FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Mukamal, KJ Mittleman, MA Muller, JE Walkoff, DS Claire, E Maclure, M AF Mukamal, KJ Mittleman, MA Muller, JE Walkoff, DS Claire, E Maclure, M TI The effect of recent exertion on the course of acute myocardial infarction SO CIRCULATION LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Wisconsin, Eau Claire, WI 54701 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 15 PY 2000 VL 101 IS 6 MA P26 BP 721 EP 722 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 284NZ UT WOS:000085339600074 ER PT J AU Meigs, JB D'Agostino, RB Rifal, N Wilson, PWF AF Meigs, JB D'Agostino, RB Rifal, N Wilson, PWF TI Cumulative effects of easting glucose on Albuminuria: The framingham offspring study SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Boston, MA 02215 USA. Childrens Hosp, Boston, MA 02115 USA. Framingham Heart Dis Epidemiol Study, Framingham, 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 15 PY 2000 VL 101 IS 6 MA P64 BP 729 EP 729 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 284NZ UT WOS:000085339600112 ER PT J AU Gelman, R Wilkening, C AF Gelman, R Wilkening, C TI Analyses of quality assessment studies using CD45 for gating lymphocytes for CD3(+)4(+)% SO CYTOMETRY LA English DT Article DE immunophenotyping; gating; CD4(+) cells; quality assessment ID GUIDELINE AB Background: The purpose of this study was to assess whether laboratories which do not use CD45 for gating lymphocytes with three- (or four-) color flow cytometry (non-CD45 laboratories) for CD3(+)4(+)% and CD3(+)8(+)% do worse on quality assessment (QA) studies than laboratories which do use CD45 (0045 laboratories), Methods: Data came from blood specimens donated by 62 donors (50 HIV-positive) assayed over 2 years (November, 1996-October, 1998) by 35 laboratories in-the NIAID DAIDS Flow Cytometry QA Program. Results: Non-CD45 laboratories were significantly more likely to be classified as having unacceptable inter-laboratory results (far from the group median) than CD45 laboratories (5.6% vs 1.5%, P = 0.005 for CD3(+)4(+)%; 10.4% vs 5.0%, P = 0.007 for CD3(+)8(+)%). The intra-laboratory range of results on blinded replicates was significantly more likely to be deemed unacceptable (range >4%) in non-CD45 laboratories than in 0045 laboratories for CD3(+)8(+)% (14.5% vs 3.5%, P = 0.002) but not for CD3(+)4(+)% (2.6% vs 1.5%, P = 0.62), These differences in favor of 0045 gating were observed even though the non-CD45 laboratories had been doing three-color flow cytometry in the QA program significantly longer (P = 0.05) than the 0045 laboratories, and so would be expected to have fewer problems with the assay, Conclusions: Laboratories which choose to use a single CD3/CD4/CD8 tube for immunophenotyping may be sacrificing both accuracy and reproducibility. (C) 2000 Wiley-Liss, Inc. C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. RP Gelman, R (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI45175, AI41110, AI38855] NR 10 TC 23 Z9 25 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 0196-4763 J9 CYTOMETRY JI Cytometry PD FEB 15 PY 2000 VL 42 IS 1 BP 1 EP 4 DI 10.1002/(SICI)1097-0320(20000215)42:1<1::AID-CYTO1>3.0.CO;2-A PG 4 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 286YB UT WOS:000085475500001 PM 10679736 ER PT J AU Li, WQ Boswell, R Wood, WB AF Li, WQ Boswell, R Wood, WB TI mag-1, a homolog of Drosophila mago nashi regulates hermaphrodite germ-line sex determination in Caenorhabditis elegans SO DEVELOPMENTAL BIOLOGY LA English DT Article DE oogenesis; spermatogenesis; posterior-group genes; embryonic elongation ID DOUBLE-STRANDED-RNA; C-ELEGANS; DETERMINATION GENE; MESSENGER-RNA; FEM GENES; SPERMATOGENESIS; EMBRYOS; PROTEIN; SWITCH; MORPHOGENESIS AB The Caenorhabditis elegans gene mag-1 can substitute functionally for its homolog mago nashi in Drosophila and is predicted to encode a protein that exhibits 80% identity and 88% similarity to Mago nashi (P. A. Newmark et al., 1997, Development 120, 3197-3207). We have used RNA-mediated interference (RNAi) to analyze the phenotypic consequences of impairing mag-1 function in C. elegans. We show here that mag-1(RNAi) causes masculinization of the germ line (Mog phenotype) in RNA-injected hermaphrodites, suggesting that mag-1 is involved in hermaphrodite germ-line sex determination. Epistasis analysis shows that ectopic sperm production caused by mag-1(RNAi) is prevented by loss-of-function (lf) mutations in fog-2, gld-1, fem-1, fem-2 fem-3, and fog-1, all of which cause germ-line feminization in XX hermaphrodites, but not by a her-1(lf) mutation which causes germ-line feminization only in XO males. These results suggest that mag-1 interacts with the fog, fem, and gld genes and acts independently of her-1. We propose that mag-1 normally allows oogenesis by inhibiting function of one or more of these masculinizing genes, which act during the fourth larval stage to promote transient sperm production in the hermaphrodite germ line. When the Mog phenotype is suppressed by a fog-2(if) mutation, mag-1(RNAi) also causes lethality in the progeny embryos of RNA-injected, mated hermaphrodites, suggesting an essential role for mag-1 during embryogenesis. The defective embryos arrest during morphogenesis with an apparent elongation defect. The distribution pattern of a JAM-1::GFP reporter, which is localized to boundaries of hypodermal cells, shows that hypodermis is disorganized in these embryos. The temporal expression pattern of the mag-1 gene prior to and during morphogenesis appears to be consistent with an essential role of mag-1 in embryonic hypodermal organization and elongation, (C) 2000 Academic Press. C1 Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA. RP Li, WQ (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. FU NICHD NIH HHS [HD-11762] NR 47 TC 38 Z9 64 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD FEB 15 PY 2000 VL 218 IS 2 BP 172 EP 182 DI 10.1006/dbio.1999.9593 PG 11 WC Developmental Biology SC Developmental Biology GA 287QJ UT WOS:000085517000006 PM 10656761 ER PT J AU Smith, JS Tachibana, I Pohl, U Lee, HK Thanarajasingam, U Portier, BP Ueki, K Ramaswamy, S Billings, SJ Mohrenweiser, HW Louis, DN Jenkins, RB AF Smith, JS Tachibana, I Pohl, U Lee, HK Thanarajasingam, U Portier, BP Ueki, K Ramaswamy, S Billings, SJ Mohrenweiser, HW Louis, DN Jenkins, RB TI A transcript map of the chromosome 19q-arm glioma tumor suppressor region SO GENOMICS LA English DT Article ID EXON AMPLIFICATION; GENE; HETEROZYGOSITY; ASTROCYTOMAS; 19Q; OLIGODENDROGLIOMAS; PROGRESSION; CANDIDATE; CLONING AB Allelic loss of the chromosome 19q arm is a frequent event in human diffuse gliomas, suggesting that it contains a tumor suppressor gene. Recent deletion mapping studies have broadly implicated a 1.6-Mb interval between D19S241E and D19S596, with a limited subset of tumors, suggesting that the region may be as narrow as 150 kb. Focusing on this smaller interval, we have used cDNA selection, exon amplification, and genomic sequencing to identify three novel transcripts (EHD2, GLTSCR1, and GLTSCR2) and to map two known genes (SEPW1 and CRX). A partial transcript map of 19 transcripts and two EST markers has been constructed for the 1.6-Mb interval D19S241E-D19S596. Ten of these transcripts, including the 5 mapped to the 150-kb deletion interval, have been examined for alterations in a panel of gliomas with allelic loss of 19q. Tumor-specific alterations have not been identified in the transcripts examined thus far. Collectively, these data should facilitate subsequent efforts to identify and characterize the remaining transcripts in the 1.6-Mb interval, (C) 2000 Academic Press. C1 Mayo Clin & Mayo Fdn, Sch Med, Dept Cytogenet, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Div Lab Genet, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Mol Neurooncol Lab, Dept Pathol Neuropathol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neurosurg Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02139 USA. Univ Calif Lawrence Livermore Natl Lab, Ctr Human Genome, Livermore, CA 94550 USA. RP Jenkins, RB (reprint author), Mayo Clin & Mayo Fdn, Sch Med, Dept Cytogenet, 200 1st St,SW, Rochester, MN 55905 USA. RI imoto, Issei/D-8065-2012 FU NCI NIH HHS [CA 69285, CA 50905] NR 41 TC 86 Z9 92 U1 1 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD FEB 15 PY 2000 VL 64 IS 1 BP 44 EP 50 DI 10.1006/geno.1999.6101 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 295VH UT WOS:000085988200005 PM 10708517 ER PT J AU Chevrette, M Joly, L Tellis, P Knapik, EW Miles, J Fishman, M Ekker, M AF Chevrette, M Joly, L Tellis, P Knapik, EW Miles, J Fishman, M Ekker, M TI Characterization of a zebrafish/mouse somatic cell hybrid panel SO GENOMICS LA English DT Article ID VERTEBRATE GENOME EVOLUTION; GENETIC-LINKAGE MAP; SUPPRESSION; TUMORIGENICITY; IDENTIFICATION; SENESCENCE; CLONING; REGIONS; MODEL AB We have characterized a collection of zebrafish/mouse somatic cell hybrids with 211 genes and markers chosen from the 25 zebrafish linkage groups. Most of the zebrafish genome is represented in this collection with 88% of genes/markers present in at least one hybrid cell line, Although most hybrids contain chromosomal fragments, there are a few instances where a complete or nearly complete zebrafish chromosome has been maintained in a mouse background, based on multiple markers covering the entire chromosome. In addition to their use in mapping studies, this collection of somatic cell hybrids should constitute an important tool as a source of specific chromosome fragments and for assessing the function of genome regions. (C) 2000 Academic Press. C1 McGill Univ, Dept Surg, Div Urol, Montreal, PQ H3G 1A4, Canada. Montreal Gen Hosp, Res Inst, Montreal, PQ H3G 1A4, Canada. Ottawa Hosp, Loeb Hlth Res Inst, Ottawa, ON K1Y 4E9, Canada. GSF, Inst Mammalian Genet, Res Ctr Environm & Hlth, D-85758 Neuherberg, Germany. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Univ Ottawa, Dept Med, Ottawa, ON K1H 8M5, Canada. Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1H 8M5, Canada. RP Ekker, M (reprint author), McGill Univ, Dept Surg, Div Urol, Montreal, PQ H3G 1A4, Canada. RI Knapik, Ela/J-6172-2014 FU NIDDK NIH HHS [DK-558383] NR 29 TC 5 Z9 5 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD FEB 15 PY 2000 VL 64 IS 1 BP 119 EP 126 DI 10.1006/geno.1999.6124 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 295VH UT WOS:000085988200015 PM 10708527 ER PT J AU Choi, SH Takahashi, K Eto, H Yoon, SS Tanabe, KK AF Choi, SH Takahashi, K Eto, H Yoon, SS Tanabe, KK TI CD44S expression in human colon carcinomas influences growth of liver metastases SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID CANCER CELLS; NUDE-MICE; BINDING; HYALURONATE; ISOFORMS; ADHESION; VARIANT; TUMORIGENICITY; GLYCOSYLATION; PROGRESSION AB CD44 is a family of cell-surface adhesion molecules which exist in several isoforms arising from mRNA alternative. Malignant transformation of colonic mucosa is associated with alterations in CD44 expression, which result in up-regulation of high-molecular-weight CD44 isoforms and downregulation of CD44s. We have demonstrated that stable transfection of CD44s into colon-carcinoma cell lines reduces their tumorigenicity, To understand the influence of CD44s expression on the metastatic potential of human colon carcinomas, we measured the ability of several different CD44s-transfected colon carcinomas to establish experimental liver metastases following splenic inoculation in mice. We observed that introduction of CD44s into 2 different human colon carcinoma cell lines, HT29 and KM12C6, resulted in reduced growth of liver metastases by as much as 75%. To explore the relationship between hyaluronate adhesion and metastasis, we transfected HT29 cells with cDNA encoding a mutant CD44s that does not bind to hyaluronate. HT29 transfectants expressing this mutant CD44s demonstrate an 84% reduction in growth of liver metastases, despite minimal binding to hyaluronate by the mutant CD44s, In concert, these results indicate that CD44s down-regulation, which occurs with malignant transformation of colonic mucosa, is associated with enhanced growth of experimental liver metastases. Consequently, the functional consequences of CD44s down-regulation in colon carcinomas may be just as significant as the consequences of up-regulation of other CD44 isoforms, Int. J. Cancer 85:523-526, 2000. (C) 2000 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Boston, MA 02114 USA. RP Tanabe, KK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Cox 626, Boston, MA 02114 USA. FU NCI NIH HHS [CA64454, CA71345]; NIDDK NIH HHS [DK43351] NR 27 TC 53 Z9 56 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 FEB 15 PY 2000 VL 85 IS 4 BP 523 EP 526 DI 10.1002/(SICI)1097-0215(20000215)85:4<523::AID-IJC13>3.0.CO;2-6 PG 4 WC Oncology SC Oncology GA 280WX UT WOS:000085127700013 PM 10699925 ER PT J AU Kawai, T Eisen-Lev, R Seki, M Eastcott, JW Wilson, ME Taubman, MA AF Kawai, T Eisen-Lev, R Seki, M Eastcott, JW Wilson, ME Taubman, MA TI Requirement of B7 costimulation for Th1-mediated inflammatory bone resorption in experimental periodontal disease SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; COLLAGEN-INDUCED ARTHRITIS; CD4(+) T-CELLS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; HUMAN-MONOCYTES; RHEUMATOID-ARTHRITIS; MOLECULAR-CLONING; ADOPTIVE TRANSFER; INTERFERON-GAMMA; GINGIVAL TISSUES AB The CD28 costimulation at TCR signaling plays a pivotal role in the regulation of the T cell response. To elucidate the role of T cells in periodontal disease, a system of cell transfer with TCR/CD28-dependent Th1 or Th2 clones was developed in rats. Gingival injection of specific Ag, Actinobacillus actinomycetemcomitans 29-kDa outer membrane protein, and LPS could induce local bone resorption 10 days after the transfer of Ag-specific Th1 clone cells, but not after transfer of Th2 clone cells, Interestingly, the presence of LPS was required not only for the induction of bone resorption but also for Ag-specific IgG2a production, LPS injection elicited the induction of expression of both B7-1 and B7-2 expression on gingival macrophages, which otherwise expressed only MHC class II when animals were injected with Ag alone. The expression of B7 molecules was observed for up to 3 days, which corresponded to the duration of retention of T clone cells in gingival tissues. Either local or systemic administration of CTLA4Ig, a functional antagonist of CD28 binding to B7, could abrogate the bone resorption induced by Th1 clone cells combined with gingival challenge with both Ag and LPS, These results suggest that local Ag:specific activation of Th1-type T cells by B7 costimulation appeared to trigger inflammatory bone resorption, whereas inhibition of B7 expression by CTLA4Ig might be a therapeutic approach for intervention with inflammatory bone resorption, The Journal of Immunology, 2000, 164: 2102-2109. C1 Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. Mitsubishi Tokyo Pharmaceut, Yokohama Res Ctr, Yokohama, Kanagawa, Japan. Univ Med & Dent New Jersey, New Jersey Dent Sch, Dent Res Ctr, Dept Oral Biol, Newark, NJ 07103 USA. RP Taubman, MA (reprint author), Forsyth Inst, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-03420, DE-10041] NR 55 TC 112 Z9 114 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 2000 VL 164 IS 4 BP 2102 EP 2109 PG 8 WC Immunology SC Immunology GA 283VK UT WOS:000085296600061 PM 10657664 ER PT J AU Plesnila, N Muller, E Guretzki, S Ringel, F Staub, F Baethmann, A AF Plesnila, N Muller, E Guretzki, S Ringel, F Staub, F Baethmann, A TI Effect of hypothermia on the volume of rat glial cells SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID INTRACELLULAR PH REGULATION; C6 GLIOMA-CELLS; BRAIN TEMPERATURE; ASTROCYTES; CULTURES; TRANSPORT; MUSCLE AB 1. The cell volume of suspended CB glioma cells and primary cultured rat astrocytes was measured at normothermia (37 degrees C), and at mild (32 degrees C) and moderate (27 degrees C) hypothermia, by flow cytometry with electrical cell sizing. 2. Under control conditions (37 degrees C), C6 glioma cells had a volume of 809 +/- 29 mu m(3). Moderate hypothermia (27 degrees C) led to rapid cell swelling, with a maximum volume of 113.1 +/- 1.3% of control being achieved after 50 min. After rewarming to 37 degrees C, cell volume recovered very slowly and incompletely (to 107.2 +/- 0.4% of control). Less severe hypothermia (32 degrees C) led to a smaller increase in cell volume (108.7 +/- 0.5 % of control). 3. The maximal cell swelling response and the kinetics of swelling were similar in C8 glioma cells and primary cultured astrocytes. 4. Hypothermia-induced cell swelling was dependent on the presence of extracellular Na+ and was reduced by the Na+-H+ antiporter inhibitor EIPA. 5. The underlying mechanisms of hypothermia-induced cell swelling are an intracellular accumulation of Na+ by (1) differential effects of hypothermia on the membrane permeabilities of Na+ and K+ and (2) activation of the Na+-H+ antiporter by a shift of its activation curve to a more alkaline value. C1 Univ Munich, Klinikum Grosshadern, Inst Surg Res, D-8000 Munich, Germany. RP Plesnila, N (reprint author), Massachusetts Gen Hosp, 149 13th St,CNY 6403, Charlestown, MA 02129 USA. RI Ringel, Florian/E-4933-2014 NR 27 TC 12 Z9 13 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD FEB 15 PY 2000 VL 523 IS 1 BP 155 EP 162 DI 10.1111/j.1469-7793.2000.00155.x PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 297FK UT WOS:000086071100014 PM 10673552 ER PT J AU Watanabe, K Clarke, TR Lane, AH Wang, XZ Donahoe, PK AF Watanabe, K Clarke, TR Lane, AH Wang, XZ Donahoe, PK TI Endogenous expression of Mullerian inhibiting substance in early postnatal rat Sertoli cells requires multiple steroidogenic factor-1 and GATA-4-binding sites SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Mullerian inhibiting substance promoter ID RIBONUCLEIC-ACID EXPRESSION; NUCLEAR RECEPTOR SF-1; GENE-EXPRESSION; SEXUAL-DIFFERENTIATION; GONADAL DEVELOPMENT; HORMONE GENE; IN-VIVO; GRANULOSA; FOLLICLE; PROMOTER AB Mullerian inhibiting substance (MIS) is a key element required to complete mammalian male sex differentiation. The expression pattern of MIS is tightly regulated in fetal, neonatal, and prepubertal testes and adult ovaries and is well conserved among mammalian species. Although several factors have been shown to be essential to MIS expression, its regulatory mechanisms are not fully understood. We have examined MIS promoter activity in 2-day postnatal primary cultures of rat Sertoli cells that continue to express endogenous MIS mRNA. Using this system, we found that the region between human MIS-269 and -192 is necessary for full MIS promoter activity. We identified by DNase I footprint and electrophoretic mobility-shift analyses a distal steroidogenic factor-1 (SF-1)-binding site that is essential for full promoter activity. Mutational analysis of this new distal SF-1 site and the previously identified proximal SF-1 site showed that both are necessary for transcriptional activation. Moreover, the proximal promoter also contains multiple GATA-4-binding sites that are essential for functional promoter activity. Thus multiple SF-1- and GATA-4-binding sites in the MIS promoter are required for normal tissue-specific and developmental expression of MIS. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Pediat Surg Res Labs, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Gene Therapy Ctr, Boston, MA 02114 USA. RP Donahoe, PK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Pediat Surg Res Labs, 32 Fruit St, Boston, MA 02114 USA. EM Donahoe.Patricia@mgh.harvard.edu FU NCI NIH HHS [R01 CA017393, CA17393] NR 36 TC 78 Z9 83 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 FEB 15 PY 2000 VL 97 IS 4 BP 1624 EP 1629 DI 10.1073/pnas.97.4.1624 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 285VU UT WOS:000085409600062 PM 10677509 ER PT J AU Kim, K Drummond, I Ibraghimov-Beskrovnaya, O Klinger, K Arnaout, MA AF Kim, K Drummond, I Ibraghimov-Beskrovnaya, O Klinger, K Arnaout, MA TI Polycystin 1 is required for the structural integrity of blood vessels SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE homologous recombination; angiogenesis; tight junctions; polycystic kidney disease ID TUMOR SUPPRESSOR GENE; SMOOTH-MUSCLE CELLS; KIDNEY-DISEASE; INTRACRANIAL ANEURYSMS; ENDOTHELIAL-CELLS; IN-VITRO; ENCODES; PROTEIN; GROWTH; PKD2 AB Autosomal dominant polycystic kidney disease (ADPKD), often caused by mutations in the PKD1 gene, is associated with life-threatening vascular abnormalities that are commonly attributed to the frequent occurrence of hypertension. A previously reported targeted mutation of the mouse homologue of PKD1 was not associated with vascular fragility, leading to the suggestion that the vascular lesion may be of a secondary nature. Here we demonstrate a primary role of PKD1 mutations in vascular fragility. Mouse embryos homozygous for the mutant allele (Pkd1(L)) exhibit s.c. edema, vascular leaks, and rupture of blood vessels, culminating in embryonic lethality at embryonic day 15.5. Kidney and pancreatic ductal cysts are present. The Pkd1-encoded protein, mouse polycystin 1, was detected in normal endothelium and the surrounding vascular smooth muscle cells. These data reveal a requisite role for polycystin 1 in maintaining the structural integrity of the vasculature as well as epithelium and suggest that the nature of the PKD1 mutation contributes to the phenotypic variance in ADPKD. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Charlestown, MA 02129 USA. Genzyme Corp, Framingham, MA 01701 USA. RP Arnaout, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [P01 DK54711, P01 DK054711] NR 50 TC 192 Z9 195 U1 4 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 FEB 15 PY 2000 VL 97 IS 4 BP 1731 EP 1736 DI 10.1073/pnas.040550097 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 285VU UT WOS:000085409600081 PM 10677526 ER PT J AU Donner, A Shoukri, MM Klar, N Bartfay, E AF Donner, A Shoukri, MM Klar, N Bartfay, E TI Testing the equality of two dependent kappa statistics SO STATISTICS IN MEDICINE LA English DT Article ID CLUSTERED BINARY DATA; INTERRATER AGREEMENT; MULTIVARIATE METHODS; OBSERVER AGREEMENT; BINOCULAR DATA; ONE LEVEL; COEFFICIENTS; RELIABILITY; SAMPLE; HYPOTHESIS AB Procedures are developed and compared for testing the equality of two dependent kappa statistics in the case of two raters and a dichotomous outcome variable. Such problems may arise when each of a sample of subjects are rated under two distinct settings, and it is of interest to compare the observed levels of inter-observer and intra-observer agreement. The procedures compared are extensions of previously developed procedures for comparing kappa statistics computed from independent samples. The results of a Monte Carlo simulation show that adjusting for the dependency between samples tends to be worthwhile only if the between-setting correlation is comparable in magnitude to the within-setting correlations, In this case, a goodness-of-fit procedure that takes into account the dependency between samples is recommended. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 Univ Western Ontario, Dept Epidemiol & Biostat, London, ON N6A 5C1, Canada. Univ Guelph, Dept Populat Med, Guelph, ON N1G 2W1, Canada. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Donner, A (reprint author), Univ Western Ontario, Dept Epidemiol & Biostat, Kiesge Bldg, London, ON N6A 5C1, Canada. NR 34 TC 45 Z9 45 U1 0 U2 8 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD FEB 15 PY 2000 VL 19 IS 3 BP 373 EP 387 DI 10.1002/(SICI)1097-0258(20000215)19:3<373::AID-SIM337>3.3.CO;2-P PG 15 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 278NZ UT WOS:000084997000008 PM 10649303 ER PT J AU Fishman, JA Doran, MT Volpicelli, SA Cosimi, AB Flood, JG Rubin, RH AF Fishman, JA Doran, MT Volpicelli, SA Cosimi, AB Flood, JG Rubin, RH TI Dosing of intravenous ganciclovir for the prophylaxis and treatment of cytomegalovirus infection in solid organ transplant recipients SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Transplantation CY MAY 15-19, 1999 CL CHICAGO, ILLINOIS SP Amer Soc Transplantat ID LIQUID-CHROMATOGRAPHY; HUMAN HERPESVIRUS-6; CONTROLLED TRIAL; ANTIVIRAL DRUGS; DISEASE; VIRUS; RESISTANCE; 9-(1,3-DIHYDROXY-2-PROPOXYMETHYL)GUANINE; INVITRO; THERAPY AB Background. The optimal regimen for the prevention and treatment of cytomegalovirus (CMV) disease in solid organ transplant recipients remains to be defined, particularly for patients with abnormal or changing renal function. Methods, A prospective trial was conducted in patients receiving i.v. ganciclovir using a standardized dosing:nomogram that corrects for renal function, Steady state peak (P) and trough (T) serum levels were determined by high-performance liquid chromatography and correlated with therapeutic outcomes and toxicities attributable to ganciclovir. Results, Over the study period, 44 individuals received ganciclovir prophylaxis (5 mg/kg/day) and 25 patients were treated (5 mg/kd q12 hr) for symptomatic CMV disease. Ganciclovir levels (mu g/ml+/-SD) achieved in prophylaxis were P: 7.98+/-3.34, T: 3.03+/-2.63; and in treatment were P: 9.00+/-3.72, T: 2.65+/-1.82. Despite corrections for renal dysfunction, undialyzed patients with serum creatinine >3.0 mg/dl had trough levels in excess of the population mean (T: range 3-8 mu g/ml). Failure of prophylaxis (disease) or therapy (relapse) occurred in 14 patients; 8 of these were at risk for primary infection (donor CMV seropositive, recipient seronegative, P<0.01). Patients at greatest risk for relapse after treatment of CMV disease Were:liver transplant recipients, patients with ganciclovir-resistant viral isolates, and renal patients with six antigen MHC donor-recipient mismatches. Conclusions. This trial demonstrates the efficacy of a nomogram for ganciclovir dosing during renal dysfunction; reduced doses can be used for prophylaxis for undialyzed patients with renal dysfunction (1.25 mg/kg/day for Cr greater than or equal to 3.0, 1.25 mg/kg QOD for Cr greater than or equal to 5.0). Some groups of transplant recipients may require more intensive: anti-CMV regimens. C1 Massachusetts Gen Hosp, Div Infect Dis, Dept Pathol,Transplant Unit, Transplant Infect Dis Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Dept Pathol,Transplant Unit, Transplant Infect Dis Program, 32 Fruit St, Boston, MA 02114 USA. NR 45 TC 45 Z9 45 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 FEB 15 PY 2000 VL 69 IS 3 BP 389 EP 394 DI 10.1097/00007890-200002150-00014 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 287RZ UT WOS:000085521100014 PM 10706048 ER PT J AU Warrens, AN Simon, AR Theodore, PR Sachs, DH Sykes, M AF Warrens, AN Simon, AR Theodore, PR Sachs, DH Sykes, M TI Cross-species compatibility of intercellular adhesion molecule-1 (CD54) with its ligands SO TRANSPLANTATION LA English DT Article ID T-CELL ACTIVATION; MONOCLONAL-ANTIBODIES; LYMPHO-HEMATOPOIESIS; ICAM-1 CD54; EXPRESSION; CLONING; CD18; INDUCTION; SEQUENCE; LFA-1 AB Background The molecular interactions of intercellular adhesion molecule-1 (ICAM-1; CD54) are potentially important in several situations in the context of pig-to-human xenotransplantation. If porcine bone marrow is to be used for the induction of xenograft tolerance in humans, the role that has been suggested for ICAM-1 in the interactions of haematopoietic stem cells makes its cross-species compatibility important. Similarly, the potential role of ICAM-1 interactions in graft rejection makes it an important molecule to study. Methods, An in vitro static cell-to-cell adhesion study was used to look at the successful interaction of ICAM-1 with its ligands across the pig-human species barrier in both directions. A second in vitro system, the standard long-term bone marrow culture (LTBMC), was used to study the functional role of ICAM-1 in haematopoiesis. Results. Human ICAM-1 was able to adhere to ligands on porcine cells, including one or more ligand that contains CD18, Conversely, human CD18-containing ligands mediated adherence to porcine cells. Using the long-term bone marrow culture system, there was no evidence that blocking the interactions of ICAM-1 inhibited hematopoiesis, either in the human-human or pig-human combinations of precursor cells and marrow stroma. Conclusions, ICAM-1 is able to interact with at least some of its ligands across the species barrier, in both pig-human and human-pig combinations. However, the interactions of ICAM-1 do not appear to be central to hematopoiesis, at least in the model system used. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [R01 HL54038]; NIAID NIH HHS [R01 AI39755] NR 34 TC 15 Z9 15 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 FEB 15 PY 2000 VL 69 IS 3 BP 394 EP 399 DI 10.1097/00007890-200002150-00015 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 287RZ UT WOS:000085521100015 PM 10706049 ER PT J AU van den Brink, MRM Moore, E Ferrara, JLM Burakoff, SJ AF van den Brink, MRM Moore, E Ferrara, JLM Burakoff, SJ TI Graft-versus-host-disease-associated thymic damage results in the appearance of T cell clones with anti-host reactivity SO TRANSPLANTATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; MINOR HISTOCOMPATIBILITY BARRIERS; MICE AB Background. We studied whether T-cell clones, which appear in the periphery as a result of the failure of thymic negative selection during graft-versus-host disease (GVHD), have any in vivo anti-host reactivity and can cause GVHD in an adoptive transfer model. Methods. We performed our studies in a murine model (B10.BR into CBA/J) for allogeneic bone marrow transplantation with major histocompatibility complex-matched and minor histocompatibility antigen-mismatched unrelated donors and unique V beta T-cell deletion patterns in donors and recipients. Results. GVHD resulted in the appearance of V beta 6+ T cells as a result of a loss of negative selection. We found that V beta 6+ T cells from normal donors proliferated in vitro and in vivo. Depletion of V beta 6+ T cells from the donor T-cell inoculum resulted in less GVHD morbidity and a decrease in the loss of thymic cellularity. To test the anti-host reactivity of de novo generated V beta 6+ T cells in animals with GVHD, we developed an adoptive transfer model of splenic T cells from CBA/J host animals with GVHD into sublethally irradiated CBA/J recipients. Depletion of V beta 6+ T cells from the splenic T cells before adoptive transfer could significantly decrease the transient GVHD morbidity in the sublethally irradiated hosts. Conclusions. Our data indicate that GVHD-associated thymic damage results in a loss of thymic negative selection, which leads to the appearance of T-cell clones with anti-host reactivity in vitro and in vivo. