 15 IS 6 BP 395 EP 397 DI 10.1006/mcpr.2001.0377 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 524RN UT WOS:000174026800010 PM 11851384 ER PT J AU O'Driscoll, M Cerosaletti, KM Girard, PM Dai, Y Stumm, M Kysela, B Hirsch, B Gennery, A Palmer, SE Seidel, J Gatti, RA Varon, R Oettinger, MA Neitzel, H Jeggo, PA Concannon, P AF O'Driscoll, M Cerosaletti, KM Girard, PM Dai, Y Stumm, M Kysela, B Hirsch, B Gennery, A Palmer, SE Seidel, J Gatti, RA Varon, R Oettinger, MA Neitzel, H Jeggo, PA Concannon, P TI DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency SO MOLECULAR CELL LA English DT Article ID STRAND BREAK REPAIR; ATAXIA-TELANGIECTASIA; V(D)J RECOMBINATION; SYNDROME CELLS; IONIZING-RADIATION; CHECKPOINT DEFECTS; GENE; FIBROBLASTS; PROTEIN; ATM AB DNA ligase IV functions in DNA nonhomologous end-joining and V(D)J recombination. Four patients with features including immunodeficiency and developmental and growth delay were found to have mutations in the gene encoding DNA ligase IV (LIG4). Their clinical phenotype closely resembles the DNA damage response disorder, Nijmegen breakage syndrome (NBS). Some of the mutations identified in the patients directly disrupt the ligase domain while others impair the interaction between DNA ligase IV and Xrcc-4. Cell lines from the patients show pronounced radiosensitivity. Unlike NBS cell lines, they show normal cell cycle checkpoint responses but impaired DNA double-strand break rejoining. An unexpected V(D)J recombination phenotype is observed involving a small decrease in rejoining frequency coupled with elevated imprecision at signal junctions. C1 Univ Sussex, Genome Damage & Stabil Unit, Brighton BN1 9RR, E Sussex, England. Virginia Mason Med Ctr, Seattle, WA 98101 USA. Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98101 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Univ Magdeburg, Inst Human Genet, D-39112 Magdeburg, Germany. Univ Minnesota, Sch Med, Dept Lab Med, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Med, Dept Pathol, Minneapolis, MN 55455 USA. Newcastle Gen Hosp, Dept Paediat Immunol, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. Univ Texas, Hlth Sci Ctr, Dept Pediat, San Antonio, TX 78284 USA. Univ Jena, Dept Clin Genet, D-07740 Jena, Germany. Univ Calif Los Angeles, Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. Charite Humboldt Univ, Inst Human Genet, D-13353 Berlin, Germany. RP O'Driscoll, M (reprint author), Univ Sussex, Genome Damage & Stabil Unit, Brighton BN1 9RR, E Sussex, England. OI Concannon, Patrick/0000-0002-5801-1859 FU NCI NIH HHS [CA 57569] NR 40 TC 305 Z9 311 U1 1 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD DEC PY 2001 VL 8 IS 6 BP 1175 EP 1185 DI 10.1016/S1097-2765(01)00408-7 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 505HR UT WOS:000172907800006 PM 11779494 ER PT J AU Sharpless, NE Ferguson, DO O'Hagan, RC Castrillon, DH Lee, C Farazi, PA Alson, S Fleming, J Morton, CC Frank, K Chin, L Alt, FW DePinho, RA AF Sharpless, NE Ferguson, DO O'Hagan, RC Castrillon, DH Lee, C Farazi, PA Alson, S Fleming, J Morton, CC Frank, K Chin, L Alt, FW DePinho, RA TI Impaired nonhomologous end-joining provokes soft tissue sarcomas harboring chromosomal translocations, amplifications, and deletions SO MOLECULAR CELL LA English DT Article ID DNA-DAMAGE CHECKPOINT; TUMOR-SUPPRESSOR GENE; V(D)J RECOMBINATION; EMBRYONIC LETHALITY; GENOMIC STABILITY; PROSTATE-CANCER; HUMAN NEOPLASMS; INK4A LOCUS; LIGASE-IV; P53 AB Although nonhomologous end-joining (NHEJ) deficiency has been shown to accelerate lymphoma formation in mice, its role in suppressing tumors in cells that do not undergo V(D)J recombination is unclear. Utilizing a tumor-prone mouse strain (ink4a/arf(-/-)), we examined the impact of haploinsufficiency of a NHEJ component, DNA ligase IV (Lig4), on murine tumorigenesis. We demonstrate that lig4 heterozygosity promotes the development of soft-tissue sarcomas that possess clonal amplifications, deletions, and translocations. That these genomic alterations are relevant in tumorigenesis is supported by the finding of frequent mdm2 amplification, a known oncogene in human sarcoma. Together, these findings support the view that loss of a single Hg4 allele results in NHEJ activity being sufficiently reduced to engender chromosomal aberrations that drive non-lymphoid tumorigenesis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Gynecol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Reprod Biol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 59 TC 125 Z9 127 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD DEC PY 2001 VL 8 IS 6 BP 1187 EP 1196 DI 10.1016/S1097-2765(01)00425-7 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 505HR UT WOS:000172907800007 PM 11779495 ER PT J AU Narlikar, GJ Phelan, ML Kingston, RE AF Narlikar, GJ Phelan, ML Kingston, RE TI Generation and interconversion of multiple distinct nucleosomal states as a mechanism for catalyzing chromatin fluidity SO MOLECULAR CELL LA English DT Article ID YEAST SWI/SNF COMPLEX; MULTISUBUNIT COMPLEX; REMODELING COMPLEXES; OCTAMER TRANSFER; GENE-PRODUCTS; SWI-SNF; DNA; TRANSCRIPTION; BINDING; PROTEIN AB We have dissected the steps in nucleosome remodeling by BRG1, the ATPase subunit of human SWI/SNF. BRG1-catalyzed DNA exposure is not enhanced by the proximity of the site to the ends of nucleosomal DNA, suggesting that the mechanism involves more than peeling or sliding of the DNA. Comparison of DNA exposure at specific sites with overall changes in the path of DNA implies that BRG1 generates multiple distinct remodeled structures and continuously interconverts them. These characteristics are shared by the entire SWI/SNF complex and have parallels, as well as interesting differences, with the activities of GroEL and Hsp70 protein chaperones. The chaperone-like activity of SWI/SNF is expected to create multiple opportunities for the binding of distinct regulatory factors, providing one mechanism by which SWI/SNF family complexes can contribute to both activation and repression of transcription. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. NR 45 TC 94 Z9 94 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD DEC PY 2001 VL 8 IS 6 BP 1219 EP 1230 DI 10.1016/S1097-2765(01)00412-9 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 505HR UT WOS:000172907800010 PM 11779498 ER PT J AU Sekiguchi, J Whitlow, S Alt, FW AF Sekiguchi, J Whitlow, S Alt, FW TI Increased accumulation of hybrid V(D)J joins in cells expressing truncated versus full-length RAGs SO MOLECULAR CELL LA English DT Article ID STRAND BREAK REPAIR; RECOMBINATION ACTIVITY; SIGNAL SEQUENCES; DNA; PROTEINS; TRANSPOSITION; REGIONS; MICE; REARRANGEMENT; DEFINITION AB RAG1 and RAG2 (RAGs) initiate V(D)J recombination by introducing breaks between two coding segments and flanking recombination signals (RSs). Nonhomologous end-joining (NHEJ) proteins then join the coding segments and join the RSs. In wild-type cells, both full-length and truncated ("core") RAGs lead to accumulation of "hybrid" V(D)J joins, in which an RS is appended to a different coding sequence. We now show that while hybrid joins do not accumulate in NHEJ-deficient cells that express full-length RAGs, they do accumulate in NHEJ-deficient cells that express the core RAGS; like those catalyzed by core RAGs in vitro, however, they are sealed on just one DNA strand. These results suggest a potential role for the non-core regions in repressing potentially harmful transposition events. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,Ctr Blood Res,Dept Genet, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,Ctr Blood Res,Dept Genet, Boston, MA 02115 USA. OI Sekiguchi, JoAnn/0000-0002-7178-4258 FU NIAID NIH HHS [AI 35714, AI 20047] NR 34 TC 54 Z9 55 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD DEC PY 2001 VL 8 IS 6 BP 1383 EP 1390 DI 10.1016/S1097-2765(01)00423-3 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 505HR UT WOS:000172907800024 PM 11779512 ER PT J AU Hanna, GJ Caliendo, AM AF Hanna, GJ Caliendo, AM TI Testing for HIV-1 drug resistance SO MOLECULAR DIAGNOSIS LA English DT Article DE genotypic; phenotypic; susceptibility; antiretroviral ID IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE GENE; HIGH-LEVEL RESISTANCE; DYNAMICS IN-VIVO; LINE PROBE ASSAY; COMBINATION THERAPY; DUAL RESISTANCE; MUTATIONS; PROTEASE; ZIDOVUDINE AB Viral resistance to antiretroviral agents may limit the efficacy of current treatment regimens for HIV-1 infection. The mutational patterns underlying resistance to each antiretroviral agent are often quite diverse, and cross-resistance patterns in each of the currently available classes are complex. Current methods for determining drug resistance include genotypic and phenotypic assays, and each has advantages and limitations. Prospective clinical trials assessing the utility of HIV-1 drug resistance testing have shown significant but modest improvement in virologic outcomes with genotypic assays. Some, but not all, trials of phenotypic resistance testing have demonstrated improved virologic outcomes. Resistance testing is currently recommended for patients who have virologic failure or have no response to an antiretroviral regimen, and for pregnant women. Testing should also be considered in treatment-naive patients in areas of high prevalence of transmitted drug-resistant virus. C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Emory Univ Hosp, Dept Pathol & Lab Med, Atlanta, GA USA. Emory Univ, Sch Med, Atlanta, GA USA. RP Hanna, GJ (reprint author), Univ Pittsburgh, Sch Med, Div Infect Dis, Scaife Hall,Suite 818C,3550 Terrace St, Pittsburgh, PA 15261 USA. FU NIAID NIH HHS [K08 AI01696] NR 65 TC 4 Z9 4 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1084-8592 J9 MOL DIAGN JI Mol. Diagn. PD DEC PY 2001 VL 6 IS 4 BP 253 EP 263 DI 10.1054/modi.2001.29156 PG 11 WC Biotechnology & Applied Microbiology; Medical Laboratory Technology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Medical Laboratory Technology; Research & Experimental Medicine GA 510EL UT WOS:000173195700007 PM 11774191 ER PT J AU Akkari, YMN Bateman, RL Reifsteck, CA D'Andrea, AD Olson, SB Grompe, M AF Akkari, YMN Bateman, RL Reifsteck, CA D'Andrea, AD Olson, SB Grompe, M TI The 4N cell cycle delay in Fanconi anemia reflects growth arrest in late S phase. SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Fanconi anemia; interstrand DNA crosslink; Fanconi anemia group A; Fanconi anemia group C ID INTERSTRAND CROSS-LINKS; NECROSIS-FACTOR-ALPHA; MITOMYCIN-C; COMPLEMENTATION GROUPS; DNA-CROSSLINKING; NUCLEAR-COMPLEX; GROUP-A; GENE; APOPTOSIS; REPAIR AB Fanconi anemia (FA) is a human genetic disorder characterized by hypersensitivity to DNA crosslinking agents. Its cellular phenotypes include increased chromosome breakage and a marked cell-cycle delay with 4N DNA content after introduction of interstrand DNA crosslinks (ICL). To further understand the nature of this delay previously described as a G2/M arrest, we introduced ICL specifically during G2 and monitored the cells for passage into mitosis. Our results showed that, even at the highest doses, postreplication ICL produced neither G2/M arrest nor chromosome breakage in FA-A or FA-C cells. This suggests that, similar to wild-type cells, DNA replication is required to trigger both responses. Therefore, the 4N cell DNA content observed in FA cells after ICL treatment also represents incomplete DNA replication and arrest in late S phase. FA fibroblasts from complementation groups A and C were able to recover from the ICL-induced cell-cycle arrest, but took similar to3 times longer than controls. These results indicate that the FA pathway is required for the efficient resolution of ICL-induced S-phase arrest. (C) 2001 Elsevier Science. C1 Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. RP Grompe, M (reprint author), Oregon Hlth Sci Univ, Dept Mol & Med Genet, 3181 SW Sam Jackson Pk Rd L103, Portland, OR 97201 USA. FU NHLBI NIH HHS [1PO1HL48546] NR 54 TC 51 Z9 54 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD DEC PY 2001 VL 74 IS 4 BP 403 EP 412 DI 10.1006/mgme.2001.3259 PG 10 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 509UZ UT WOS:000173169200001 PM 11749045 ER PT J AU Methia, N Andre, P Hafezi-Moghadam, A Economopoulos, M Thomas, KL Wagner, DD AF Methia, N Andre, P Hafezi-Moghadam, A Economopoulos, M Thomas, KL Wagner, DD TI ApoE deficiency compromises the blood brain barrier especially after injury SO MOLECULAR MEDICINE LA English DT Article ID DENSITY-LIPOPROTEIN RECEPTOR; APOLIPOPROTEIN-E; ALZHEIMERS-DISEASE; ENDOTHELIAL-CELLS; KNOCKOUT MICE; HYPERCHOLESTEROLEMIA; ATHEROSCLEROSIS; ASTROCYTES; MODELS; EDEMA AB Background: Apolipoprotein E (apoE) mediates lipoprotein uptake by receptors such as the LDL receptor (LDLR). The isoform apoE4 has been linked to Alzheimer's disease and to poor outcomes after brain injury. Astrocytes that induce blood brain barrier (BBB) properties in endothelium also produce apoE. We decided to investigate the role of apoE in BBB function and in the restoration of BBB after brain injury. Materials and Methods: Wild-type (WT) mice and mice deficient in apoE or LDLR were fed normal chow or diets rich in fat and cholesterol. The BBB leakage was determined through injection of Evans blue dye and measurement of the amount of dye extravasated in the brains 3 hours later. Brain injury was induced by applying dry ice directly onto the excised parietal region of the brain. The mice were given 7 days to recover. in some experiments, peroxidase was infused to observe the site of leakage by histology. Results: We found 70% more spontaneous leakage of injected Evans blue dye in the brains of apoE-/- mice than in wild type. This increase fit permeability appeared selective for the brain. The leaky BBB in apoE-/- mice may provide an explanation for the neurological deficits seen in these animals. in an established model of BBB leakage induced by trauma (cold injury), the apoE-/- mice showed even more compromised BBB function, compared with WT mice, suggesting that apoE is important for BBB recovery. No deficit in BBB was observed in injured LDLR-/- mice, even on Western Diet. In contrast, higher plasma cholesterol levels in apoE-/- mice further increased BBB leakage after injury. We extracted 5x more Evans blue from these brains than from WT. In the injury model, injection of peroxidase resulted in prominent retention of this protein in the cortex of apoE-/- but not in WT. Conclusions: Our results show that the combination of loss of apoE function with high plasma cholesterol and especially brain injury results in dramatic BBB defects in the cortex and may explain in part the importance of apoE in Alzheimer's disease and in successful recovery from brain injury. C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [R01 HL053756, R01 HL 53756] NR 32 TC 69 Z9 72 U1 0 U2 3 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD DEC PY 2001 VL 7 IS 12 BP 810 EP 815 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 528WE UT WOS:000174266600004 PM 11844869 ER PT J AU Yoshida, K Kufe, D AF Yoshida, K Kufe, D TI Negative regulation of the SHPTP1 protein tyrosine phosphatase by protein kinase c delta in response to DNA damage SO MOLECULAR PHARMACOLOGY LA English DT Article ID MYELOID-LEUKEMIA CELLS; IONIZING-RADIATION; SH2 DOMAIN; PROTEOLYTIC ACTIVATION; CELLULAR-RESPONSE; STRESS-RESPONSE; MOTH-EATEN; 1-BETA-D-ARABINOFURANOSYLCYTOSINE; EXPRESSION; INDUCTION AB The SHPTP1 protein tyrosine phosphatase is activated by the c-Abl and Lyn tyrosine kinases in the cellular response to genotoxic stress. However, signaling mechanisms involved in the negative regulation of SHPTP1 are unknown. This study demonstrates that protein kinase C delta (PKC delta) associates with SHPTP1. The PKC delta catalytic domain binds directly to SHPTP1. The results also demonstrate that PKC delta is required, at least in part, for phosphorylation and inactivation of SHPTP1. The phosphatase activity of SHPTP1 was attenuated by coincubation with PKC delta in vitro. In addition, treatment of U-937 human myeloid leukemia cells with 1-beta -D-arabinofuranosylcytosine (ara-C) was associated with induction of the PKC delta kinase function and inhibition of SHPTP1 activity. Down-regulation of SHPTP1 by ara-C was blocked by the PKC delta inhibitor rottlerin but not by the PKC alpha and -beta inhibitor Go6976. Moreover, transient coexpression studies with a dominant-negative mutant of PKC delta demonstrate that the kinase activity of PKC delta is required for the down-regulation of SHPTP1. These findings support the functional interaction between PKC delta and SHPTP1 in the cellular response to DNA damage. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA29431] NR 45 TC 35 Z9 35 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 2001 VL 60 IS 6 BP 1431 EP 1438 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 500LQ UT WOS:000172629400034 PM 11723252 ER PT J AU Cramer, SC Fray, E Tievsky, A Parker, RA Riskind, PN Stein, MC Wedeen, V Rosen, BR AF Cramer, SC Fray, E Tievsky, A Parker, RA Riskind, PN Stein, MC Wedeen, V Rosen, BR TI Changes in motor cortex activation after recovery from spinal cord inflammation SO MULTIPLE SCLEROSIS LA English DT Article DE recovery; inflammation; spinal cord; plasticity; sensorimotor cortex ID ACUTE TRANSVERSE MYELITIS; AMYOTROPHIC-LATERAL-SCLEROSIS; HUMAN CEREBRAL-CORTEX; MULTIPLE-SCLEROSIS; FUNCTIONAL REORGANIZATION; POSTSTROKE HEMIPARESIS; CORTICAL FUNCTION; STROKE; STIMULATION; PLASTICITY AB Diseases of the spinal cord are associated with reactive changes in cerebral cortex organization. Many studies in this area have examined spinal cord conditions not associated with recovery, making it difficult to consider the value of these cortical events in the restoration of neurological function. We studied patients with myelitis, a syndrome of transient spinal cord inflammation, in order to probe cortical changes that might contribute to recovery after disease of the spinal cord. Seven patients, each of whom showed improvement in hand motor function after a diagnosis of myelitis involving cervical spinal cord, were clinically evaluated then studied with functional MRI, During right and left index finger tapping, activation volumes were assessed in three cortical motor regions within each hemisphere. Results were compared with findings in nine control subjects. Compared to the control group, myelitis patients had larger activation volumes within contralateral sensorimotor as well as contralateral premotor cortex. The degree of daily hand use showed a significant correlation with the volume of activation in controlateral sensorimotor cortex. Recovery from myelitis is associated with an enlarged activation volume in contralateral motor cortices. This change in motor cortex function is related to behavioral experience, and thus may contribute to motor improvement The expanded activation in motor cortex, seen with several forms of spinal cord insult, may have maximal utility when corticospinal tract axons are preserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Harvard Univ, Sch Med, Harvard Mit Div Hlth Sci & Technol, Clin Investigator Training Program, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pfizer Inc,Beth Israel Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Biometr Ctr, Boston, MA USA. RP Cramer, SC (reprint author), Univ Washington, 1959 NE Pacific St,Box 356465, Seattle, WA 98195 USA. NR 39 TC 12 Z9 12 U1 0 U2 0 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD DEC PY 2001 VL 7 IS 6 BP 364 EP 370 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 502GY UT WOS:000172736600004 PM 11795457 ER PT J AU Dowd, B Feldman, R Maciejewski, M Pauly, MV AF Dowd, B Feldman, R Maciejewski, M Pauly, MV TI The effect of tax-exempt out-of-pocket premiums on health plan choice SO NATIONAL TAX JOURNAL LA English DT Article; Proceedings Paper CT International Tax Policy Forum Conference CY APR 30, 2001 CL BROOKINGS INST, WASHINGTON, D.C. HO BROOKINGS INST ID ADVERSE SELECTION; INSURANCE; DEMAND; BENEFITS; REFORM; MARKET AB Market-based health care reform proposals typically rely on 1) consumer choice among competing health plans, 2) premiums paid out-of-pocket for higher priced plans, and 3) a significant out-of-pocket premium-p rice elasticity of health plan choice, Section 125 of the Internal Revenue Code exempts employee out-of-pocket premiums from personal income taxes and FICA taxes. The predicted effect is attenuation of the out-of-pocket premium-price elasticity of health plan choice. Using 1994 data from a national sample of large public employers, we find that employees are sensitive to out-of-pocket premiums, but tax-exempt out-of-pocket premiums reduce substantially the price elasticity of health plan choice. C1 Univ Minnesota, Sch Publ Hlth, Div Hlth Serv Res & Policy, Minneapolis, MN 55455 USA. VA Puget Sound Hlth Care Syst, HSR&D 152, Seattle, WA 98108 USA. Univ Penn, Wharton Sch, Hlth Care Syst Dept, Philadelphia, PA 19104 USA. RP Dowd, B (reprint author), Univ Minnesota, Sch Publ Hlth, Div Hlth Serv Res & Policy, Minneapolis, MN 55455 USA. NR 32 TC 6 Z9 8 U1 1 U2 3 PU NATL TAX ASSOC PI WASHINGTON PA 725 15TH ST, N W #600, WASHINGTON, DC 20005-2109 USA SN 0028-0283 J9 NATL TAX J JI Natl. Tax J. PD DEC PY 2001 VL 54 IS 4 BP 741 EP 756 PG 16 WC Business, Finance; Economics SC Business & Economics GA 506BQ UT WOS:000172950400004 ER PT J AU Ayte, J Schweitzer, C Zarzov, P Nurse, P DeCaprio, JA AF Ayte, J Schweitzer, C Zarzov, P Nurse, P DeCaprio, JA TI Feedback regulation of the MBF transcription factor by cyclin Cig2 SO NATURE CELL BIOLOGY LA English DT Article ID YEAST SCHIZOSACCHAROMYCES-POMBE; DNA-SYNTHESIS GENES; B-TYPE CYCLINS; FISSION YEAST; CELL-CYCLE; S-PHASE; SACCHAROMYCES-CEREVISIAE; NEGATIVE REGULATION; PROTEIN; START AB The Mlu1-binding factor (MBF) from the fission yeast Schizosaccharomyces pombe contains the proteins Res1p and Res2p and binds to the Mlu1 cell-cycle box (MCB) element in DNA, activating the transcription of genes required for S phase. We report here that the cell-cycle-regulated expression of the cyclin cig2 gene is dependent on MBF Deletion of MCB elements in the cig2 promoter perturbed the expression not only of cig2 but also of other MBF-dependent genes, indicating that Cig2p could regulate MBF activity. Cig2p can bind to Res2p, promote the phosphorylation of Res1p and inhibit MBF-dependent gene transcription. Cig2p thus forms an autoregulating feedback-inhibition loop with MBF which is important for normal regulation of the cell cycle. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Imperial Canc Res Fund, London WC2A 3PX, England. Univ Pompeu Fabra, Dept Ciencias Expt & Salut, Cell Signalling Unit, Barcelona 08003, Spain. RP Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM james_decaprio@dfci.harvard.edu RI Ayte, Jose/L-5217-2014 OI Ayte, Jose/0000-0002-6354-0536 NR 48 TC 30 Z9 31 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 EI 1476-4679 J9 NAT CELL BIOL JI Nat. Cell Biol. PD DEC PY 2001 VL 3 IS 12 BP 1043 EP 1050 DI 10.1038/ncb1201-1043 PG 8 WC Cell Biology SC Cell Biology GA 500AM UT WOS:000172603700009 PM 11781565 ER PT J AU Ge, H Liu, ZH Church, GM Vidal, M AF Ge, H Liu, ZH Church, GM Vidal, M TI Correlation between transcriptome and interactome mapping data from Saccharomyces cerevisiae SO NATURE GENETICS LA English DT Article ID EXPRESSION; GENOMES; YEAST AB Genomic and proteomic approaches can provide hypotheses concerning function for the large number of genes predicted from genome sequences(1-5). Because of the artificial nature of the assays, however, the information from these high-throughput approaches should be considered with caution. Although it is possible that more meaningful hypotheses could be formulated by integrating the data from various functional genomic and proteomic projects(6), it has yet to be seen to what extent the data can be correlated and how such integration can be achieved. We developed a 'transcriptome-interactome correlation mapping' strategy to compare the interactions between proteins encoded by genes that belong to common expression-profiling clusters with those between proteins encoded by genes that belong to different clusters. Using this strategy with currently available data sets for Saccharomyces cerevisiae, we provide the first global evidence that genes with similar expression profiles are more likely to encode interacting proteins. We show how this correlation between transcriptome and interactome data can be used to improve the quality of hypotheses based on the information from both approaches. The strategy described here may help to integrate other functional genomic and proteomic data, both in yeast and in higher organisms. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, Boston, MA USA. Harvard Univ, Sch Med, Ctr Neurol Dis, Boston, MA USA. Harvard Univ, Sch Med, Lipper Ctr Computat Genet, Boston, MA USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Vidal, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. FU NHGRI NIH HHS [1 RO1 HG01715-01] NR 18 TC 377 Z9 398 U1 2 U2 17 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2001 VL 29 IS 4 BP 482 EP 486 DI 10.1038/ng776 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 498JZ UT WOS:000172507500027 PM 11694880 ER PT J AU Carroll, M AF Carroll, M TI Innate immunity in the etiopathology of autoimmunity SO NATURE IMMUNOLOGY LA English DT Editorial Material ID DISEASE C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Carroll, M (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. NR 3 TC 38 Z9 40 U1 0 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD DEC PY 2001 VL 2 IS 12 BP 1089 EP 1090 DI 10.1038/ni1201-1089 PG 2 WC Immunology SC Immunology GA 497UE UT WOS:000172473200005 PM 11725293 ER PT J AU McIntire, JJ Umetsu, SE Akbari, O Potter, M Kuchroo, VK Barsh, GS Freeman, GJ Umetsu, DT DeKruyff, RH AF McIntire, JJ Umetsu, SE Akbari, O Potter, M Kuchroo, VK Barsh, GS Freeman, GJ Umetsu, DT DeKruyff, RH TI Identification of Tapr (an airway hyperreactivity regulatory locus) and the linked Tim gene family SO NATURE IMMUNOLOGY LA English DT Article ID HEPATITIS-A VIRUS; ETHNICALLY DIVERSE POPULATIONS; HEAT-KILLED LISTERIA; GENOME-WIDE SEARCH; CD4(+) T-CELLS; CELLULAR RECEPTOR; CHROMOSOME 5Q31-Q33; ATOPIC DISORDER; ASTHMA; MICE AB To simplify the analysis of asthma susceptibility genes located at human chromosome 5q23-35, we examined congenic mice that differed at the homologous chromosomal segment. We identified a Mendelian trait encoded by T cell and Airway Phenotype Regulator (Tapr). Tapr is genetically distinct from known cytokine genes and controls the development of airway hyperreactivity and T cell production of interleukin 4 (IL-4) and IL-13. Positional cloning identified a gene family that encodes T cell membrane proteins (TIMs); major sequence variants of this gene family (Tim) completely cosegregated with Tapr. The human homolog of TIM-I is the hepatitis A virus (HAV) receptor, which may explain the inverse relationship between HAV infection and the development of atopy. C1 Stanford Univ, Dept Pediat, Div Immunol & Allergy, Stanford, CA 94305 USA. Stanford Univ, Dept Genet, Stanford, CA 94305 USA. Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA. NCI, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP DeKruyff, RH (reprint author), Stanford Univ, Dept Pediat, Div Immunol & Allergy, Stanford, CA 94305 USA. EM rdk@stanford.edu RI Jones, Jennifer/C-8691-2015 OI Jones, Jennifer/0000-0002-9488-7719 FU NCI NIH HHS [CA84500, CA09302]; NIAID NIH HHS [AI-24571] NR 63 TC 321 Z9 372 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD DEC PY 2001 VL 2 IS 12 BP 1109 EP 1116 DI 10.1038/ni739 PG 8 WC Immunology SC Immunology GA 497UE UT WOS:000172473200012 PM 11725301 ER PT J AU Gonzalez, A Andre-Schmutz, I Carnaud, C Mathis, D Benoist, C AF Gonzalez, A Andre-Schmutz, I Carnaud, C Mathis, D Benoist, C TI Damage control, rather than unresponsiveness, effected by protective DX5+T cells in autoimmune diabetes SO NATURE IMMUNOLOGY LA English DT Article ID CD4(+) T-CELLS; LYMPHOCYTE-ASSOCIATED ANTIGEN-4; IMMUNOLOGICAL SELF-TOLERANCE; REGULATORY CELLS; NKT CELLS; MICE; DISEASE; REPERTOIRE; DEFICIENCY; INITIATION AB The progression of autoimmune diabetes is regulated. We examined here the cellular controls exerted on disease that developed in the BDC2.5 T cell receptor-transgenic model. We found that all BDC2.5 mice with a monoclonal, beta cell-reactive,T cell repertoire developed diabetes before 4 weeks of age; transfer of splenocytes from young standard NOD (nonobese diabetic) mice into perinatal monoclonal BDC2.5 animals protected them from diabetes. The protective activity was generated by CD4(+) alpha beta T cells, which operated for a short time at disease initiation, could be partitioned according to DX5 cell surface marker expression and split into two components. Protection did not involve clonal deletion or anergy of the autoreactive BDC2.5 cells, permitting their full activation and attack of pancreatic islets; rather, it tempered the aggressiveness of the insulitic lesion and the extent of beta cell destruction. C1 ULP, CNRS, INSERM, Inst Genet & Biol Mol & Cellulaire, Strasbourg, France. Hop Necker Enfants Malad, INSERM U25, Paris, France. RP Mathis, D (reprint author), Harvard Univ, Brigham & Womens Hosp, Joslin Diabet Ctr, Dept Med,Sect Immunol & Immunogenet, Boston, MA 02115 USA. RI Gonzalez, Antonio/C-4444-2008; Andre-Schmutz, Isabelle/F-6263-2013; Andre-Schmutz, Isabelle/M-1279-2016 OI Gonzalez, Antonio/0000-0002-2624-0606; NR 52 TC 122 Z9 127 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD DEC PY 2001 VL 2 IS 12 BP 1117 EP 1125 DI 10.1038/ni738 PG 9 WC Immunology SC Immunology GA 497UE UT WOS:000172473200013 PM 11713466 ER PT J AU Tzachanis, D Freeman, GJ Hirano, N van Puijenbroek, AAFL Delfs, MW Berezovskaya, A Nadler, LM Boussiotis, VA AF Tzachanis, D Freeman, GJ Hirano, N van Puijenbroek, AAFL Delfs, MW Berezovskaya, A Nadler, LM Boussiotis, VA TI Tob is a negative regulator of activation that is expressed in anergic and quiescent T cells SO NATURE IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR; TRANSCRIPTION FACTORS; SIGNAL-TRANSDUCTION; TARGETED DISRUPTION; TOB/BTG1 FAMILY; MESSENGER-RNA; TGF-BETA; PROTEIN; IDENTIFICATION; COMPONENT AB During a search for genes that maintain T cell quiescence, we determined that Tob, a member of an anti-proliferative gene family, was highly expressed in anergic T cell clones. Tob was also expressed in unstimulated peripheral blood T lymphocytes and down-regulated during activation. Forced expression of Tob inhibited T cell proliferation and transcription of cytokines and cyclins. In contrast, suppression of Tob with an antisense oligonucleotide augmented CD3-mediated responses and abrogated the requirement of costimulation for maximal proliferation and cytokine secretion. Tob associated with Smad2 and Smad4 and enhanced Smad DNA-binding. The inhibitory effect of Tob on interleukin 2 (IL-2) transcription was not mediated by blockade of NFAT, AP-1 or NF-kappaB transactivation but by enhancement of Smad binding on the -105 negative regulatory element of the IL-2 promoter. Thus,T cell quiescence is an actively maintained phenotype that must be suppressed for T cell activation to occur. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Div Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Dept Pathol, Boston, MA 02115 USA. RP Boussiotis, VA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Div Med Oncol, Boston, MA 02115 USA. EM vassiliki_boussiotis@dfci.harvard.edu FU NHLBI NIH HHS [HL 54786]; NIAID NIH HHS [AI 41584, AI 43552] NR 47 TC 177 Z9 183 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD DEC PY 2001 VL 2 IS 12 BP 1174 EP 1182 DI 10.1038/ni730 PG 9 WC Immunology SC Immunology GA 497UE UT WOS:000172473200021 PM 11694881 ER PT J AU Wagner, AD AF Wagner, AD TI Synchronicity: when you're gone I'm lost without a trace? SO NATURE NEUROSCIENCE LA English DT Editorial Material ID MEMORY AB Recordings from the human medial temporal lobe suggest that synchronization of oscillations between rhinal cortex and hippocampus may contribute to building declarative memories. C1 MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, Ctr Learning & Memory, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Wagner, AD (reprint author), MIT, Dept Brain & Cognit Sci, NE20-463, Cambridge, MA 02139 USA. NR 15 TC 19 Z9 19 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD DEC PY 2001 VL 4 IS 12 BP 1159 EP 1160 DI 10.1038/nn1201-1159 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 498RV UT WOS:000172525000005 PM 11723457 ER PT J AU Nathan, D Benz, EJ AF Nathan, D Benz, EJ TI Comprehensive Cancer Centres and the war on cancer SO NATURE REVIEWS CANCER LA English DT Editorial Material ID CHRONIC MYELOID-LEUKEMIA; ABL TYROSINE KINASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; COMBINATION CHEMOTHERAPY; COLORECTAL-CANCER; BREAST-CANCER; INHIBITOR; TUMOR; CELL; STATISTICS AB Comprehensive Cancer Centres are now recognized as an important weapon in the war on cancer, but they had to fight a very different battle to become accepted by the academic community. Why were these centres developed? How do they contribute to cancer research? Have they achieved the aims for which they were set up? And how should they be improved? It is important to answer these questions because we believe that cancer centres, though in need of improvement, are vital parts of our anticancer strategy. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nathan, D (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 40 TC 5 Z9 5 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD DEC PY 2001 VL 1 IS 3 BP 240 EP 245 DI 10.1038/35106102 PG 6 WC Oncology SC Oncology GA 635KC UT WOS:000180397200016 PM 11902579 ER PT J AU Poy, F Lepourcelet, M Shivdasani, RA Eck, MJ AF Poy, F Lepourcelet, M Shivdasani, RA Eck, MJ TI Structure of a human Tcf4-beta-catenin complex SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID BETA-CATENIN BINDING; FUNCTIONAL INTERACTION; COLORECTAL-CANCER; CRYSTAL-STRUCTURE; E-CADHERIN; PROTEIN; APC; LEF-1; TCF; CRYSTALLOGRAPHY AB The multifunctional protein beta -catenin is important for cell adhesion, because it binds cadherins, and the Wnt signal transduction pathway, where it interacts with the Adenomatous polyposis coli (APC) protein and TCF/Lef family transcription factors. Mutations in APC or in beta -catenin are estimated to trigger formation of over 90% of all colon cancers. In colonic epithelia, these mutations produce elevated levels of Tcf4-beta -catenin, which stimulates a transcriptional response that initiates polyp formation and eventually malignant growth. Thus, disruption of the Tcf4-beta -catenin interaction may be an attractive goal for therapeutic intervention. Here we describe the crystal structure of a human Tcf4-beta -catenin complex and compare it with recent structures of beta -catenin in complex with Xenopus Tcf3 (XTcf3) and mammalian E-cadherin. The structure reveals anticipated similarities with the closely related XTcf3 complex but unexpectedly lacks one component observed in the XTcf3 structure. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Eck, MJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. NR 34 TC 96 Z9 104 U1 0 U2 10 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD DEC PY 2001 VL 8 IS 12 BP 1053 EP 1057 DI 10.1038/nsb720 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 498RM UT WOS:000172524300014 PM 11713476 ER PT J AU Barker, FG Chang, SM Larson, DA Sneed, PK Wara, WM Wilson, CB Prados, MD AF Barker, FG Chang, SM Larson, DA Sneed, PK Wara, WM Wilson, CB Prados, MD TI Age and radiation response in glioblastoma multiforme SO NEUROSURGERY LA English DT Article DE age; glioblastoma; prognostic factors; radiation response ID MALIGNANT BRAIN-TUMORS; THERAPY-ONCOLOGY-GROUP; LONG-TERM SURVIVAL; ELDERLY PATIENTS; CLINICAL-TRIALS; SURGICAL RESECTION; CEREBRAL GLIOMAS; P53 GENE; RADIOTHERAPY; CHEMOTHERAPY AB OBJECTIVE: Advanced age is a strong predictor of shorter survival in patients with glioblastoma multiforme (GM), especially for those who receive multimodality treatment. Radiographically assessed tumor response to external beam radiation therapy is an important prognostic factor in GM. We hypothesized that older GM patients might have more radioresistant tumors. METHODS: We studied radiographically assessed response to external beam radiation treatment (five-level scale) in relation to age and other prognostic factors in a cohort of 301 GM patients treated on two prospective clinical protocols. A total of 223 patients (74%) were assessable for radiographically assessed radiation response. A proportional odds ordinal regression model was used for univariate and multivariate analysis. RESULTS: Younger age (P = 0.006), higher Karnofsky Performance Scale score before radiotherapy (P = 0.027), and more extensive surgical resection (P = 0.028) predicted better radiation response in univariate analyses. Results were similar when clinical criteria were used to classify an additional 61 patients without radiographically assessed radiation response (stable versus progressive disease). In multivariate analyses, age and extent of resection were significant independent predictors of radiation response (P < 0.05); Karnofsky Performance Scale score was of borderline significance (P = 0.07). CONCLUSION: Older GM patients are less likely to have good responses to postoperative external beam radiation therapy. Karnofsky Performance Scale score before radiation treatment and extent of surgical resection are additional predictors of radiographically assessed radiation response in GM. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Neurosurg Serv, Boston, MA 02114 USA. Univ Calif San Francisco, Neurooncol Serv, Brain Tumor Res Ctr, Dept Neurol Surg, San Francisco, CA USA. Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, Neurosurg Serv, Cox 315,32 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [CA 13525, CA 09291] NR 77 TC 52 Z9 55 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 DEC PY 2001 VL 49 IS 6 BP 1288 EP 1297 DI 10.1097/00006123-200112000-00002 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 497UU UT WOS:000172474500003 PM 11846927 ER PT J AU Hoh, BL Putman, CM Budzik, RF Ogilvy, CS AF Hoh, BL Putman, CM Budzik, RF Ogilvy, CS TI Surgical and endovascular flow disconnection of intracranial pial single-channel arteriovenous fistulae SO NEUROSURGERY LA English DT Article DE arteriovenous fistula; arteriovenous malformation; embolization; endovascular; Guglielmi detachable coil; hemorrhage; venous varix ID OSLER-WEBER DISEASE; VASCULAR MALFORMATIONS; PERFUSION-PRESSURE; VENOUS DRAINAGE; HEMORRHAGE; OCCLUSION; BRAIN; RESECTION; CHILDREN; VARICES AB INTRODUCTION: Intracranial pial single-channel arteriovenous (AV) fistulae are rare vascular lesions of the brain. They differ from AV malformations in that they lack a true "nidus" and are composed of one or more direct arterial connections to a single venous channel. They often are associated with a venous varix because of their high-flow nature. The pathological aspects of pial AV fistulae arise from their high-flow dynamics; therefore, we think that disconnection of the AV shunt is enough to obliterate the lesion, and that lesion resection is unnecessary. Flow disconnection can be accomplished via surgical or endovascular means. Certain lesions have angiogeometric configurations, however, that are unfavorable for endovascular treatment. We reviewed the experience in our combined neurosurgical and neuroendovascular unit in the treatment of patients with pial single-channel AV fistulae. METHODS: From 1991 to 1999, the combined neurovascular unit at the Massachusetts General Hospital treated nine consecutive patients with nontraumatic intracranial pial single-channel AV fistulae. Carotid-cavernous fistulae and vein of Galen malformations were excluded from this analysis. The combined neurovascular team planned the treatment strategy for each patient on the basis of the anatomic location and the angiogeometry of each lesion. We retrospectively reviewed the medical records, office charts, operative reports, endovascular reports, and x-rays for each patient. Radiographic outcome was assessed by use of posttreatment angiography. Clinical outcome was assessed by an independent nurse practitioner. RESULTS: A treatment strategy of flow disconnection was used in all nine patients and was accomplished surgically in six patients, endovascularly in two patients, and by combined techniques in one patient. All nine lesions were completely obliterated as demonstrated radiographically, including obliteration of the venous varices associated with three of the lesions. With a mean long-term clinical follow-up of 3.2 years (range, 0.3-8.4 yr), four patients were neurologically excellent with no deficits, two patients had pretreatment neurological deficits that did not worsen after treatment, one patient had transient dysphonia and dysphagia postoperatively that resolved, one patient had mild weakness after treatment, and one patient had moderate homonymous hemianopia after treatment. CONCLUSION: Single-channel pial AV fistulae can be treated by a strategy of flow disconnection. Resection of the lesion is not necessary. Flow disconnection can be accomplished either surgically or endovascularly; however, certain angiogeometric configurations are more favorable for surgical treatment. An experienced combined neurosurgical and neuroendovascular team can carefully determine the most appropriate treatment modality on the basis of patient-specific and angiospecific factors. C1 Harvard Univ, AVM Ctr,Med Sch, Neurosurg Serv, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, AVM Ctr,Med Sch, Intervent Neuroradiol Serv, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ogilvy, CS (reprint author), Harvard Univ, AVM Ctr,Med Sch, Neurosurg Serv, Massachusetts Gen Hosp, VBK-710,Fruit St, Boston, MA 02114 USA. NR 36 TC 61 Z9 65 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD DEC PY 2001 VL 49 IS 6 BP 1351 EP 1363 DI 10.1097/00006123-200112000-00011 PG 13 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 497UU UT WOS:000172474500017 PM 11846934 ER PT J AU Krings, T Chiappa, KH Foltys, H Reinges, MHT Cosgrove, GR Thron, A AF Krings, T Chiappa, KH Foltys, H Reinges, MHT Cosgrove, GR Thron, A TI Introducing navigated transcranial magnetic stimulation as a refined brain mapping methodology SO NEUROSURGICAL REVIEW LA English DT Article DE brain mapping; motor system; presurgical planning; neuronavigation; functional imaging ID HUMAN MOTOR CORTEX; EVOKED-POTENTIALS; FUNCTIONAL REORGANIZATION; CEREBRAL-CORTEX; INTACT MAN; INDUCTION; PATHWAYS; SPEECH; SAFETY; HAND AB A major intrinsic limitation of transcranial magnetic stimulation (TMS) to map the human brain lies in the unclear relationship between the position of the stimulating coil on the scalp and the underlying stimulated cortex. The relationship between structure and function as the major feature constituting a brain mapping modality can therefore not be established. Recent advances in image processing allowed us to refine TMS by combining magnetic resonance imaging (MRI) modalities with TMS using a neuronavigation system to measure the position of the stimulating coil and map this position onto a MRI data set. This technique has several advantages over recent TMS mapping strategies. The position of the coil on the scalp can be held constant as verified by real time visual guidance. When evaluating higher cortical functions, the relationship between underlying cortical anatomy and the scalp stimulation site can be accurately assessed. Cortical motor output maps can be easily obtained for preoperative planning and decision making for mass lesions near rolandic cortex in patients. In conclusion, navigated TMS is a reliable alternative for localizing cortical functions and therefore may be a useful adjunct or in selected patients even a helpful alternative to other functional neuroimaging methods. C1 Tech Univ Aachen Hosp, Interdisciplinary Ctr Clin Res Cent Nervous Syst, Aachen, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Tech Univ Aachen Hosp, Dept Neurosurg & Neuroradiol, D-52057 Aachen, Germany. RP Krings, T (reprint author), Tech Univ Aachen Hosp, Interdisciplinary Ctr Clin Res Cent Nervous Syst, Aachen, Germany. EM tkrings@izkf.rwth-aachen.de NR 58 TC 52 Z9 55 U1 1 U2 5 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5607 J9 NEUROSURG REV JI Neurosurg. Rev. PD DEC PY 2001 VL 24 IS 4 BP 171 EP 179 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 505VY UT WOS:000172937300004 PM 11778822 ER PT J AU de Silva, AM Walder, KR Boyko, EJ Whitecross, KF Nicholson, G Kotowicz, M Pasco, J Collier, GR AF de Silva, AM Walder, KR Boyko, EJ Whitecross, KF Nicholson, G Kotowicz, M Pasco, J Collier, GR TI Genetic variation and obesity in Australian women: A prospective study SO OBESITY RESEARCH LA English DT Article DE polymorphisms; longitudinal; white; body composition ID LEPTIN RECEPTOR GENE; BODY-MASS INDEX; INSULIN-RESISTANCE; BETA(3)-ADRENERGIC RECEPTOR; MORBID-OBESITY; ADRENERGIC-RECEPTOR; TRP64ARG MUTATION; DIABETES-MELLITUS; WEIGHT-GAIN; POLYMORPHISM AB Objective: A number of candidate genes have been implicated in the pathogenesis of obesity in humans. This study examines associations between longitudinal changes in body mass and composition and the presence of polymorphisms in the beta -3 adrenergic receptor, tumor necrosis factor-alpha, leptin, and leptin receptor (Lepr) in a cohort of Australian women. Research Methods and Procedures: Healthy white Australian women (n = 335) were randomly selected from the Barwon region of Victoria and underwent baseline anthropometry and double-energy X-ray absorptiometry for assessment of body mass and adiposity. These measurements were repeated again at 2-year follow-up. Genomic DNA was extracted and used for polymerase chain reaction-based genotyping of all polymorphisms. Results: The Pro1019Pro Lepr polymorphism was associated with longitudinal increases in body weight (p = 0.02), fat mass (p = 0.05), and body mass index (p = 0.01) in this study, and individuals homozygous for the A allele at this locus had a greater propensity to gain body fat over time. The largest effects on body composition seemed to be in individuals already obese at baseline. Changes in body weight, fat mass., percent body fat, and body mass index over a 2-year period were not associated with genetic variation in the beta -3 adrenergic receptor (Trp64Arg), tumor necrosis factor-alpha promoter, or leptin genes in non-obese or obese women. Discussion: These results suggest that a Lepr polymorphism is involved in the regulation of body mass and adiposity in obese Australian white women, which may have implications for the treatment of obesity in this population. C1 Deakin Univ, Sch Hlth Sci, Metab Res Unit, Geelong, Vic 3217, Australia. Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Melbourne, Dept Clin & Biomed Sci, Geelong, Vic, Australia. RP de Silva, AM (reprint author), Deakin Univ, Sch Hlth Sci, Metab Res Unit, Geelong, Vic 3217, Australia. RI Nicholson, Geoffrey/F-1901-2010; OI Nicholson, Geoffrey/0000-0002-0152-1153; Kotowicz, Mark/0000-0002-8094-1411 NR 33 TC 21 Z9 21 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD DEC PY 2001 VL 9 IS 12 BP 733 EP 740 DI 10.1038/oby.2001.101 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 505BU UT WOS:000172892000001 PM 11743056 ER PT J AU Chan, RY Yannuzzi, LA Foster, CS AF Chan, RY Yannuzzi, LA Foster, CS TI Ocular Whipple's disease - Earlier definitive diagnosis SO OPHTHALMOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; OCULOFACIAL-SKELETAL MYORHYTHMIA; PROGRESSIVE SUPRANUCLEAR PALSY; TRIMETHOPRIM-SULFAMETHOXAZOLE; OCULOMASTICATORY MYORHYTHMIA; UVEITIS; MANIFESTATIONS; BACILLUS; BRAIN; IDENTIFICATION AB Purpose: Whipple's disease is a rare, chronic, and multiorgan bacterial disease that predominantly involves the gut and its lymphatic drainage in middle-aged Caucasian men but may involve the eye. It is often difficult to diagnose and treat. We report results of one more polymerase chain reaction (PCR) analysis-diagnosed ocular Whipple's disease (OWD) case and the care of three new patients with ocular inflammation caused by OWD. Design: Retrospective noncomparative case series. Participants: Three patients. Methods: Diagnostic PCR was performed on a vitreous sample, medical records of three patients with OWD were reviewed, and a literature review (1907 to present) located 74 OWD cases. Analysis of published OWD cases to seek out factors that contribute to earlier, definitive diagnosis and treatment of OWD is made. Main Outcome Measures: Response of ocular inflammation and vision to treatment. Results: One of 3 new and 4 of 74 published OWD cases reviewed were diagnosed with PCR on vitreous samples and subsequently successfully treated with antibiotics without devastating central nervous system (CNS) sequelae. Conclusion: Diagnostic PCR on vitreous samples and recognition of key presenting symptoms in patients with OWD allows earlier definitive diagnosis, when the disease may be more amenable to antibiotic treatment, compared with "late" CNS Whipple's disease in the cases reviewed. (C) 2001 by the American Academy of Ophthalmology. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Immunol & Uveitis Serv,Dept Ophthalmol, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Immunol & Uveitis Serv,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 52 TC 15 Z9 15 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 DEC PY 2001 VL 108 IS 12 BP 2225 EP 2231 DI 10.1016/S0161-6420(01)00818-1 PG 7 WC Ophthalmology SC Ophthalmology GA 496VM UT WOS:000172417800035 PM 11733263 ER PT J AU Ripandelli, G Coppe, AM Fedeli, R Parisi, V D'Amico, DJ Stirpe, M AF Ripandelli, G Coppe, AM Fedeli, R Parisi, V D'Amico, DJ Stirpe, M TI Evaluation of primary surgical procedures for retinal detachment with macular hole in highly myopic eyes - A randomized comparison of vitrectomy versus posterior episcleral buckling surgery SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Ophthalmology CY OCT 22-25, 2000 CL DALLAS, TEXAS SP Amer Acad Ophthalmol ID OPTICAL COHERENCE TOMOGRAPHY; TERM FOLLOW-UP AB Purpose: To evaluate postoperative outcomes between pars plana vitrectomy (PPV) and posterior episcleral buckle procedure (PEBP) in myopic eyes with retinal detachment (RD) and macular hole (MH). Design: Retrospective nonrandomized comparative interventional trial. Participants and Intervention: The study included 30 phakic, highly myopic eyes (from 19-30 negative diopters) of 30 patients with an RD and MH. The patients were divided into two groups: They were assigned to PPV (15 eyes, group A) or to PEBP (15 eyes, group B). No significant (P > 0.01) differences in preoperative visual acuity (VA) between group A and group B eyes were found. Follow-up was 12 months. Main Outcome Measures: Anatomic attachment of the retina was determined, and VA was measured. Results: Retinal reattachment was obtained on 11 of 15 (73.3%) eyes of group A and on 14 of 15 (93.3%) eyes of group B. In group A eyes the VA was substantially unmodified after surgical treatment, whereas in group B eyes the VA observed after surgical treatment increased significantly (P < 0.001) with respect to the preoperative values. Conclusions: PEBP resulted in better postoperative anatomic and functional results compared with PPV in eyes with extreme degrees of myopia, pronounced posterior staphyloma, and posterior vitreous schisis affected with RD caused by MH. (C) 2001 by the American Academy of Ophthalmology. C1 Fdn GB Bietti Oftalmol, Rome, Italy. Univ Roma Tor Vergata, Cattedra Clin Oculist, I-00173 Rome, Italy. Oculist Osped Fatebenefratelli, CRCCS, AFaR, Rome, Italy. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. RP Ripandelli, G (reprint author), Via Pasubio 6, I-00195 Rome, Italy. NR 12 TC 58 Z9 62 U1 0 U2 2 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 DEC PY 2001 VL 108 IS 12 BP 2258 EP 2264 DI 10.1016/S0161-6420(01)00861-2 PG 7 WC Ophthalmology SC Ophthalmology GA 496VM UT WOS:000172417800039 PM 11733267 ER PT J AU Woog, JJ AF Woog, JJ TI Endoscopic-guided trephination dacryocystorhinostomy (Hesham DCR) - Technique and pilot trial - Discussion SO OPHTHALMOLOGY LA English DT Editorial Material ID LASER-ASSISTED DACRYOCYSTORHINOSTOMY; MITOMYCIN-C; LACRIMAL SURGERY C1 Massachusetts Eye & Ear Infirm, New England Eye Ctr, Ctr Eye Res, Ophthalm Consultants Boston, Boston, MA 02114 USA. RP Woog, JJ (reprint author), 50 Staniford St Suite 700, Boston, MA 02114 USA. NR 11 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 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 2001 VL 108 IS 12 BP 2345 EP 2346 DI 10.1016/S0161-6420(01)00814-4 PG 2 WC Ophthalmology SC Ophthalmology GA 496VM UT WOS:000172417800055 ER PT J AU Oaklander, AL AF Oaklander, AL TI The density of remaining nerve endings in human skin with and without postherpetic neuralgia after shingles (vol 92, pg 139, 2001) SO PAIN LA English DT Correction C1 Johns Hopkins Med Inst, Dept Neurol Surg, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesiol Neurol & Neuropathol, Boston, MA USA. RP Oaklander, AL (reprint author), Johns Hopkins Med Inst, Dept Neurol Surg, Boston, MA USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD DEC PY 2001 VL 94 IS 3 BP 325 EP 325 DI 10.1016/S0304-3959(01)00362-1 PG 1 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 504RV UT WOS:000172870400011 ER PT J AU Butler, WE Khan, SA AF Butler, WE Khan, SA TI The application of controlled intracranial hypertension in slit ventricle syndrome patients with obstructive hydrocephalus and shunt malfunction SO PEDIATRIC NEUROSURGERY LA English DT Article DE hydrocephalus; slit ventricle syndrome; endoscopic third ventriculocisternostomy; shunt infection or malfunction ID 3RD VENTRICULOSTOMY; ANTI-SIPHON; DEVICE; PRESSURE AB When a shunted patient with slit-ventricle syndrome (SVS) presents with a shunt malfunction or infection, the third ventricle may not be of sufficient caliber, despite the shunt malfunction, to allow atraumatic passage of an endoscope to the floor of the third ventricle. We describe four slit ventricle syndrome patients with respectively 24, 12, 18 and 2 prior shunt revisions who presented with shunt infection. In each patient the shunt was externalized and controlled intracranial hypertension (CIH) was applied over an average of 5.8 days by raising the height of the external ventricular drain (EVD) bag to a mean height of 18.8 cm above EAM. This increased the mean transverse third ventricular diameter from an average of 0.28 cm on admission to 1.13 cm after application of CIH. Endoscopic third ventriculocisternostomy (ETV) was satisfactorily performed in three of the four patients who remain shunt free after a mean follow-up of 21.3 months. CIH followed by ETV is an option in selected SVS patients who present with shunt malfunction or infection. Copyright (C) 2001 S. Karger AG, Basel. C1 Harvard Univ, Massachusetts Gen Hosp, Wang Ambulatory Care Ctr 331, Neurosurg Serv, Boston, MA 02114 USA. RP Butler, WE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Wang Ambulatory Care Ctr 331, Neurosurg Serv, Fruit St, Boston, MA 02114 USA. NR 20 TC 16 Z9 16 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1016-2291 J9 PEDIATR NEUROSURG JI Pediatr. Neurosurg. PD DEC PY 2001 VL 35 IS 6 BP 305 EP 310 DI 10.1159/000050442 PG 6 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 511BH UT WOS:000173243500004 PM 11786698 ER PT J AU Matthews, BD Noviski, N AF Matthews, BD Noviski, N TI Management of oxygenation in pediatric acute hypoxemic respiratory failure SO PEDIATRIC PULMONOLOGY LA English DT Review DE children; pediatrics; acute respiratory distress syndrome; oxygenation; mechanical ventilation; respiratory failure; ventilator-induced lung injury ID INHALED NITRIC-OXIDE; ACUTE LUNG INJURY; FREQUENCY OSCILLATORY VENTILATION; INVERSE RATIO VENTILATION; END-EXPIRATORY PRESSURE; CONVENTIONAL MECHANICAL VENTILATION; EXTRACORPOREAL MEMBRANE-OXYGENATION; EUROPEAN CONSENSUS CONFERENCE; RANDOMIZED CONTROLLED TRIAL; DISTRESS-SYNDROME ARDS AB The prognosis for patients with acute respiratory distress syndrome (ARDS) in adults and children has improved since its formal acceptance as a clinical entity in 1967. Because acute hypoxemic respiratory failure is the hallmark of acute lung injury and ARDS, the management of oxygenation is crucial. Physicians managing pediatric patients with acute lung injury or ARDS are faced with a complex array of options influencing oxygenation. Certain treatment strategies can influence clinical outcomes, such as a lung-protective ventilation strategy that specifies a low tidal volume (6 mL/kg) and a plateau pressure limit (30 cm H2O) (Acute Respiratory Distress Network, N Engl J Med 2000;342:1301-1308). Other lung-protective strategies such as different levels of positive end-expiratory pressure, altered inspiratory:expiratory ratios, recruitment maneuvers, prone positioning, and extraneous gases or drugs may impact clinical outcomes but require further clinical study. This paper reviews state-of-the-art strategies on the management of oxygenation in acute hypoxemic respiratory failure and attempts to guide pediatric pulmonologists in managing children with respiratory failure. (C) 2001 Wiley-Liss, Inc. C1 MassGen Hosp Children, Div Pediat Crit Care Med, Boston, MA USA. RP Noviski, N (reprint author), Massachusetts Gen Hosp, Ellison 317,55 Fruit St, Boston, MA 02114 USA. NR 117 TC 11 Z9 15 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD DEC PY 2001 VL 32 IS 6 BP 459 EP 470 DI 10.1002/ppul.1159 PG 12 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 497NG UT WOS:000172461800008 PM 11747250 ER PT J AU Francis, SC Raizada, MK Mangi, AA Melo, LG Dzau, VJ Vale, PR Isner, JM Losordo, DW Chao, J Katovich, MJ Berecek, KH AF Francis, SC Raizada, MK Mangi, AA Melo, LG Dzau, VJ Vale, PR Isner, JM Losordo, DW Chao, J Katovich, MJ Berecek, KH TI Genetic targeting for cardiovascular therapeutics: are we near the summit or just beginning the climb? SO PHYSIOLOGICAL GENOMICS LA English DT Review DE gene therapy; angiogenesis; vascular endothelial growth factor; myocardial and limb ischemia; neointimal hyperplasia ID ENDOTHELIAL GROWTH-FACTOR; MUSCLE CELL-PROLIFERATION; DELIVERY ATTENUATES HYPERTENSION; SALT-SENSITIVE RATS; KALLIKREIN INDUCES HYPOTENSION; ADENOASSOCIATED VIRUS VECTORS; CONVERTING ENZYME-INHIBITION; ISCHEMIA-REPERFUSION INJURY; BRADYKININ B-2 RECEPTOR; CORONARY-ARTERY DISEASE AB This article is based on an Experimental Biology symposium held in April 2001 and presents the current status of gene therapy for cardiovascular diseases in experimental studies and clinical trials. Evidence for the use of gene therapy to limit neointimal hyperplasia and confer myocardial protection was presented, and it was found that augmenting local nitric oxide (NO) production using gene transfer (GT) of NO synthase or interruption of cell cycle progression through a genetic transfer of cell cycle regulatory genes limited vascular smooth muscle hyperplasia in animal models and infra- inguinal bypass patients. The results of application of vascular endothelial growth factor (VEGF) GT strategies for therapeutic angiogenesis in critical limb and myocardial ischemia in pilot clinical trials was reviewed. In addition, experimental evidence was presented that genetic manipulation of peptide systems (i. e., the renin- angiotensin II system and the kallikrein- kinin system) was effective in the treatment of systemic cardiovascular diseases such as hypertension, heart failure, and renal failure. Although, as of yet, there are no well controlled human trials proving the clinical benefits of gene therapy for cardiovascular diseases, the data presented here in animal models and in human subjects show that genetic targeting is a promising and encouraging modality, not only for the treatment and long- term control of cardiovascular diseases, but for their prevention as well. C1 Univ Florida, Coll Med, Dept Physiol & Funct Genom, Inst Brain, Gainesville, FL 32610 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Tufts Univ, Sch Med, St Elizabeths Med Ctr, Dept Vasc Med, Boston, MA 02135 USA. Tufts Univ, Sch Med, St Elizabeths Med Ctr, Dept Cardiol, Boston, MA 02135 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Univ Florida, Coll Pharm, Dept Pharmacodynam, Gainesville, FL 32610 USA. Univ Alabama, Dept Physiol & Biophys, Birmingham, AL 35294 USA. RP Berecek, KH (reprint author), Univ Alabama, Dept Physiol & Biophys, 1530 3rd Ave S,MCLM 988, Birmingham, AL 35294 USA. NR 141 TC 20 Z9 24 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD DEC PY 2001 VL 7 IS 2 BP 79 EP 94 PG 16 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 505HE UT WOS:000172906700003 PM 11773594 ER PT J AU Hsiao, LL Dangond, F Yoshida, T Hong, R Jensen, RV Misra, J Dillon, W Lee, KF Clark, KE Haverty, P Weng, ZP Mutter, GL Frosch, MP MacDonald, ME Milford, EL Crum, CP Bueno, R Pratt, RE Mahadevappa, M Warrington, JA Stephanopoulos, G Stephanopoulos, G Gullans, SR AF Hsiao, LL Dangond, F Yoshida, T Hong, R Jensen, RV Misra, J Dillon, W Lee, KF Clark, KE Haverty, P Weng, ZP Mutter, GL Frosch, MP MacDonald, ME Milford, EL Crum, CP Bueno, R Pratt, RE Mahadevappa, M Warrington, JA Stephanopoulos, G Stephanopoulos, G Gullans, SR TI A compendium of gene expression in normal human tissues SO PHYSIOLOGICAL GENOMICS LA English DT Article DE microarrays; human tissues; gene expression; bioinformatics ID FIBRINOGEN CARACAS-V; CDNA MICROARRAYS; ALDOSE REDUCTASE; INHIBITOR; TUMORS; CLASSIFICATION; HYPERLIPIDEMIA; SUBSTITUTION; DISCOVERY; PATTERNS AB This study creates a compendium of gene expression in normal human tissues suitable as a reference for defining basic organ systems biology. Using oligonucleotide microarrays, we analyze 59 samples representing 19 distinct tissue types. Of similar to 7,000 genes analyzed, 451 genes are expressed in all tissue types and designated as housekeeping genes. These genes display significant variation in expression levels among tissues and are sufficient for discerning tissue-specific expression signatures, indicative of fundamental differences in biochemical processes. In addition, subsets of tissue-selective genes are identified that define key biological processes characterizing each organ. This compendium highlights similarities and differences among organ systems and different individuals and also provides a publicly available resource (Human Gene Expression Index, the HuGE Index, http:// www. hugeindex. org) for future studies of pathophysiology. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Renal Div, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. Wesleyan Univ, Dept Phys, Middletown, CT 06459 USA. MIT, Dept Chem Engn, Bioinformat & Metab Engn Lab, Cambridge, MA 01890 USA. Boston Univ, Dept Biomed Engn, Bioinformat Program, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol,Div Neuropathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02139 USA. Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Affymetrix Inc, Santa Clara, CA 95051 USA. RP Gullans, SR (reprint author), 65 Landsdowne, Cambridge, MA 02140 USA. RI Mutter, George/C-5819-2009 FU NCI NIH HHS [CA-80084]; NIDDK NIH HHS [DK-09987, DK-36031, DK-58533, DK-58849]; NINDS NIH HHS [NS-16367] NR 41 TC 248 Z9 257 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 DEC PY 2001 VL 7 IS 2 BP 97 EP 104 PG 8 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 505HE UT WOS:000172906700005 PM 11773596 ER PT J AU Sheen, J AF Sheen, J TI Signal transduction in maize and Arabidopsis mesophyll protoplasts SO PLANT PHYSIOLOGY LA English DT Review ID EVACUOLATED PARSLEY PROTOPLASTS; BARLEY ALEURONE PROTOPLASTS; GREEN-FLUORESCENT PROTEIN; MESSENGER-RNA EXPRESSION; AUXIN RESPONSE ELEMENTS; GUARD-CELL PROTOPLASTS; SYNTHASE GENE PROMOTER; VIRUS MOVEMENT PROTEIN; ABSCISIC-ACID; TRANSIENT EXPRESSION AB Plant protoplasts show physiological perceptions and responses to hormones, metabolites, environmental cues, and pathogen-derived elicitors, similar to cell-autonomous responses in intact tissues and plants. The development of defined protoplast transient expression systems for high-throughput screening and systematic characterization of gene functions has greatly contributed to elucidating plant signal transduction pathways, in combination with genetic, genomic, and transgenic approaches. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Genet,Dept Mol Biol, Boston, MA 02114 USA. RP Sheen, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Genet,Dept Mol Biol, Wellman 11,50 Blossom St, Boston, MA 02114 USA. NR 145 TC 329 Z9 354 U1 5 U2 55 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD DEC PY 2001 VL 127 IS 4 BP 1466 EP 1475 DI 10.1104/pp.010820 PG 10 WC Plant Sciences SC Plant Sciences GA 503WK UT WOS:000172824500023 PM 11743090 ER PT J AU Keefe, AD Wilson, DS Seelig, B Szostak, JW AF Keefe, AD Wilson, DS Seelig, B Szostak, JW TI One-step purification of recombinant proteins using a nanomolar-affinity streptavidin-binding peptide, the SBP-tag SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID IN-VITRO SELECTION; PHAGE DISPLAY; FUSIONS AB We describe the use of the SBP-tag, a new streptavidin-binding peptide, for both the one-step purification and the detection of recombinant proteins. The SBP-tag sequence is 38 amino acids long and binds to streptavidin with an equilibrium dissociation constant of 2.5 nM. We demonstrate that a single-step purification of SBP-tagged proteins from bacterial extract yields samples that are more pure than those purified using maltose-binding protein or the His-tag. The capacity of the immobilized streptavidin used to purify SBP-tagged proteins is about 0.5 mg per milliliter of matrix, which is high enough to isolate large quantities of proteins for further study. Also, the elution conditions from the streptavidin column are very mild and specific, consisting of the wash buffer plus biotin. This combination of high-affinity, high-yield, mild elution conditions, and simplicity of use makes the SBP-tag suitable for high-throughput protein expression/ purification procedures, including robotically manipulated protocols with microtiter plates. Additionally, the SBP-tag can be used for detection since a wide variety of streptavidin-conjugated fluorescent and enzymatic systems are commercially available. We also present a new, rapid, method for the measurement of protein-protein, protein-peptide, or protein-small molecule equilibrium dissociation constants that require as little as 1 fmol of labeled protein. We call this method the spin-filter binding inhibition assay. (C) 2001 Academic Press. C1 Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Keefe, AD (reprint author), Archemix Inc, 20 Hampden St, Boston, MA 02119 USA. RI Seelig, Burckhard/D-1042-2013 OI Seelig, Burckhard/0000-0001-8598-0586 NR 19 TC 125 Z9 130 U1 2 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD DEC PY 2001 VL 23 IS 3 BP 440 EP 446 DI 10.1006/prep.2001.1515 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 512CT UT WOS:000173304100010 PM 11722181 ER PT J AU Radomsky, AS Otto, MW AF Radomsky, AS Otto, MW TI Cognitive-behavioral therapy for social anxiety disorder SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID INDIVIDUAL-RESPONSE PATTERNS; PANIC DISORDER; NEGATIVE BELIEFS; PHOBIA; EXPOSURE; METAANALYSIS; MODEL AB The efficacy of cognitive-behavior therapy (CBT) for treating social anxiety disorder (SAD) has been demonstrated repeatedly in controlled clinical trials. The trajectory of outcome over followup periods suggests that during acute treatment, patients learn a method for approaching their social fears and avoidance, such that patients extend initial gains over time. This finding is consistent with the model of CBT of social phobia, where patients are informed about the nature of maladaptive patterns characterizing SAD, are provided with tools for counteracting these patterns, and then rehearse the process of change. This is accomplished with the use of psychoeducation, a working model of SAD, gaining a critical awareness of thoughts and beliefs, and with exposure exercises and behavioral experiments, This article reviews the cognitive-behavioral model of SAD, the elements of treatment, and the outcome associated with these interventions. C1 Concordia Univ, Dept Psychol, Montreal, PQ H4B 1R6, Canada. Massachusetts Gen Hosp, Cognit Behav Therapy Program, Boston, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. RP Radomsky, AS (reprint author), Concordia Univ, Dept Psychol, 7141 Sherbrooke St W, Montreal, PQ H4B 1R6, Canada. OI Radomsky, Adam/0000-0003-2807-184X NR 40 TC 8 Z9 8 U1 0 U2 10 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 2001 VL 24 IS 4 BP 805 EP + DI 10.1016/S0193-953X(05)70264-1 PG 13 WC Psychiatry SC Psychiatry GA 490ZU UT WOS:000172084200012 PM 11723634 ER PT J AU Garrick, T Morrow, N Shalev, AY Eth, S AF Garrick, T Morrow, N Shalev, AY Eth, S TI Stress-induced enhancement of auditory startle: An animal model of posttraumatic stress disorder SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID VIETNAM VETERANS; PHYSIOLOGICAL-RESPONSES; AMYGDALOID NUCLEUS; CONDITIONED FEAR; LOUD TONES; COMMUNITY; RELEVANCE; PTSD; RATS AB AN innovative animal model of, posttraumatic stress disorder (PTSD) is proposed in which nonhabituation of the acoustic startle response is developed in rats subsequent to tailshock exposure. Subjects (n = 3 1) received 3 0 minutes of intermittent tail shock on 2 days followed by exposure to the tailshock apparatus on the third day. Compared to baseline startle reactions, 9 of 31 tailshock-exposed rats developed nonhabituation of startle response reactions during the subsequent 3 weeks of testing. No control rats developed nonhabituation of startle reactions over a similar time period. These data suggest that this system models useful aspects of clinical PTSD emphasizing nonhabituation of startle reactions as a dependent variable. The method consistently identifies a subgroup of rats that develop persistent nonhabituation of startle in response to a tailshock-stress paradigm. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. St Vincents Catholic Med Ctr New York, New York, NY USA. RP Garrick, T (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 37 TC 40 Z9 44 U1 2 U2 5 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD WIN PY 2001 VL 64 IS 4 BP 346 EP 354 DI 10.1521/psyc.64.4.346.18600 PG 9 WC Psychiatry SC Psychiatry GA 513EZ UT WOS:000173366100006 PM 11822211 ER PT J AU Loo, CM Fairbank, JA Scurfield, RM Ruch, LO King, DW Adams, LJ Chemtob, CM AF Loo, CM Fairbank, JA Scurfield, RM Ruch, LO King, DW Adams, LJ Chemtob, CM TI Measuring exposure to racism: Development and validation of a Race-Related Stressor Scale (RRSS) for Asian American Vietnam veterans SO PSYCHOLOGICAL ASSESSMENT LA English DT Article ID DISORDER; COMBAT; SELF; STIGMA AB This article describes the development and validation of the Race-Related Stressor Scale (RRSS), a questionnaire that assesses exposure to race-related stressors in the military and war zone. Validated on a sample of 300 Asian American Vietnam veterans, the RRSS has high internal consistency and adequate temporal stability. Hierarchical regression analyses revealed that exposure to race-related stressors accounted for a significant proportion of the variance in posttraumatic stress disorder (PTSD) symptoms and general psychiatric symptoms, over and above (by 20% and 19%, respectively) that accounted for by combat exposure and military rank. The RRSS appears to be a psychometrically sound measure of exposure to race-related stressors for this population. Race-related stressors as measured by the RRSS appear to contribute uniquely and substantially to PTSD symptoms and generalized psychiatric distress. C1 Natl Ctr PTSD, Pacific Isl Div, Honolulu, HI 96813 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Univ So Mississippi, Hattiesburg, MS 39406 USA. Univ Hawaii Manoa, Honolulu, HI 96822 USA. Natl Ctr PTSD, Boston, MA USA. Vet Adm Med & Reg Off Ctr, Boston, MA USA. Vet Adm Med & Reg Off Ctr, Honolulu, HI USA. RP Loo, CM (reprint author), Natl Ctr PTSD, Pacific Isl Div, 1132 Bishop St 307, Honolulu, HI 96813 USA. RI Fairbank, John/F-8972-2013 OI Fairbank, John/0000-0003-2604-7256 NR 56 TC 57 Z9 57 U1 1 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD DEC PY 2001 VL 13 IS 4 BP 503 EP 520 DI 10.1037//1040-3590.13.4.503 PG 18 WC Psychology, Clinical SC Psychology GA 504GJ UT WOS:000172848700008 PM 11793894 ER PT J AU Bradley, KA Bush, KR Davis, TM Dobie, DJ Burman, ML Rutter, CM Kivlahan, DR AF Bradley, KA Bush, KR Davis, TM Dobie, DJ Burman, ML Rutter, CM Kivlahan, DR TI Binge drinking among female veterans affairs patients: Prevalence and associated risks SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article ID ALCOHOL-CONSUMPTION QUESTIONS; PRIMARY-CARE PATIENTS; NATIONAL SURVEY; SCREENING INSTRUMENTS; COLLEGE-STUDENTS; EMERGENCY ROOM; AUDIT; WOMEN; HEALTH; SEX AB This study evaluated the prevalence and associated risks of binge drinking, defined as having greater than or equal to4 drinks on an occasion in the past year, in a female patient population. Of 1,259 female Veterans Affairs patients surveyed, 780 reported drinking alcohol in the past year, and 305 (24% of respondents, 39% of drinkers) reported binge drinking in the past year; 84 (11% of drinkers) had done so monthly or more often. Age-adjusted logistic regression analyses indicated that women who reported past-year binge drinking monthly or more often reported significantly increased odds of morning drinking (odds ratio [OR] = 40.3), others worrying about their drinking (OR = 38.6), arguments after drinking (OR = 13.5), hepatitis or cirrhosis (OR = 3.1), frequent injuries (OR = 2.6), smoking (OR = 3.7), drug use (OR = 22.2), and multiple sexual partners (OR = 4.6). C1 Vet Affairs Puget Sound Hlth Care Syst, HSR&D 152, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. RP Bradley, KA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, HSR&D 152, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIAAA NIH HHS [AA00313] NR 42 TC 27 Z9 27 U1 3 U2 4 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD DEC PY 2001 VL 15 IS 4 BP 297 EP 305 DI 10.1037//0893-164X.15.4.297 PG 9 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 500BP UT WOS:000172606300004 PM 11767260 ER PT J AU Hawighorst, H Huisman, T Berger, MF Zach, GA Michel, D AF Hawighorst, H Huisman, T Berger, MF Zach, GA Michel, D TI MRI in injuries of the spinal cord SO RADIOLOGE LA German DT Article DE injuries of spinal cord; magnetic resonance imaging (MRI) ID SYRINGOMYELIA; MANAGEMENT AB The improvement of preclinical emergency medicine has increased the long-term survival of patients which sustained severe injuries of the spinal cord. However the incidence of late complications has been increased due to the long-term survival. With the increasing use of magnetic resonance imaging (MRI) in this patient group the diagnosis of typical late complications of the spinal cord has improved. In this article we suggest the following terms to describe late complications of the spinal cord: syrinx, atrophy, cyst, malacia, disruption, and thethering. C1 Schweizer Paraplegiker Zentrum, Abt Radiol, CH-6207 Nottwil, Switzerland. Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Boston, MA USA. RP Hawighorst, H (reprint author), Schweizer Paraplegiker Zentrum, Abt Radiol, Postfach, CH-6207 Nottwil, Switzerland. NR 5 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-832X J9 RADIOLOGE JI Radiologe PD DEC PY 2001 VL 41 IS 12 BP 1033 EP 1037 DI 10.1007/s001170170002 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 506HQ UT WOS:000172964600002 PM 11793927 ER PT J AU Huisman, TAGM Hawighorst, H Benoit, CH Sorensen, AG AF Huisman, TAGM Hawighorst, H Benoit, CH Sorensen, AG TI Diffusion weighted magnetic resonance imaging: Ischemic and traumatic injury of the central nervous system SO RADIOLOGE LA German DT Article DE diffusion weighted MRI; apparent diffusion coefficient; anisotropic diffusion; anisotropic diffusion; trauma; stroke ID RAT SPINAL-CORD; ACUTE STROKE; IN-VIVO; MR; ANISOTROPY AB Diffusion weighted magnetic resonance imaging (DWI) represents a recent development that extends imaging from the depiction of the neuroanatomy into the field of functional and physiologic processes. DWI measures a fundamentally different physiologic parameter than conventional MRI. Image contrast is related to differences in the microscopic motion (diffusion) of water molecules within brain tissue rather than a change in total tissue water. Consequently, DWI can reveal pathology where conventional T1- and T2-weighted MR images are negative. DWI has clinically proven its value in the assessment of acute cerebral stroke and trauma by showing cerebral injury early due to ist ability to discriminate between lesions with cytotoxic edema (decreased diffusion) from lesions with vasogenic edema (increased diffusion). Full tensor DWI allows to calculate a variety of functional maps, the most widely used maps include maps of apparent diffusion coefficients and isotropic diffusion. In addition maps of anisotropic diffusion can be calculated which are believed to give information about the integrity and location of fiber tracts. This functional-anatomical information will most probably play an increasingly important role in the early detection of primary and secondary tissue injury from various reasons and could guide and validate current and future neuroprotective treatments. C1 Massachusetts Gen Hosp, NMR Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Swiss Parapleg Ctr, Inst Radiol, Nottwil, Switzerland. RP Huisman, TAGM (reprint author), Massachusetts Gen Hosp, NMR Ctr, Mailingcode 149,2301, Charlestown, MA 02119 USA. NR 18 TC 10 Z9 12 U1 0 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-832X J9 RADIOLOGE JI Radiologe PD DEC PY 2001 VL 41 IS 12 BP 1038 EP + DI 10.1007/s001170170003 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 506HQ UT WOS:000172964600003 PM 11793928 ER PT J AU Stone, ME AF Stone, ME TI The Louisa May Alcott Encyclopedia. SO REFERENCE & USER SERVICES QUARTERLY LA English DT Book Review C1 Massachusetts Gen Hosp, Treadwell Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp, Treadwell Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER LIBRARY ASSOC PI CHICAGO PA 50 E HURON ST, CHICAGO, IL 60611 USA SN 1094-9054 J9 REF USER SERV Q JI Ref. User Serv. Q. PD WIN PY 2001 VL 41 IS 2 BP 195 EP 195 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 513VQ UT WOS:000173401300032 ER PT J AU Jain, RK Carmeliet, PF AF Jain, RK Carmeliet, PF TI Vessels of death or life SO SCIENTIFIC AMERICAN LA English DT Article C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Edwin L Steele Lab, Boston, MA 02114 USA. RP Jain, RK (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 3 TC 62 Z9 70 U1 1 U2 5 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 0036-8733 J9 SCI AM JI Sci.Am. PD DEC PY 2001 VL 285 IS 6 BP 38 EP 45 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 497DP UT WOS:000172437700025 PM 11759584 ER PT J AU Anderson, KC AF Anderson, KC TI Introduction: New approaches to the treatment of multiple myeloma SO SEMINARS IN ONCOLOGY LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2001 VL 28 IS 6 BP 535 EP 535 DI 10.1016/S0093-7754(01)90020-X PG 1 WC Oncology SC Oncology GA 499JC UT WOS:000172567200001 ER PT J AU D'Amato, RJ Lentzsch, S Anderson, KC Rogers, MS AF D'Amato, RJ Lentzsch, S Anderson, KC Rogers, MS TI Mechanism of action of thalidomide and 3-aminothalidomide in multiple myeloma SO SEMINARS IN ONCOLOGY LA English DT Review ID TUMOR-NECROSIS-FACTOR; BONE-MARROW ANGIOGENESIS; TNF-ALPHA PRODUCTION; PHASE-II; INHIBITORY ACTIVITY; POTENT INHIBITORS; BREAST-CANCER; CELL; ANALOGS; NEOVASCULARIZATION C1 Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP D'Amato, RJ (reprint author), Childrens Hosp, 300 Longwood Ave,Enders 1006, Boston, MA 02115 USA. RI Rogers, Michael/A-9814-2009; Ain, Kenneth/A-5179-2012 OI Rogers, Michael/0000-0002-5250-8434; Ain, Kenneth/0000-0002-2668-934X NR 47 TC 48 Z9 49 U1 0 U2 11 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2001 VL 28 IS 6 BP 597 EP 601 DI 10.1053/sonc.2001.28601 PG 5 WC Oncology SC Oncology GA 499JC UT WOS:000172567200012 PM 11740816 ER PT J AU Hideshima, T Chauhan, D Podar, K Schlossman, RL Richardson, P Anderson, KC AF Hideshima, T Chauhan, D Podar, K Schlossman, RL Richardson, P Anderson, KC TI Novel therapies targeting the myeloma cell and its bone marrow microenvironment SO SEMINARS IN ONCOLOGY LA English DT Review ID HUMAN MULTIPLE-MYELOMA; NF-KAPPA-B; ENDOTHELIAL GROWTH-FACTOR; NECROSIS-FACTOR-ALPHA; PROTEASOME INHIBITOR; THALIDOMIDE; CYTOKINE; PROGRESSION; EXPRESSION; INTERLEUKIN-6 C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 50947, CA 78378] NR 41 TC 145 Z9 156 U1 1 U2 10 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2001 VL 28 IS 6 BP 607 EP 612 DI 10.1043/sonc.2001.28608 PG 6 WC Oncology SC Oncology GA 499JC UT WOS:000172567200014 PM 11740818 ER PT J AU Hau, MA Fox, EJ Rosenberg, AE Mankin, HJ AF Hau, MA Fox, EJ Rosenberg, AE Mankin, HJ TI Chondromyxoid fibroma of the metacarpal SO SKELETAL RADIOLOGY LA English DT Article DE chondromyxoid fibroma; metacarpal; radiograph ID BONE AB This report describes a chondromyxoid fibroma which developed in the distal part of the second metacarpal of a 12-year-old girl. The tumor is rare, perhaps the rarest of all bone tumors, and the occurrence in a metacarpal of a young female is extraordinarily uncommon. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Oncol Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Orthopaed Serv, Boston, MA 02114 USA. RP Mankin, HJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Oncol Serv, Boston, MA 02114 USA. NR 14 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD DEC PY 2001 VL 30 IS 12 BP 719 EP 721 DI 10.1007/s002560100428 PG 3 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 507QZ UT WOS:000173040300010 PM 11810171 ER PT J AU Heyman, B AF Heyman, B TI Functions of antibodies in the regulation of B cell responses in vivo SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Article ID HUMORAL IMMUNE-RESPONSE; ANTI-HAPTEN ANTIBODIES; LOW-AFFINITY RECEPTOR; FC-GAMMA-RII; IGM-MEDIATED ENHANCEMENT; T-DEPENDENT ANTIGEN; IN-VIVO; COMPLEMENT ACTIVATION; IMMUNOGLOBULIN-E; DEFICIENT MICE C1 Uppsala Univ, Dept Genet & Pathol, Rudbeck Lab, Uppsala, Sweden. RP Heyman, B (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. NR 78 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PD DEC PY 2001 VL 23 IS 4 BP 421 EP 432 DI 10.1007/s281-001-8168-4 PG 12 WC Immunology; Pathology SC Immunology; Pathology GA 516LH UT WOS:000173554400007 PM 11826618 ER PT J AU Barrett, KM Ackerman, RH Gahn, G Romero, JM Candia, M AF Barrett, KM Ackerman, RH Gahn, G Romero, JM Candia, M TI Basilar and middle cerebral artery reserve - A comparative study using transcranial Doppler and breath-holding techniques SO STROKE LA English DT Article DE basilar artery; cerebrovascular circulation; middle cerebral artery; stroke, ischemic; ultrasonography, Doppler, transcranial ID REACTIVITY; FLOW; CO2 AB Background and Putpose-A 1997 report suggests that the posterior circulation of the normal brain has diminished vasoreactivity compared with the anterior circulation. To further study this, we quantified and compared the vasodilatory capacities of the middle cerebral (MCA) and basilar artery (BA) territories in response to chancres in PaCO2, as indices of respective cerebrovascular reserve (CVR). If posterior circulation CVR is indeed physiologically lower than that of the MCA, it might indicate a greater risk of low-flow ischemia distal to basilar obstructive cerebrovascular lesions and provide a rationale for earlier treatment of such lesions with interventional techniques. We also wished to establish normal baseline CVR values for the posterior circulation. Methods-Twelve patients with signs and/or symptoms suggestive of posterior circulation disease but without flow-limiting obstructive changes and 11 normal controls were entered into the study. With the use of transcranial Doppler techniques, alterations in blood flow velocity in response to sequential breath-holding trials of varying duration were simultaneously monitored in both MCAs and the BA. CVR was measured as the percent velocity increase (during breath-holding) from resting baseline values. Results-No significant differences were found in CVR between the MCA and BA territories in or between patients and controls. Conclusions-Our study suggests that the anterior and posterior circulations have similar reserve capacities in individuals without flow-limiting cerebrovascular obstructive lesions and that the BA territory, relative to the MCA territory, is not at increased risk for low-flow stroke on the basis of limited reserve potential. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Ackerman, RH (reprint author), Massachusetts Gen Hosp, Dept Neurol, GRB 254, Boston, MA 02114 USA. NR 7 TC 25 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 2001 VL 32 IS 12 BP 2793 EP 2796 DI 10.1161/hs1201.098640 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 499YX UT WOS:000172599500015 PM 11739975 ER PT J AU Chung, MH Pisegna, J Spirt, M Giuliano, AE Ye, W Ramming, KP Bilchik, AJ AF Chung, MH Pisegna, J Spirt, M Giuliano, AE Ye, W Ramming, KP Bilchik, AJ TI Hepatic cytoreduction followed by a novel long-acting somatostatin analog: A paradigm for intractable neuroendocrine tumors metastatic to the liver SO SURGERY LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR 28-MAY 01, 2001 CL ATLANTA, GEORGIA SP Amer Assoc Endocrine Surg ID MALIGNANT CARCINOID-SYNDROME; RADIOFREQUENCY ABLATION; ENDOCRINE TUMORS; RESECTION; MANAGEMENT; INTERFERON AB Background. Optimal management of symptomatic neuroendocrine tumors that metastasize to the liver is controversial. We investigated aggressive hepatic cytoreduction and postoperative administration of octreotide long acting release (LAR), a long-acting somatostatin analog. Methods. Between December 1992 and August 2000, 31 patients underwent hepatic surgical cytoreduction (20 carcinoid, 10 islet cell, and 1 medullary). All patients had progressive symptoms refractory to conventional therapy. Results. Hepatic cytoreduction (resection, cryosurgery, and/or radiofrequency ablation) eliminated symptoms in 27 patients (87%) and decreased secretion of hormones by an overall mean of 59%. When minor symptoms returned and/or hormonal levels increased during follow-up, adjuvant therapy was started. Ten patients received adjuvant octreotide LAR once a month, and 21 received other adjuvants. At a median postoperative follow-up of 26 months, 16 patients had progressive/recurrent disease. 13 had died of their disease, and 2 remained free of disease. Median symptom-free interval was 60 months (95% confidence interval, 48-72) with octreotide LAR and 16 months (95% confidence interval, 10-29) with other adjuvants (P =.0007). Two-year symptom-free survival rate was 100% with octreotide LAR and 33% with other adjuvants. Conclusions. Hepatic surgical cytoreduction can palliate progressive symptoms associated with liver metastases from intractable neuroendocrine tumors. Postoperative adjuvant therapy with octreotide LAR can prolong symptom-free survival. C1 St Johns Hlth Ctr, John Wayne Canc Inst, Santa Monica, CA 90404 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Century City Hosp, Century City Canc Ctr, Century City, CA USA. RP Bilchik, AJ (reprint author), St Johns Hlth Ctr, John Wayne Canc Inst, 2200 Santa Monica Blvd, Santa Monica, CA 90404 USA. NR 25 TC 44 Z9 44 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 2001 VL 130 IS 6 BP 954 EP 962 DI 10.1067/msy.2001.118388 PG 9 WC Surgery SC Surgery GA 507FA UT WOS:000173015300016 PM 11742323 ER PT J AU Thatcher, WW Guzeloglu, A Mattos, R Binelli, M Hansen, TR Pru, JK AF Thatcher, WW Guzeloglu, A Mattos, R Binelli, M Hansen, TR Pru, JK TI Uterine-conceptus interactions and reproductive failure in cattle SO THERIOGENOLOGY LA English DT Article; Proceedings Paper CT Symposium on Practical Considerations in Dealing wit Embryos CY JAN 16, 2002 CL FOZ DO IGUASSU, BRAZIL DE endometrium; conceptus; interferon-tau; prostaglandin; signal transduction ID RECOMBINANT INTERFERON-TAU; BOVINE ENDOMETRIAL CELLS; CROSS-REACTIVE PROTEIN; NF-KAPPA-B; EPITHELIAL-CELLS; CELLULAR MECHANISMS; OXYTOCIN RECEPTOR; EARLY-PREGNANCY; PROSTAGLANDIN PRODUCTION; EICOSAPENTAENOIC ACID AB The dialogue between trophectoderm cells of the conceptus and epithelial cells of the endometrium. is critical to CL maintenance and embryo survival. The signal transduction mechanisms by which bovine interferon (IFN)-tau regulates cyclooxygenase (COX)-2 expression and secretion of prostaglandin F-2 alpha (PGF(2 alpha)) in bovine endometrial (BEND) cells is examined. Stimulation of Protein Kinase C with a phorbol ester (phorbol 12, 13 dibutyrate [PDBu]) activates COX-2 gene expression and PGF(2 alpha) secretion via the mitogen-activated protein kinase (MAPK) pathway. Interferon-tau attenuates PDBu activation of PGF(2 alpha), secretion, but this inhibitory effect appears to be independent of the MAPK pathway. Embryonic IFN-tau, acting through a Type I IFN receptor, activates the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway resulting in activation or repression of interferon-stimulated genes. Experimental evidence is provided that IFN-tau regulation of STATs regulates gene expression of COX-2 in a manner that decreases secretion of PGF(2 alpha), Maternal regulation of the antiluteolytic pathway is discussed relative to the ability of the polyunsaturated fatty acid, eicosapentaenoic (EPA), to decrease endometrial secretion of PGF(2 alpha), and progesterone to increase both conceptus development and IFN-tau secretion. (C) 2001 by Elsevier Science Inc. C1 Univ Florida, Dept Anim Sci, Gainesville, FL 32610 USA. Univ Sao Paulo, Fac Med Vet & Zootecn, Ctr Biotecnol Reprod Anim, BR-13630000 Pirassununga, SP, Brazil. Univ Wyoming, Dept Anim Sci, Laramie, WY 82071 USA. Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. RP Thatcher, WW (reprint author), Univ Florida, Dept Anim Sci, Gainesville, FL 32610 USA. RI Binelli, Mario/I-5991-2013 OI Binelli, Mario/0000-0002-5995-3944 NR 57 TC 136 Z9 142 U1 1 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0093-691X J9 THERIOGENOLOGY JI Theriogenology PD DEC 1 PY 2001 VL 56 IS 9 SI SI BP 1435 EP 1450 DI 10.1016/S0093-691X(01)00645-8 PG 16 WC Reproductive Biology; Veterinary Sciences SC Reproductive Biology; Veterinary Sciences GA 501DP UT WOS:000172667800007 PM 11768809 ER PT J AU Washizu, J Berthiaume, F Mokuno, Y Tompkins, RG Toner, M Yarmush, ML AF Washizu, J Berthiaume, F Mokuno, Y Tompkins, RG Toner, M Yarmush, ML TI Long-term maintenance of cytochrome P450 activities by rat hepatocyte/3T3 cell co-cultures in heparinized human plasma SO TISSUE ENGINEERING LA English DT Article ID BIOARTIFICIAL LIVER SUPPORT; GENE-EXPRESSION; PORCINE HEPATOCYTES; INDUCTION; DEALKYLATION; ENZYMES; PATHWAY; SUPPLEMENTATION; MONOOXYGENASE; METABOLISM AB Little information on the effect of plasma on hepatocyte cytochrome P450 (CYP) activities is currently available. We characterized the effect of plasma on CYPs of hepatocyte-mesenchymal cell co-cultures, which exhibit stable liver specific functions and may be potentially useful for bioartificial liver design. Rat hepatocyte-mouse 3T3-J2 cell co-cultures were maintained for 6 days in medium, and then switched to heparinized human plasma containing 3-methylcholanthrene (3MC; 2 muM), phenobarbital (PB; 1 mM), or no inducer for up to 7 days. CYP activities were measured in situ based on the o-dealkylation of ethoxy(EROD), methoxy- (MROD), pentoxy- (PROD), or benzyloxy- (BROD) resorufin. Plasma alone increased PROD/BROD but not EROD/MROD. The endogenous inducer was in the high molecular weight fraction (>5 kD) of plasma and inhibited by >5 nM okadaic acid and >10 muM dibutyryl cyclic AMP, two inhibitors of PB-inducible CYPs. Furthermore, plasma increased CYP1A1 and CYP2B1/2 mRNA levels. In plasma, 3MC induced EROD/MROD to about 60% of the level induced in culture medium while PB induced PROD/BROD that were three- to 10-fold above levels induced in medium. CYP activities decreased between days 2 and 7 of plasma exposure, but were enhanced by plasma supplementation with amino acids, insulin, glucagon, and hydrocortisone. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Surg Serv, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA USA. RP Yarmush, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Surg Serv, GRB1401,55 Fruit St, Boston, MA 02114 USA. RI Yu, weiting/I-7417-2013 FU NIDDK NIH HHS [DK43371]; NIGMS NIH HHS [GM58125] NR 46 TC 20 Z9 20 U1 1 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD DEC PY 2001 VL 7 IS 6 BP 691 EP 703 DI 10.1089/107632701753337654 PG 13 WC Cell & Tissue Engineering SC Cell Biology GA 505FQ UT WOS:000172903100002 PM 11749727 ER EF