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, Boston, MA 02215 USA. Univ Michigan, Ctr Canc, Ann Arbor, MI 48109 USA. RP van den Brink, MRM (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Box 111,1275 York Ave, New York, NY 10021 USA. FU NCI NIH HHS [5PO1 CA39542] NR 11 TC 47 Z9 49 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 FEB 15 PY 2000 VL 69 IS 3 BP 446 EP 449 DI 10.1097/00007890-200002150-00026 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 287RZ UT WOS:000085521100026 PM 10706060 ER PT J AU Stoeckle, JD AF Stoeckle, JD TI The market pushes education from ward to office, from acute to chronic illness and prevention - Will case method teaching-learning change? SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID MEDICAL-EDUCATION; CARE SETTINGS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Stoeckle, JD (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 81 TC 8 Z9 8 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD FEB 14 PY 2000 VL 160 IS 3 BP 273 EP 280 DI 10.1001/archinte.160.3.273 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 280ZQ UT WOS:000085134000001 PM 10668828 ER PT J AU Balas, EA Weingarten, S Garb, CT Blumenthal, D Boren, SA Brown, GD AF Balas, EA Weingarten, S Garb, CT Blumenthal, D Boren, SA Brown, GD TI Improving preventive care by prompting physicians SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; COMPUTERIZED REMINDERS; HEALTH MAINTENANCE; CLINICAL-TRIALS; MEDICAL RECORDS; BLOOD-PRESSURE; CANCER; INTERVENTIONS; PERFORMANCE; VACCINATION AB Objectives: To assess the impact of prompting physicians on health maintenance, answer questions regarding the mode of delivery, and identify opportunities and limitations of this information intervention. Methods: Systematic electronic and manual searches (January 1, 1966, to December 31, 1996) were conducted to identify clinical trial reports on prompting clinicians. Three eligibility criteria were applied: (1) randomized controlled clinical trial, (2) clinician prompt, alert, or reminder in the study group and no similar intervention in the control group, and (3) measurement of the intervention effect on the frequency of preventive care procedures. Data were abstracted by independent reviewers using a standardized abstraction form, and quality of methodology was scored. A series of meta-analyses on triggering clinical actions was performed using the random-effects method. The statistical analyses included 33 eligible studies, which involved 1547 clinicians and 54 693 patients. Results: Overall, prompting can significantly increase preventive care performance by 13.1% (95% confidence interval [CI], 10.5%-15.6%). However, the effect ranges from 5.8% (95% CI, 1.5%-10.1%) for Papanicolaou smear to 18.3% (95% CI, 11.6%-25.1%) for influenza vaccination. The effect is not cumulative, and the length of intervention period did not show correlation with effect size (R = -0.015, P = .47). Academic affiliation, ratio of residents, and technique of delivery did not have a significant impact on the clinical effect of prompting. Conclusions: Dependable performance improvement in preventive care can be accomplished through prompting physicians. Vigorous application of this simple and effective information intervention could save thousands of lives annually. Health care organizations could effectively use prompts, alerts, or reminders to provide information to clinicians when patient care decisions are made. C1 Univ Missouri, Sch Med, Columbia, MO 65211 USA. Cedars Sinai Med Ctr, Hlth Serv Res, Los Angeles, CA 90048 USA. Massachusetts Gen Hosp, Hlth Policy Res & Dev Unit, Boston, MA 02114 USA. RP Balas, EA (reprint author), Univ Missouri, Sch Med, 313 Clark Hall, Columbia, MO 65211 USA. RI Boren, Suzanne/M-6589-2014 OI Boren, Suzanne/0000-0003-4727-399X FU NLM NIH HHS [LM05545] NR 64 TC 227 Z9 229 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD FEB 14 PY 2000 VL 160 IS 3 BP 301 EP 308 DI 10.1001/archinte.160.3.301 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 280ZQ UT WOS:000085134000004 PM 10668831 ER PT J AU Polanczyk, CA Rohde, LEP Dec, GW Disalvo, T AF Polanczyk, CA Rohde, LEP Dec, GW Disalvo, T TI Ten-year trends in hospital care for congestive heart failure - Improved outcomes and increased use of resources SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ADJUSTED MORTALITY; SEVERITY; MORBIDITY; INDEX; RATES AB Background: Scarce data are available on long-term trends in hospital mortality, length of stay (LOS), and costs in congestive heart failure (CHF). Objective: To assess 10-year trends in the outcomes of patients hospitalized with CHF. Methods: We studied all 6676 patients with a primary discharge diagnosis of CHF hospitalized from January 1, 1986, through July 31, 1996, at an academic tertiary care center. Hospital mortality, LOS, and costs were, adjusted for sociodemographic characteristics, comorbidities, invasive procedures, hospital disposition, and LOS where appropriate. Results: The mean (+/-SD) age of patients was 70 +/- 13 years; 54.1% were male; 87.0% were white. There was a significant increasing trend in heart failure severity as assessed by a CHF-specific risk-adjustment index. The proportion of patients who underwent invasive procedures (eg, cardiac catheterization, coronary angioplasty, coronary artery bypass surgery, defibrillator and pacemaker implantation) was significantly higher in the 1994-1996 period. The standardized mortality ratio (observed mortality/predicted mortality) progressively fell during the study period. Compared with patients admitted before 1991, those admitted after 1991 had a 24% lower observed than predicted mortality. Adjusted LOS exhibited a downward trend, ie, 7.7 days in 1986-1987 to 5.6 days in 1994-1996 (P < .001). Unadjusted cost peaked during 1992-1993 and declined thereafter. Adjusted costs in 1994-1996 were not significantly different from those in 1990-1991. Conclusions: After risk adjustment for sociodemographic characteristics, comorbidities, and disease severity, a significant decrease in in-hospital mortality was observed during the study decade. This decline in hospital mortality occurred in parallel with decreasing LOS and increasing use of cardiac procedures and costs. C1 Massachusetts Gen Hosp, Heart Failure & Cardiac Transplantat Unit, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Disalvo, T (reprint author), Massachusetts Gen Hosp, Heart Failure Ctr, Bigelow 628,55 Fruit St, Boston, MA 02114 USA. RI Polanczyk, Carisi/D-6208-2013; Rohde, Luis Eduardo/I-4216-2013 NR 19 TC 59 Z9 61 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD FEB 14 PY 2000 VL 160 IS 3 BP 325 EP 332 DI 10.1001/archinte.160.3.325 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 280ZQ UT WOS:000085134000007 PM 10668834 ER PT J AU Vazquez, F Sellers, WR AF Vazquez, F Sellers, WR TI The PTEN tumor suppressor protein: an antagonist of phosphoinositide 3-kinase signaling SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review ID PHOSPHATIDYLINOSITOL KINASE-ACTIVITY; GLYCOGEN-SYNTHASE KINASE-3; PAX3-FKHR FUSION PROTEIN; FACTOR-I RECEPTOR; PTEN/MMAC1 GENE; ALVEOLAR RHABDOMYOSARCOMA; PROSTATE-CANCER; GERMLINE MUTATIONS; BREAST CARCINOMAS; COWDEN-DISEASE C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Dana Farber Canc Inst,Dept Adult Oncol, Boston, MA 02115 USA. RP Sellers, WR (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Dana Farber Canc Inst,Dept Adult Oncol, Boston, MA 02115 USA. NR 125 TC 181 Z9 188 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD FEB 14 PY 2000 VL 1470 IS 1 BP M21 EP M35 DI 10.1016/S0304-419X(99)00032-3 PG 15 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA 287XP UT WOS:000085533000003 PM 10656987 ER PT J AU Allen, DN Anastasiou, A Goldstein, G Gilbertson, M van Kammen, DP AF Allen, DN Anastasiou, A Goldstein, G Gilbertson, M van Kammen, DP TI Influence of haloperidol on the relationship of frontal lobe function to psychomotor poverty and disorganization syndromes SO PSYCHIATRY RESEARCH LA English DT Article DE schizophrenia; frontal lobes; neuropsychology ID CEREBRAL BLOOD-FLOW; SCHIZOPHRENIC SYNDROMES; PERFORMANCE AB The aim of the study was to examine effects of haloperidol on the relationships between neuropsychological measures of frontal lobe functioning and the schizophrenia syndromes of psychomotor poverty and disorganization. Twenty-one participants with schizophrenia were initially evaluated when clinically stable and chronically treated with haloperidol, and 19 were evaluated again after a 3-week haloperidol-free period. Participants were evaluated with the Trail Making Test, the Wisconsin Card Sorting Test, the Purdue Pegboard, and psychiatric rating scales at each evaluation. There were significant correlations between schizophrenia syndromes and the tests sensitive to frontal lobe function when participants were medicated but not when drug-free. No significant changes in symptom severity or motor function occurred from the medication to the medication-free evaluation. The results indicate that haloperidol mediates the relationship between tests sensitive to frontal lobe function and the schizophrenia syndromes of psychomotor poverty and disorganization. This mediation effect was not attributable to changes in overall symptom severity or motor function. (C) 2000 Elsevier Science ireland Ltd. All rights reserved. C1 Univ Nevada, Dept Psychol, Las Vegas, NV 89154 USA. VA Pittsburgh Healthcare Syst, Highland Dr Div, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. VA Med Ctr, Manchester, NH USA. Robert Wood Johnson Pharmaceut Res Inst, Raritan, NJ USA. RP Allen, DN (reprint author), Univ Nevada, Dept Psychol, 4505 Maryland Pkwy,Box 455030, Las Vegas, NV 89154 USA. FU NIMH NIH HHS [MH44841] NR 22 TC 15 Z9 15 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD FEB 14 PY 2000 VL 93 IS 1 BP 33 EP 39 DI 10.1016/S0165-1781(00)00112-8 PG 7 WC Psychiatry SC Psychiatry GA 301AF UT WOS:000086285400004 PM 10699226 ER PT J AU Schneider, H Guerette, B Guntermann, C Rudd, CE AF Schneider, H Guerette, B Guntermann, C Rudd, CE TI Resting lymphocyte kinase (Rlk/Txk) targets lymphoid adaptor SLP-76 in the cooperative activation of interleukin-2 transcription in T-cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE KINASES; X-LINKED AGAMMAGLOBULINEMIA; ANTIGEN-RECEPTOR; SRC FAMILY; THYMOCYTE DEVELOPMENT; GENETIC-EVIDENCE; MICE LACKING; PHOSPHORYLATION; ZAP-70; ITK AB Blk/Txk is a T-cell-specific member of the Btk/Tec family of tyrosine kinases, whereas SLP-76 is a lymphoid adaptor that is essential for pre-TcR and mature TcR signaling, Although Rlk deficient T-cells show partial defects in T-cell proliferation, Rlk can complement ITK-/- cells with multiple defects in TcR initiated early events and interleukin (IL)-2 production. A key question is the nature of the target of Rlk responsible for bridging the TcR with the activation of IL-2 transcription. In this study, we identify a pathway in which Rlk phosphorylates SLP-76 leading to the phosphorylation of PLC gamma 1, activation of ERKs, and the synergistic up-regulation of TcR-driven IL-2 NFAT/AP-1 transcription, Rlk phosphorylated the N-terminal region of SLP-76, a region that has been previously shown to serve as a target for ZAP-70. Loss of N-terminal YESP/YEPP sites of SLP-76 or the Rlk kinase activity attenuated cooperativity between Rlk and SLP-76. These observations support a model where the TcR can utilize Rlk (as well as ZAP-70) in the phosphorylation of key sites in SLP-76 leading to the up-regulation of Th1 preferred cytokine IL-2. C1 Dana Farber Canc Inst, Dept Canc Immunol & 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, CE (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 43 TC 44 Z9 47 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 11 PY 2000 VL 275 IS 6 BP 3835 EP 3840 DI 10.1074/jbc.275.6.3835 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 283RJ UT WOS:000085288800018 PM 10660534 ER PT J AU Lambrecht, N Munson, K Vagin, O Sachs, G AF Lambrecht, N Munson, K Vagin, O Sachs, G TI Comparison of covalent with reversible inhibitor binding sites of the gastric H,K-ATPase by site-directed mutagenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COMPETITIVE PHOTOAFFINITY INHIBITOR; H+/K+-ATPASE; BETA-SUBUNIT; SARCOPLASMIC-RETICULUM; ALPHA-SUBUNIT; MEMBRANE TOPOLOGY; H+,K+-ATPASE; OMEPRAZOLE; PUMP; IDENTIFICATION AB The gastric H,K-ATPase is covalently inhibited by substituted pyridyl-methylsulfinyl-benzimidazoles, such as omeprazole, that convert to thiophilic probes of luminally accessible cysteines in the acid space. The K+ competitive inhibitor, SCH28080, prevented inhibition of acid transport by omeprazole. In stably expressing HEK293 cells, the benzimidazole-reactive cysteines, Cys-321 (transmembrane helix (TM) 3), Cys-813 and Cys-822 (TM5/6), and Cys-892 (TM7/8) were mutated to the amino acids found in the SCH28080-resistant Na,K-ATPase and kinetic parameters of H,K-ATPase activity analyzed. Mutations of Cys-822 and Cys-892 had insignificant effects:an the K-i(app), K-m(app) or V-max, but mutations of Cys-813 to threonine and Cys-321 to alanine decreased the affinity for SCH28080, Mutation of Cys-321 to alanine produced mixed kinetics of inhibition, still with higher affinity for the cation-free form of phosphoenzyme. Since the phenylmethoxy ring of the imidazo-pyridine inhibitors binds to TM1/2, as shown by earlier photoaffinity studies, and the mutations in TM6 (Cys-813 --> Thr) as well as the end of TM3 (Cys-321 --> Ala) decrease the affinity for SCH28080, the TM1/2, TM3, and TM6 helices lie within: similar to 16 Angstrom of each other based on the size of the active, extended conformation of SCH28080. C1 Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90073 USA. RP Vet Affairs Greater Los Angeles Hlth Care Syst, Bldg 113,Rm 326, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK41301, DK17294, DK40615] NR 34 TC 37 Z9 37 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 11 PY 2000 VL 275 IS 6 BP 4041 EP 4048 DI 10.1074/jbc.275.6.4041 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 283RJ UT WOS:000085288800045 PM 10660561 ER PT J AU Mao, J Price, DD Lu, J Keniston, L Mayer, DJ AF Mao, J Price, DD Lu, J Keniston, L Mayer, DJ TI Two distinctive antinociceptive systems in rats with pathological pain SO NEUROSCIENCE LETTERS LA English DT Article DE antinociception; cannabinoids; morphine; pathological pain ID MORPHINE-TOLERANCE; NEUROPATHIC PAIN; MICE; HYPERALGESIA; MECHANISMS; ANALGESIA; MONONEUROPATHY; CANNABINOIDS AB A common obstacle in clinical management of pathological pain is the poor response to opioid analgesics. We now report that Delta(9)-tetrahydrocannabinol (Delta(9)-THC)-induced antinociception remained effective in rats with pathological pain. The selective central cannabinoid receptor antagonist SR141716A, but not the generic opioid receptor antagonist naloxone, blocked the Delta(9)-THC antinociception. Moreover, there is no cross-tolerance between the antinociceptive effects of morphine and Delta(9)-THC in pathological pain states. The results indicate that Delta(9)-THC antinociception is both effective and independent of opioid receptors in rats with pathological pain. Thus, the cannabinoid analgesic system may be superior to opioids in alleviating intractable pathological pain syndromes. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,MGH Pain Ctr, Boston, MA 02114 USA. Univ Florida, Hlth Sci Ctr, Gainesville, FL 32610 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Anesthesiol, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Anat, Richmond, VA 23298 USA. RP Mao, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,MGH Pain Ctr, 15 Parkman St,Suite WACC-324, Boston, MA 02114 USA. RI Price, Donald/A-3094-2008; Keniston, Les/O-1782-2013 OI Price, Donald/0000-0002-8971-7184; Keniston, Les/0000-0001-9730-0074 FU NIDA NIH HHS [DA08835] NR 18 TC 67 Z9 67 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD FEB 11 PY 2000 VL 280 IS 1 BP 13 EP 16 DI 10.1016/S0304-3940(99)00998-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 282ZE UT WOS:000085251000004 PM 10696800 ER PT J AU Shimamura, A Ballif, BA Richards, SA Blenis, J AF Shimamura, A Ballif, BA Richards, SA Blenis, J TI Rsk1 mediates a MEK-MAP kinase cell survival signal SO CURRENT BIOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; RIBOSOMAL S6 KINASE; BCL-2 FAMILY; PHOSPHORYLATION; BAD; DEATH; RAS; IDENTIFICATION; EXPRESSION; APOPTOSIS AB Background: Growth factors activate an array of cell survival signaling pathways. Mitogen-activated protein (MAP) kinases transduce signals emanating from their upstream activators MAP kinase kinases (MEKs). The MEK-MAP kinase signaling cassette is a key regulatory pathway promoting cell survival. The downstream effecters of the mammalian MEK-MAP kinase cell survival signal have not been previously described. Results: We identify here a pro-survival role for the serine/threonine kinase Rsk1, a downstream target of the MEK-MAP kinase signaling pathway. In cells that are dependent on interleukin-3 (IL-3) for survival, pharmacological inhibition of MEKs antagonized the IL-3 survival signal. In the absence of IL-3, a kinase-dead Rsk1 mutant eliminated the survival effect afforded by activated MEK, Conversely, a novel constitutively active Rsk1 allele restored the MEK-MAP kinase survival signal. Experiments in vitro and in vivo demonstrated that Rsk1 directly phosphorylated the pro-apoptotic protein Bad at the serine residues that, when phosphorylated, abrogate Bad's pro-apoptotic function. Constitutively active Rsk1 caused constitutive Bad phosphorylation and protection from Bad-modulated cell death. Kinase-inactive Rsk1 mutants antagonize Bad phosphorylation. Bad mutations that prevented phosphorylation by Rsk1 also inhibited Rsk1-mediated cell survival. Conclusions: These data support a model in which Rsk1 transduces the mammalian MEK-MAP kinase signal in part by phosphorylating Bad. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Hematol & Oncol, Boston, MA 02115 USA. RP Blenis, J (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA46595] NR 43 TC 205 Z9 212 U1 0 U2 6 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD FEB 10 PY 2000 VL 10 IS 3 BP 127 EP 135 DI 10.1016/S0960-9822(00)00310-9 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 284VT UT WOS:000085354100015 PM 10679322 ER PT J AU Leder, BZ Longcope, C Catlin, DH Ahrens, B Schoenfeld, DA Finkelstein, JS AF Leder, BZ Longcope, C Catlin, DH Ahrens, B Schoenfeld, DA Finkelstein, JS TI Oral androstenedione administration and serum testosterone concentrations in young men SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ANABOLIC-STEROIDS; ADIPOSE-TISSUE; MUSCLE; AROMATIZATION; ANDROGENS; AGE AB Context Androstenedione, a steroid hormone and the major precursor to testosterone, is available without prescription and is purported to increase strength and athletic performance. The hormonal effects of androstenedione, however, are unknown. Objective To determine if oral administration of androstenedione increases serum testosterone levels in healthy men. Design Open-label randomized controlled trial conducted between October 1998 and April 1999. Setting General clinical research center of a tertiary-care, university-affiliate hospital. Participants Forty-two healthy men aged 20 to 40 years, Intervention Subjects were randomized to receive oral androstenedione (either 100 mg/d [n = 15] or 300 mg/d [n = 14]) or no androstenedione (n = 13) for 7 days. Main Outcome Measures Changes in serum testosterone, androstenedione, estrone, and estradiol levels, measured by frequent blood sampling, compared among the 3 treatment groups. Results Mean (SE) changes in the area under the curve (AUC) for serum testosterone concentrations were -2% (7%), -4% (4%), and 34% (14%) in the groups receiving 0, 100, and 300 mg/d of androstenedione, respectively. When compared with the control group, the change in testosterone AUC was significant for the 300-mg/d group (P<.001) but not for the 100-mg/d group (P = .48). Baseline testosterone levels, drawn 24 hours after androstenedione administration, did not change. Mean (SE) changes in the AUC for serum estradiol concentrations were 4% (6%), 42% (12%), and 128% (24%) in the groups receiving 0, 100, and 300 mg/d of androstenedione, respectively. When compared with the control group, the change in the estradiol AUC was significant for both the 300-mg/d (P<.001) and 100-mg/d (P = .002) groups. There was marked variability in individual responses for all measured sex steroids. Conclusions Our data suggest that oral androstenedione, when given in dosages of 300 mg/d, increases serum testosterone and estradiol concentrations in some healthy men. C1 Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. Univ Massachusetts, Sch Med, Dept Obstet & Gynecol, Worcester, MA USA. Univ Calif Los Angeles, Dept Med, Olymp Analyt Lab, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA USA. RP Finkelstein, JS (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Bulfinch 327, Boston, MA 02114 USA. FU NCRR NIH HHS [RR-1066]; NIDDK NIH HHS [K24 DK02759, 5 R29 DK443341] NR 23 TC 85 Z9 87 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 FEB 9 PY 2000 VL 283 IS 6 BP 779 EP 782 DI 10.1001/jama.283.6.779 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 280XL UT WOS:000085129000030 PM 10683057 ER PT J AU Dubey, DP Husain, Z Levitan, E Zurakowski, D Mirza, N Younes, S Coronell, C Yunis, D Yunis, EJ AF Dubey, DP Husain, Z Levitan, E Zurakowski, D Mirza, N Younes, S Coronell, C Yunis, D Yunis, EJ TI The MHC influences NK and NKT cell functions associated with immune abnormalities and lifespan SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE lifespan; cytokines; NKT; MHC congenic mice; NK ID NK1.1(+) T-CELLS; AGE-ASSOCIATED DECLINE; HISTOCOMPATIBILITY COMPLEX; CYTOKINE PRODUCTION; CALCIUM RESPONSE; OLD MICE; ACTIVATION; ANTI-CD3; YOUNG; LYMPHOCYTES AB The lifespans of H-2 congenic mice differ significantly. The B10.AKM (H-2(m)) strain has a median survival time (MST) of 15 months, whereas the B10.BR (H-2(k)) strain has an MST of 24 months. It was previously shown that B10.AKM mice at 13-15 months of age have immunological function comparable to those of B10.BR mice at 22-26 months of age. These functions include: a low proliferative response, reduced levels of intracellular calcium release [Ca2+](i), and an increase in the frequency of memory helper T-cells (CD4(+) CD44(hi)CD45RB(lo)). In this report similar deficiencies were demonstrated in B10.AKM mice at 2-4 months of age and show that activated spleen NK1.1(+)CD4(+) T (NKT) cells from young B10.AKM mice produce a significantly higher level of IL-4 but a lower level of IFN-gamma as compared to NKT cells from B10.BR mice of the same age. Also, the cytotoxic activity of natural killer (NK) cells from spleens of young (2-4 months) as well as adult (12-16 months) B10.AKM mice is significantly lower (P < 0.01) than that of NK cells from B10.BR mice. These findings suggest that the NKT activity in young B10.AKM mice is a factor for the early onset of immune dysfunction leading to a shorter lifespan. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. RP Dubey, DP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-29583]; NIA NIH HHS [AG-02329]; NIAID NIH HHS [AI-26817] NR 35 TC 8 Z9 10 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing. Dev. PD FEB 7 PY 2000 VL 113 IS 2 BP 117 EP 134 DI 10.1016/S0047-6374(99)00102-5 PG 18 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 282KM UT WOS:000085217300004 PM 10708259 ER PT J AU Head, MW Hurwitz, L Kegel, K Goldman, JE AF Head, MW Hurwitz, L Kegel, K Goldman, JE TI alpha B-crystallin regulates intermediate filament organization in situ SO NEUROREPORT LA English DT Article DE astrocyte; alpha B-crystallin; chaperone; glial fibrillary acidic protein; hsp27; intermediate filaments; stress protein ID HEAT-SHOCK PROTEIN; CHAPERONE ACTIVITY; CELLS; STRESS; ACTIN; HSP27; ACCUMULATION; ASSOCIATION; EXPRESSION AB alpha B-crystallin is a small heat shock protein (hsp) and molecular chaperone that can interact with a wide spectrum of cellular components including intermediate filaments (IF). The significance of these interactions is not currently known. We have tested whether increased alpha B-crystallin expression effects changes in the IF systems in situ. Adenoviral-mediated gene transfer was used to overexpress alpha B-crystallin in primary astrocytes. A positive correlation was observed between overexpression of alpha B-crystallin and diffuse, filigree IF. alpha B-crystallin did not appear to alter the polymerization state of IF proteins. These data show that an increase in alpha B-crystallin expression in the absence of stress can modify the organizational state of IF and that alpha B-crystallin can function as an IF debundling protein. NeuroReport 11:361-365 (C) 2000 Lippincott Williams & Wilkins. C1 Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Ctr Neurobiol & Behav, New York, NY 10032 USA. Univ Edinburgh, Western Gen Hosp, CJD Surveillance Unit, Edinburgh, Midlothian, Scotland. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Head, MW (reprint author), Columbia Univ Coll Phys & Surg, Dept Pathol, 630 W 168th St, New York, NY 10032 USA. FU NEI NIH HHS [EY09331] NR 25 TC 27 Z9 29 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD FEB 7 PY 2000 VL 11 IS 2 BP 361 EP 365 DI 10.1097/00001756-200002070-00028 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 278LX UT WOS:000084992200029 PM 10674487 ER PT J AU Abbenante, G Kovacs, DM Leung, DL Craik, DJ Tanzi, RE Fairlie, DP AF Abbenante, G Kovacs, DM Leung, DL Craik, DJ Tanzi, RE Fairlie, DP TI Inhibitors of beta-amyloid formation based on the beta-secretase cleavage site SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ALZHEIMERS-DISEASE; PRECURSOR PROTEIN AB A series of inhibitors of beta-amyloid formation have been developed based on the beta-secretase cleavage site (VNL-DA) of the Swedish mutant Amyloid Precursor Protein. A simple tripeptide aldehyde was found to be the most potent (IC50 = 700 nM) in the series displaying an inhibitory profile which is different from reported inhibitors of beta-amyloid formation. (C) 2000 Academic Press. C1 Univ Queensland, Ctr Drug Design & Dev, Brisbane, Qld 4072, Australia. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Genet & Aging Unit, Charlestown, MA 02129 USA. RP Abbenante, G (reprint author), Univ Queensland, Ctr Drug Design & Dev, Brisbane, Qld 4072, Australia. RI Fairlie, David/F-8865-2014; Craik, David/B-1695-2010 OI Craik, David/0000-0003-0007-6796 NR 20 TC 37 Z9 38 U1 0 U2 1 PU ACADEMIC PRESS INC 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 FEB 5 PY 2000 VL 268 IS 1 BP 133 EP 135 DI 10.1006/bbrc.2000.2098 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 281RA UT WOS:000085173500026 PM 10652226 ER PT J AU Abi-Younes, S Sauty, A Mach, F Sukhova, GK Libby, P Luster, AD AF Abi-Younes, S Sauty, A Mach, F Sukhova, GK Libby, P Luster, AD TI The stromal cell-derived factor-1 chemokine is a potent platelet agonist highly expressed in atherosclerotic plaques SO CIRCULATION RESEARCH LA English DT Article DE stromal cell-derived factor-1; chemokine; platelet; atherosclerosis ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; RECEPTOR-DEFICIENT MICE; LYMPHOCYTE CHEMOATTRACTANT; ALPHA-CHEMOKINE; CXCR4; SDF-1; MIGRATION; LIGAND; LYMPHOPOIESIS; INFLAMMATION AB Chemokines are chemotactic cytokines that activate and direct the migration of leukocytes. However, their role in modulating platelet function has not been shown. We studied the direct effect of chemokines on human platelets and found that of the 16 tested only stromal cell- derived factor (SDF)-1 induced platelet aggregation, accompanied by a rise in intracellular calcium. Platelets expressed the SDF-1 receptor, CXCR4, and an antibody to CXCR4 and pertussis toxin inhibited SDF-1-induced platelet aggregation, confirming that this effect is mediated through CXCR4, a G alpha i-coupled receptor. SDF-1-induced platelet aggregation was also inhibited by wortmannin, LY294002, and genistein, suggesting that phosphatidylinositol 3-kinase and tyrosine kinase are likely involved in SDF-1-induced platelet aggregation. Because chemokines are produced from multiple vascular cells and atherosclerotic vessels are prone, to develop platelet-rich thrombi, we examined the expression of SDF-1 in human atheroma. SDF-1 protein was highly expressed in smooth muscle cells, endothelial cells, and macrophages in human atherosclerotic plaques but not in normal vessels. Our studies demonstrate a direct effect of a chemokine in inducing platelet activation and suggest a role for SDF-1 in the pathogenesis of atherosclerosis and thrombo-occlusive diseases. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Luster, AD (reprint author), Massachusetts Gen Hosp E, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA 69212]; NHLBI NIH HHS [P50 HL56985]; NIAID NIH HHS [AI 40618] NR 46 TC 214 Z9 230 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD FEB 4 PY 2000 VL 86 IS 2 BP 131 EP 138 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 284PW UT WOS:000085342000007 PM 10666407 ER PT J AU McBride, AE Weiss, VH Kim, HK Hogle, JM Silver, PA AF McBride, AE Weiss, VH Kim, HK Hogle, JM Silver, PA TI Analysis of the yeast arginine methyltransferase Hmt1p/Rmt1p and its in vivo function - Cofactor binding and substrate interactions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MYELIN BASIC-PROTEIN; SACCHAROMYCES-CEREVISIAE; S-ADENOSYLMETHIONINE; DEPENDENT METHYLTRANSFERASES; N-METHYLTRANSFERASE; RECOGNITION MOTIF; SHUTTLE VECTORS; NUCLEAR EXPORT; RNA; METHYLATION AB Many eukaryotic RNA-binding proteins are modified by methylation of arginine residues. The yeast Saccharomyces cerevisiae contains one major arginine methyltransferase, Hmt1p/Rmt1p, which is not essential for normal cell growth, However, cells missing HIMT1 and also bearing mutations in the mRNA-binding proteins Np13p or Cbp80p can no longer survive, providing genetic backgrounds in which to study Hmt1p function. We now demonstrate that the catalytically active form of Hmt1p is required for its activity in vivo. Amino acid changes in the putative Kmt1p S-adenosyl-L-methionine-binding site were generated and shown to be unable to catalyze methylation of Np13p in vitro and in vivo or to restore growth to strains that require HMT1. In addition these mutations affect nucleocytoplasmic transport of Np13p. A cold-sensitive mutant of Hmt1p was generated and showed reduced methylation of Np13p, but not of other substrates, at 14 degrees C. These results define new aspects of Hmt1 and reveal the importance of its activity in vivo. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Silver, PA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [R01 AI020566]; NIGMS NIH HHS [GM19236, GM57476] NR 44 TC 70 Z9 71 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 FEB 4 PY 2000 VL 275 IS 5 BP 3128 EP 3136 DI 10.1074/jbc.275.5.3128 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 281FD UT WOS:000085146500018 PM 10652296 ER PT J AU Lam, EWF Glassford, J Banerji, L Thomas, NSB Sicinski, P Klaus, GGB AF Lam, EWF Glassford, J Banerji, L Thomas, NSB Sicinski, P Klaus, GGB TI Cyclin D3 compensates for loss of cyclin D2 in mouse B-lymphocytes activated via the antigen receptor and CD40 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-CYCLE; RETINOBLASTOMA PROTEIN; GENE-EXPRESSION; DEPENDENT KINASES; E2F; PROLIFERATION; FAMILY; D1; TRANSCRIPTION; ACCUMULATION AB Cyclin D2 is the only D-type cyclin expressed in mature mouse B-lymphocytes, and its expression is associated with retinoblastoma protein (pRB) and pRB-related protein phosphorylation and induction of E2F activity, as B-cells enter the cell cycle following stimulation via surface IgM and/or CD40. Cyclin D-dependent kinase activity is required for cell proliferation, yet cyclin D2(-/-) mice have normal levels of mature B-lymphocytes. Here we show that B-lymphocytes from cyclin D2(-/-) mice can proliferate in response to anti-IgM and anti-CD40, but the time taken to enter S-phase is longer than for the corresponding cyclin D2(+/+) cells. This is due to the compensatory induction of cyclin D3, but not cyclin D1, which causes pRb phosphorylation on CDK4-specific sites. This is the first demonstration that loss of a D-type cyclin causes specific expression and functional compensation by another member of the family in vivo and provides a rationale for the presence of mature B-lymphocytes in cyclin D2(-/-) mice. C1 Univ London Imperial Coll Sci Technol & Med, Ludwig Inst Canc Res, St Marys, London W2 1PG, England. Univ London Imperial Coll Sci Technol & Med, Sect Virol & Cell Biol, London W2 1PG, England. UCL Royal Free & Univ Coll Med Sch, Dept Haematol, London WC1E 6HX, England. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Natl Inst Med Res, Div Cellular Immunol, London NW7 1AA, England. RP Lam, EWF (reprint author), Univ London Imperial Coll Sci Technol & Med, Ludwig Inst Canc Res, St Marys Campus,Norfolk Pl, London W2 1PG, England. EM eric.lam@ic.ac.uk NR 45 TC 90 Z9 92 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 FEB 4 PY 2000 VL 275 IS 5 BP 3479 EP 3484 DI 10.1074/jbc.275.5.3479 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 281FD UT WOS:000085146500064 PM 10652342 ER PT J AU Wessler, S Hocker, M Fischer, W Wang, TC Rosewicz, S Haas, R Wiedenmann, B Meyer, TF Naumann, M AF Wessler, S Hocker, M Fischer, W Wang, TC Rosewicz, S Haas, R Wiedenmann, B Meyer, TF Naumann, M TI Helicobacter pylori activates the histidine decarboxylase promoter through a mitogen-activated protein kinase pathway independent of pathogenicity island-encoded virulence factors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENTEROCHROMAFFIN-LIKE CELLS; NF-KAPPA-B; PHORBOL 12-MYRISTATE 13-ACETATE; GASTRIC EPITHELIAL-CELLS; GENE-EXPRESSION; SIGNAL-TRANSDUCTION; ISCHEMIA-REPERFUSION; HISTAMINE SYNTHESIS; CANCER CELLS; INFECTION AB Helicobacter pylori infection of the gastric mucosa is accompanied by an activated histamine metabolism. Histamine plays a central role in the regulation of gastric acid secretion and is involved in the pathogenesis of gastroduodenal ulcerations. Histidine decarboxylase (HDC) is the rate-limiting enzyme for histamine production, and its activity is regulated through transcriptional mechanisms. The present study investigated the effect of H. pylori infection on the transcriptional activity of the human HDC (hHDC) promoter in a gastric epithelial cell line (AGS) and analyzed the underlying molecular mechanisms. Our studies demonstrate that H, pylori infection potently transactivated the hHDC promoter. The H. pylori-responsive element of the hHDC gene was mapped to the sequence +1 to +27 base pairs, which shows no homology to known cis-acting elements and also functions as a gastrin-responsive element. H. pylori regulates the activity of this element via a Raf-1/MEK/ERK pathway, which was activated in a Ras-independent manner. Furthermore, we found that H. pylori-induced transactivation of the hHDC promoter was independent of the cag pathogenicity island and the vacuolating cytotoxin A gene and therefore may be exerted through (a) new virulence factor(s), A better understanding of H. pylori-directed hHDC transcription can provide novel insights into the molecular mechanisms of H, pylori-dependent gene regulation in gastric epithelial cells and may lead to new therapeutic approaches. C1 Max Planck Inst Infektionsbiol, Mol Biol Abt, D-10117 Berlin, Germany. Humboldt Univ, Klinikum Charite, Med Klink Schwerpunkt Gastroenterol & Hepatol, D-1086 Berlin, Germany. Max Von Pettenkofer Inst Med Mikrobiol & Hyg, Abt Bakteriol, D-80336 Munich, Germany. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Naumann, M (reprint author), Max Planck Inst Infektionsbiol, Mol Biol Abt, Monbijoustr 2, D-10117 Berlin, Germany. RI Meyer, Thomas F./J-2485-2013; Naumann, Michael/B-5285-2011; Wessler, Silja/C-6309-2015 OI Meyer, Thomas F./0000-0002-6120-8679; Naumann, Michael/0000-0002-8060-2313; Wessler, Silja/0000-0001-7011-6162 NR 56 TC 58 Z9 60 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 4 PY 2000 VL 275 IS 5 BP 3629 EP 3636 DI 10.1074/jbc.275.5.3629 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 281FD UT WOS:000085146500081 PM 10652359 ER PT J AU Ashkar, S Weber, GF Panoutsakopoulou, V Sanchirico, ME Jansson, M Zawaideh, S Rittling, SR Denhardt, DT Glimcher, MJ Cantor, H AF Ashkar, S Weber, GF Panoutsakopoulou, V Sanchirico, ME Jansson, M Zawaideh, S Rittling, SR Denhardt, DT Glimcher, MJ Cantor, H TI Eta-1 (osteopontin): An early component of type-1 (cell-mediated) immunity SO SCIENCE LA English DT Article ID HERPES STROMAL KERATITIS; DENDRITIC CELLS; IN-VITRO; SECRETED PHOSPHOPROTEIN; BACTERIAL-INFECTION; GRANULOMA-FORMATION; GENETIC-RESISTANCE; AUTOIMMUNE-DISEASE; ESCHERICHIA-COLI; UP-REGULATION AB Cell-mediated (type-1) immunity is necessary for immune protection against most intracellular pathogens and, when excessive, can mediate organ-specific autoimmune destruction. Mice deficient in Eta-1 (also called osteopontin) gene expression have severely impaired type-1 immunity to viral infection [herpes simplex virus-type 1 (KOS strain)] and bacterial infection (Listeria monocytogenes) and do not develop sarcoid-type granulomas. Interleukin-12 (IL-12) and interferon-gamma production is diminished, and IL-10 production is increased. A phosphorylation-dependent interaction between the amino-terminal portion of Eta-1 and its integrin receptor stimulated IL-12 expression, whereas a phosphorylation-independent interaction with CD44 inhibited IL-10 expression. These findings identify Eta-1 as a key cytokine that sets the stage for efficient type-1 immune responses through differential regulation of macrophage IL-12 and IL-10 cytokine expression. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp,Dept Orthoped Surg, Lab Skeletal Disorders & Rehabil, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Rutgers State Univ, Fac Arts & Sci, Div Life Sci, Piscataway, NJ 08854 USA. RP Cantor, H (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. OI Panoutsakopoulou, Vily/0000-0002-1569-1508 FU NCI NIH HHS [CA76176]; NIAID NIH HHS [AI37833, AI12184] NR 52 TC 722 Z9 764 U1 0 U2 17 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 FEB 4 PY 2000 VL 287 IS 5454 BP 860 EP 864 DI 10.1126/science.287.5454.860 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 281AR UT WOS:000085136400048 PM 10657301 ER PT J AU Perez, GI Trbovich, AM Gosden, RG Tilly, JL AF Perez, GI Trbovich, AM Gosden, RG Tilly, JL TI Reproductive biology - Mitochondria and the death of oocytes SO NATURE LA English DT Article ID APOPTOSIS; OVARY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Univ Leeds, Leeds Gen Infirm, Ctr Reprod Growth & Dev, Leeds LS2 9NS, W Yorkshire, England. RP Perez, GI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, VBK137E-GYN, Boston, MA 02114 USA. NR 14 TC 92 Z9 104 U1 0 U2 10 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 3 PY 2000 VL 403 IS 6769 BP 500 EP 501 DI 10.1038/35000651 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 282PM UT WOS:000085227300035 PM 10676949 ER PT J AU Sze, JY Victor, M Loer, C Shi, Y Ruvkun, G AF Sze, JY Victor, M Loer, C Shi, Y Ruvkun, G TI Food and metabolic signaling defects in a Caenorhabditis elegans serotonin-synthesis mutant SO NATURE LA English DT Article ID C-ELEGANS; PROTEINS; EXPRESSION; LONGEVITY; GENETICS; NEURONS; LONG; PHEROMONE; BEHAVIOR; DAF-2 AB The functions of serotonin have been assigned through serotonin-receptor-specific drugs and mutants(1,2); however because a constellation of receptors remains when a single receptor subtype is inhibited, the coordinate responses to modulation of serotonin levels may be missed. Here we report the analysis of behavioural and neuroendocrine defects caused by a complete lack of serotonin signalling. Analysis of the C. elegans genome sequence showed that there is a single tryptophan hydroxylase gene (tph-1)-the key enzyme for serotonin biosynthesis. Animals bearing a tph-1 deletion mutation do not synthesize serotonin but are fully viable. The tph-1 mutant shows abnormalities in behaviour and metabolism that are normally coupled with the sensation and ingestion of food: rates of feeding and egg laying are decreased; large amounts of fat are stored; reproductive lifespan is increased; and some animals arrest at the metabolically inactive dauer stage. This metabolic dysregulation is, in part, due to downregulation of tranforming growth factor-beta and insulin-like neuroendocrine signals. The action of the C. elegans serotonergic system in metabolic control is similar to mammalian serotonergic input to metabolism and obesity. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ San Diego, Dept Biol, San Diego, CA 92110 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. NR 30 TC 337 Z9 355 U1 3 U2 44 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 3 PY 2000 VL 403 IS 6769 BP 560 EP 564 DI 10.1038/35000609 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 282PM UT WOS:000085227300054 PM 10676966 ER PT J AU Wolfe, J Grier, HE Klar, N Levin, SB Ellenbogen, JM Salem-Schatz, S Emanuel, EJ Weeks, JC AF Wolfe, J Grier, HE Klar, N Levin, SB Ellenbogen, JM Salem-Schatz, S Emanuel, EJ Weeks, JC TI Symptoms and suffering at the end of life in children with cancer. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PALLIATIVE CARE; FAMILY MEMBERS; PAIN AB Background: Cancer is the second leading cause of death in children, after accidents. Little is known, however, about the symptoms and suffering at the end of life in children with cancer. Methods: In 1997 and 1998, we interviewed the parents of children who had died of cancer between 1990 and 1997 and who were cared for at Children's Hospital in Boston, the Dana-Farber Cancer Institute, or both. Additional data were obtained by reviewing medical records. Results: Of 165 eligible parents, we interviewed 103 (62 percent), 98 by telephone and 5 in person. The interviews were conducted a mean (+/-SD) of 3.1+/-1.6 years after the death of the child. Almost 80 percent died of progressive disease, and the rest died of treatment-related complications. Forty-nine percent of the children died in the hospital; nearly half of these deaths occurred in the intensive care unit. According to the parents, 89 percent of the children suffered "a lot'' or "a great deal'' from at least one symptom in their last month of life, most commonly pain, fatigue, or dyspnea. Of the children who were treated for specific symptoms, treatment was successful in 27 percent of those with pain and 16 percent of those with dyspnea. On the basis of a review of the medical records, parents were significantly more likely than physicians to report that their child had fatigue, poor appetite, constipation, and diarrhea. Suffering from pain was more likely in children whose parents reported that the physician was not actively involved in providing end-of-life care (odds ratio, 2.6; 95 percent confidence interval, 1.0 to 6.7). Conclusions: Children who die of cancer receive aggressive treatment at the end of life. Many have substantial suffering in the last month of life, and attempts to control their symptoms are often unsuccessful. Greater attention must be paid to palliative care for children who are dying of cancer. (N Engl J Med 2000;342:326-33.) (C) 2000, Massachusetts Medical Society. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Weeks, JC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU AHRQ HHS [5 T32 HS00063] NR 28 TC 492 Z9 504 U1 2 U2 17 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 3 PY 2000 VL 342 IS 5 BP 326 EP 333 DI 10.1056/NEJM200002033420506 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 279XL UT WOS:000085070300006 PM 10655532 ER PT J AU King, GL Suzuma, K AF King, GL Suzuma, K TI Pigment-epithelium-derived factor - A key coordinator of retinal neuronal and vascular functions. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR C1 Joslin Diabet Ctr, Boston, MA 02215 USA. RP King, GL (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. NR 5 TC 50 Z9 55 U1 0 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 3 PY 2000 VL 342 IS 5 BP 349 EP 351 DI 10.1056/NEJM200002033420511 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 279XL UT WOS:000085070300011 PM 10655537 ER PT J AU Willers, H McCarthy, EE Wu, B Wunsch, H Tang, W Taghian, DG Xia, F Powell, SN AF Willers, H McCarthy, EE Wu, B Wunsch, H Tang, W Taghian, DG Xia, F Powell, SN TI Dissociation of p53-mediated suppression of homologous recombination from G1/S cell cycle checkpoint control SO ONCOGENE LA English DT Article DE p53; homologous recombination; G1/S cell cycle checkpoint; genomic stability ID TEMPERATURE-SENSITIVE MUTANT; WILD-TYPE P53; DNA-BINDING; NUCLEAR-LOCALIZATION; GAMMA-IRRADIATION; TERMINAL DOMAIN; MAMMALIAN-CELLS; PROTEIN; EXPRESSION; GROWTH AB The tumor suppressor p53 is considered as the guardian of the genome which is activated following genotoxic stress. In many cell types, p53 mediates G1 cell cycle arrest as the predominant cellular response. Inactivation of wild-type p53 leads to loss of G1/S checkpoint control and to genomic instability, including increased spontaneous homologous recombination (HR), To determine whether regulation of the G1/S checkpoint is required for suppression of HR, we assessed recombination events using a plasmid substrate that stably integrated into the genome of p53-null mouse fibroblasts. Exogenous expression of a temperature-sensitive p53 protein (Ala135 to Val), which had lost trans-activation function and could not regulate G1/S transition,when in mutant conformation, reduced HR rates to the same extent as wild-type p53. Furthermore, a p53 construct with an alternatively-spliced carboxy terminus also retained this ability in the absence of both activities, G1/S control and non-sequence specific DNA binding as mediated by the carboxy terminus. Our data dissociate regulation of HR by p53 from its role as a cell cycle checkpoint protein. The results support a model which extends p53's role as a guardian of the genome to include transactivation-independent regulatory functions in DNA repair, replication and recombination. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Lab Mol & Cellulare Radiat Biol, Charlestown, MA 02129 USA. Univ Hamburg, Hosp Eppendorf, Dept Radiat Oncol, D-20246 Hamburg, Germany. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Powell, SN (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Radiat Oncol, Cox 3,100 Blossom St, Boston, MA 02114 USA. RI Xia, Fen/G-3708-2013 FU NCI NIH HHS [CA 58985] NR 53 TC 77 Z9 79 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 3 PY 2000 VL 19 IS 5 BP 632 EP 639 DI 10.1038/sj.onc.1203142 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 281ZU UT WOS:000085192000005 PM 10698508 ER PT J AU Schrag, D Kuntz, KM Garber, JE Weeks, JC AF Schrag, D Kuntz, KM Garber, JE Weeks, JC TI Life expectancy gains from cancer prevention strategies for women with breast cancer and BRCA1 or BRCA2 mutations SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Conference of the Society-for-Medical-Decision-Making CY OCT 24-28, 1998 CL BOSTON, MASSACHUSETTS SP Soc Med Decis Making ID CORONARY HEART-DISEASE; 20-YEAR FOLLOW-UP; OVARIAN-CANCER; DECISION-ANALYSIS; PROPHYLACTIC MASTECTOMY; COST-EFFECTIVENESS; RISK FACTOR; MORTALITY; SURVIVAL; CARCINOMA AB Context Women with BRCA1- or BRCA2-associated breast cancer are at increased risk for contralateral breast cancer and ovarian cancer and therefore may consider secondary cancer prevention strategies, such as prophylactic surgery and tamoxifen therapy. It is not proven to what extent these strategies reduce risk of second cancers in such patients. Objective To examine the effect of tamoxifen therapy, bilateral prophylactic oophorectomy (PO), prophylactic contralateral mastectomy (PCM), and combinations of these strategies on life expectancy for women with unilateral breast cancer and a BRCA1 or BRCA2 gene mutation. Design and Setting Decision analysis using a Markov model. Probabilities for developing contralateral breast cancer and ovarian cancer, dying from these cancers, dying from primary breast cancer, and the reduction in cancer incidence and mortality due to prophylactic surgeries and/or tamoxifen were estimated from published studies. Participants Hypothetical breast cancer patients with BRCA1 or BRCA2 mutations facing decisions about secondary cancer prevention strategies. Interventions Seven strategies, including 5 years of tamoxifen use, PO, PCM, and combinations of these strategies, compared with careful surveillance. Main Outcome Measures Total and incremental life expectancy (LE) with each intervention strategy. Results Depending on the assumed penetrance of the BRCA mutation, compared with surveillance alone, 30-year-old early-stage breast cancer patients with BRCA mutations gain in LE 0.4 to 1.3 years from tamoxifen therapy, 0.2 to 1.8 years from PO, and 0.6 to 2.1 years from PCM, The magnitude of these gains is least for women with low-penetrance mutations (assumed contralateral breast cancer risk of 24% and ovarian cancer risk of 6%) and greatest for those with high-penetrance mutations (assumed contralateral breast cancer risk of 65% and ovarian cancer risk of 40%.) Older age and poorer prognosis from primary breast cancer further attenuate these gains. Conclusions Interventions to prevent second cancers, particularly PCM, may offer substantial LE gain for young women with BRCA-associated early-stage breast cancer. Estimates of LE gain may help women and their physicians consider the uncertainties, risks, and advantages of these interventions and lead to more informed choices about cancer prevention strategies. C1 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 Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Schrag, D (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, Hlth Outcomes Res Grp, 1275 York Ave, New York, NY 10021 USA. NR 57 TC 137 Z9 138 U1 0 U2 9 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 FEB 2 PY 2000 VL 283 IS 5 BP 617 EP 624 DI 10.1001/jama.283.5.617 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 277WL UT WOS:000084956500027 PM 10665701 ER PT J AU Lee, SJ Earle, CC Weeks, JC AF Lee, SJ Earle, CC Weeks, JC TI Outcomes research in oncology: History, conceptual framework, and trends in the literature SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID HEALTH-CARE; MEDICAL-PRACTICE; MANAGEMENT AB "Outcomes research") is a commonly used term, but what does it really mean? In this review article, we 1) briefly review the historic background of outcomes research, paying particular attention to the social and political movements that helped shape the field; 2) present a conceptual framework to help classify the major areas of research and provide a working definition of outcomes research; and 3) review the oncology literature in the English language from 1966 through 1998 to examine temporal trends and characterize the body of work being presented to the practicing oncology community, We conclude that outcomes research is a broad concept, which, in its current usage, describes an array of distinct types of research, However, common themes are apparent when outcomes research is viewed in the context of its historic origins and is contrasted with other established disciplines, especially clinical trials. Our literature review shows that outcomes studies are increasing in absolute numbers, in relative proportion of the oncology literature, and in quality, We suggest that as different branches of investigation develop their own literature and methodology-in effect, outgrowing the generic label of outcomes research-they, become identified by separate, more precise terms. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Lee, SJ (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA75267-01] NR 41 TC 44 Z9 47 U1 0 U2 1 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 FEB 2 PY 2000 VL 92 IS 3 BP 195 EP 204 DI 10.1093/jnci/92.3.195 PG 10 WC Oncology SC Oncology GA 279FE UT WOS:000085033100009 PM 10655436 ER PT J AU Marchant, BP Norbury, J Perumpanani, AJ AF Marchant, BP Norbury, J Perumpanani, AJ TI Traveling shock waves arising in a model of malignant invasion SO SIAM JOURNAL ON APPLIED MATHEMATICS LA English DT Article DE traveling waves; phase plane; singular barrier; hole in the wall; shock; Lax entropy condition AB Members of a family of traveling wave solutions for a simple two-variable model of malignant invasion driven by haptotaxis are shown to have shocks (which satisfy an entropy condition) and to be computationally stable. By seeking traveling wave solutions, a PDE model, equivalent to three first order PDEs defined on the real space and time axes, may be reduced to an ordinary differential equation system, which can be studied in a two-dimensional phase plane. This phase plane is shown to contain a singular barrier and a "hole" in this barrier which admits two singular phase trajectories. Thus orbits are able to smoothly cross this barrier along either of the two singular trajectories. Once this has occurred, the barrier seems to prevent any heteroclinic steady-state connections. However, we will show that shocks admitted by the PDEs allow the orbit to jump back over the singular barrier. This process leads to a previously unnoticed family of solutions for malignant invasion which have slower wavespeeds than the family of smooth traveling wave solutions (extending over the whole real axis) admitted by the model. The existence of a minimum-speed wave with semi-infinite support is demonstrated. The practical stability of these new shock solutions is confirmed via numerical solutions of the model. The minimum speed solution is found to evolve from specific nonsmooth initial data, whereas smooth initial data extending over the whole real axis evolves to faster waves. C1 Math Inst, Ctr Math Biol, Oxford OX1 3LB, England. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Shriners Burns Inst, Boston, MA 02114 USA. RP Marchant, BP (reprint author), Math Inst, Ctr Math Biol, 24-29 St Giles, Oxford OX1 3LB, England. OI Marchant, Ben/0000-0001-7633-1920 NR 10 TC 37 Z9 37 U1 0 U2 0 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 USA SN 0036-1399 J9 SIAM J APPL MATH JI SIAM J. Appl. Math. PD FEB 2 PY 2000 VL 60 IS 2 BP 463 EP 476 PG 14 WC Mathematics, Applied SC Mathematics GA 290JC UT WOS:000085672300005 ER PT J AU Palepu, A Carr, PL Friedman, RH Ash, AS Moskowitz, MA AF Palepu, A Carr, PL Friedman, RH Ash, AS Moskowitz, MA TI Specialty choices, compensation, and career satisfaction of underrepresented minority faculty in academic medicine SO ACADEMIC MEDICINE LA English DT Article ID DEBT; STUDENTS; PHYSICIANS; INTENTIONS; SCHOOL; WOMEN; RANK; MEN AB Purpose. Despite efforts to increase the numbers of underrepresented minorities (URMs), only 3.9% of medical school faculty are URMs, The authors compared the specialty choices, compensation, and career satisfaction of minority faculty with those of their majority counterparts to determine whether there were differences that might affect the recruitment and retention of minority faculty. Method. In 1995, the authors mailed a self-administered survey to a stratified random sample of 3,013 eligible full-time salaried faculty in 24 randomly selected medical schools. Those schools, which had at least 200 faculty, did not include the Puerto Rican or historically black medical schools. Results. Of the eligible faculty surveyed, 1,807 (60%) responded; 1,463 were majority faculty, 195 were URM faculty, and 149 were other-minority faculty. Similar proportions of the three groups were in the primary care specialties. Only 11% of the URM respondents were in basic science departments. There was no significant difference in adjusted mean compensation between majority, URM, and other minority faculty. However, URM faculty were significantly less satisfied with their careers (adjusted scores: 60 versus > 65; P =.001) and more often considered leaving academic medicine within five years (58% versus < 45%). Conclusion. Given the demographic changes of the U.S. population, these issues should be addressed by deans and department heads in order to enhance recruitment and facilitate retention of URM faculty in academic medicine. C1 Boston Univ, Med Ctr, Dept Med, Gen Internal Med Sect, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Cambridge, MA 02138 USA. RP Palepu, A (reprint author), Univ British Columbia, St Pauls Hosp, Ctr Hlth Evaluat & Outcome Sci, Div Gen Internal Med, Room 620-B Burrard Bldg,1081 Burrard St, Vancouver, BC V6Z 1Y6, Canada. OI Palepu, Anita/0000-0002-7881-4800 NR 15 TC 58 Z9 58 U1 0 U2 7 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD FEB PY 2000 VL 75 IS 2 BP 157 EP 160 DI 10.1097/00001888-200002000-00014 PG 4 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 286CH UT WOS:000085425700010 PM 10693848 ER PT J AU Asbury, RF Lipsitz, S Graham, D Falkson, CI Baez, L Benson, AB AF Asbury, RF Lipsitz, S Graham, D Falkson, CI Baez, L Benson, AB TI Treatment of squamous cell esophageal cancer with topotecan - An Eastern Cooperative Oncology Group study (E2293) SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE esophageal cancer; topotecan ID TOPOISOMERASE-I INHIBITOR; DNA AB Seventeen patients with enhanced measurable squamous cell carcinoma of the esophagus were treated with topotecan 1.5 mg/m(2) daily for 5 days repeated every 21 days. Toxicity was severe, with 1 death from myelotoxicity and 10 patients with life-threatening myelotoxicity. Severe gastrointestinal toxicity consisting of vomiting was also seen in three patients. No response was seen in any of the patients in the study. Topotecan given in this manner has no activity in squamous cell carcinoma of the esophagus. C1 Interlakes Oncol & Hematol PC, Rochester, NY 14623 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Carle Clin Assoc, Urbana, IL USA. Univ Pretoria, ZA-0002 Pretoria, South Africa. San Juan City Hosp, San Juan, PR USA. Northwestern Univ, Sch Med, Chicago, IL USA. RP Asbury, RF (reprint author), Interlakes Oncol & Hematol PC, 211 White Spruce Blvd, Rochester, NY 14623 USA. FU NCI NIH HHS [CA16395, CA21692, CA23318] NR 12 TC 4 Z9 5 U1 0 U2 0 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 FEB PY 2000 VL 23 IS 1 BP 45 EP 46 DI 10.1097/00000421-200002000-00013 PG 2 WC Oncology SC Oncology GA 283AF UT WOS:000085253400013 PM 10683076 ER PT J AU Delgado, JC Greene, MF Winkelman, JW Tanasijevic, MJ AF Delgado, JC Greene, MF Winkelman, JW Tanasijevic, MJ TI Comparison of disaturated phosphatidylcholine and fetal lung maturity surfactant/albumin ratio in diabetic and nondiabetic pregnancies SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE fetal lung maturity; surfactant/albumin ratio; diabetes mellitus; phosphatidylcholine ID RESPIRATORY-DISTRESS SYNDROME; LECITHIN-SPHINGOMYELIN RATIO; TDX-FLM ASSAY; AMNIOTIC-FLUID; MATURATION; PREDICTION; PHOSPHATIDYLGLYCEROL; MELLITUS; WOMEN; MICROALBUMINURIA AB We studied fetal lung maturity (FLM) ty the amniotic fluid surfactant/albumin (FLM S/A) ratio and the disaturated phosphatidylcholine (DSPC) amniotic fluid levels at different gestational ages in diabetic (179 women with type 1 diabetes mellitus antedating pregnancy; infants delivered within 72 hours after amniotic fluid testing for DSPC level and FLM S/A ratio) and nondiabetic pregnancies (2 independent nondiabetic groups, 300 for FLM S/A ratio and 1,231 for DSP level). The degree of maternal glycemia during gestation was estimated by serial measurements of hemoglobin A(1). Multiple regression analyses, including gestational age (GAs) and diabetic status as independent variables and FLM S/A ratio and DSPC level as dependent variables, revealed significant effect from diabetic status and GA for FLM S/A ratio and a significant effect from GA but not from diabetic status for DSPC level. Glucose levels were controlled adequately throughout gestation as reflected by mean total glycated hemoglobin levels. Amniotic fluid levels of DSPC, the major surface tension-lowering component of pulmonary surfactant, are not significantly different between diabetic and nondiabetic pregnancies at different GAs. C1 Brigham & Womens Hosp, Dept Pathol, Clin Labs, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. RP Tanasijevic, MJ (reprint author), Brigham & Womens Hosp, Dept Pathol, Clin Labs, Amory 215A,75 Francis St, Boston, MA 02115 USA. NR 33 TC 6 Z9 7 U1 0 U2 1 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD FEB PY 2000 VL 113 IS 2 BP 233 EP 239 PG 7 WC Pathology SC Pathology GA 277KJ UT WOS:000084932500007 PM 10664625 ER PT J AU Schuna, AA Megeff, C AF Schuna, AA Megeff, C TI New drugs for the treatment of rheumatoid arthritis SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Review DE anakinra; anti-inflammatory agents; arthritis; celecoxib; CGP-28238; drugs; etanercept; infliximab; leflunomide; mechanism of action; meroxicam; nimesulide; rofecoxib; toxicity ID COX-2 INHIBITION; FUSION PROTEIN; DOUBLE-BLIND; LEFLUNOMIDE; PLACEBO; EFFICACY; METHOTREXATE; COMPLICATIONS; IMPROVEMENT; MELOXICAM AB New pharmacologic treatment options for rheumatoid arthritis (RA) are described Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for RA but are limited by the risk of adverse effects, especially gastrointestinal and renal toxicity. The therapeutic effects of these agents are mediated primarily through inhibition of cyclooxygenase (COX) and prevention of subsequent formation of prostaglandins and related inflammatory mediators. Nonspecific COX inhibition appears to be responsible for much of the toxicity of NSAIDs. Agents have been developed that can selectively inhibit the COX-2 isoforms, while sparing COX-1. Celecoxib and other COX-2 inhibitors appear to be no more efficacious than conventional NSAIDs, but offer superior safety. COX-2 inhibitors should be considered for patients who are candidates for NSAID therapy but at risk for GI bleeding. Unlike disease-modifying antirheumatic drugs (DMARDs), these agents do not alter underlying disease progression. Leflunomide is a newer DMARD that reduces pyrimidine synthesis, thus decreasing rheumatoid inflammation. Leflunomide appears to be as effective as methotrexate but, unlike that drug, does not necessitate monitoring for bone marrow toxicity. Etanercept, the first biological agent with FDA-approved labeling for use in RA, has shown efficacy and minimal toxicity, except for injection-site reactions. Other biologicals that have been investigated for use in RA include infliximab and interleukin-1-receptor antagonist. COX-2 inhibitors, leflunomide, and etanercept are promising new drugs available for treating RA. Other agents are underdevelopment. C1 Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA. St Louis Univ, Coll Pharm, St Louis, MO 63103 USA. St Louis Univ, Dept Community & Family Med, St Louis, MO 63103 USA. RP Schuna, AA (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace, Madison, WI 53705 USA. NR 48 TC 48 Z9 50 U1 2 U2 3 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD FEB 1 PY 2000 VL 57 IS 3 BP 225 EP 234 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 281AC UT WOS:000085135100015 PM 10674776 ER PT J AU Lunetta, KL Faraone, SV Biederman, J Laird, NM AF Lunetta, KL Faraone, SV Biederman, J Laird, NM TI Family-based tests of association and linkage that use unaffected sibs, covariates, and interactions SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; DOPAMINE TRANSPORTER GENE; TRANSMISSION/DISEQUILIBRIUM TESTS; RECEPTOR POLYMORPHISM; QUANTITATIVE TRAITS; DRD4 GENE; TRANSMISSION; DISEQUILIBRIUM; ADHD; LOCI AB We extend the methodology for family-based tests of association and linkage to allow for both variation in the phenotypes of subjects and incorporation of covariates into general-score tests of association. We use standard association models for a phenotype and any number of predictors. Fire then construct a score statistic, using likelihoods for the distribution of phenotype, given genotype. The distribution of the score is computed as a function of offspring genotypes, conditional on parental genotypes and trait values for offspring and parents. This approach provides a natural extension of the transmission/disequilibrium test to any phenotype and to multiple genes or environmental factors and allows the study of gene-gene and gene-environment interaction. When the trait varies among subjects or when covariates are included in the association model, the score statistic depends on one or more nuisance parameters. We suggest two approaches for obtaining parameter estimates: (1) choosing the estimate that minimizes the variance of the test statistic and (2) maximizing the statistic over a nuisance parameter and using a corrected P value. We apply our methods to a sample of families with attention-deficit/hyperactivity disorder and provide examples of how covariates and gene-environment and gene-gene interactions can be incorporated. C1 Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Child Psychiat Serv, Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Lunetta, KL (reprint author), Dana Farber Canc Inst, Dept Biostat Sci, 44 Binney St, Boston, MA 02115 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [R01 HD037694]; NIMH NIH HHS [R01MH59532, R01 MH057934, R01 MH059532, R01MH41314, R01MH57934] NR 36 TC 124 Z9 130 U1 6 U2 11 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD FEB PY 2000 VL 66 IS 2 BP 605 EP 614 DI 10.1086/302782 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 337QL UT WOS:000088373100027 PM 10677320 ER PT J AU Litvak, E Long, MC Schwartz, JS AF Litvak, E Long, MC Schwartz, JS TI Cost-effectiveness analysis under managed care: Not yet ready for prime time? SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Editorial Material C1 Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Harvard Ctr Risk Anal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Litvak, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Harvard Ctr Risk Anal, 718 Huntington Ave, Boston, MA 02115 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD FEB PY 2000 VL 6 IS 2 BP 254 EP 256 PG 3 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 285CW UT WOS:000085372700007 PM 10977424 ER PT J AU McDonald, DM Munn, L Jain, RK AF McDonald, DM Munn, L Jain, RK TI Vasculogenic mimicry: How convincing, how novel, and how significant? SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Editorial Material ID CILIARY BODY MELANOMAS; TUMOR BLOOD-VESSELS; UVEAL MELANOMA; MICROCIRCULATION ARCHITECTURE; CHOROIDAL MELANOMAS; VASCULAR PATTERNS; PROGRESSION; HEMORRHAGE; CELLS; FLOW C1 Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Edwin L Steele Lab, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP McDonald, DM (reprint author), Univ Calif San Francisco, Cardiovasc Res Inst, Box S-1363, San Francisco, CA 94143 USA. FU NCI NIH HHS [R35-CA-56591]; NHLBI NIH HHS [HL-24136, HL-59157, P01 HL024136, R01 HL059157] NR 46 TC 120 Z9 134 U1 0 U2 6 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD FEB PY 2000 VL 156 IS 2 BP 383 EP 388 DI 10.1016/S0002-9440(10)64740-2 PG 6 WC Pathology SC Pathology GA 283VJ UT WOS:000085296500003 PM 10666365 ER PT J AU Chan, WY Cheung, KK Schorge, JO Huang, LW Welch, WR Bell, DA Berkowitz, RS Mok, SC AF Chan, WY Cheung, KK Schorge, JO Huang, LW Welch, WR Bell, DA Berkowitz, RS Mok, SC TI Bcl-2 and p53 protein expression, apoptosis, and p53 mutation in human epithelial ovarian cancers SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID WILD-TYPE P53; CELL LUNG-CANCER; K-RAS; ONCOPROTEIN EXPRESSION; FOLLICULAR LYMPHOMA; NERVOUS-SYSTEM; BREAST-CANCER; GENE MUTATION; CARCINOMAS; TUMORS AB Bcl-2 and p53 gene products have been both linked to cell death by apoptosis. In the present study, we examined the relationship of Bcl-2 and p53 protein expression,p53 mutation and apoptosis in normal human ovaries and different types of human ovarian epithelial tumors by immunohistochemical localization, in situ terminal transferase-mediated dUTP nick end labeling and polymerase chain reaction-single strand conformation polymorphism. It was found that Bcl-2 expressed strongly in the surface epithelium of normal ovaries and benign and borderline ovarian tumors but weakly in the malignant tumors. On the contrary, strong protein expression of p53 was found in 54% (25/46) of the malignant epithelial tumors examined but similar expression of p53 was not observed in borderline and benign tumors and normal ovarian surface epithelium, A significant inverse correlation between Bcl-2 and p53 expression was found in the malignant ovarian tumors examined. p53 gene mutation at exons 5-11 was however not a pre-requisite for p53 expression in both borderline and malignant tumors. Apoptotic activities, as reflected by apoptotic indices, were low in normal ovarian surface epithelium and. benign tumors but were increased in borderline and malignant tumors, with the highest average apoptotic index found in grade III malignant tumors. Statistical analyses showed a positive correlation between apoptosis and p53 expression, but similar correlation was not found between apoptosis and Bcl-2 expression. Our results also indicate that although expression of Bcl-2 is important during ovarian carcinogenesis, the Bcl-2 protein may have other roles to play apart from being a modulator of apoptosis in human ovarian epithelial cancers. C1 Chinese Univ Hong Kong, Fac Med, Dept Anat, Hong Kong, Hong Kong, Peoples R China. Harvard Univ, Sch Med, Lab Gynecol Oncol, Dept Obstet Gynecol & Reprod Biol, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Mok, SC (reprint author), 221 Longwood Ave,BL1 449B, Boston, MA 02115 USA. FU NCI NIH HHS [CA69453, CA69291] NR 65 TC 108 Z9 122 U1 0 U2 7 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD FEB PY 2000 VL 156 IS 2 BP 409 EP 417 DI 10.1016/S0002-9440(10)64744-X PG 9 WC Pathology SC Pathology GA 283VJ UT WOS:000085296500007 PM 10666369 ER PT J AU Gukovskaya, AS Gukovsky, S Pandol, SJ AF Gukovskaya, AS Gukovsky, S Pandol, SJ TI Endoplasmic reticulum Ca2+-ATPase inhibitors stimulate membrane guanylate cyclase in pancreatic acinar cells SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE calcium transport; cyclopiazonic acid; 2,5-di-(t-butyl)-1,4-hydroquinone; guanosine 3 ',5 '-cyclic monophosphate ID NATRIURETIC-PEPTIDE RECEPTOR; CA2+ TRANSPORT ATPASES; NITRIC-OXIDE; CYCLIC-GMP; SARCOPLASMIC-RETICULUM; PROTEIN; CALCIUM; BINDING; ATRIAL; FAMILY AB In this study, we show that particulate guanylate cyclase (GC) is present in rat pancreatic acinar cells and is located both on plasma membrane and membranes of endoplasmic reticulum (ER). Western blot analysis indicates that the enzyme isoform GC-A is present in the acinar cell membranes. The specific inhibitors of ER Ca2+-ATPase thapsigargin, 2,5-di-(t-butyl)-1,4-hydroquinone (BHQ), and cyclopiazonic acid all activated particulate GC in pancreatic acini, both in membrane fractions and intact cells. These inhibitors also induced dephosphorylation of GC. Dose dependencies of Ca2+-ATPase inhibition and GC activation by BHQ are very similar, and those for thapsigargin partially overlap. ER Ca2+-ATPase and GC are coimmunoprecipitated both by antisera against membrane CC and by antisera against ER Ca2+-ATPase, suggesting a physical association between the two enzymes. The results suggest that thapsigargin and the other inhibitors act through ER Ca2+-ATPase to activate membrane GC in pancreatic acinar cells, although their direct effect, on GC cannot be excluded. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. RP Gukovskaya, AS (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,Bldg 258,Rm 340, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-33010] NR 42 TC 3 Z9 3 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD FEB PY 2000 VL 278 IS 2 BP C363 EP C371 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 282RD UT WOS:000085231400015 PM 10666032 ER PT J AU Brown, D AF Brown, D TI Targeting of membrane transporters in renal epithelia: when cell biology meets physiology SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Review DE protein sorting; epithelial polarity; cytoskeleton; vesicle trafficking; membrane recycling ID AQUAPORIN-2 WATER CHANNEL; TRANSMEMBRANE CONDUCTANCE REGULATOR; POLYMERIC IMMUNOGLOBULIN RECEPTOR; GLUT4 GLUCOSE-TRANSPORTER; DUCT PRINCIPAL CELLS; CANINE KIDNEY-CELLS; GTP-BINDING-PROTEIN; TRANS-GOLGI NETWORK; VACUOLAR H+-ATPASE; RAT-KIDNEY AB Epithelial cells in the kidney have highly specialized transport mechanisms that differ among the many tubule segments, and among the different cell types that are present in some regions. The purpose of this brief review is to examine some of the major intracellular mechanisms by which the membrane proteins that participate in these differentiated cellular functions are addressed, sorted, and delivered to specific membrane domains of epithelial cells. Unraveling these processes is important not only for our understanding of normal cellular function but is also critical for the interpretation of pathophysiological dysfunction in the context of newly generated molecular and cellular information concerning hereditary and acquired transporter abnormalities. Among the topics covered are sorting signals on proteins, role of the cytoskeleton, vesicle coat proteins, the fusion machinery, and exo- and endocytosis of recycling proteins. Examples of these events in renal epithelial cells are highlighted throughout this review and are related to the physiology of the kidney. C1 Harvard Univ, Sch Med, Program Membrane Biol, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Renal Unit, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Brown, D (reprint author), Massachusetts Gen Hosp East, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. EM brown@receptor.mgh.harvard.edu FU NIDDK NIH HHS [DK-42956, DK-38452] NR 134 TC 25 Z9 25 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD FEB PY 2000 VL 278 IS 2 BP F192 EP F201 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 282QR UT WOS:000085230000003 PM 10662723 ER PT J AU Gustafson, CE Katsura, T McKee, M Bouley, R Casanova, JE Brown, D AF Gustafson, CE Katsura, T McKee, M Bouley, R Casanova, JE Brown, D TI Recycling of AQP2 occurs through a temperature- and bafilomycin-sensitive trans-Golgi-associated compartment SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE aquaporin-2; endocytosis; vacuolar proton-adenosinetriphosphatase; proton pump; water channels ID NEPHROGENIC DIABETES-INSIPIDUS; AQUAPORIN-2 WATER CHANNEL; CELL-SURFACE; EPITHELIAL-CELLS; MICROTUBULE DISRUPTION; REGULATED TRAFFICKING; MEMBRANE-PROTEINS; LATE ENDOSOMES; RAT-KIDNEY; VASOPRESSIN AB The exo- and endocytotic pathway in which aquaporin-2 (AQPB) travels between the plasma membrane and intracellular vesicles is only partially characterized. It is known that the antidiuretic hormone vasopressin induces a translocation of AQP2 from an intracellular to a plasma membrane location, both in kidney collecting duct principal cells and in transfected epithelial cells. Here we provide evidence suggesting that while AQPB shifts from an intracellular location to the cell surface in response to vasopressin, AQPB also constitutively recycles through a similar pathway in transfected LLC-PK(1) cells even in the absence of hormonal stimulation. Incubating cells at 20 degrees C blocks AQP2 recycling in a perinuclear compartment, regardless of whether vasopressin is present. The H(+)-ATPase inhibitor bafilomycin A1 also blocks the recycling pathway ofAQP2 in a perinuclear compartment adjacent to the Golgi in the presence and absence ofvasopressin stimulation, indicating a role of vesicle acidification in both the constitutive and regulated recycling ofAQP2. Colocalization of AQP2 with clathrin, but not with giantin, after both bafilomycin treatment and a 20 degrees C block suggests that the compartment in which recycling AQP2 is blocked may be the trans-Golgi, and not cis- and medial-Golgi cisternae. C1 Massachusetts Gen Hosp, Program Membrane Biol, Renal Unit, Boston, MA 02129 USA. Massachusetts Gen Hosp, Pediat Gastroenterol Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02129 USA. RP Brown, D (reprint author), Massachusetts Gen Hosp East, Renal Unit, 149 13th St,8th Floor, Charlestown, MA 02129 USA. EM brown@receptor.mgh.harvard.edu RI chen, xuanlan/H-4158-2011 FU NIDDK NIH HHS [DK-38452, DK-42956] NR 55 TC 56 Z9 57 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD FEB PY 2000 VL 278 IS 2 BP F317 EP F326 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 282QR UT WOS:000085230000016 PM 10662736 ER PT J AU Van Hoek, AN Ma, TH Yang, BX Verkman, AS Brown, D AF Van Hoek, AN Ma, TH Yang, BX Verkman, AS Brown, D TI Aquaporin-4 is expressed in basolateral membranes of proximal tubule S3 segments in mouse kidney SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE freeze-fracture electron microscopy; immunocytochemistry; orthogonal arrays; square array; aquaporin-4-knockout ID INSENSITIVE WATER CHANNEL; PLASMA-MEMBRANES; INTRINSIC PROTEIN; CELLS; LOCALIZATION; LACKING; FAMILY; MICE; SDS AB Because of the availability of knockout mouse models to examine renal transport mechanisms, it has become increasingly important to describe the cellular distribution of major renal transporters in mice. We have used immunocytochemistry and freeze-fracture electron microscopy to compare the renal distribution of aquaporin-4 (AQP4) with that previously described in rat. In rat kidney AQP4 is present exclusively in basolateral membranes of collecting duct principal cells. In mice, however, AQP4 was also detected by immunocytochemistry in basolateral membranes of proximal tubule S3 segments, and not detected in S1 and S2 segments of proximal tubule. Freeze-fracture electron microscopy revealed orthogonal arrays of intramembrane particles (OAPs) on the basolateral membranes of the S3 segment. In AQP4-knockout mice, immunostaining was absent and OAPs were found neither in collecting ducts nor in the S3 segment of the proximal tubule. The urinary concentrating capacity after deletion of both AQP1 and AQP4 was further reduced compared with that of AQP1 or AQP4 null mice, suggesting an additive effect of AQP1 and AQP4 in the concentrating mechanism. The functional significance of the apparent species-dependent expression of AQP4 in proximal tubules is unknown, but may relate to physiological differences between rats and mice. C1 Massachusetts Gen Hosp, Program Membrane Biol, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. RP Van Hoek, AN (reprint author), Massachusetts Gen Hosp East, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. EM vanhoek@receptor.mgh.harvard.edu FU NIDDK NIH HHS [DK-35124, DK-38452, DK-55864] NR 25 TC 53 Z9 53 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD FEB PY 2000 VL 278 IS 2 BP F310 EP F316 PG 7 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 282QR UT WOS:000085230000015 PM 10662735 ER PT J AU Viguera, AC Nonacs, R Cohen, LS Tondo, L Murray, A Baldessarini, RJ AF Viguera, AC Nonacs, R Cohen, LS Tondo, L Murray, A Baldessarini, RJ TI Risk of recurrence of bipolar disorder in pregnant and nonpregnant women after discontinuing lithium maintenance SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PUERPERAL PSYCHOSIS; GRADUAL DISCONTINUATION; POSTPARTUM PSYCHOSES; PROPHYLACTIC LITHIUM; ANXIETY DISORDERS; BABY ADMISSIONS; ILLNESS; DEPRESSION; CLASSIFICATION; MANAGEMENT AB Objective: Pregnancy poses major challenges for the treatment of bipolar disorder, and information to guide clinical care remains very sparse. The authors sought to determine the illness recurrence risk for women with bipolar disorder who discontinue lithium maintenance during pregnancy. Method: The authors retrospectively compared recurrence rates and survival functions for 101 women with DSM-IV bipolar disorder (68 type 1, 33 type ii) during pregnancy and postpartum (N=42) or during equivalent periods (weeks 1-40 and 41-64) for age-matched nonpregnant subjects (N=59) after either rapid (1-14 days) or gradual (15-30 days) discontinuation of lithium. Recurrence rates also were obtained for the year before discontinuing lithium. Results: Rates of recurrence during the first 40 weeks after lithium discontinuation were similar for pregnant (52%) and nonpregnant women (58%) but had been much lower for both in the year before treatment was discontinued (21%). Among subjects who remained stable over the first 40 weeks after lithium discontinuation, postpartum recurrences were 2.9 times more frequent than recurrences in nonpregnant women during weeks 41-64 (70% versus 24%), Depressive or dysphoric-mixed episodes were more prevalent in pregnant than nonpregnant women (63% versus 38% of recurrences). Recurrence risk was greater after rapid than after gradual discontinuation, and for patients with more prior affective episodes, but was similar for diagnostic types I and II. Conclusions: Rates of recurrence during the first 40 weeks after lithium discontinuation were similar for pregnant and nonpregnant women but then sharply increased postpartum. Risk was much lower during preceding treatment and less with gradual discontinuation. Treatment planning for potentially pregnant women with bipolar disorder should consider the relative risks of fetal exposure to mood stabilizers versus the high recurrence risks after discontinuing lithium. C1 Harvard Univ, Perinatal & Reprod Psychiat Serv, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. McLean Hosp, Bipolar & Psychot Disorders Program, Belmont, MA 02178 USA. Univ Cagliari, Dept Psychol, Cagliari, Italy. RP Viguera, AC (reprint author), Harvard Univ, Perinatal & Reprod Psychiat Serv, Massachusetts Gen Hosp, Sch Med, WACC-812,Fruit St, Boston, MA 02114 USA. FU NIMH NIH HHS [MH-47370, MH-01609] NR 58 TC 193 Z9 199 U1 0 U2 7 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 FEB PY 2000 VL 157 IS 2 BP 179 EP 184 DI 10.1176/appi.ajp.157.2.179 PG 6 WC Psychiatry SC Psychiatry GA 281PC UT WOS:000085169000005 PM 10671384 ER PT J AU Henke, KG Frantz, DE Kuna, ST AF Henke, KG Frantz, DE Kuna, ST TI An oval elastic mandibular advancement device for obstructive sleep apnea SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID ORAL APPLIANCES; AIRWAY-PATENCY; SITE; UVULOPALATOPHARYNGOPLASTY; EFFICACY AB Oral mandibular advancement devices are becoming an increasingly important treatment alternative for obstructive sleep apnea (OSA). The first aim of the study was to determine whether a new oral elastic mandibular advancement device (EMA) prevents pharyngeal air-way closure during sleep in patients with OSA. The second aim of the study was to determine if the polysomnographic response to the oral mandibular advancement device: was dependent on the site of airway closure. Overnight polysomnograms were performed in 28 untreated OSA subjects with and without EMA. A third polysomnogram was performed in 12 of the subjects to determine the site of airway closure without the device. Site of airway closure above or below the oropharynx was determined by measuring the respective presence or absence of respiratory fluctuations in oropharyngeal pressure during induced occlusions in non-rapid eye movement (NREM) sleep, Mean apnea-hypopnea: index (AHI) was 52.6 +/- 28.2 (SD) events/h without the device and 21.2 +/- 19.3 events/h with the device, Nineteen subjects (68%) had at least a 50% reduction in AHI with the device. The change in AHI with the, device (AHI without device - AHI with device) was directly related to the AHI without the device. All three subjects with airway closure in the lower pharyngeal airway had a greater than 80% reduction in AHI with the device. Two of the nine subjects with airway closure in the velopharynx had a similar therapeutic response. The results show the effectiveness of EMA in the treatment of OSA, The results also indicate that polysomnographic severity of OSA and the site of airway closure should not be used to exclude patients from this oral device treatment. C1 Sleep Disorders Ctr Virginia, Richmond, VA USA. Univ Texas, Med Branch, Dept Internal Med, Galveston, TX 77550 USA. RP Kuna, ST (reprint author), Philadelphia Vet Affairs Med Ctr 111P, Pulm Crit Care & Sleep Sect, Univ & Woodland Ave, Philadelphia, PA 19104 USA. FU NCRR NIH HHS [RR-73]; NHLBI NIH HHS [HL-61272] NR 23 TC 58 Z9 62 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB PY 2000 VL 161 IS 2 BP 420 EP 425 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 285ED UT WOS:000085376000016 PM 10673180 ER PT J AU Harris, RS Hess, DR Venegas, JG AF Harris, RS Hess, DR Venegas, JG TI An objective analysis of the pressure-volume curve in the acute respiratory distress syndrome SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID END-EXPIRATORY PRESSURE; AIRWAY-CLOSURE; MECHANICAL VENTILATION; ALVEOLAR RECRUITMENT; LUNG; FAILURE; SCAN; ARDS AB To assess the interobserver and intraobserver variability in the clinical evaluation of the quasi-static pressure-volume (P-V) curve, we analyzed 24 sets of inflation and deflation P-V curves obtained from patients with ARDS. We used a recently described sigmoidal equation to curve-fit the P-V data sets and objectively define the point of maximum compliance increase of the inflation limb (P-mci,P-i) and the true inflection point of the deflation limb (P-inf,P-d). These points were compared with graphic determinations of lower Pflex by seven clinicians. The graphic and curve-fitting methods were, also compared for their ability to reproduce the same parameter value in data sets with reduced number of data points. The sigmoidal equation fit the P-V data with great accuracy (R-2 = 0.9992). The average of Pflex determinations was found to be correlated with P-mci,P-i (R = 0.89) and P-inf,P-d (R = 0.76). Individual determinations of Pflex were less correlated with the corresponding objective parameters (R = 0.67 and 0.62 respectively). Pflex + 2 cm H2O was a more accurate estimator of P-inf,P-d (2 SD = +/-6.05 cm H2O) than Pflex was of P-mci,P-i (2 SD = +/-8.02 cm H2O). There was significant interobserver variability in Pflex, with a maximum difference of 11 cm H2O for the same patient (SD = 1.9 cm H2O). Clinicians had difficulty reproducing Pflex in smaller data sets with differences as great as 17 cm H2O (SD = 2.8 cm H2O). In contrast, the curve-fitting method reproduced P-mci,P-i with great accuracy in reduced data sets (maximum difference of 1.5 cm H2O and SD = 0.3 cm H2O). We conclude that Pflex rarely coincided with the point of maximum compliance increase, defined by a sigmoid curve-fit with large differences in Pflex seen both among and within observers. Calculating objective parameters such as P-mci,P-i or P-inf,P-d from curve-fitted P-V data can minimize this large variability. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. RP Harris, RS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Bulfinch 148,55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-38267] NR 24 TC 108 Z9 121 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB PY 2000 VL 161 IS 2 BP 432 EP 439 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 285ED UT WOS:000085376000018 PM 10673182 ER PT J AU Kradin, RL Sakamoto, H Preffer, FI Dombkowski, D Springer, KM Leary, CP AF Kradin, RL Sakamoto, H Preffer, FI Dombkowski, D Springer, KM Leary, CP TI Accumulation of macrophages with dendritic cell characteristics in the pulmonary response to Listeria SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID ALVEOLAR MACROPHAGES; INFLAMMATORY RESPONSE; IMMUNE-RESPONSE; DOWN-REGULATION; NITRIC-OXIDE; LUNG; RECRUITMENT; INHIBITION; INDUCTION; SURFACE AB Pulmonary immunity reflects a balance between proinflammatory and immunosuppressive factors in the lung. To determine the immune activities of exudate macrophages in the pulmonary immune response, Lewis rats were injected intratracheally with heat-killed Listeria (HKL), labeled ex vivo with the lipophilic dye PKH-26. At 24 h, macrophages from bronchoalveolar lavage fluid were purified on the basis of their surface membrane expression of RMA, a macrophage-specific antigen, which is brightly expressed by resident alveolar macrophages but dimly expressed by monocytes. Pulmonary macrophages were analyzed for uptake of PKH-26-HKL, and RMA(bright/dim) macrophages sorted by FAGS were compared for cytokine expression, nitric oxide (NO) release, and APC activities. RMA(bright) macrophages were OX-62(-), B7(-), and factor XIIIa(-); they were the dominant mediators of phagocytosis when low doses of HKL were administered intratracheally but did not support the proliferation of T lymphocytes. RMA(dim) exudate macrophages were OX-62(+), B7(+), and factor XIIIa(+). They expressed more IL-1 and TNF, but less nitric oxide, than did RMA(bright) macrophages; they were excellent APCs for T cell responses. We conclude that a subset of RMA(dim) exudate macrophages shows phenotypic and functional evidence of dendritic cell differentiation. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Dept Pathol, 100 Blossom St,Cox 5, Boston, MA 02114 USA. FU PHS HHS [R01A139054] NR 26 TC 10 Z9 11 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB PY 2000 VL 161 IS 2 BP 535 EP 542 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 285ED UT WOS:000085376000033 PM 10673197 ER PT J AU Cullen, AR Cannon, CL Mark, EJ Colin, AA AF Cullen, AR Cannon, CL Mark, EJ Colin, AA TI Mycobacterium abscessus infection in cystic fibrosis: Colonization or infection? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID RAPIDLY GROWING MYCOBACTERIA; NONTUBERCULOUS MYCOBACTERIA; PULMONARY-DISEASE; AVIUM COMPLEX; IBUPROFEN; DIAGNOSIS AB We present a case of a patient with cystic fibrosis who was thought to be colonized with Mycobacterium abscessus for 13 yr prior to developing clinically apparent mycobacterial infection. However, histologic evidence indicated that invasive mycobacterial disease was present from the onset. While accepting that chronic endobronchial colonization with atypical mycobacteria may occur in patients with cystic fibrosis, the repeated isolation of mycobacteria from the sputum of these patients should alert the clinician to the possibility of indolent disease. Early consideration of treatment for this infection should occur in any patient with cystic fibrosis in whom there is an unexplained deterioration in lung function. The recent introduction of high dose ibuprofen raises concerns about its possible contribution to the progression of the infection. C1 Childrens Hosp, Dept Pulmonol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Cullen, AR (reprint author), Childrens Hosp, Dept Pulmonol, 300 Longwood Ave, Boston, MA 02115 USA. RI Cannon, Carolyn/A-4402-2008 NR 25 TC 93 Z9 94 U1 2 U2 4 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB PY 2000 VL 161 IS 2 BP 641 EP 645 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 285ED UT WOS:000085376000048 PM 10673211 ER PT J AU McLoud, TC AF McLoud, TC TI In my view: A centennial essay SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dept Thorac & Cardiac Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP McLoud, TC (reprint author), Harvard Univ, Sch Med, Dept Thorac & Cardiac Radiol, POB 9657,55 Fruit St, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 FEB PY 2000 VL 174 IS 2 BP 301 EP 302 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 276NU UT WOS:000084885000003 PM 10658693 ER PT J AU Smith, JJ Berlin, L AF Smith, JJ Berlin, L TI The disabled patient SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material C1 Rush N Shore Med Ctr, Skokie, IL 60076 USA. Rush Med Coll, Chicago, IL 60612 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Berlin, L (reprint author), Rush N Shore Med Ctr, 9600 Gross Point Rd, Skokie, IL 60076 USA. NR 4 TC 0 Z9 0 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 FEB PY 2000 VL 174 IS 2 BP 303 EP 306 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 276NU UT WOS:000084885000004 PM 10658694 ER PT J AU Goldberg, SN Gazelle, GS Mueller, PR AF Goldberg, SN Gazelle, GS Mueller, PR TI Thermal ablation therapy for focal malignancy: A unified approach to underlying principles, techniques, and diagnostic imaging guidance SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID RADIOFREQUENCY TISSUE ABLATION; INTERSTITIAL LASER PHOTOCOAGULATION; PERCUTANEOUS MICROWAVE COAGULATION; HEPATOCELLULAR-CARCINOMA; LIVER METASTASES; TUMOR ABLATION; INDUCED THERMOTHERAPY; HEPATIC METASTASES; ETHANOL INJECTION; BLOOD-FLOW C1 Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Goldberg, SN (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. NR 67 TC 557 Z9 602 U1 5 U2 36 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 FEB PY 2000 VL 174 IS 2 BP 323 EP 331 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 276NU UT WOS:000084885000009 PM 10658699 ER PT J AU Bennett, GL Petersein, A Mayo-Smith, WW Hahn, PF Schima, W Saini, S AF Bennett, GL Petersein, A Mayo-Smith, WW Hahn, PF Schima, W Saini, S TI Addition of gadolinium chelates to heavily T2-weighted MR imaging: Limited role in differentiating hepatic hemangiomas from metastases SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CONVENTIONAL SPIN-ECHO; FOCAL LIVER-LESIONS; CONTRAST-ENHANCED CT; CAVERNOUS HEMANGIOMA; GD-DTPA; TUMORS; IMAGES; SEQUENCES; FLASH; DISTINCTION AB OBJECTIVE. The purpose of this study was to determine whether the addition of gadolinium-enhanced imaging to heavily T2-weighted MR imaging of the liver is valuable in differentiating hemangiomas from metastases. The T2 relaxation time was also included in our analysis. SUBJECTS AND METHODS. Fifty-one patients with 52 proven liver lesions (24 hemangiomas and 28 metastases) larger than 1 cm underwent MR imaging at 1.5 T with T2-weighted spin-echo (TR/TE, 3000/80, 160) and gadolinium chelate-enhanced dynamic T1-weighted gradient-recalled echo (80/2.6, 80) pulse sequences. Images were reviewed by observers who were unaware of the patients' clinical history; first, only T2-weighted images were reviewed and then T2-weighted plus dynamic images were reviewed together. The T2 relaxation times were calculated:for each lesion. Diagnostic accuracy by each method was compared using receiver operating characteristic analysis. RESULTS. Mean T2 relaxation times were 76 +/- 26 msec for metastases and 133 +/- 25 msec for hemangiomas. The addition of dynamic scanning to the T2-weighted sequence made a statistically significant difference for only one observer (p = 0.03). However, it did not make a statistically significant contribution for either observer when compared with the T2 relaxation time. Although addition of the dynamic images resulted in correct diagnosis of six lesions, three lesions were misdiagnosed after having been correctly characterized on the T2-weighted images alone. CONCLUSION. When optimized T2-weighted images are obtained and the T2 relaxation time is calculated, routine use of gadolinium enhancement for differentiation of hemangiomas from metastases is unnecessary although dynamic scanning is valuable in selected cases. C1 Brown Univ, Rhode Isl Hosp, Sch Med, Dept Diagnost Imaging, Providence, RI 02903 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. RP Bennett, GL (reprint author), NYU, Med Ctr, Dept Abdominal Imaging, 560 1st Ave, New York, NY 10016 USA. NR 35 TC 32 Z9 35 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 FEB PY 2000 VL 174 IS 2 BP 477 EP 485 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 276NU UT WOS:000084885000039 PM 10658728 ER PT J AU Nucci, MR Young, RH Fletcher, CDM AF Nucci, MR Young, RH Fletcher, CDM TI Cellular pseudosarcomatous fibroepithelial stromal polyps of the lower female genital tract: An underrecognized lesion often misdiagnosed as sarcoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE fibroepithelial polyp; pseudosarcoma; female genital tract; vulva; vagina; cervix; soft tissue ID BENIGN NEOPLASM DISTINCT; AGGRESSIVE ANGIOMYXOMA; UTERINE CERVIX; MALIGNANT SCHWANNOMA; GIANT-CELLS; SOFT-TISSUE; ANGIOMYOFIBROBLASTOMA; VAGINA; VULVA; BOTRYOIDES AB Fibroepithelial stromal polyps of the vulvovaginal region are benign lesions that, when bland or hypocellular, are readily recognized. However those that exhibit bizarre cytomorphology, atypical mitoses, or hypercellularity, raising the possibility of malignancy, continue to be underrecognized, The authors reviewed a series of fibroepithelial stromal polyps to characterize further the morphologic features that can lead to a misdiagnosis of sarcoma. A total of 33 of 65 consecutive cases of fibroepithelial stromal polyps retrieved from the authors' consultation files were remarkable for marked hypercellularity (33 of 33), marked cytologic pleomorphism (21 of 33), mitotic counts of:more than 10 mitoses per 10 high-power fields (12 of 33), and the presence of atypical mitoses (14 of 33). A total of 16 of 33 lesions had three or more of these features. Important morphologic clues to the diagnosis (shared with usual polyps at this site) were lack of an identifiable lesional margin, extension of abnormal stromal tissue up to the mucosal-submucosal interface, and the frequent presence of individually scattered multinucleate stromal cells, most often located close to the surface epithelium. Immunohistochemically, seven of 12 cases were desmin positive and one of 11 cases were smooth muscle actin positive, The age range of patients was 16 to 75 years (median, 32 years), and 21 patients (64%) were premenopausal. Sites included the vagina (18 of 33), cervix (seven of 33), and vulva (eight of 33). A total of 14 of 33 patients were pregnant, three patients were taking Tamoxifen, and one patient was on oral progesterone. Eight of 33 patients had multiple lesions at the time of presentation, of whom five were pregnant. Clinical follow-up was available in 21 of 33 patients. Three of 21 patients with follow-up had local, nondestructive recurrence. Two of these patients had multiple recurrences. None of the patients followed-developed metastases. Cytologic atypia has been a previously recognized feature in these lesions; however, the occurrence of marked stromal cellularity and a mitotic rate of more than 10 mitoses per 10 high-power fields have not been emphasized previously. Moreover, the combination of these features has only rarely been documented. Awareness of the spectrum of histologic features that these lesions can exhibit is crucial in their accurate recognition, thus avoiding potential overtreatment. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Dept Pathol, Boston, MA 02114 USA. RP Fletcher, CDM (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 40 TC 65 Z9 72 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD FEB PY 2000 VL 24 IS 2 BP 231 EP 240 DI 10.1097/00000478-200002000-00009 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 280ZM UT WOS:000085133700009 PM 10680891 ER PT J AU Cheema, MA Rahman, MU Whittum-Hudson, JA Hudson, AP AF Cheema, MA Rahman, MU Whittum-Hudson, JA Hudson, AP TI Rapid communication: Cervical Chlamydia trachomatis in women at low risk for infection SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE chlamydia; inapparent infection; molecular hybridization; clinical screening; polymerase chain reaction ID ROUTINE GYNECOLOGIC CARE; REITERS-SYNDROME AB Background: Evidence suggests that the bacterium Chlamydia trachomatis can cause asymptomatic genital infection in persons at risk for acquisition of the organism. We employed 2 independent molecular screening systems to assess such inapparent cervical chlamydial infections in low-risk female patients attending general (non-STD) clinics in 2 locations. Methods: Three hundred seventy-five cervical swab samples were obtained in duplicate from patients attending a general women's clinic (278 samples) and a colposcopy clinic (97 samples). One set of samples from the general clinic was screened by a highly-specific molecular hybridization system, using a probe targeting the chlamydial 16S ribosomal RNA; the other set was screened with the use of the Chlamydiazyme test. Samples from the colposcopy clinic were screened using a sensitive and specific polymerase chain reaction (PCR) assay system targeting chlamydia; the duplicates were assayed by direct fluorescent antibody assay (DFA). Results: Of the 278 patients screened by RNA-directed hybridization, 6.5% were positive for C trachomatis, in contrast to screening of duplicate samples via Chlamydiazyme, which indicated that 3.6% were infected. PCR-based screening of the additional 97 patients gave a positivity rate of 17.5% for the organism, whereas DFA on duplicate samples from this group showed only 7.5% positive. Conclusions: These observations suggest that the level of asymptomatic cervical C trachomatis infection is significant even in women who are at low risk for such infections; the data also indicate that results from standard laboratory screening for chlamydia should be viewed with caution. C1 Wayne State Univ, Sch Med, Dept Immunol & Microbiol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Med, Detroit, MI 48201 USA. Massachusetts Gen Hosp, Dept Med, Arthrit Unit, Boston, MA 02114 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Frost Lab Cytopathol, Baltimore, MD 21205 USA. RP Hudson, AP (reprint author), Wayne State Univ, Sch Med, Dept Immunol & Microbiol, Gordon H Scott Hall,540 E Canfield Ave, Detroit, MI 48201 USA. FU NIAMS NIH HHS [AR42541]; PHS HHS [ET03324] NR 11 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD FEB PY 2000 VL 319 IS 2 BP 123 EP 125 DI 10.1097/00000441-200002000-00010 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 285EL UT WOS:000085376700010 PM 10698098 ER PT J AU Olsen, I Paster, BJ Dewhirst, FE AF Olsen, I Paster, BJ Dewhirst, FE TI Taxonomy of spirochetes SO ANAEROBE LA English DT Review DE spirochetes; chemistry; classification; identification ID FRAGMENT-LENGTH-POLYMORPHISM; RIBOSOMAL-RNA GENE; BURGDORFERI SENSU-LATO; MULTILOCUS ENZYME ELECTROPHORESIS; RESTRICTION ENDONUCLEASE ANALYSIS; POLYACRYLAMIDE-GEL-ELECTROPHORESIS; HYODYSENTERIAE COMB-NOV; SUB-SPECIFIC DIFFERENTIATION; INTERROGANS SEROVAR HARDJO; LYME-DISEASE PATIENTS AB The taxonomy of spirochetes has improved considerably over the last few years. Even non-cultivable spirochetes have been classified and identified and highly discriminating analytical methods have been used to distinguish these unique organisms. The present article reviews major characteristics and techniques that have been applied in recent molecular taxonomy and chemotaxonomy of spirochetes. These comprise cellular lipids, carbohydrates, peptidoglycan, enzymes, cell proteins, cytoplasmic fibrils, metabolites, genome size, structure and base composition, restriction endonuclease analysis, restriction fragment length polymorphism, multilocus enzyme electrophoresis, pulsed-field gel electrophoresis, DNA-DNA hybridization, arbitrarily primed polymerase chain reaction/randomly amplified polymorphic DNA fingerprinting, ribosomal (r) RNA cataloguing and sequencing, characterization of intergenic spacer regions of rRNA genes, ospA, lipoprotein and flagellin gene sequencing, and rRNA gene organization. Characteristics and techniques such as those listed above have contributed to the recognition of new spirochetal genera and species and have made spirochetal taxonomy polyphasic. Despite these improvements, significant reservoirs of hitherto unrecognized. spirochetal diversity probably still exist. (C) 2000 Academic Press. C1 Univ Oslo, Fac Dent, Inst Oral Biol, N-0316 Oslo, Norway. Forsyth Inst, Dept Mol Genet, Boston, MA USA. RP Olsen, I (reprint author), Univ Oslo, Fac Dent, Inst Oral Biol, POB 1052 Blindern, N-0316 Oslo, Norway. NR 167 TC 17 Z9 17 U1 1 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1075-9964 J9 ANAEROBE JI Anaerobe PD FEB PY 2000 VL 6 IS 1 BP 39 EP 57 DI 10.1006/anae.1999.0319 PG 19 WC Microbiology SC Microbiology GA 309GY UT WOS:000086761200006 ER PT J AU Ceccarelli, P Bigatello, LM Hess, D Kwo, J Melendez, L AF Ceccarelli, P Bigatello, LM Hess, D Kwo, J Melendez, L TI Inhaled nitric oxide delivery by anesthesia machines SO ANESTHESIA AND ANALGESIA LA English DT Article ID VENTILATION AB Inhaled nitric oxide (NO) is a selective pulmonary vasodilator used to treat intraoperative pulmonary hypertension and hypoxemia. In contrast to NO delivered by critical fare ventilators, NO delivered by anesthesia machines can be complicated by rebreathing. We evaluated two methods of administering NO intraoperatively: via the nitrous oxide (N2O) flowmeter and via the INOvent (Datex-Ohmeda, Madison, WI). We hypothesized that both systems would deliver NO accurately when the fresh gas flow (FGF) rate was higher than the minute ventilation ((V) over dot E). Each system was set to deliver NO to a lung model. Rebreathing of NO was obtained by decreasing FGF and by simulating partial NO uptake by the lung. At FGF greater than or equal to (V) over dot E (6 L/min), both systems delivered an inspired NO concentration ([NO]) within approximately 10% of the [NO] set, At FGF < (V) over dot E and complete NO uptake, the N2O flowmeter delivered a lower [NO] (70 and 40% of the [NO] set at 4 and 2 L/min, respectively) and the INOvent delivered a higher [NO] (10 and 23% higher than the [NO] set at 4 and 2 L/min, respectively). Decreasing the NO uptake increased the inspired [NO] similarly with both systems. At 4 L/min FGF, [NO] increased by 10%-20% with 60% uptake and by 18%-23% with 30% uptake. At 2 L/min, [NO] increased by 30%-33% with 60% uptake and by 60%-69% with 30% uptake. We conclude that intraoperative NO inhalation is accurate when administered either by the N2O flowmeter of an anesthesia machine or by the INOvent when FGF greater than or equal to (V) over dot E. Implications: Inhaled nitric oxide (NO) is a selective pulmonary vasodilator. In a lung model, we demonstrated that NO can be delivered accurately by a N2O flowmeter or by a commercial device. We provide guidelines for intraoperative NO delivery. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Clin 3, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. RP Bigatello, LM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Clin 3, 55 Fruit St, Boston, MA 02114 USA. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 14 TC 6 Z9 6 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 FEB PY 2000 VL 90 IS 2 BP 482 EP 488 DI 10.1097/00000539-200002000-00045 PG 7 WC Anesthesiology SC Anesthesiology GA 278KX UT WOS:000084989900045 PM 10648344 ER PT J AU Kaplan, RF Hannallah, R Denman, W Cote, C Ginsberg, B Hummer, K AF Kaplan, RF Hannallah, R Denman, W Cote, C Ginsberg, B Hummer, K TI A multicenter study to assess the efficacy and safety of IM rapacuronium (ORG9487) in infants and children SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract C1 Childrens Natl Med Ctr, Washington, DC 20010 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Mem Ctr, Chicago, IL USA. Univ Med Ctr, Durham, NC 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 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD FEB PY 2000 VL 90 IS 2 SU S MA S362 BP U216 EP U216 PG 1 WC Anesthesiology SC Anesthesiology GA 279FQ UT WOS:000085034100362 ER PT J AU Baba, H Shimoji, K Yoshimura, M AF Baba, H Shimoji, K Yoshimura, M TI Norepinephrine facilitates inhibitory transmission in substantia gelatinosa of adult rat spinal cord (Part 1) - Effects on axon terminals of GABAergic and glycinergic neurons SO ANESTHESIOLOGY LA English DT Article DE antinociception; blind patch-clamp recording; descending pain control system; inhibitory transmission; in vitro; transmitter release ID MINIATURE SYNAPTIC CURRENTS; LONG-TERM POTENTIATION; DORSAL HORN NEURONS; BLOOD-FLOW; IN-VITRO; NORADRENERGIC PROJECTIONS; SUBARACHNOID LIDOCAINE; NORADRENALINE; PHENYLEPHRINE; RESPONSES AB Background: The activation of descending norepinephrine containing fibers from the brain stem inhibits nociceptive transmission at the spinal level. How these descending noradrenergic pathways exert the analgesic effect is not understood fully. Membrane hyperpolarization of substantia gelatinosa (Rexed lamina II) neurons by the activation of alpha(2) receptors may account for depression of pain transmission. In addition, it is possible that norepinephrine affects transmitter release in the substantia gelatinosa. Methods: Adult male Sprague-Dawley rats (9-10 weeks of age, 250-300 g) were used in this study. Transverse spinal cord slices were cut from the isolated lumbar cord. The blind whole-cell patch-clamp technique was used to record from neurons. The effects of norepinephrine on the frequency and amplitude of miniature excitatory and inhibitory postsynaptic currents were evaluated. Results: In the majority of substantia gelatinosa neurons tested, norepinephrine (10-100 mu M) dose-dependently increased the frequency of gamma-aminobutyric acid (GABA)-ergic and glycinergic miniature inhibitory postsynaptic currents; miniature excitatory postsynaptic currents were unaffected, This augmentation was mimicked by an alpha(1)-receptor agonist, phenylephrine (10-60 mu M), and inhibited by alpha(1)-receptor antagonists prazosin (0.5 mu M) and 2-(2,6-dimethoxyphenoxyethyl) aminomethyl-1,4-benzodioxane (0.5 mu M). Neither postsynaptic responsiveness to exogenously applied GABA and glycine nor the kinetics of GABAergic and glycinergic inhibitory postsynaptic currents were affected by norepinephrine. Conclusion: These results suggest that norepinephrine enhances inhibitory synaptic transmission in the substantia gelatinosa through activation of presynaptic alpha(1) receptors, thus providing a mechanism underlying the clinical use of of, agonists with local anesthetics in spinal anesthesia. C1 Niigata Univ, Sch Med, Dept Anesthesiol, Niigata, Japan. RP Baba, H (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care Med, Neural Plast Res Grp, 4th Floor,149 13th St, Charlestown, MA USA. NR 51 TC 83 Z9 86 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD FEB PY 2000 VL 92 IS 2 BP 473 EP 484 DI 10.1097/00000542-200002000-00030 PG 12 WC Anesthesiology SC Anesthesiology GA 280AC UT WOS:000085078600026 PM 10691235 ER PT J AU Baba, H Goldstein, PA Okamoto, M Kohno, T Ataka, T Yoshimura, M Shimoji, K AF Baba, H Goldstein, PA Okamoto, M Kohno, T Ataka, T Yoshimura, M Shimoji, K TI Norepinephrine facilitates inhibitory transmission in substantia gelatinosa of adult rat spinal cord (Part 2) - Effects on somatodendritic sites of GABAergic neurons SO ANESTHESIOLOGY LA English DT Article DE antinociception; blind patch; clamp recording; intracellular recording; IPSC ID NORADRENALINE AB Background: It has been reported previously that norepinephrine, when applied to the spinal cord dorsal horn, excites a subpopulation of dorsal horn neurons, presumably inhibitory interneurons, in the current study, the authors tested whether norepinephrine could activate inhibitory interneurons, specifically those that are ''GABAergic.'' Methods: A transverse slice was obtained from a segment of the lumbar spinal cord isolated from adult male Sprague-Dawley rats. Whole-cell patch-clamp recordings were made from substantia gelatinosa neurons using the blind patch-clamp technique. The effects of norepinephrine on spontaneous GABAergic inhibitory postsynaptic currents were studied. Results: In the majority of substantia gelatinosa neurons tested, norepinephrine (10-60 mu M) significantly increased both the frequency and the amplitude of GABAergic inhibitory postsynaptic currents, These increases were blocked by tetrodotoxin (1 mu M). The effects of norepinephrine mere mimicked by the alpha(1)-receptor agonist phenylephrine (10-80 mu M) and inhibited by the alpha(1)-receptor antagonist WB-4101 (0.5 mu M). Primary-afferent-evoked polysynaptic excitatory postsynaptic potentials or excitatory postsynaptic currents in wide-dynamic-range neurons of the deep dorsal horn were also attenuated by phenylephrine (40 mu M). Conclusion: The observations suggest that GABAergic interneurons possess somatodendritic alpha(1) receptors, and activation of these receptors excites inhibitory interneurons, The alpha(1) actions reported herein may contribute to the analgesic action of intrathecally administered phenylephrine. C1 Niigata Univ, Sch Med, Dept Anesthesiol, Niigata 95021, Japan. RP Baba, H (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, Neural Plast Res Grp, MGH-E 4th Floor,149 13th St, Charlestown, MA 02129 USA. NR 11 TC 61 Z9 65 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD FEB PY 2000 VL 92 IS 2 BP 485 EP 492 DI 10.1097/00000542-200002000-00031 PG 8 WC Anesthesiology SC Anesthesiology GA 280AC UT WOS:000085078600027 PM 10691236 ER PT J AU Block, SD AF Block, SD CA ACP ASIM End Life Care Consensus P TI Assessing and managing depression in the terminally ill patient SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID STRUCTURED PSYCHIATRIC INTERVENTION; CANCER PAIN RELIEF; MEDICAL ILLNESS; PSYCHOLOGICAL SYMPTOMS; BREAST-CANCER; DISORDERS; ANTIDEPRESSANTS; SUICIDE; PREVALENCE; THERAPY RP Block, SD (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA66818-05] NR 94 TC 186 Z9 189 U1 4 U2 17 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 1 PY 2000 VL 132 IS 3 BP 209 EP 218 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 276XE UT WOS:000084903000006 PM 10651602 ER PT J AU Zietman, AL Shipley, WU Kaufman, DS AF Zietman, AL Shipley, WU Kaufman, DS TI Organ-conserving approaches to muscle-invasive bladder cancer: future alternatives to radical cystectomy SO ANNALS OF MEDICINE LA English DT Article DE chemotherapy; invasive bladder cancer; radiation ID TRANSITIONAL-CELL-CARCINOMA; 5-YEAR FOLLOW-UP; COMBINED-MODALITY PROGRAM; NEOADJUVANT CHEMOTHERAPY; ADJUVANT CHEMOTHERAPY; RADIATION-THERAPY; CISPLATIN CHEMOTHERAPY; TRANSURETHRAL SURGERY; SPARING TREATMENT; PROSPECTIVE TRIAL AB In the USA radical surgery remains the golden standard for invasive bladder cancer. Yet in most other areas of surgical oncology the trend of the 1990s has been towards organ conservation with chemoradiation with or without limited local surgery. Patients with breast, oesophageal, anal, lung and larynx cancer are routinely offered conservative therapies as valid options in the management of their diseases but bladder stands apart from the crowd. Evidence is presented here to show that this need not be the case. Four older randomized trials failed to show a survival advantage when immediate cystectomy was compared with radiation followed by salvage cystectomy, if required. Five and 8-year survival rates for clinically staged patients treated by transurethral resection and chemoradiation (trimodality therapy) in several modern, large and mature series show survival rates comparable to those reported in contemporary radical cystectomy series. Eighty per cent of those alive 5 years after chemoradiation still retain their native bladder. Although superficial relapse occurs in 20% of cases, it remains responsive to BCG (Bacilles bilie de Calmetre-Guerin) in the manner of de novo superficial disease. Quality-of-life studies show that the retained bladder functions well. At the Massachusetts General Hospital and in the multicentre prospective trials, less than 1% of patients needed cystectomy for bladder morbidity. It is of note that continent diversions may be performed as salvage after contemporary radiation therapy. Trimodality therapy is a novel and contemporary approach that owes little to the radiation treatment offered in the 1970s. While it will never entirely take the place of radical cystectomy, it should be offered as a reasonable alternative to patients with a new diagnosis of bladder cancer. This multidisciplinary approach will allow uro-oncology to keep in step with the oncological vanguard. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Zietman, AL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Box 302, Boston, MA 02114 USA. NR 58 TC 19 Z9 22 U1 0 U2 0 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 FEB PY 2000 VL 32 IS 1 BP 34 EP 42 DI 10.3109/07853890008995908 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 287UV UT WOS:000085525600006 PM 10711576 ER PT J AU Solano, SM Miller, DW Augood, SJ Young, AB Penney, JB AF Solano, SM Miller, DW Augood, SJ Young, AB Penney, JB TI Expression of alpha-synuclein, parkin, and ubiquitin carboxy-terminal hydrolase L1 mRNA in human brain: Genes associated with familial Parkinson's disease SO ANNALS OF NEUROLOGY LA English DT Article ID MULTIPLE SYSTEM ATROPHY; LEWY BODY DISEASE; RECESSIVE JUVENILE PARKINSONISM; MESSENGER-RNA; PGP 9.5; CYTOPLASMIC INCLUSIONS; ALZHEIMERS-DISEASE; MOLECULAR-CLONING; PROTEIN; MUTATION AB Mutations in the alpha-synuclein, parkin, and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) genes have been linked to some cases of familial Parkinson's disease. To provide insight into how these genes may relate to each other and contribute to the pathology of Parkinson's disease, their expression was examined in normal human brain. Tissue sections from multiple regions of 11 normal human brains were hybridized with radiolabeled and digoxygenin-labeled cRNA probes for alpha-synuclein, parkin, and UCH-LI mRNA. Expression of each of these three genes was predominantly neuronal. alpha-Synuclein and parkin mRNAs were expressed in a restricted number of brain regions, whereas UCH-LI mRNA was more uniformly expressed throughout brain. The melanin-containing dopamine neurons of the substantia nigra had particularly robust expression. The expression patterns of alpha-synuclein and parkin mRNAs were similar, suggesting that these two proteins may be involved in common pathways contributing to the pathophysiology of Parkinson's disease. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Young, AB (reprint author), Massachusetts Gen Hosp, Dept Neurol, Fruit St,Warren 401, Boston, MA 02114 USA. FU NINDS NIH HHS [NS38372] NR 49 TC 133 Z9 136 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD FEB PY 2000 VL 47 IS 2 BP 201 EP 210 DI 10.1002/1531-8249(200002)47:2<201::AID-ANA10>3.0.CO;2-F PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 280TR UT WOS:000085120300010 PM 10665491 ER PT J AU Gleeson, JG Luo, RF Grant, PE Guerrini, R Huttenlocher, PR Berg, MJ Ricci, S Cusmai, R Wheless, JW Berkovic, S Scheffer, I Dobyns, WB Walsh, CA AF Gleeson, JG Luo, RF Grant, PE Guerrini, R Huttenlocher, PR Berg, MJ Ricci, S Cusmai, R Wheless, JW Berkovic, S Scheffer, I Dobyns, WB Walsh, CA TI Genetic and neuroradiological heterogeneity of double cortex syndrome SO ANNALS OF NEUROLOGY LA English DT Article ID SUBCORTICAL LAMINAR HETEROTOPIA; NEURONAL MIGRATION; PATTERNS AB Mutations in the X-linked doublecortin gene appear in many sporadic cases of double cortex (DC; also known as subcortical band heterotopia), a neuronal migration disorder causing epilepsy and mental retardation. The purpose of this study was to examine why a significant percentage of sporadic DC patients had been found not to harbor doublecortin mutations and to determine whether clinical features or magnetic resonance imaging scan appearance could distinguish between patients with and without doublecortin mutations. Magnetic resonance imaging scan analysis differentiated patients into the following four groups: anterior biased/global DC with doublecortin mutation (16 of 30; 53%), anterior biased/global DC without mutation (8 of 30; 27%), posterior biased DC without mutation (3 of 30; 10%), and limited/unilateral DC without mutation (3 of 30; 10%). The presence of these atypical phenotypes suggests that other genetic loci or mosaicism at the doublecortin locus may be responsible for this diversity of DC cases. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Neurogenet,Inst Med,Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Inst Med, Program Neurosci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Inst Med, Program Biol & Biomed Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Univ Pisa, Inst Child Neurol & Psychiat, IRCCS, Stella Maris Fdn, Calambrone, Italy. Univ Rome La Sapienza, Dept Neurol Sci, Epilepsy Ctr, Dept Neurol Sci, Rome, Italy. Osped Pediat Bambino Gesu, Rome, Italy. Univ Chicago, Dept Pediat & Neurol, Chicago, IL 60637 USA. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA. Univ Texas, Sch Med, Texas Comprehens Epilepsy Program, Houston, TX USA. Univ Melbourne, Austin & Repatriat Med Ctr, Heidelberg, Vic, Australia. RP Walsh, CA (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Neurogenet,Inst Med,Dept Neurol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. RI Scheffer, Ingrid/G-1668-2013; OI Scheffer, Ingrid/0000-0002-2311-2174; Berkovic, Samuel/0000-0003-4580-841X; Dobyns, William/0000-0002-7681-2844 FU NINDS NIH HHS [5K12NS01701-04, R01 NS041537, R01-NS35129, R01-NS35515] NR 9 TC 65 Z9 65 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD FEB PY 2000 VL 47 IS 2 BP 265 EP 269 DI 10.1002/1531-8249(200002)47:2<265::AID-ANA22>3.0.CO;2-N PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 280TR UT WOS:000085120300022 PM 10665503 ER PT J AU Lee, SY Yeh, TH Lou, PJ Tan, CT Su, MC Montgomery, WW AF Lee, SY Yeh, TH Lou, PJ Tan, CT Su, MC Montgomery, WW TI Mucociliary transport pathway on laryngotracheal tract and stented glottis in guinea pigs SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE glottis; guinea pig; laryngotrachea; mucociliary transport; stent C1 Natl Taiwan Univ, Coll Med, Dept Otolaryngol, Taipei 10018, Taiwan. Chung Shan Med Coll, Dept Otolaryngol, Taichung, Taiwan. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Lee, SY (reprint author), Natl Taiwan Univ Hosp, Dept Otolaryngol, 7 Chung-Shan S Rd, Taipei, Taiwan. OI Tan, Ching-Ting/0000-0001-8317-2235; LOU, PEI-JEN/0000-0002-3383-8593 NR 5 TC 2 Z9 2 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 FEB PY 2000 VL 109 IS 2 BP 210 EP 215 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 283CD UT WOS:000085257800017 PM 10685575 ER PT J AU Lin, TYD Dierickx, CC Campos, VB Farinelli, WA Rosenthal, J Anderson, RR AF Lin, TYD Dierickx, CC Campos, VB Farinelli, WA Rosenthal, J Anderson, RR TI Reduction of regrowing hair shaft size and pigmentation after ruby and diode laser treatment SO ARCHIVES OF DERMATOLOGICAL RESEARCH LA English DT Article DE hair shaft diameter; optical transmission; laser; hair removal ID SCALP HAIR; STEM-CELLS; FOLLICLES; GROWTH; RADIATION; LOCATION; REMOVAL; PULSES; SKIN AB Laser pulses which selectively damage pigmented hair follicles are a useful treatment for hypertrichosis. Clinically, regrowing hairs are often thinner and lighter after treatment, In this study, hair shaft diameter and optical transmission (700 nm) were measured before and after ruby (694 nm) and diode (800 nm) laser irradiation. Hair was collected from 47 and 41 subjects treated with ruby (0.3 ms and 3 ms) and diode (10-20 ms) lasers, respectively. "Responders" were defined as subjects with significant long-term hair loss as determined by hair counts at 9 and/or 12 months after treatment. In ruby laser responders (34/47), regrowing hairs were significantly both thinner (decreased diameter) and lighter (increased transmission), In "nonreeponders" (13/47), regrowing hairs were lighter, but not thinner. The regrowing hair shaft absorption coefficient (as calculated assuming Beer's law) was significantly decreased by 0.3 ms ruby laser treatment, but was not changed by 3 ms ruby laser or diode laser treatment. After diode laser treatment, 38 of the 41 subjects were responders and regrowing hairs mere both thinner and lighter. These results show that laser treatments can affect structural recovery (size of hair), follicular pigmentation (hair absorption coefficient), or both. Regrowth of thinner hair (decreased shaft diameter) occurs in conjunction with actual loss of hair. After long pulses (3 ms ruby; diode), regrowing hair was thinner and also lighter to an extent related to the decrease in hair diameter, In contrast, short ruby laser pulses (0.3 ms) appeared to be capable of inhibiting follicular pigmentation per se, in addition to affecting the hair diameter. This may account for the complete regrowth of lighter hair in "nonresponders'' treated with 0.3 Iris pulses, Laser-induced reduction in hair diameter and/or pigmentation are both long-term responses which confer cosmetic benefits in addition to actual hair loss. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. RP Lin, TYD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. NR 31 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-3696 J9 ARCH DERMATOL RES JI Arch. Dermatol. Res. PD FEB-MAR PY 2000 VL 292 IS 2-3 BP 60 EP 67 DI 10.1007/s004030050011 PG 8 WC Dermatology SC Dermatology GA 286UN UT WOS:000085467300003 PM 10749557 ER PT J AU van Dyck, CH Newhouse, P Falk, WE Mattes, JA AF van Dyck, CH Newhouse, P Falk, WE Mattes, JA CA Physostigmine Study Grp TI Extended-release physostigmine in Alzheimer disease - A multicenter, double-blind, 12-week study with dose enrichment SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; ORAL PHYSOSTIGMINE; CLINICAL-TRIALS; SENILE DEMENTIA; RATING-SCALE; TACRINE; DONEPEZIL; NEURONS; SAFETY; MEMORY AB Background: The efficacy of extended-release physostigmine salicylate, an acetylcholinesterase inhibitor, was evaluated in 850 subjects with mild-to-moderate Alzheimer disease (AD) in a multicenter trial. Methods: Subjects initially entered a dose-enrichment phase in which they received 1 week each of physostigmine salicylate, 24 mg/d and 30 mg/d, and daily placebo. Among the subjects who completed this phase, 35.9% responded to Physostigmine treatment, whereas 62.4% were considered nonresponders, and 1.6% could not be evaluated be cause of missing data. After a 4-week placebo-washout phase, 176 responder subjects were randomized to receive their best dose of physostigmine or placebo in a 12-week double-blind phase. Primary efficacy measures included the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog), the Clinician's Interview-Based Impression of Change With Caregiver Input (CIBIC+), and the Clinical Global Impression of Change (CGIC). Results: In the intent-to-treat analysis of the double-blind phase, physostigmine-treated subjects scored -2.02 points better than placebo-treated subjects on the ADAS-Cog (F-1,F-167 = 6.42 [P =.01]) and 0.33 points higher on the CIBIC+ (F-1,F-150 = 5.68 [P =.02]). No significant improvement was observed on the CGIC or the secondary outcome measures. Nausea and vomiting were experienced by 47.0% of all physostigmine-treated subjects during the double-blind phase. Conclusions: Physostigmine demonstrated a statistically significant benefit compared with placebo on a clinical global rating of change and an objective test of cognitive function. Given the frequency of gastrointestinal side effects, the role of this agent in clinical use remains to be determined. C1 Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. Univ Vermont, Coll Med, Burlington, VT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Psychopharmacol Res Assoc Princeton, Princeton, NJ USA. RP van Dyck, CH (reprint author), Yale Univ, Sch Med, Dept Psychiat, 333 Cedar St, New Haven, CT 06520 USA. RI Newhouse, Paul/J-4597-2014 NR 34 TC 14 Z9 14 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD FEB PY 2000 VL 57 IS 2 BP 157 EP 164 DI 10.1001/archpsyc.57.2.157 PG 8 WC Psychiatry SC Psychiatry GA 280DC UT WOS:000085086100007 PM 10665618 ER PT J AU Baldessarini, RJ Tondo, L AF Baldessarini, RJ Tondo, L TI Does lithium treatment still work? Evidence of stable responses over three decades SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID RECURRENT AFFECTIVE DISORDERS; MANIC-DEPRESSIVE PATIENTS; BIPOLAR DISORDER; PROPHYLACTIC LITHIUM; MAINTENANCE TREATMENT; FOLLOW-UP; AFFECTIVE-ILLNESS; ANTI-DEPRESSANTS; RAPID RECURRENCE; MOOD DISORDERS AB To evaluate whether lithium treatment has been overvalued and may be no longer as effective as formerly, we reviewed published reports on long-term lithium treatment (1970-1996) as well as analyzing its clinical effects on 360 patients with DSM-IV bipolar disorder who entered into lithium maintenance monotherapy after 1970, Neither reported recurrence rates nor average proportions of time ill nor patient improvement of 50% or more during lithium maintenance therapy in a stable clinic setting has changed significantly since the 1970s. Unfavorable results in some settings may reflect accumulation over time of patients with complex, less treatment-responsive illnesses. Lithium is unmatched in research support for long-term clinical effectiveness against morbidity and mortality associated with depression or mania in bipolar I and II disorders. Data evaluated heroin did not support suggestions that benefits of lithium have been exaggerated in the past or have been lost recently. C1 Int Consortium Bipolar Disorder Res, Boston, MA USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. Massachusetts Gen Hosp, McLean Div, Bipolar & Psychot Disorders Program, Belmont, MA USA. Univ Cagliari, Dept Psychol, Cagliari, Sardinia, Italy. Ctr Lucio Bini, Cagliari, Sardinia, Italy. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr 312, 115 Mill St, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH-47370] NR 50 TC 113 Z9 114 U1 2 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD FEB PY 2000 VL 57 IS 2 BP 187 EP 190 DI 10.1001/archpsyc.57.2.187 PG 4 WC Psychiatry SC Psychiatry GA 280DC UT WOS:000085086100011 PM 10665622 ER PT J AU Binetti, G Locascio, JJ Corkin, S Vonsattel, JP Growdon, JH AF Binetti, G Locascio, JJ Corkin, S Vonsattel, JP Growdon, JH TI Differences between Pick disease and Alzheimer disease in clinical appearance and rate of cognitive decline SO ARCHIVES OF NEUROLOGY LA English DT Article ID NEUROFIBRILLARY TANGLES; SEMANTIC MEMORY; SENILE PLAQUES; TEMPORAL-LOBE; DEMENTIA; DIAGNOSIS; DURATION; SEVERITY; SPECTRUM; FLUENCY AB Objectives: To define the cognitive characteristics of Pick disease (PcD), and to determine which features distinguish PcD from Alzheimer disease (AD), in a cross-sectional and longitudinal study. Methods: The participants were 44 patients with PcD (10 pathologically verified), 121 patients with AD (14 pathologically verified), and 60 normal control subjects. We obtained information regarding the initial symptom of dementia from each patient's caregiver, estimated global dementia severity by the Blessed Dementia Scale and the Activities of Daily Living Scale, and assessed specific cognitive domains by administering 10 tests of memory, language, visuospatial, and reasoning abilities and selective attention. Results: Among initial symptoms reported by caregivers, personality change and language impairment were significantly more common in PcD than AD; deficits in memory were common in both groups but more prevalent in AD (P<.001). At initial cognitive testing, the scores of patients with PcD were inferior to those of normal controls on all tests, except on a measure of visuospatial function; the scores of patients with AD were inferior to those of controls on all tests. Patients with PcD were superior to patients with AD on measures of explicit memory (P<.001) and visuospatial function (P = .001) but had greater impairments on the Activities of Daily Living Scale (P<.05). During the course of illness, patients with PcD declined significantly faster than those with AD on language tests and on global measures of dementia severity (P<.05), whereas measures of explicit memory and visuospatial and reasoning abilities worsened equally in both patient groups. Conclusions: There is a characteristic cognitive profile and course of dementia in PcD. Nonetheless, cognitive test performance does not clearly distinguish PcD from AD. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, Clin Res Ctr, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Neuropathol, Lab Mol Neuropathol, Charlestown, MA USA. Ist Ricovero & Cura Carattere Sci, Alzheimers Dis Res Unit, Brescia, Italy. RP Growdon, JH (reprint author), Massachusetts Gen Hosp, Dept Neurol, WACC 830, Boston, MA 02114 USA. RI Binetti, Giuliano/K-4519-2016 OI Binetti, Giuliano/0000-0003-2759-5844 FU NCRR NIH HHS [RR 00088]; NIA NIH HHS [AG05134, AG06605] NR 63 TC 59 Z9 59 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD FEB PY 2000 VL 57 IS 2 BP 225 EP 232 DI 10.1001/archneur.57.2.225 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 282GB UT WOS:000085208700010 PM 10681082 ER PT J AU Kim, JC Mankarious, LA AF Kim, JC Mankarious, LA TI Novel cell proliferation marker for identification of a growth center in the developing human cricoid SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID SPLIT; TRACHEOTOMY; CARTILAGE AB Background: Developmental histomorphology of the human cricoid cartilage has never been well described. Regional growth centers in the cricoid have been hypothesized, but have never been demonstrated in histological sections. Objectives: To apply Mib-1 immunostaining, a monoclonal antibody directed at a nuclear proliferation marker, in human cricoids to identify a growth center and to study the changing histomorphology of the developing cricoid. Design: Immunohistochemical Mib-1 studies were performed on postmortem cricoid sections of 2 fetuses (gestational age, 18.5 and 33 weeks), 1 newborn (full term, 41 weeks), and 3 children (aged 1, 4, and 13 years, respectively). Cell counts, surface areas, and organizational patterns of the chondrocytes were studied and described in hemotoxylin-eosin-stained sections. Results: Differential Mib-1 staining was found. The 18.5-week fetus showed diffuse cell proliferation throughout the cricoid. The cricoid sections of the 33-week fetus and 1-year-old child revealed a distinct ring of proliferation in the outer third of the cricoid ring. The 4- and 13-year-old exhibited no cell proliferation. Histomorphologically, with increasing age came chondrocyte hypertrophy, decreasing cell count per standard square, and increasing organization from a scattered to radial columnar pattern. Conclusions: Growth of the cricoid involves a diffuse pattern of cell proliferation throughout the cricoid in fetal tissue. At term and until age 1 year, the region of proliferation is more restricted to the outer subperichondrial surface. By age 4 years, cell proliferation has stopped. Histomorphologic changes in the developing cricoid include decreasing cell counts per standard unit area, but increasing surface area with age. The aging chondrocytes develop an increasingly organized layout to form a radially arranged columnar pattern similar to that in the growth plate of the developing limb bud. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Mankarious, LA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 17 TC 7 Z9 8 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD FEB PY 2000 VL 126 IS 2 BP 197 EP 202 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 282PH UT WOS:000085226900010 PM 10680871 ER PT J AU Palmer-Toy, DE AF Palmer-Toy, DE TI Therapeutic monitoring of vancomycin SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Palmer-Toy, DE (reprint author), Massachusetts Gen Hosp, Dept Pathol, MGH Warren 2, Boston, MA 02114 USA. NR 7 TC 5 Z9 6 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD FEB PY 2000 VL 124 IS 2 BP 322 EP 323 PG 2 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 283VQ UT WOS:000085297100029 PM 10656750 ER PT J AU Feng, DL Tofler, GH Larson, MG O'Donnell, CJ Lipinska, I Schmitz, C Sutherland, PA Johnstone, MT Muller, JE D'Agostino, RB Levy, D Lindpaintner, K AF Feng, DL Tofler, GH Larson, MG O'Donnell, CJ Lipinska, I Schmitz, C Sutherland, PA Johnstone, MT Muller, JE D'Agostino, RB Levy, D Lindpaintner, K TI Factor VII gene polymorphism, factor VII levels, and prevalent cardiovascular disease - The Framingham Heart Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE factor VII; genetics; polymorphisms; cardiovascular disease; risk factors ID COAGULATION-FACTOR-VII; PLASMA FACTOR-VII; ACUTE CORONARY SYNDROMES; DIETARY-FAT INTAKE; MYOCARDIAL-INFARCTION; UNSTABLE ANGINA; TISSUE FACTOR; HEMOSTATIC FUNCTION; BLOOD-COAGULATION; ANTIGEN LEVELS AB Elevated factor VII levels have been associated with increased cardiovascular risk in some studies. The arginine/glutamine (Arg/Gln) polymorphism of the factor VII gene has been previously shown to modify factor VII levels. However, the presence of a gene/environment interaction on factor VII levels or a link with cardiovascular disease (CVD) remains uncertain, We studied subjects from the Framingham Heart Study to determine (1) the extent to which this genetic polymorphism affects factor VII levels; (2) whether interactions exist between this polymorphism and environmental factors on factor VII levels; and (3) the association between the polymorphism and CVD, Genotype data and factor VII antigen levels were available in 1816 subjects. Factor VII levels differed significantly among genotypes in an additive fashion: Gin homozygous, 82.7+/-2.5%; heterozygous, 92.2+/-0.7%; and Arg homozygous, 100.5+/-0.4% (P<0.0001). The polymorphism was the strongest, single predictor of factor VII levels, explaining 7.7% of the total variance of factor VII levels, whereas other traditional risk factors combined explained an additional 11.5% of the variance. There was an interaction (P=0.02) between the genotype and total cholesterol on factor VII levels, such that the correlation coefficient and slope (factor VII level/total cholesterol) were greatest in Gln/Gln subjects. Among 3204 subjects characterized for genotype and CVD, there was no significant relationship between the genotype and CVD (P=0.12), In the Framingham Heart Study, the Arg/Gln polymorphism was significantly associated with factor VII antigen levels. The strength of the association suggests that generic variation plays an important role in determining factor VII levels. However, despite being associated with factor VII levels, the Arg/Gln polymorphism was not associated with prevalent CVD. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Inst Prevent Cardiovasc Dis, Boston, MA USA. Royal N Shore Hosp, Sydney, NSW, Australia. NHLBI, Framingham Heart Study, Framingham, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Boston Univ, Dept Math, Boston, MA 02215 USA. RP Lindpaintner, K (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St,Thorn 1203, Boston, MA 02115 USA. FU NHLBI NIH HHS [K04-HL-03138-01, R01-HC38038] NR 44 TC 45 Z9 52 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD FEB PY 2000 VL 20 IS 2 BP 593 EP 600 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 281UM UT WOS:000085179200042 PM 10669660 ER PT J AU Choi, HK Merkel, PA Walker, AM Niles, JL AF Choi, HK Merkel, PA Walker, AM Niles, JL TI Drug-associated antineutrophil cytoplasmic antibody-positive vasculitis - Prevalence among patients with high titers of antimyeloperoxidase antibodies SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; SULFASALAZINE-INDUCED LUPUS; CRESCENTIC GLOMERULONEPHRITIS; PROPYLTHIOURACIL THERAPY; WEGENERS-GRANULOMATOSIS; RHEUMATOID-ARTHRITIS; GBM ANTIBODIES; GRAVES-DISEASE; ANCA; AUTOANTIBODIES AB Objective. The triggers that induce antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis (APV) are largely unknown. However, there have been reports suggesting that hydralazine, propylthiouracil, and several other drugs may cause some cases of APV, and the majority of these cases have been associated with antimyeloperoxidase (anti-MPO) ANCA, Our experience led us to hypothesize that cases of high titers of anti-MPO antibodies are often drug-associated. Methods. In this study, we determined the prevalence of exposure to hydralazine, propylthiouracil, and other drugs previously implicated in APV among 30 patients with vasculitis and the highest titers of anti-MPO antibodies newly detected in our laboratory between 1994 and 1998, The clinical, histologic, and other serologic features of these 30 patients were also examined. Results. The 30 study patients accounted for 12% of the 250 new patients with APV and anti-MPO who were tested during the study period, All 30 study subjects had anti-MPO titers that were more than 12 times the median titer of the 250 patients. Ten (33%) of the 30 patients had been exposed to hydralazine and 3 (10%) had been exposed to propylthiouracil, An additional 5 patients (17%) had been exposed to 1 of the other previously reported candidate drugs: 2 to penicillamine, 2 to allopurinol, and 1 to sulfasalazine, One of the patients exposed to hydralazine had also been exposed to allopurinol, In all cases, the clinical and histologic findings were typical of APV. There was a strong association between the presence of antielastase and/or antilactoferrin antibodies and exposure to candidate drugs. Conclusion. These data suggest that a sizable proportion of cases of APV with high titers of anti-MPO antibodies are drug-associated, especially following exposure to hydralazine or propylthiouracil. We recommend that the use of these drugs should be sought in cases of anti-MPO-positive vasculitis, particularly among patients with high titers of these antibodies. C1 Massachusetts Gen Hosp, Arthrit Unit, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Choi, HK (reprint author), Massachusetts Gen Hosp, Arthrit Unit, Bulfinch 165,Fruit St, Boston, MA 02114 USA. NR 45 TC 176 Z9 196 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD FEB PY 2000 VL 43 IS 2 BP 405 EP 413 DI 10.1002/1529-0131(200002)43:2<405::AID-ANR22>3.0.CO;2-5 PG 9 WC Rheumatology SC Rheumatology GA 284ZM UT WOS:000085362800022 PM 10693882 ER PT J AU Fabunmi, RP Moore, KJ Libby, P Freeman, MW AF Fabunmi, RP Moore, KJ Libby, P Freeman, MW TI Stromelysin-1 (MMP-3) expression driven by a macrophage-specific promoter results in reduced viability in transgenic mice SO ATHEROSCLEROSIS LA English DT Article DE macrophage-specific promoter; stromelysin-1; macrophages; transgenic mice ID TETRACYCLINE-RESPONSIVE PROMOTER; GENE-EXPRESSION; MATRIX METALLOPROTEINASES; ATHEROSCLEROTIC PLAQUES; SCAVENGER RECEPTOR; TEMPORAL CONTROL; PROCOLLAGENASE; MORPHOGENESIS; ACTIVATION; REGIONS AB Macrophage expression of matrix degrading metalloproteinases (MMPs) in human atheroma has been found to occur in rupture-prone areas of plaques. To investigate the effect of metalloproteinase activity on plaque stability, we attempted to generate mice that expressed a stromelysin-l (MMP-3) transgene specifically in macrophages. Promoter sequences taken from a macrophage-tropic lentivirus (visna) were used to drive transgene expression. The transgene construct was expressed in macrophages in vitro and its autoactivation was established by casein zymography. Transgenic mice generated with this construct died at or before birth. No gross anatomical changes were observed in these mice. Embryos arising from a second round of oocyte injections with the transgene were examined at day 16 of gestation. Of the products of conception, similar to 40% resulted in vacant conceptuses. Only one animal of 38 examined carried the transgene and its expression of MMP-3 mRNA at E16 was faintly detected by RT-PCR. When a non-toxic reporter gene, luciferase, was substituted for the MMP-3 cDNA, healthy transgenic mice were produced that expressed the reporter gene in a wide variety of tissue macrophages, including those located in the brain, testis, lung, and thymus. These studies suggest that constitutive expression of MMP-3 in diverse populations of tissue macrophages leads to prenatal or neonatal death in the mouse. It appears likely that more sophisticated transcriptional control of MMP-3 expression will be required in order to generate stromelysin-l transgenic mice that could be useful models for studying overexpression of this metalloproteinase's activity in the lesional macrophages of atherosclerotic plaques. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Freeman, MW (reprint author), Massachusetts Gen Hosp, Lipid Metab Unit, GRJ 1328,55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL 45098, HL-56985] NR 30 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD FEB PY 2000 VL 148 IS 2 BP 375 EP 386 DI 10.1016/S0021-9150(99)00405-0 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 289DR UT WOS:000085605700019 PM 10657574 ER PT J AU Caplan, D AF Caplan, D TI Lesion location and aphasic syndrome do not tell us whether a patient will have an isolated deficit affecting the coindexation of traces SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material ID SENTENCE COMPREHENSION; NEUROPSYCHOLOGY; DETERMINANTS AB Data from published case and group studies bear on the trace deletion hypothesis. The deficit-lesion correlational literature does not support Grodzinsky's claim that lesions in an around Broca's area inevitably lead to comprehension deficits specifically related to coindexation of traces or his claim that other lesions spare this function. C1 Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02225 USA. Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02116 USA. RP Caplan, D (reprint author), Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02225 USA. NR 21 TC 7 Z9 7 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD FEB PY 2000 VL 23 IS 1 BP 25 EP + DI 10.1017/S0140525X00272397 PG 11 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 342MG UT WOS:000088647900007 ER PT J AU Lewandrowski, KU Gresser, JD Wise, DL White, RL Trantolo, DJ AF Lewandrowski, KU Gresser, JD Wise, DL White, RL Trantolo, DJ TI Osteoconductivity of an injectable and bioresorbable poly(propylene glycol-co-fumaric acid) bone cement SO BIOMATERIALS LA English DT Article DE injectable; resorbable; bone cement; osteoconductivity; poly(propylene glycol-co-fumaric acid) ID TOTAL HIP-ARTHROPLASTY; HYDROXYAPATITE; POLYMETHYLMETHACRYLATE; METHYLMETHACRYLATE AB We have investigated an injectable form of a resorbable bone cement based on in situ crosslinking of the unsaturated polyester, poly(propylene glycol-co-fumaric acid) (PPF). This material, filled with calcium gluconate/hydroxyapatite (CG/HA), cures to a hard cement degradable by hydrolysis. The purpose of this study was to evaluate the osteoconductive properties of this injectable cement. The cement was used as an adjunct to fixation with an intramedullary rod in the rat femoral osteotomy model. Ingrowth of new bone into the cement was examined in vivo. Negative and positive controls with rigid and loose internal fixation were included for comparison. Animals were evaluated histologically and histomorphometrically at 4 weeks postoperatively. Results of this study showed osteoblastic activity and new bone formation at the interface between the femoral bone and the cement in the experimental group. However, there was little bone remodeling at the endosteal surface in positive and negative controls. Histologic evaluation of the cement revealed the formation of cavitations, which likely resulted from leaching of the highly soluble calcium gluconate portion of the filler from the cement. These cavitations were sites of ingrowth of vascular and bony tissues. Intimate contact between the bone cement and the endosteal surface of the cortex was found. Quantitative histomorphometric analysis corroborated these observations. Findings of this study demonstrated the osteoconductivity of this type of injectable PPF-based bone cement. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Cambridge Sci Inc, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. RP Trantolo, DJ (reprint author), Cambridge Sci Inc, 180 Fawcett St, Cambridge, MA 02138 USA. FU NIAMS NIH HHS [AR 45062, 2 R44 AR44317-02A1] NR 17 TC 27 Z9 28 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD FEB PY 2000 VL 21 IS 3 BP 293 EP 298 DI 10.1016/S0142-9612(99)00180-5 PG 6 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 273KB UT WOS:000084705500010 PM 10646946 ER PT J AU Teoh, G Tai, YT Urashima, M Shirahama, S Matsuzaki, M Chauhan, D Treon, SP Raje, N Hideshima, T Shima, Y Anderson, KC AF Teoh, G Tai, YT Urashima, M Shirahama, S Matsuzaki, M Chauhan, D Treon, SP Raje, N Hideshima, T Shima, Y Anderson, KC TI CD40 activation mediates p53-dependent cell cycle regulation in human multiple myeloma cell lines SO BLOOD LA English DT Article ID PROTEIN-KINASE CASCADE; MARROW STROMAL CELLS; INTERLEUKIN-6 SECRETION; P53 MUTANT; B-CELLS; PROLIFERATION; ADHESION; GROWTH; IL-6; TRANSCRIPTION AB It has been reported that the activation of multiple myeloma (MM) cells by CD40 induces proliferation, growth arrest, and apoptosis. To determine whether the biologic sequelae of CD40 activation in MM cells depends on p53 function, we identified temperature-sensitive p53 mutations in the RPMI 8226 (tsp53E285K) and the HS Sultan (tsp53Y163H) MM cell lines. These cells were then used as a model system of inducible wtp53-like function because wild-type-like p53 is induced at permissive (30 degrees C) but not at restrictive (37 degrees C) temperatures. Using p21-luciferase reporter assays, we confirmed that CD40 induces p53 transactivation in RPMI 8226 and HS Sultan cells cultured under permissive, but not restrictive, conditions. Furthermore, CD40 activation of these MM cells under permissive, but not restrictive, temperatures increased the expression of p53 and p21 mRNA and protein. Importantly, CD40 activation induced the proliferation of RPMI 8226 and HS Sultan cells at restrictive temperatures and growth arrest and increased subG1 phase cells at permissive temperatures. These data confirmed that CD40 activation might have distinct biologic sequelae in MM cells, depending on their p53 status. (C) 2000 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Singapore Gen Hosp, Dept Hematol, Singapore 0316, Singapore. Jikei Univ, Sch Med, Dept Pediat, Tokyo, Japan. SRL Inc, Ctr Mol Biol & Cytogenet, Tokyo, Japan. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA50947, CA78378] NR 42 TC 45 Z9 48 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 2000 VL 95 IS 3 BP 1039 EP 1046 PG 8 WC Hematology SC Hematology GA 278MN UT WOS:000084993700042 PM 10648420 ER PT J AU Kwiatkowski, BA Zielinska-Kwiatkowska, AG Bauer, TR Hickstein, DD AF Kwiatkowski, BA Zielinska-Kwiatkowska, AG Bauer, TR Hickstein, DD TI The ETS family member Tel antagonizes the Fli-1 phenotype in hematopoietic cells SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE Tel; Fli-1; K562 cells; GPIIb; GPIX; GPIb alpha ID ACUTE LYMPHOBLASTIC-LEUKEMIA; MYELOGENOUS LEUKEMIA; LINE; EXPRESSION; FUSION; GENE; PROTEIN; DNA; DIFFERENTIATION; TRANSLOCATION AB The ETS family member Tel is rearranged in human leukemia of both myeloid and lymphoid origin while the ETS member Fli-1 is insertionally activated in Friend erythroleukemia in mice and is translocated to the EWS locus in Ewing's sarcoma. In previous studies we demonstrated that Tel binds to Fli-1 and blocks transactivation of megakaryocytic promoters by Fli-1. In this study we demonstrate that expression of Fli-1 in the leukemia cell line K562 induces a megakaryocytic phenotype and the expression of the platelet markers GPIX, GP1b alpha, and GPIIb. Introduction of Tel blocked the megakaryocytic phenotype induced by Fli-1, suggesting a biological correlation to the biochemical interaction of Tel and Fli-1 reported previously. (C) 2000 Academic Press. C1 VA Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. RP Hickstein, DD (reprint author), VA Puget Sound Hlth Care Syst, Med Res Serv, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 26 TC 9 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD FEB PY 2000 VL 26 IS 1 BP 84 EP 90 DI 10.1006/bcmd.2000.0282 PG 7 WC Hematology SC Hematology GA 331GM UT WOS:000088010000024 PM 10772879 ER PT J AU Hurley, CK Baxter-Lowe, LA Begovich, AB Fernandez-Vina, M Noreen, H Schmeckpeper, B Awdeh, Z Chopek, M Salazar, M Williams, TM Yunis, EJ Kitajima, D Shipp, K Splett, J Winden, T Kollman, C Johnson, D Ng, J Hartzman, RJ Hegland, J AF Hurley, CK Baxter-Lowe, LA Begovich, AB Fernandez-Vina, M Noreen, H Schmeckpeper, B Awdeh, Z Chopek, M Salazar, M Williams, TM Yunis, EJ Kitajima, D Shipp, K Splett, J Winden, T Kollman, C Johnson, D Ng, J Hartzman, RJ Hegland, J TI The extent of HLA class II allele level disparity in unrelated bone marrow transplantation: analysis of 1259 National Marrow Donor Program donor-recipient pairs SO BONE MARROW TRANSPLANTATION LA English DT Article DE bone marrow transplantation; HLA matching ID CHRONIC MYELOID-LEUKEMIA; VERSUS-HOST DISEASE; LINKAGE DISEQUILIBRIUM; IDENTICAL SIBLINGS; IMPACT; MLC; INCOMPATIBILITY; POLYMORPHISM; NOMENCLATURE; FREQUENCIES AB A comprehensive analysis of the HLA-D region loci, DRB1, DRB3, DRB5, DQA1, DQB1, DPA1 and DPB1, was performed to determine allelic diversity and underlying HLA disparity in 1259 bone marrow recipients and their unrelated donors transplanted through the National Marrow Donor Program. Although 43.0% of DRB1 alleles known to exist at the beginning of the study were found in this predominantly Caucasian transplant population, a few alleles predominated at each locus. In recipients, 67.1% of DRB1 alleles identified were one or two of six common DRB1 alleles, Only 118 (9.4%) donor-recipient pairs were matched for all alleles of DRB1, DQA1, DQB1, DPA1 and DPB1, While 79.4% of the pairs were matched for DRB1, only 13.2% were matched for DPB1 alleles, Almost 66% of pairs differed by more than one allele mismatch and 59.0% differed at more than one HLA-D locus. DQB1 was matched in 85.9% of DRB1-matched pairs. In contrast, only 13.9% of the pairs matched for DRB1, DQA1 and DQB1 were also matched for DPA1 and DPB1, This database, highlighting the underlying HLA disparity within the pairs, forms the foundation of an ongoing study to establish the relationship between HLA matching and successful outcome in unrelated allogeneic stem cell transplant. C1 Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. Univ S Carolina, Ctr Canc Treatment & Res, Columbia, SC 29208 USA. Roche Mol Syst, Alameda, CA USA. Amer Red Cross, Baltimore, MD USA. Fairview Univ, Med Ctr, Immunol Histocompatibil Lab, Minneapolis, MN USA. Johns Hopkins Univ, Immunogenet Labs, Baltimore, MD USA. CBR Labs Inc, Boston, MA USA. Amer Red Cross, Dedham, MA USA. Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Natl Marrow Donor Program, Minneapolis, MN USA. Pacific Irwin Ctr, Ctr Blood, San Francisco, CA USA. USN, Med Res Ctr, Bethesda, MD 20084 USA. RP Hurley, CK (reprint author), Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, E404 Res Bldg,3970 Reservoir Rd NW, Washington, DC 20007 USA. NR 37 TC 37 Z9 39 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD FEB PY 2000 VL 25 IS 4 BP 385 EP 393 DI 10.1038/sj.bmt.1702161 PG 9 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 287VT UT WOS:000085527700007 PM 10723581 ER PT J AU De Franceschi, L Bachir, D Galacteros, F Tchernia, G Cynober, T Neuberg, D Beuzard, Y Brugnara, C AF De Franceschi, L Bachir, D Galacteros, F Tchernia, G Cynober, T Neuberg, D Beuzard, Y Brugnara, C TI Oral magnesium pidolate: effects of long-term administration in patients with sickle cell disease SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE anaemia; antisickling agents; erythrocytes; magnesium pidolate; sickle cell anaemia ID RED-BLOOD-CELLS; ERYTHROCYTE DEHYDRATION; DIETARY MAGNESIUM; K+ TRANSPORT; INHIBITION; CLOTRIMAZOLE; THERAPY; DENSITY; CATION; VOLUME AB Prevention of erythrocyte dehydration by specific blockade of the transport pathways promoting loss of potassium (K) is a potential therapeutic strategy for sickle cell (SS) disease. Dietary magnesium (Mg) pidolate supplementation over a 4-week period has been shown to inhibit K-Cl co-transport and reduce dehydration. We report here the results in 17 of 20 patients with SS disease treated in an open-label unblinded study of the effects of long-term (6 months) oral Mg pidolate administration (540 mg Mg/d). A significant decrease (P < 0.0025) was observed with Mg therapy in the distribution widths for red cell mean cell haemoglobin concentration (MCHC) (haemoglobin distribution width; HDW), reticulocyte mean cell volume (red cell distribution width of reticulocytes; RDWr) and MCHC (reticulocyte HDW; HDWr), activity of red cell K-Cl co-transport, Na/Mg exchanger and Ca2+-activated (Gardos) K+ channel, whereas red cell K and Mg contents were significantly increased. Hb levels and absolute reticulocyte counts did pat change with Mg therapy. Two patients did not complete the trial because of diarrhoea and one did not complete the trial for unrelated reasons. Although the median number of painful days in a 6-month period decreased from IS (range 0-60) in the year before the trial to 1 (range 0-18; P < 0.0005) during the period of Mg therapy, no firm conclusion on therapeutic efficacy could be drawn from this unblinded open-label trial. C1 Univ Verona, Dept Clin & Expt Med, I-37100 Verona, Italy. Hop Henri Mondor, INSERM, U91, F-94010 Creteil, France. Ctr Hosp Bicetre, Le Kremlin Bicetre, France. Childrens Hosp, Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Hop St Louis, Expt Lab Gene Therapy, Paris, France. Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. RP De Franceschi, L (reprint author), Univ Verona, Policlin Borgo Roma, Dipartimento Med Interna, I-37134 Verona, Italy. RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 FU NCRR NIH HHS [MO1 RR02172]; NHLBI NIH HHS [P60-HL5157]; NIDDK NIH HHS [R01-DK50422] NR 27 TC 55 Z9 57 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD FEB PY 2000 VL 108 IS 2 BP 284 EP 289 PG 6 WC Hematology SC Hematology GA 295MG UT WOS:000085970600013 PM 10691856 ER PT J AU Menon, U Talaat, A Rosenthal, AN Macdonald, ND Jeyerajah, AR Skates, SJ Sibley, K Oram, DH Jacobs, IJ AF Menon, U Talaat, A Rosenthal, AN Macdonald, ND Jeyerajah, AR Skates, SJ Sibley, K Oram, DH Jacobs, IJ TI Performance of ultrasound as a second line test to serum CA125 in ovarian cancer screening SO BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article ID ASYMPTOMATIC WOMEN; ULTRASONOGRAPHY; COLOR AB Objective To assess the performance of ultrasonography in a multimodal ovarian cancer screening strategy. Design Prospective ovarian cancer screening trial between December 1986 and June 1993. Setting General practice, occupational health departments and an ovarian cancer screening clinic at a London teaching hospital. Population Postmenopausal women, greater than or equal to 45 years with a raised CA125. Methods Volunteers with a CA125 greater than or equal to 30 U/mL underwent a pelvic ultrasound. Scans were classified as normal, abnormal (ovarian volume greater than or equal to 8.8 mL) or equivocal (normal volume with abnormal morphology). Abnormal ovarian morphology was subclassified as simple cyst (single, thin walled cyst with no septa or papillary projections) or complex (all other abnormalities). Volunteers with abnormal scans were referred for a gynaecological opinion. Follow up was via the cancer registry and postal questionnaires. Main outcome measures Sensitivity, specificity and positive predictive value of different ultrasound criteria for detection of index cancer (e.g. primary invasive epithelial carcinoma of the ovary and fallopian tube). Results Seven hundred and forty-one women underwent 1219 scans and 20 index cancers occurred during a median follow up of 6.8 years. The sensitivity for detection of ovarian cancer of different ultrasound criteria was 100% for abnormal morphology, 89.5% for abnormal volume and 84% for complex morphology. The highest specificity (97%) and positive predictive value (37.2%) was achieved using complex morphology. Conclusion A variety of ultrasound criteria can achieve high sensitivity, specificity and positive predictive value for index cancers in postmenopausal women with an elevated CA125. Use of ovarian morphology to interpret ultrasound may increase sensitivity and use of complex ovarian morphology may increase the positive predictive value. C1 St Bartholomews Hosp, Royal Hosp NHS Trust, Gynaecol Canc Res Unit, London EC1A 7BE, England. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jacobs, IJ (reprint author), St Bartholomews Hosp, Royal Hosp NHS Trust, Gynaecol Canc Res Unit, London EC1A 7BE, England. RI Menon, Usha/C-4716-2008; Jacobs, Ian/F-1743-2013 OI Jacobs, Ian/0000-0002-8112-4624 NR 14 TC 33 Z9 36 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0306-5456 J9 BRIT J OBSTET GYNAEC JI Br. J. Obstet. Gynaecol. PD FEB PY 2000 VL 107 IS 2 BP 165 EP 169 DI 10.1111/j.1471-0528.2000.tb11685.x PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 284WM UT WOS:000085355900003 PM 10688498 ER PT J AU Rosen, HN Moses, AC Garber, J Iloputaife, ID Ross, DS Lee, SL Greenspan, SL AF Rosen, HN Moses, AC Garber, J Iloputaife, ID Ross, DS Lee, SL Greenspan, SL TI Serum CTX: A new marker of bone resorption that shows treatment effect more often than other markers because of low coefficient of variability and large changes with bisphosphonate therapy SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE CTX; NTX; bone resorption; bone turnover; pamidronate ID HORMONE REPLACEMENT THERAPY; LINKED N-TELOPEPTIDES; ONE-STEP ELISA; I COLLAGEN; BIOCHEMICAL MARKERS; DEGRADATION PRODUCTS; URINARY-EXCRETION; CROSS-LINKS; BIOLOGICAL VARIABILITY; FOLLOW-UP AB Serum CrossLaps is a new assay for measuring carboxy-terminal collagen crosslinks (CTX) in serum. This measurement is reported to be more specific to bone resorption than other measurements. However, the utility of this and other markers in monitoring patients on antiresorptive therapy depends on how often changes anticipated with therapy exceed changes attributable to random variability. In a study where subjects received either placebo or pamidronate, we calculated the minimum significant change (MSC), that is, the change that was sufficiently large that it was unlikely to be due to spontaneous variability. We also examined the changes in markers of bone turnover in subjects treated with pamidronate (APD) (30 mg I.V. in 500 mi D5W over 4 hours) to see how often observed changes in turnover after treatment exceeded the MSG. The MSC for serum CTX was 30.2%, and was significantly (P < 0.05) lower than the MSC for urinary NTX (54.0%), and not significantly different from the MSC of urinary DPD (20.6%). Ninety percent of subjects treated with APD had a decline in serum CTX that exceeded the MSG, compared with 74% for bone-specific alkaline phophatase (BSAP), 57% for urinary N-telopeptide cross-links (NTX), and 48% for free deoxypyridinoline. Changes in serum CTX correlated reasonably well with changes in spine BMD after 2 years (r = 0.47), but this correlation did not quite reach statistical significance because of the small number of subjects. In conclusion, the serum CTX assay shows greater utility for assessing efficacy of antiresorptive treatment than some previously described markers. C1 Hebrew Rehabil Ctr Aged Res & Training Inst, Boston, MA USA. Beth Israel Deaconess Med Ctr, Div Bone & Mineral Metab, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA. Harvard Pilgrim HealthCare, Hlth Ctr Div, Endocrinol Sect, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Thyroid Unit, Boston, MA 02114 USA. New England Med Ctr, Dept Med, Endocrinol Diabet Metab & Mol Med Div, Boston, MA 02111 USA. Charles A Dana Res Inst, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Harvard Thorndike Lab, Dept Med, Boston, MA USA. RP Rosen, HN (reprint author), Beth Israel Deaconess Med Ctr, Div Bone & Mineral Metab, RA414,330 Brookline Ave, Boston, MA 02215 USA. FU NCRR NIH HHS [M01RR01032] NR 21 TC 153 Z9 164 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD FEB PY 2000 VL 66 IS 2 BP 100 EP 103 DI 10.1007/PL00005830 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 275HL UT WOS:000084814700004 PM 10652955 ER PT J AU Kao, GD Devine, P AF Kao, GD Devine, P TI Use of complementary health practices by prostate carcinoma patients undergoing radiation therapy SO CANCER LA English DT Article DE prostate carcinoma; complementary health practices; complementary medicine; radiation therapy ID ALTERNATIVE MEDICINE; CANCER MEDICINE; UNITED-STATES; PREVALENCE AB BACKGROUND. There has been increasing interest in complementary health practices among patients, popular media, and even institutional health care providers. However, there is still surprisingly little information on the use of alternative medicine by patients undergoing treatment for prostate carcinoma. METHODS. A prospective study of 50 consecutive patients undergoing radiation treatment for prostate carcinoma at a tertiary care referral center was conducted. Patients were surveyed after the initiation of radiation therapy whether they had used complementary health practices at any time. RESULTS. The authors found that a surprisingly high proportion of patients (37%) relied on complementary health practices not prescribed by physicians. In contrast, according to a separate survey of the treating physicians, the physicians believed that on average only 4% of their patients resorted to such practices. The use of complementary health practices usually continued even after the initiation of definitive treatment for prostate carcinoma. Patients who used complementary health practices tended to have higher levels of education and income, whereas there were no differences in age, religion, perception of health status, stage of prostate carcinoma, or prostate specific antigen level. Herbal remedies were the most frequently utilized, by 60% of those using complementary health practices, followed by old-lime remedies (47%), high dose vitamins (41%), chiropractic/ massage therapy and relaxation techniques (18% each), and special diets (12%). CONCLUSIONS. Patients undergoing radiation therapy for prostate carcinoma frequently rely on complementary health practices not prescribed by their treating physicians. Patients who do so tend to have higher education and income levels and continue their complementary practices during the conventional treatment. As the health implications of these practices are unclear, further research is clearly needed. (C) 2000 American Cancer Society. C1 Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Dept Radiat Oncol, Philadelphia, PA 19104 USA. RP Kao, GD (reprint author), Hosp Univ Penn, Dept Radiat Oncol, 3400 Spruce St,2 Donner, Philadelphia, PA 19104 USA. NR 14 TC 84 Z9 85 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 0008-543X J9 CANCER JI Cancer PD FEB 1 PY 2000 VL 88 IS 3 BP 615 EP 619 DI 10.1002/(SICI)1097-0142(20000201)88:3<615::AID-CNCR18>3.0.CO;2-P PG 5 WC Oncology SC Oncology GA 276JQ UT WOS:000084874900018 PM 10649255 ER PT J AU Malin, JL Asch, SM Kerr, EA McGlynn, EA AF Malin, JL Asch, SM Kerr, EA McGlynn, EA TI Evaluating the quality of cancer care - Development of cancer quality indicators for a global quality assessment tool SO CANCER LA English DT Article DE cancer; oncology; health services research; quality of care; quality assessment; quality methods ID PERFORMANCE AB BACKGROUND. The rise of managed care has increased interest in measuring, reporting, and improving quality of care. To date, quality assessment has relied on a leading indicator approach, which may miss important variations in care. The authors developed cancer specific indicators using a novel case-based approach for a quality measurement tool designed to compare different managed care organizations. METHODS. Based on a review of the literature, quality indicators were developed for 6 types of cancer and the human immunodeficiency virus (HIV) as well as 39 general adult conditions (GAC). The validity and feasibility of these candidate indicators were evaluated using three modified Delphi expert panels. The strength of evidence, type of care (preventive, acute, or chronic), function (screening, diagnosis, treatment, and follow-up), and modality (history, physical examination, laboratory, medication, or other intervention) of the cancer/HIV quality indicators were compared with indicators developed for GAG. RESULTS. The final system included 117 of the 145 proposed cancer/HIV quality indicators (81%) and 569 of the 705 proposed GAC indicators (81%). A greater percentage of the cancer/HIV indicators were based on evidence from clinical trials compared with the GAC indicators (59% vs. 31%; P = 0.001). Cancer/HIV had significantly more indicators pertaining to chronic care than did GAC (74% vs. 56%; P = 0.001) as well as more indicators for treatment (53% vs. 39%; P = 0.004). CONCLUSIONS. Using the case-based approach, it is feasible to develop quality indicators for cancer that cover the continuum of care. Future studies will evaluate the reliability and validity of measurements made using these indicators in three managed care plans. (C) 1999 American Cancer Society. C1 Univ Calif Los Angeles, Div Canc Prevent & Control Res, Dept Med, Los Angeles, CA 90095 USA. W Los Angeles Vet Adm, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. Vet Adm Ann Arbor Healthcare Syst, Vet Adm Ctr Practice Management & Outcomes Res, Ann Arbor, MI USA. Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. RP Malin, JL (reprint author), Univ Calif Los Angeles, Div Canc Prevent & Control Res, Dept Med, A2-125 CHS Box 956900, Los Angeles, CA 90095 USA. NR 12 TC 51 Z9 52 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 0008-543X J9 CANCER JI Cancer PD FEB 1 PY 2000 VL 88 IS 3 BP 701 EP 707 DI 10.1002/(SICI)1097-0142(20000201)88:3<701::AID-CNCR29>3.0.CO;2-V PG 7 WC Oncology SC Oncology GA 276JQ UT WOS:000084874900029 PM 10649266 ER PT J AU Emmons, KM AF Emmons, KM TI A research agenda for tobacco control SO CANCER CAUSES & CONTROL LA English DT Article C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Cambridge, MA 02138 USA. RP Emmons, KM (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [1RO1CA77780, 1RO1CA73242]; NHLBI NIH HHS [1RO1HL50017] NR 4 TC 2 Z9 2 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD FEB PY 2000 VL 11 IS 2 BP 193 EP 194 DI 10.1023/A:1008971508040 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 275GE UT WOS:000084811800013 PM 10710205 ER PT J AU Dessain, SK Yu, HY Reddel, RR Beijersbergen, RL Weinberg, RA AF Dessain, SK Yu, HY Reddel, RR Beijersbergen, RL Weinberg, RA TI Methylation of the human telomerase gene CpG island SO CANCER RESEARCH LA English DT Article ID DNA METHYLATION; CELL-LINES; CANCER; MECHANISM; SUBUNIT; LENGTH AB The acquisition of expression of hTERT, the catalytic subunit of the telomerase enzyme, seems to be an essential step in the development of a majority of human tumors. However, little is known about the mechanisms preventing telomerase gene expression in normal and transformed cells that do not express hTERT, Using a methylation-specific PCR-based assay, we have found that the CpG island associated with the hTERT gene is unmethylated in telomerase-negative primary tissues and nonimmortalized cultured cells, indicating that mechanisms independent of DNA methylation are sufficient to prevent hTERT expression. The hTERT CpG island is methylated in many telomerase-negative and telomerase-positive cultured cells and tumors, but the extent of methylation did not correlate with expression of hTERT, Demethylation of DNA with 5-azacytidine in two cell lines induced expression of hTERT, suggesting that DNA methylation can contribute to hTERT repression in some cells. Together, these data show that the hTERT CpG island can undergo cytosine methylation in cultured cells and tumors and that DNA methylation may contribute to the regulation of the hTERT gene, but that CpG island methylation is not responsible for repressing hTERT expression in most telomerase-negative cells. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Med Res Inst, Westmead, NSW 2145, Australia. Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands. RP Weinberg, RA (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. RI Reddel, Roger/A-6635-2014 OI Reddel, Roger/0000-0002-6302-6107 FU NCI NIH HHS [T32 CA713452] NR 24 TC 128 Z9 138 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2000 VL 60 IS 3 BP 537 EP 541 PG 5 WC Oncology SC Oncology GA 282TU UT WOS:000085235600009 PM 10676632 ER PT J AU Guang, RJ Ford, JL Fu, YN Li, YZ Shaw, LM Pardee, AB AF Guang, RJ Ford, JL Fu, YN Li, YZ Shaw, LM Pardee, AB TI Drg-1 as a differentiation-related, putative metastatic suppressor gene in human colon cancer SO CANCER RESEARCH LA English DT Article ID HISTONE DEACETYLASE COMPLEX; RETINOID-X-RECEPTOR; CELL-LINES; TERMINAL DIFFERENTIATION; COLORECTAL-CANCER; DNA METHYLATION; CPG METHYLATION; PPAR-GAMMA; CARCINOMA; MICROMETASTASES AB A gene related to cell differentiation was identified by differential display as a candidate suppressor of metastases in colon cancer. This gene, with a full-length cDNA of 3 kb, is expressed in normal colon and primary colon cancer tissues and cell lines but not in their metastatic counterparts. A GenBank search found that it is identical to a recently cloned gene, differentiation-related gene-1 (Drg-1), isolated from differentiated HT-29 colon cancer cells. Stable transfection of the SW620 metastatic colon cancer cell line with Drg-l cDNA induced morphological changes consistent with differentiation and up-regulated the expression of several colonic epithelial cell differentiation markers (alkaline phosphatase, carcinoembryonic antigen, and E-cadherin). Moreover, the expression of Drg-1 is controlled by several known cell differentiation reagents, such as ligands of peroxisome proliferator-activated receptor gamma (troglitazone and BRL46593) and of retinoid X receptor (LG268), and histone deacetylase inhibitors (trichostatin A, suberoylanilide hydroxamic acid, and tributyrin). A synergistic induction of Drg-1 expression was seen with the combination of tributyrin and a low dose of 5'-aza-2'-dexoycytidine (100 nM), an inhibitor-of DNA methylation. Functional studies revealed that overexpression of Drg-1 in metastatic colon cancer cells reduced in vitro invasion through Matrigel and suppressed in vivo liver metastases in nude mice. We propose that Drg-1 suppresses colon cancer metastasis by inducing colon cancer cell differentiation and partially reversing the metastatic phenotype. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Gastroenterol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Guang, RJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, D602,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R0-1 CA61253] NR 45 TC 236 Z9 269 U1 2 U2 6 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 FEB 1 PY 2000 VL 60 IS 3 BP 749 EP 755 PG 7 WC Oncology SC Oncology GA 282TU UT WOS:000085235600040 PM 10676663 ER PT J AU Preston, GA Srinivasan, D Barrett, JC AF Preston, GA Srinivasan, D Barrett, JC TI Apoptotic response to growth factor deprivation involves cooperative interactions between c-Fos and p300 SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE p300; c-Fos; apoptosis; p53; transcription factor ID CREB-BINDING-PROTEIN; ADENOVIRUS E1A PROTEINS; PROGRAMMED CELL-DEATH; TUMOR-SUPPRESSOR GENE; HAMSTER EMBRYO CELLS; NF-KAPPA-B; TRANSCRIPTIONAL ACTIVATION; NEOPLASTIC PROGRESSION; COACTIVATOR P300; IN-VITRO AB Two preneoplastic cell lines have been utilized to study changes in the regulation of apoptosis during neoplastic progression [sup(+)I (stage I) and sup(-)II (stage II)]. Sup(+)I cells are prone to undergo apoptosis, while sup(-)II cells are relatively resistant. We report that induction of apoptosis in sup(+)I cells is tightly correlated with the formation of c-Fos/p300 complexes, which were not present in the non-apoptotic sup(-)II cells under the same conditions. When apoptosis was induced in the sup(-)II cells by over-expression of c-Fos, concomitant c-Fos:p300 complexes were detected. Overexpression of p300 resulted in apoptosis in sup(-)II cells and also in p53(wt) human tumor cells, but not in p53(mutant) human tumor cells. Over-expression of the C-terminal fragment of p300, which contains the c-fos binding site, enhanced apoptosis, suggesting that the c-fos:p300 complex is actively involved in apoptosis. We propose that p300 could function as a general mediator of transcription factor-induced apoptosis. C1 NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Med, Div Nephrol, Chapel Hill, NC 27599 USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Grad Program Biol & Biomed Sci, Charlestown, MA 02129 USA. RP Preston, GA (reprint author), Univ N Carolina, Div Nephrol & Hypertens, CB 7155,346 MacNider Bld, Chapel Hill, NC 27599 USA. NR 70 TC 19 Z9 20 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD FEB PY 2000 VL 7 IS 2 BP 215 EP 226 DI 10.1038/sj.cdd.4400637 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 292VU UT WOS:000085816600009 PM 10713736 ER PT J AU Vanduffel, W Tootell, RBH Orban, GA AF Vanduffel, W Tootell, RBH Orban, GA TI Attention-dependent suppression of metabolic activity in the early stages of the macaque visual system SO CEREBRAL CORTEX LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; LATERAL GENICULATE-NUCLEUS; CEREBRAL GLUCOSE-UTILIZATION; SPATIAL SELECTIVE ATTENTION; STRIATE CORTEX; ORIENTATION DISCRIMINATION; FUNCTIONAL-ANATOMY; CORTICAL AREAS; RETINOTOPIC ORGANIZATION; VISUOSPATIAL ATTENTION AB In this study we used a modified double-label deoxyglucose procedure to investigate attention-dependent modulations of deoxyglucose uptake at the earliest stages of the macaque visual system. Specifically, we compared activity levels evoked during two tasks with essentially identical visual stimulation requiring different attentional demands. During a featural-attention task, the subjects had to discriminate the orientation of a grating: during a control spatial-attention task, they had to localize the position of a target point. Comparison of the resulting activity maps revealed attention-dependent changes in metabolic activity in portions of the magnocellular layers of the lateral geniculate nucleus, and the magnocellular-recipient layers 4C alpha and 4B of the striate cortex. In these early stages of the visual system, attention to the orientation of the grating suppressed the metabolic activity in a retinotopically specific band peripheral to the representation of the stimulus. These results favor an early selection model of attention. After a thalamic attention dependent gating mechanism, irrelevant visual information outside the focus of attention may be suppressed at the level of the striate cortex, which would then result in an increased signal-to-noise ratio for the processing of the attended feature in higher-tier, less retinotopically organized, extrastriate visual areas. C1 Katholieke Univ Leuven, Lab Neuro Psychofysiol, B-3000 Louvain, Belgium. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. RP Vanduffel, W (reprint author), Katholieke Univ Leuven, Lab Neuro Psychofysiol, Campus Gasthuisberg,Herestr 49, B-3000 Louvain, Belgium. NR 82 TC 107 Z9 111 U1 2 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD FEB PY 2000 VL 10 IS 2 BP 109 EP 126 DI 10.1093/cercor/10.2.109 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 277XB UT WOS:000084957900001 PM 10667980 ER PT J AU Machens, HG Morgan, JR Sachse, C Berger, AC Mailander, P AF Machens, HG Morgan, JR Sachse, C Berger, AC Mailander, P TI Gene-therapy possibilities in plastic surgery SO CHIRURG LA German DT Review DE plastic surgery; gene-therapy ID ENDOTHELIAL-CELLS; GROWTH-FACTOR; RETROVIRAL VECTORS; WOUND REPAIR; ATHYMIC MICE; EXPRESSION; SKIN; RAT; RECEPTOR; INTERLEUKIN-1 AB Advances in gene technologies have meanwhile reached plastic surgery. Important contributions in this field (which are not all included in the paper) come not only from plastic surgeons, but also from neighboring specialities like dermatology, trauma surgery, orthopedics and vascular surgery. The uniting principle for all this work is improving wound healing and reconstructing tissue defects taking into consideration functional and aesthetic aspects. Gene-therapy is gaining further importance in the clinical field of plastic surgery. In this regard, every clinician has to be aware of the fact that progress in experimental and experimental clinical work will be achieved only with the help of basic science. On the other hand, basic science needs the clinical input to get relevant patient-oriented studies started. Further intensive cooperation between clinicians and basic scientists is therefore mandatory. In plastic surgery, 2 years ago we founded a forum called ECSAPS (European Conference of Scientists and Plastic Surgeons), which takes place in European city every year. C1 Univ Klinikum, Klin Plast Hand & Wiederherstellungschirurg, Bereich Plast & Handchirurg, Zentrum Schwerbranverletzte, D-23538 Lubeck, Germany. Med Hsch Hannover, Klin Plast Hand & Wiederherstellungschirurg, Hannover, Germany. Med Hsch Hannover, Inst Klin Chem 2, Hannover, Germany. Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Shriners Burns Inst, Boston, MA USA. RP Machens, HG (reprint author), Univ Klinikum, Klin Plast Hand & Wiederherstellungschirurg, Bereich Plast & Handchirurg, Zentrum Schwerbranverletzte, Ratzeburger Allee 160, D-23538 Lubeck, Germany. NR 41 TC 2 Z9 2 U1 1 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 FEB PY 2000 VL 71 IS 2 BP 152 EP 158 PG 7 WC Surgery SC Surgery GA 290ZM UT WOS:000085707800005 PM 10734583 ER PT J AU Kraeft, SK Sutherland, R Gravelin, L Hu, GH Ferland, LH Richardson, P Elias, A Chen, LB AF Kraeft, SK Sutherland, R Gravelin, L Hu, GH Ferland, LH Richardson, P Elias, A Chen, LB TI Detection and analysis of cancer cells in blood and bone marrow using a rare event imaging system SO CLINICAL CANCER RESEARCH LA English DT Article ID POLYMERASE CHAIN-REACTION; MICROMETASTATIC CARCINOMA-CELLS; LASER-SCANNING CYTOMETRY; MINIMAL RESIDUAL DISEASE; EPITHELIAL TUMOR-CELLS; PRIMARY BREAST-CANCER; PERIPHERAL-BLOOD; PROGNOSTIC-SIGNIFICANCE; IMMUNOCYTOCHEMICAL DETECTION; LUNG-CANCER AB An automated rare event detection system (Rare Event Imaging System) is described for the recognition of cancer cells that appear at low frequencies (1 in 1 million) in peripheral blood (PB) or bone marrow (BM). The instrumentation includes an automated fluorescence microscope (Nikon Microphot-FXA) with a cooled charge coupled device camera and a 60-MHz Pentium personal computer. Main features of the system are rapid analysis of large microscopic fields, including a total cell count, detection of fluorescently labeled cells, and a display of digitally stored images of the detected cells. Furthermore, the X,Y coordinates of each identified object are stored and can be recalled for morphological analysis of the cell using higher magnification or different fluorescent filter sets. The preparation of the blood or BM samples for automated analysis consists of lysis of the RBCs, attachment of sample cells onto adhesion slides, fixation, and fluorescent labeling with anticytokeratin antibodies. Cytokeratin-positive cells, however, were detected in 17% of the samples from healthy blood donors using this procedure (mean number, similar to 7/10(6) mononuclear tells in positive samples), To improve the specificity of the rare event detection, a double-labeling protocol combining intracellular cytokeratin with epithelial cell adhesion molecule (Ep-CAM) (breast, ovarian, colon, and lung carcinoma antigen) or disialo-ganglioside (GD2) antigen (small cell lung carcinoma, neuroblastoma, melanoma antigen) was developed. Examples of doubly labeled cultured cells and cancer cells from breast and small cell lung cancer patients are shown. Using the double-labeling protocol, no ''positive" cells were seen in samples of healthy blood donors. Automated rare event detection (cytokeratin single-staining) was applied to 355 PR, BM, and stem cell (SC) samples from breast cancer patients before autologous BM transplantation, Cytokeratin-positive cells were found in 52% of BM, 35% of PB, and 27% of SC samples at frequencies of 1-1020 positive cells/10(6) mononuclear cells, thereby establishing the efficacy of the technique in the detection of rare cancer cells in hematopoietic tissue samples of cancer patients. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Chen, LB (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Room SM1058,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA13849] NR 59 TC 63 Z9 69 U1 0 U2 5 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 FEB PY 2000 VL 6 IS 2 BP 434 EP 442 PG 9 WC Oncology SC Oncology GA 287JK UT WOS:000085502600017 PM 10690521 ER PT J AU Chmura, SJ Dolan, ME Cha, A Mauceri, HJ Kufe, DW Weichselbaum, RR AF Chmura, SJ Dolan, ME Cha, A Mauceri, HJ Kufe, DW Weichselbaum, RR TI In vitro and in vivo activity of protein kinase C inhibitor chelerythrine chloride induces tumor cell toxicity and growth delay in vivo SO CLINICAL CANCER RESEARCH LA English DT Article ID SQUAMOUS CARCINOMA-CELLS; MYELOID-LEUKEMIA CELLS; IONIZING-RADIATION; INDUCED APOPTOSIS; PHARMACOLOGICAL INHIBITORS; DNA FRAGMENTATION; CALPHOSTIN-C; ACTIVATION; P53; INDUCTION AB Although clonogenic or divisional death is the main mechanism by which DNA-damaging agents demonstrate antitumor activity, recent data indicate that strategies specifically designed to trigger apoptosis may also prove to be useful antitumor agents. Protein kinase C (PKC) isoenzymes are involved in the regulation of cell proliferation, differentiation, and survival. Whereas pharmacological inhibition of PKC activity triggers apoptosis in most mammalian cells, cell line and tissue differences in sensitivities to these inhibitors remain. Whereas PKC inhibitors have potential as antitumor agents, issues of kinase specificity and solubility have remained obstacles to their clinical use. In this report, we investigated the antitumor activity of the PKC inhibitor chelerythrine chloride (chelerythrine), a selective inhibitor of group A and B PKC isoforms, Chelerythrine exhibited cytotoxic activity against nine human tumor cell lines tested in vitro. On the basis of the finding that radioresistant and chemoresistant squamous cell carcinoma lines (HNSCC) undergo apoptosis rapidly after treatment with chelerythrine in vitro, we assessed the effects of this agent on p53-deficient SQ-20B HNSCC cells in vivo. The results demonstrate that chelerythrine treatment of nude mice bearing SQ-20B is associated with significant tumor growth delay, Significantly, treatment with chelerythrine resulted in minimal toxicity. These findings demonstrate a potential for chelerythrine as an antitumor drug against squamous cell carcinoma. C1 Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. Univ Chicago, Dept Med, Div Biol Sci, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Weichselbaum, RR (reprint author), Univ Chicago Hosp, Dept Radiat Oncol, 5841 S Maryland Ave,MC 1089, Chicago, IL 60637 USA. FU NCI NIH HHS [5-R01-CA41068]; NIDCR NIH HHS [C50 DE/CA11921]; NIGMS NIH HHS [GM07183] NR 52 TC 99 Z9 110 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 FEB PY 2000 VL 6 IS 2 BP 737 EP 742 PG 6 WC Oncology SC Oncology GA 287JK UT WOS:000085502600057 PM 10690561 ER PT J AU Bursell, SE King, GL AF Bursell, SE King, GL TI The potential use of glutathionyl hemoglobin as a clinical marker of oxidative stress SO CLINICAL CHEMISTRY LA English DT Editorial Material ID LOW-DENSITY-LIPOPROTEIN; ATHEROSCLEROSIS; ATHEROGENESIS C1 Joslin Diabet Ctr, Boston, MA 02215 USA. RP Bursell, SE (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. NR 29 TC 31 Z9 34 U1 0 U2 8 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD FEB PY 2000 VL 46 IS 2 BP 145 EP 146 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 283RF UT WOS:000085288500001 PM 10657367 ER PT J AU Luley, C Ronquist, G Reuter, W Paal, V Gottschling, HD Westphal, S King, GL Bakker, SLJ Heine, RJ Hattemer, A AF Luley, C Ronquist, G Reuter, W Paal, V Gottschling, HD Westphal, S King, GL Bakker, SLJ Heine, RJ Hattemer, A TI Point-of-care testing of triglycerides: Evaluation of the accutrend triglycerides system SO CLINICAL CHEMISTRY LA English DT Article ID CORONARY-ARTERY DISEASE; METABOLISM C1 Univ Magdeburg, Inst Clin Chem, D-39120 Magdeburg, Germany. Uppsala Acad Hosp, Inst Clin Chem, S-75185 Uppsala, Sweden. Univ Leipzig, Dept Clin 4, D-04103 Leipzig, Germany. Bonifatius Hosp, Cent Lab, D-49809 Lingen Ems, Germany. Karlsburg Clin, Cent Lab, D-17495 Karlsburg, Germany. Joslin Diabet Ctr, Boston, MA 02215 USA. Vrije Univ Amsterdam, Univ Hosp, Dept Endocrinol, NL-1007 MB Amsterdam, Netherlands. Roche Diagnost GmbH, Evaluat Patient Care, D-68298 Mannheim, Germany. RP Luley, C (reprint author), Univ Magdeburg, Inst Clin Chem, D-39120 Magdeburg, Germany. RI Bakker, Stephan/J-4023-2015 OI Bakker, Stephan/0000-0003-3356-6791 NR 11 TC 33 Z9 33 U1 0 U2 3 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD FEB PY 2000 VL 46 IS 2 BP 287 EP 291 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 283RF UT WOS:000085288500024 PM 10657390 ER PT J AU Hooper, DC AF Hooper, DC TI New uses for new and old quinolones and the challenge of resistance SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID ACUTE BACTERIAL EXACERBATIONS; COMMUNITY-ACQUIRED PNEUMONIA; IN-VITRO ACTIVITY; RESPIRATORY-TRACT PATHOGENS; CHRONIC-BRONCHITIS; DOUBLE-BLIND; ESCHERICHIA-COLI; STAPHYLOCOCCUS-AUREUS; STREPTOCOCCUS-PNEUMONIAE; CIPROFLOXACIN-RESISTANT C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. RP Hooper, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. NR 109 TC 88 Z9 95 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB PY 2000 VL 30 IS 2 BP 243 EP 254 DI 10.1086/313677 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 293JX UT WOS:000085849400004 PM 10671323 ER PT J AU Miller, LG Asch, SM Yu, EI Knowles, L Gelberg, L Davidson, P AF Miller, LG Asch, SM Yu, EI Knowles, L Gelberg, L Davidson, P TI A population-based survey of tuberculosis symptoms: How atypical are atypical presentations? SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PULMONARY TUBERCULOSIS; CLINICAL-FEATURES; DIAGNOSIS; EXPERIENCE; PNEUMONIA; INFECTION; ADULTS; YOUNG AB There is scant information on tuberculosis symptoms from a population-based perspective. We prospectively identified 526 tuberculosis cases reported in Los Angeles County over a 6-month period. Of 313 persons who completed our questionnaire, 72.7% had cough, 48.2% for >2 weeks, and 52.3% had fever, 29.4% for >2 weeks. Among those with pulmonary disease, only 52.4% had cough for >2 weeks, In a multivariate model, persons with significant symptoms typical of tuberculosis disease (defined as cough or fever for >2 weeks, weight loss, or hemoptysis) were associated with lack of medical insurance, negative tuberculin skin test, diagnosis during a process other than screening, and non-Asian race, In summary, classic symptoms of prolonged cough and fever are insensitive predictors of tuberculosis. Our data suggest that Asians may need to be added to the list of persons who present with tuberculosis atypically. We believe that the Infectious Diseases Society of America guidelines for community-acquired pneumonia should emphasize demographic features in addition to clinical symptoms when suggesting which patients require evaluation for Mycobacterium tuberculosis. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Los Angeles, CA USA. Univ Calif Los Angeles, Med Ctr, Div Infect Dis, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Med Ctr, Dept Family Med, Los Angeles, CA 90024 USA. Los Angeles Cty Dept Hlth, Los Angeles Cty TB Control, Los Angeles, CA USA. RP Miller, LG (reprint author), Univ Calif Los Angeles, Los Angeles Cty Harbor Med Ctr, Div Infect Dis, 1124 W Carson St,Box 466, Torrance, CA 90502 USA. NR 40 TC 35 Z9 36 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB PY 2000 VL 30 IS 2 BP 293 EP 299 DI 10.1086/313651 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 293JX UT WOS:000085849400013 PM 10671331 ER PT J AU Berry, DJ Sutherland, CJ Trousdale, RT Colwell, CW Chandler, HP Ayres, D Yashar, AA AF Berry, DJ Sutherland, CJ Trousdale, RT Colwell, CW Chandler, HP Ayres, D Yashar, AA TI Bilobed oblong porous coated acetabular components in revision total hip arthroplasty SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID FOLLOW-UP; RECONSTRUCTION; ALLOGRAFTS AB Thirty-eight oblong bilobed noncustom uncemented, porous-coated titanium acetabular components were used to reconstruct failed hip arthroplasties with large superior segmental acetabular bone deficiencies. No structural bone grafts were used. till patients were followed up for 2 to 5 years (mean, 3 years) after the operation. One patient (whose socket rested primarily on a structural hone graft from a previous procedure) had revision surgery for acetabular loosening, No other patients have had revision surgery or had another ipsilateral hip operation. At latest followup, 35 patients had no or mild pain and two patients had moderate pain. Two implants migrated more than 2 mm in the first year, then stabilized. On the latest radiographs, two implants had bead shedding, but there was no measurable migration or change in position. For selected patients with large superolateral acetabular bone deficiencies, this implant facilitated a complex reconstruction, provided good clinical results, and showed satisfactory stability at early to midterm followup in most patients. C1 Mayo Clin, Dept Orthoped Surg, Rochester, MN 55905 USA. Toledo Clin, Toledo, OH USA. Green Hosp, La Jolla, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Vanguard Med Associates, Somerville, MA USA. Caritas Med Plaza, Louisville, KY USA. RP Berry, DJ (reprint author), Mayo Clin, Dept Orthoped Surg, 200 1st St SW, Rochester, MN 55905 USA. NR 19 TC 43 Z9 48 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD FEB PY 2000 IS 371 BP 154 EP 160 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 285PP UT WOS:000085397700020 ER PT J AU Mohler, DG Kessler, JI Earp, BE AF Mohler, DG Kessler, JI Earp, BE TI Augmented amputations of the lower extremity SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID SOFT-TISSUE SARCOMA; PROGNOSTIC FACTORS; AMPUTEES AB Ten patients who had amputations of a lower extremity for high-grade sarcomas underwent bone augmentation with either allograft or autograft between 1988 and 1996, There were eight transfemoral amputations and two transtibial amputations. The transferred segments consisted of one proximal tibia and sis distal tibia autografts, two allografts, one autograft taler dome and first metatarsal, and one with a patellar cap of a supracondylar amputation. The average length of followup was 54 months. There were no nonunions of any of the grafts. There were three wound problems requiring additional operations. One autograft resorbed, and one autograft had a late infection. There was one local recurrence. Augmentation to pro,ide length resulted in a 42% increase in bone length in those performed purely for length. Ail patients were able to use standard prostheses. Functional outcome was appropriate to the amputation level. Half of the patients avoided more proximal levels of amputation because of the ability to augment the osteotomy, The use of nonvascularized structural autografts or allografts is a simple procedure that can produce a superior residual limb in patients undergoing amputation. Its use should be considered in patients for whom traditional amputation techniques will result in poor function, difficulty in fitting a prosthesis, or greater than necessary anatomic loss. C1 Stanford Univ, Sch Med, Div Orthopaed, Stanford, CA 94305 USA. Univ Utah, Primary Childrens Med Ctr, Salt Lake City, UT USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Mohler, DG (reprint author), 300 Pasteur Dr R144, Stanford, CA 94305 USA. NR 19 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD FEB PY 2000 IS 371 BP 183 EP 197 PG 15 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 285PP UT WOS:000085397700024 PM 10693566 ER PT J AU Cohen, L Wilens, T Biederman, J Abrams, A Neft, D Melnick, K Kurtze, D Sinha, V AF Cohen, L Wilens, T Biederman, J Abrams, A Neft, D Melnick, K Kurtze, D Sinha, V TI Pharmacokinetics of fluoxetine in pediatric patients. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Lilly Lab Clin Res, Indianapolis, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2000 VL 67 IS 2 MA PII57 BP 129 EP 129 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 288CA UT WOS:000085543200159 ER PT J AU Marinkovic, K Trebon, P Chauvel, P Halgren, E AF Marinkovic, K Trebon, P Chauvel, P Halgren, E TI Localised face processing by the human prefrontal cortex: Face-selective intracerebral potentials and post-lesion deficits SO COGNITIVE NEUROPSYCHOLOGY LA English DT Article ID DEPTH-RECORDED POTENTIALS; FRONTAL-CORTEX; WORKING-MEMORY; FUNCTIONAL-ORGANIZATION; SPATIOTEMPORAL STAGES; RECOGNITION; AMYGDALA AB The patient described in the companion paper by Vignal, Chauvel, and Halgren (this issue) was studied with event related potentials (ERPs) recorded directly within the brain substance, as well as with neuropsychological tests before and after therapeutic cortectomy. Large ERPs were evoked in the prefrontal cortex to faces, as compared to sensory controls and words. The largest such ERPs were highly localised to the same right anterior inferior prefrontal site where direct electrical stimulation resulted in face hallucinations. Face-selective ERPs were also evoked in the right prefrontal sites that had shown projected activity during face hallucinations, and near the right anterior superior temporal sulcus. Selective responses began about 150msec after face onset. Words, but not faces or sensory controls, evoked large ERPs in distinct locations, mainly in the left hemisphere. A successful surgical therapy was performed by removing the cortex surrounding the right prefrontal site where face-selective responses were recorded and where face hallucinations were evoked by stimulation. This cortectomy resulted in a severe deficit in the recognition of emotional facial expressions, especially fear. No change was noted, however, in the recall of emotional words, or other tasks. The current results provide strong support for the early, specific, and sustained involvement of a multi-focal network in the right inferior fronto-temporal cortex in face-processing. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Boston, MA 02129 USA. CHU Pontchaillou Neurol, Rennes, France. INSERM, E9926, F-13258 Marseille, France. RP Marinkovic, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Bldg 149,13th St, Boston, MA 02129 USA. FU NINDS NIH HHS [R01 NS018741] NR 37 TC 52 Z9 54 U1 0 U2 2 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0264-3294 J9 COGNITIVE NEUROPSYCH JI Cogn. Neuropsychol. PD FEB-MAY PY 2000 VL 17 IS 1-3 BP 187 EP 199 PG 13 WC Psychology; Psychology, Experimental SC Psychology GA 305QC UT WOS:000086550900012 PM 20945179 ER PT J AU Tong, F Nakayama, K Moscovitch, M Weinrib, O Kanwisher, N AF Tong, F Nakayama, K Moscovitch, M Weinrib, O Kanwisher, N TI Response properties of the human fusiform face area SO COGNITIVE NEUROPSYCHOLOGY LA English DT Article ID HUMAN EXTRASTRIATE CORTEX; TEMPORAL CORTEX; INFEROTEMPORAL CORTEX; HUMAN HIPPOCAMPUS; VISUAL-CORTEX; RECOGNITION; PERCEPTION; NEURONS; MONKEY; INVERSION AB We used functional magnetic resonance imaging to study the response properties of the human fusiform face area (FFA: Kanwisher, McDermott, & Chun, 1997) to a variety of face-like stimuli in order to clarify the functional role of this region. FFA responses were found to be (1) equally strong for cat, cartoon and human faces despite very different image properties, (2) equally strong for entire human faces and faces with eyes occluded but weaker for eyes shown alone, (3) equal for front and profile views of human heads, but declining in strength as faces rotated away from view, and (4) weakest for nonface objects and houses. These results indicate that generalisation of the FFA response across very different face types cannot be explained in terms of a specific response to a salient facial feature such as the eyes or a more general response to heads. Instead, the FFA appears to be optimally tuned to the broad category of faces. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA USA. Univ Toronto, Toronto, ON, Canada. MIT, Cambridge, MA 02139 USA. RP Tong, F (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. RI Hoang, Nick/N-5738-2015 OI Hoang, Nick/0000-0001-7097-7114 NR 44 TC 179 Z9 183 U1 1 U2 13 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0264-3294 J9 COGNITIVE NEUROPSYCH JI Cogn. Neuropsychol. PD FEB-MAY PY 2000 VL 17 IS 1-3 BP 257 EP 279 PG 23 WC Psychology; Psychology, Experimental SC Psychology GA 305QC UT WOS:000086550900016 PM 20945183 ER PT J AU Vignal, JP Chauvel, P Halgren, E AF Vignal, JP Chauvel, P Halgren, E TI Localised face processing by the human prefrontal cortex: Stimulation-evoked hallucinations of faces SO COGNITIVE NEUROPSYCHOLOGY LA English DT Article ID HUMAN EXTRASTRIATE CORTEX; TEMPORAL-LOBE EPILEPSY; POSITRON EMISSION TOMOGRAPHY; DEPTH-RECORDED POTENTIALS; VISUAL WORKING-MEMORY; FUNCTIONAL-ORGANIZATION; EXPERIENTIAL PHENOMENA; SPATIOTEMPORAL STAGES; FRONTAL-CORTEX; NEURAL SYSTEM AB Left and right prefrontal, premotor, and anterior temporal sites were stereotaxically implanted in order to direct surgical therapy for epilepsy. Direct electrical stimulation of the right anterior inferior frontal gyrus resulted in face-related hallucinations and illusions. When the patient was viewing a blank background, stimulation induced the experience of a rapid succession of faces. When the patient was viewing a real face, stimulation induced a series of modifications to that face. Effective stimulations induced afterdischarges that remained localised to right ventrolateral prefrontal cortex (VLPFC). Stimulation of other frontal and anterior temporal sites, bilaterally, induced no face-related hallucinations or illusions. This result supports a contribution of right VLPFC to face processing, and is consistent with models wherein it activates representations in working or declarative memories. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Boston, MA 02129 USA. INSERM, E9926, F-13258 Marseille, France. Univ Nancy, Nancy, France. Fac Med Marseille, F-13385 Marseille, France. RP Halgren, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, 149 13th St, Boston, MA 02129 USA. FU NINDS NIH HHS [R01 NS018741] NR 49 TC 26 Z9 27 U1 0 U2 5 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0264-3294 J9 COGNITIVE NEUROPSYCH JI Cogn. Neuropsychol. PD FEB-MAY PY 2000 VL 17 IS 1-3 BP 281 EP 291 PG 11 WC Psychology; Psychology, Experimental SC Psychology GA 305QC UT WOS:000086550900017 PM 20945184 ER PT J AU Kilzieh, N AF Kilzieh, N TI The eclipse of the state mental hospital: Policy, stigma and organization SO COMMUNITY MENTAL HEALTH JOURNAL LA English DT Book Review C1 VA Puget Sound Hlth Care Syst, Amer Lake Div, Tacoma, WA 98493 USA. RP Kilzieh, N (reprint author), VA Puget Sound Hlth Care Syst, Amer Lake Div, 116 MHC,Bldg 85B, Tacoma, WA 98493 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0010-3853 J9 COMMUNITY MENT HLT J JI Community Ment. Health J. PD FEB PY 2000 VL 36 IS 1 BP 126 EP 127 PG 2 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 284NL UT WOS:000085338400010 ER PT J AU Gamel, JW Weller, EA Wesley, MN Feuer, EJ AF Gamel, JW Weller, EA Wesley, MN Feuer, EJ TI Parametric cure models of relative and cause-specific survival for grouped survival times SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE LA English DT Article DE parametric cure model; relative survival; cause-specific survival; lognormal model; loglogistic model; Weibull model; gompertz ID TUMOR AB With parametric cure models, we can express survival parameters (e.g. cured fraction, location and scale parameters) as functions of covariates. These models can measure survival from a specific disease process, either by examining deaths due to the cause under study (cause-specific survival), or by comparing all deaths to those in a matched control population (relative survival). We present a binomial maximum likelihood algorithm to be used for actuarial data, where follow-up times are grouped into specific intervals. Our algorithm provides simultaneous maximum likelihood estimates for all the parameters of a cure model and can be used for cause-specific or relative survival analysis with a variety of survival distributions. Current software does not provide the flexibility of this unified approach. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Vet Adm Hosp, Louisville, KY 40292 USA. Univ Louisville, Sch Med, Louisville, KY 40292 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Informat Management Serv, Silver Spring, MD 20904 USA. NCI, Div Canc Prevent & Control, Bethesda, MD 20892 USA. RP Gamel, JW (reprint author), Vet Adm Hosp, 301 E Muhammed Ali Blvd, Louisville, KY 40292 USA. NR 13 TC 9 Z9 10 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-2607 J9 COMPUT METH PROG BIO JI Comput. Meth. Programs Biomed. PD FEB PY 2000 VL 61 IS 2 BP 99 EP 110 DI 10.1016/S0169-2607(99)00022-X PG 12 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA 271XJ UT WOS:000084619900003 PM 10661395 ER PT J AU Imanaka, H Nishimura, M Takeuchi, M Kimball, WR Yahagi, N Kumon, K AF Imanaka, H Nishimura, M Takeuchi, M Kimball, WR Yahagi, N Kumon, K TI Autotriggering caused by cardiogenic oscillation during flow-triggered mechanical ventilation SO CRITICAL CARE MEDICINE LA English DT Article DE cardiogenic oscillation; autotriggering; flow triggering; synchronized intermittent mandatory ventilation; pressure support ventilation; cardiac surgery; cardiothoracic ratio ID PRESSURE-SUPPORT VENTILATION; INTERMITTENT MANDATORY VENTILATION; POSITIVE AIRWAY PRESSURE; RESPIRATORY-FAILURE; INSPIRATORY WORK; SYSTEMS AB Objectives: We noticed that in some patients after cardiac surgery, when flow triggering was used, cardiogenic oscillation might be autotriggering the ventilatory support. In a prospective study, we evaluated the degree of cardiogenic oscillation and the frequency rate of autotriggering. We suspected that autotriggering caused by cardiogenic oscillation was more common than clinically appreciated. Design: Prospective, nonrandomized, clinical study. Setting: Surgical intensive care unit in a national heart institute. Patients: A total of 104 adult patients were enrolled after cardiac surgery. Interventions: During the study period, patients were paralyzed and ventilated with intermittent mandatory ventilation at a rate of 10 breaths/min, pressure support of 10 cm H2O, and flow triggering with a sensitivity of 1 L/min. Measurements and Main Results: Because the patients would not he able to breathe spontaneously, we counted pressure-support (PS) breaths as instances of autotriggering. Then, we classified the patients into two groups according to the number of PS breaths: an "AT group" (PS breaths of >5/min) and a "non-AT group" (PS breaths of less than or equal to 5/min). If autotriggering occurred, we decreased the sensitivity so autotriggering disappeared (threshold triggering sensitivity). The intensity of cardiogenic oscillation was assessed as the flow and airway pressure at the airway opening. A total of 23 patients (22%) demonstrated more than five autotriggered breaths/min. During mechanical ventilation, the inspiratory flow fluctuation caused by cardiogenic oscillation was significantly greater in the AT group than in the non-AT group (4.67 +/- 1.26 L/min vs. 2.03 +/- 0.86 L/min; p < .01). The AT group also showed larger cardiac output, higher ventricular filling pressures, larger heart size, and lower respiratory system resistance than the non-AT group. As the inspiratory flow fluctuation caused by cardiogenic oscillation increased, the level of triggering sensitivity also was increased to avoid autotriggering. In the AT group with 1 L/min of sensitivity, the respiratory rate increased (19.9 +/- 2.7 vs. 10 +/- 0 breaths/min, p < .01), Pace, decreased (30.8 +/- 4.0 torr [4.11 +/- 0.36 kPa] vs. 37.6 +/- 4.3 torr [5.01 +/- 0.57 kPa]; p < .01), and mean esophageal pressure increased (7.7 +/- 3.0 vs. 6.9 +/- 3.0 cm H2O; p < .01) compared with the threshold triggering sensitivity. Conclusions: Autotriggering caused by cardiogenic oscillation is common in postcardiac surgery patients when flow triggering is used. Autotriggering occurred more often in patients with more dynamic circulation. Autotriggering caused respiratory alkalosis and hyperinflation of the lungs. C1 Natl Cardiovasc Ctr, Surg Intens Care Unit, Suita, Osaka 5658565, Japan. Osaka Univ Hosp, Intens Care Unit, Osaka 553, Japan. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Imanaka, H (reprint author), Natl Cardiovasc Ctr, Surg Intens Care Unit, 5-7-1 Fujishiro Dai, Suita, Osaka 5658565, Japan. NR 17 TC 59 Z9 60 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 FEB PY 2000 VL 28 IS 2 BP 402 EP 407 DI 10.1097/00003246-200002000-00019 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 288CB UT WOS:000085543300019 PM 10708174 ER PT J AU Rogers, PL Jacob, H Thomas, EA Harwell, M Willenkin, RL Pinsky, MR AF Rogers, PL Jacob, H Thomas, EA Harwell, M Willenkin, RL Pinsky, MR TI Medical students can learn the basic application, analytic, evaluative, and psychomotor skills of critical care medicine SO CRITICAL CARE MEDICINE LA English DT Article DE education, medical; students, medical; critical care; teaching; educational measurement; clinical clerkship; intensive care unit; learning; clinical competence ID STRUCTURED CLINICAL EXAMINATION; RELIABILITY; COMPETENCE AB Objective: To determine whether fourth-year medical students can learn the basic analytic, evaluative, and psychomotor skills needed to initially manage a critically ill patient, Design: Student learning was evaluated using a performance examination, the objective structured clinical examination (OSCE). Students were randomly assigned to one of two clinical scenarios before the elective. After the elective, students completed the other scenario, using a crossover design. Setting: Five surgical intensive care units in a tertiary care university teaching hospital, Participants: Forty fourth-year medical students enrolled in the critical care medicine (CCM) elective. Interventions: AII students evaluated a live "simulated critically ill" patient, requested physiologic data from a nurse, ordered laboratory tests, received data in real time, and intervened as they deemed appropriate. Measurements and Main Results: Student performance of specific behavioral objectives was evaluated at five stations. They were expected to a) assess airway, breathing, and circulation in appropriate sequence; b) prepare a manikin for intubation, obtain an acceptable airway on the manikin, demonstrate bag-mouth ventilation, and perform acceptable laryngoscopy and intubation; c) provide appropriate mechanical ventilator settings; d) manage hypotension; and e) request and interpret pulmonary artery data and initiate appropriate therapy. OSCEs were videotaped and reviewed by two faculty members masked to time of examination, A checklist of key behaviors was used to evaluate performance. The primary outcome measure was the difference in examination score before and after the rotation. Secondary outcomes included the difference in scores at each rotation, The mean preelective score was 57.0% +/- 8.3% compared with 85.9% +/- 7.4% (p < .0001) after the elective. Significant improvement was demonstrated at each station except station I. Conclusion: Fourth-year medical students without a CCM elective do not possess the basic cognitive and psychomotor skills necessary to initially manage critically ill patients. After an appropriate I-month CGM elective, students' thinking and application skills required to initially manage critically ill patients improved markedly, as demonstrated by an OSCE using a live simulated "patient" and manikin. C1 Univ Pittsburgh, Med Ctr, Dept Anesthesiol & Crit Care Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Educ Psychol, Pittsburgh, PA USA. RP Rogers, PL (reprint author), VA Pittsburgh Hlth Care Syst, Crit Care Serv 124U, Univ Dr, Pittsburgh, PA 15240 USA. NR 10 TC 22 Z9 23 U1 3 U2 4 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 FEB PY 2000 VL 28 IS 2 BP 550 EP 554 DI 10.1097/00003246-200002000-00043 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 288CB UT WOS:000085543300043 PM 10708198 ER PT J AU Faraone, SV AF Faraone, SV TI Attention deficit hyperactivity disorder in adults: Implications for theories of diagnosis SO CURRENT DIRECTIONS IN PSYCHOLOGICAL SCIENCE LA English DT Article DE adult ADHD; diagnostic validity; nosology; psychometrics AB The diagnosis of attention deficit hyperactivity disorder (ADHD) in adults has been a source of controversy, with some prominent researchers questioning its very existence and others suggesting it is an urgent clinical problem. This article reviews five domains of data addressing the validity of adult ADHD: clinical correlates, family history, treatment response, laboratory studies, and long-term outcome. It then shows how the debate over adult ADHD reflects a clash of theoretical paradigms and concludes by suggesting ways in which psychological science can collect the data needed to clarify the validity of adult ADHD. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Faraone, SV (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, ACC 725,15 Parkman St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 NR 13 TC 37 Z9 37 U1 1 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0963-7214 J9 CURR DIR PSYCHOL SCI JI Curr. Dir. Psychol. PD FEB PY 2000 VL 9 IS 1 BP 33 EP 36 DI 10.1111/1467-8721.00055 PG 4 WC Psychology, Multidisciplinary SC Psychology GA 297PC UT WOS:000086090400009 ER PT J AU Artandi, SE DePinho, RA AF Artandi, SE DePinho, RA TI A critical role for telomeres in suppressing and facilitating carcinogenesis SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID NORMAL HUMAN-CELLS; HUMAN FIBROBLASTS; TUMOR SUPPRESSION; CATALYTIC SUBUNIT; MOUSE TELOMERASE; LIFE-SPAN; CELLULAR SENESCENCE; EPITHELIAL-CELLS; IMMORTAL CELLS; INK4A LOCUS AB Progressive telomere shortening occurs with the division of primary human cells and activates tumor suppressor pathways, triggering senescence and inhibiting tumorigenesis. Loss of p53 function, however, allows continued cell division despite increasing telomere dysfunction and entry into telomere crisis. Recent data suggest that the severe chromosomal instability of telomere crisis promotes secondary genetic changes that facilitate carcinogenesis. Reactivation of telomerase stabilizes telomere ends and allows continued tumor growth. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NEI NIH HHS [R01EY11267]; NICHD NIH HHS [R01HD28317] NR 66 TC 212 Z9 218 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD FEB PY 2000 VL 10 IS 1 BP 39 EP 46 DI 10.1016/S0959-437X(99)00047-7 PG 8 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 287XY UT WOS:000085533800005 PM 10679392 ER PT J AU Tan, MW Ausubel, FM AF Tan, MW Ausubel, FM TI Caenorhabditis elegans: a model genetic host to study Pseudomonas aeruginosa pathogenesis SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID ENHANCED DISEASE SUSCEPTIBILITY; DROSOPHILA TOLL; IMMUNITY; DEFENSE; ARABIDOPSIS; EXPRESSION; MUTANTS; GATA; RESPONSES; COMMON AB In the past year, a Caenorhabditis elegans-Pseudomonas aeruginosa pathogenesis model has been developed to facilitate the systematic dissection of both host and pathogen genes involved in pathogenic interactions. Analysis of the P. aeruginosa-C. elegans interaction should shed light on the larger question of how organisms interact at the molecular level in antagonistic relationships. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. RP Tan, MW (reprint author), Harvard Univ, Sch Med, Dept Genet, Wellman 10, Boston, MA 02114 USA. NR 40 TC 104 Z9 126 U1 2 U2 7 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 FEB PY 2000 VL 3 IS 1 BP 29 EP 34 DI 10.1016/S1369-5274(99)00047-8 PG 6 WC Microbiology SC Microbiology GA 284NX UT WOS:000085339400004 PM 10679415 ER PT J AU Lee, SH Sheng, M AF Lee, SH Sheng, M TI Development of neuron-neuron synapses SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Review ID SYNAPTIC AMPA; GLUTAMATE RECEPTORS; HIPPOCAMPAL-NEURONS; SPINAL NEURONS; SYNAPTOGENESIS; STABILIZATION; PROTEIN AB Our understanding of neuronal synapse development has advanced in recent years. The development of glycinergic synapses appears to depend on gephyrin and glycine receptor activity. Molecular characterization of the structure and development of glutamatergic synapses is in progress, but the underlying mechanisms remain unclear. Activity-dependent mechanisms and specific molecules that regulate the morphological development of dendritic spines have recently been identified. C1 Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lee, SH (reprint author), Massachusetts Gen Hosp, Dept Neurobiol, 50 Blossom St, Boston, MA 02114 USA. FU NINDS NIH HHS [NS35050] NR 57 TC 79 Z9 82 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD FEB PY 2000 VL 10 IS 1 BP 125 EP 131 DI 10.1016/S0959-4388(99)00046-X PG 7 WC Neurosciences SC Neurosciences & Neurology GA 289VL UT WOS:000085642600016 PM 10679427 ER PT J AU Goodman, A AF Goodman, A TI Role of routine human papillomavirus subtyping in cervical screening SO CURRENT OPINION IN OBSTETRICS & GYNECOLOGY LA English DT Article ID INTRAEPITHELIAL NEOPLASIA; PAPANICOLAOU SMEARS; HYBRID CAPTURE; HPV DNA; INFECTION; WOMEN; CANCER; GRADE; ABNORMALITIES; POPULATION AB Human papillomavirus testing has been evaluated as an adjunct to cervical cytologic screening. There is a well-established association between high-risk malignant subtypes of human papillomavirus infection and the development of neoplastic change. Although human papillomavirus infection is a necessary condition for malignant transformation, it is not a sufficient condition. Multiple cofactors are necessary for progression to dysplasia and then to invasive cervical cancer. Because of the multifactorial nature of malignant transformation, current methods of human papillomavirus testing do not add sufficient predictive and diagnostic information over that obtained by cytology and colposcopic biopsy to warrant routine clinical use. (C) 2000 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. RP Goodman, A (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, WACC 231, Boston, MA 02114 USA. NR 40 TC 8 Z9 10 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-872X J9 CURR OPIN OBSTET GYN JI Curr. Opin. Obstet. Gynecol. PD FEB PY 2000 VL 12 IS 1 BP 11 EP 14 DI 10.1097/00001703-200002000-00002 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 289HV UT WOS:000085615200002 PM 10752510 ER PT J AU Parsons, SK AF Parsons, SK TI Oncology practice patterns in the use of hematopoietic growth factors SO CURRENT OPINION IN PEDIATRICS LA English DT Review ID COLONY-STIMULATING FACTOR; RECOMBINANT-HUMAN-ERYTHROPOIETIN; ACUTE LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW TRANSPLANTATION; STEM-CELL TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; PEDIATRIC-PATIENTS; FEBRILE NEUTROPENIA; RANDOMIZED TRIAL; DOUBLE-BLIND AB Recombinant hematopoietic growth factors were introduced into clinical practice a decade ago: erythropoietin in 1989, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in 1991, and interleukin-11 in 1997, The role of these agents in supportive therapy for children with cancer is still under considerable evaluation. This pediatric-based review summarizes current clinical applications, practice guidelines, and practice patterns for hematopoietic growth factors in the supportive care of children with cancer. It also discusses ongoing controversies and unanswered questions. Curr Opin Pediatr 2000, 12:10-17 (C) 2000 Lippincott Williams & Wilkins, Inc. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Parsons, SK (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. NR 41 TC 8 Z9 8 U1 0 U2 0 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 FEB PY 2000 VL 12 IS 1 BP 10 EP 17 DI 10.1097/00008480-200002000-00003 PG 8 WC Pediatrics SC Pediatrics GA 298FB UT WOS:000086127700003 PM 10676768 ER PT J AU Karp, SJ Schipani, E St-Jacques, B Hunzelman, J Kronenberg, H McMahon, AP AF Karp, SJ Schipani, E St-Jacques, B Hunzelman, J Kronenberg, H McMahon, AP TI Indian hedgehog coordinates endochondral bone growth and morphogenesis via Parathyroid Hormone related-Protein-dependent and -independent pathways SO DEVELOPMENT LA English DT Article DE Indian hedgehog (Ihh); Parathyroid Hormone-related Protein (PTHrP); endochondral bone; chondrocyte; cartilage ID CARTILAGE DIFFERENTIATION; TRANSGENIC MICE; COLLAGEN GENE; PEPTIDE GENE; EXPRESSION; CHONDROCYTES; RECEPTOR; CHONDRODYSPLASIA AB Indian hedgehog (Ihh) and Parathyroid Hormone-related Protein (PTHrP) play a critical role in the morphogenesis of the vertebrate skeleton. Targeted deletion of Ihh results in short-limbed dwarfism, with decreased chondrocyte proliferation and extensive hypertrophy, features shared by mutants in PTHrP and its receptor. Activation of Ihh signaling upregulates PTHrP at the articular surface and prevents chondrocyte hypertrophy in wild-type but not PTHrP null explants, suggesting that Ihh acts through PTHrP, To investigate the relationship between these factors during development of the appendicular skeleton, mice were produced with various combinations of an Ihh null mutation (Ihh(-/-)), a PTHrP null mutation (PTHrP(-/-)), and a constitutively active PTHrP/Parathyroid hormone Receptor expressed under the control of the Collagen II promoter (PTHrPR*), PTHrPR* rescues PTHrP(-/-) embryos, demonstrating this construct can completely compensate for PTHrP signalling. At 18.5 dpc, limb skeletons of Ihh, PTHrP compound mutants were identical to Ihh single mutants suggesting Ihh is necessary for PTHrP function. Expression of PTHrPR* in chondrocytes of Ihh(-/-) mice prevented premature chondrocyte hypertrophy but did not rescue either the short-limbed dwarfism or decreased chondrocyte proliferation, These experiments demonstrate that the molecular mechanism that prevents chondrocyte hypertrophy is distinct from that which drives proliferation. Ihh positively regulates PTHrP, which is sufficient to prevent chondrocyte hypertrophy and maintain a normal domain of cells competent to undergo proliferation. In contrast, Ihh is necessary for normal chondrocyte proliferation in a pathway that can not be rescued by PTHrP signaling. This identifies Ihh as a coordinator of skeletal growth and morphogenesis, and refines the role of PTHrP in mediating a subset of Ihh's actions. C1 Harvard Univ, Dept Mol & Cellular Biol, Biolabs, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP McMahon, AP (reprint author), Harvard Univ, Dept Mol & Cellular Biol, Biolabs, Cambridge, MA 02138 USA. FU NICHD NIH HHS [HD08356]; NIDDK NIH HHS [DK56246]; NINDS NIH HHS [NS33642] NR 24 TC 285 Z9 296 U1 1 U2 10 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD FEB PY 2000 VL 127 IS 3 BP 543 EP 548 PG 6 WC Developmental Biology SC Developmental Biology GA 285MW UT WOS:000085393700010 PM 10631175 ER PT J AU Dobens, LL Peterson, JS Treisman, J Raftery, LA AF Dobens, LL Peterson, JS Treisman, J Raftery, LA TI Drosophila bunched integrates opposing DPP and EGF signals to set the operculum boundary SO DEVELOPMENT LA English DT Article DE oogenesis; bunched; TSC-22; decapentaplegic; TGF beta family signaling ID FAINT-LITTLE-BALL; RECEPTOR HOMOLOG; GENE-EXPRESSION; EYE DEVELOPMENT; BETA FAMILY; CELL FATES; OOGENESIS; MELANOGASTER; PATHWAYS; GROWTH AB The Drosophila BMP homolog DPP can function as a morphogen, inducing multiple cell fates across a developmental field. However, it is unknown how graded levels of extracellular DPP are interpreted to organize a sharp boundary between different fates. Here we show that opposing DPP and EGF signals set the boundary for an ovarian follicle cell fate. First, DPP regulates gene expression in the follicle cells that will create the operculum of the eggshell. DPP induces expression of the enhancer trap reporter A359 and represses expression of bunched, which encodes a protein similar to the mammalian transcription factor TSC-22. Second, DPP signaling indirectly regulates A359 expression in these cells by downregulating expression of bunched, Reduced bunched function restores A359 expression in cells that lack the Smad protein MAD; ectopic expression of BUNCHED suppresses A359 expression in this region. Importantly, reduction of bunched function leads to an expansion of the operculum and loss of the collar at its boundary. Third, EGF signaling upregulates expression of bunched. We previously demonstrated that the bunched expression pattern requires the EGF receptor ligand GURKEN, Here we show that activated EGF receptor is sufficient to induce ectopic bunched expression. Thus, the balance of DPP and EGF signals sets the boundary of bunched expression. We propose that the juxtaposition of cells with high and low BUNCHED activity organizes a sharp boundary for the operculum fate. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. NYU, Med Ctr, Skirball Inst Biomol Med, New York, NY USA. RP Raftery, LA (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RI Raftery, Laurel/H-1406-2012 OI Raftery, Laurel/0000-0003-4797-4163 NR 51 TC 71 Z9 71 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD FEB PY 2000 VL 127 IS 4 BP 745 EP 754 PG 10 WC Developmental Biology SC Developmental Biology GA 290AC UT WOS:000085653300008 PM 10648233 ER PT J AU Dominguez, I Green, JBA AF Dominguez, I Green, JBA TI Dorsal downregulation of GSK3 beta by a non-Wnt-like mechanism is an early molecular consequence of cortical rotation in early Xenopus embryos SO DEVELOPMENT LA English DT Article DE GSK3 beta; Wnt; GBP; beta-catenin; Xenopus; dorsal axis ID GLYCOGEN-SYNTHASE KINASE-3; AXIS-INDUCING ACTIVITY; FIRST CELL-CYCLE; BETA-CATENIN; SPEMANN ORGANIZER; SIGNALING PATHWAY; DORSOVENTRAL AXIS; INDUCTION; EGGS; LAEVIS AB Cortical rotation and concomitant dorsal translocation of cytoplasmic determinants are the earliest events known to be necessary for dorsoventral patterning in Xenopus embryos. The earliest known molecular target is beta-catenin, which is essential for dorsal development and becomes dorsally enriched shortly after cortical rotation. In mammalian cells cytoplasmic accumulation of beta-catenin follows reduction of the specific activity of glycogen synthase kinase 3-beta (GSK3 beta), In Xenopus embryos, exogenous GSK3 beta suppresses dorsal development as predicted and GSK3 beta dominant negative (kinase dead) mutants cause ectopic axis formation. However, endogenous GSK3 beta regulation is poorly characterized. Here we demonstrate two modes of GSK3 beta regulation in Xenopus. Endogenous mechanisms cause depletion of GSK3 beta protein on the dorsal side of the embryo. The timing, location and magnitude of the depletion correspond to those of endogenous beta-catenin accumulation. uv and D2O treatments that abolish and enhance dorsal character of the embryo, respectively, correspondingly abolish and regulator of GSK3 beta, GSK3-binding protein (GBP), known to be essential for axis formation, also induces depletion of GSK3 beta, Depletion of GSK3 beta is a previously undescribed mode of regulation of this signal transducer. The other mode of regulation is observed in response to Wnt and dishevelled expression. Neither Wnt nor dishevelled causes depletion but instead they reduce GSK3 beta-specific activity. Thus, Wnt/Dsh and GBP appear to effect two biochemically distinct modes of GSK3 beta regulation. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Green, JBA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. RI Green, Jeremy/F-3630-2010 OI Green, Jeremy/0000-0002-6102-2620 NR 40 TC 50 Z9 51 U1 1 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD FEB PY 2000 VL 127 IS 4 BP 861 EP 868 PG 8 WC Developmental Biology SC Developmental Biology GA 290AC UT WOS:000085653300019 PM 10648244 ER PT J AU Krook, A Bjornholm, M Galuska, D Jiang, XJ Fahlman, R Myers, MG Wallberg-Henriksson, H Zierath, JR AF Krook, A Bjornholm, M Galuska, D Jiang, XJ Fahlman, R Myers, MG Wallberg-Henriksson, H Zierath, JR TI Characterization of signal transduction and glucose transport in skeletal muscle from type 2 diabetic patients SO DIABETES LA English DT Article ID INSULIN-RECEPTOR SUBSTRATE-1; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; GLYCOGEN-SYNTHASE; TYROSINE KINASE; PHOSPHOTYROSINE PROTEIN; NIDDM SUBJECTS; OBESE SUBJECTS; ANIMAL-MODELS; MESSENGER-RNA; MELLITUS AB We characterized metabolic and mitrogenic signaling pathways in isolated skeletal muscle from well-matched type 2 diabetic and control subjects. Time course studies of the insulin receptor, insulin receptor substrate (IRS)-1/2, and phosphatidylinositol (PI) 3-kinase revealed that signal transduction through this pathway was engaged between 4 and 40 min, Insulin-stimulated (0.6-60 nmol/l) tyrosine phosphorylation of the insulin receptor beta-subunit, mitogen-activated protein (MAP) kinase phosphorylation, and glycogen synthase activity were not altered in type 2 diabetic subjects. In contrast, insulin-stimulated tyrosine phosphorylation of IRS-1 and anti-phosphotyrosine-associated PI 3-kinase activity were reduced 40-55% in type 2 diabetic subjects at high insulin concentrations (2.4 and 60 nmol/l, respectively). Impaired glucose transport activity was noted at an insulin concentrations (0.6-60 nmol/l). Aberrant, protein expression cannot; account for these insulin-signaling defects because expression of insulin receptor, IRS-1, IRS-2, MAP kinase, or glycogen synthase was similar between type 2 diabetic and control subjects. In skeletal muscle from type 2 diabetic subjects, IRS-1 phosphorylation, PI 3-kinase activity, and glucose transport activity were impaired, whereas insulin receptor tyrosine phosphorylation, MAP kinase phosphorylation, and glycogen synthase activity were normal. Impaired insulin signal transduction in skeletal muscle from type 2 diabetic patients may partly account for reduced insulin-stimulated glucose transport; however, additional defects are likely to play a role. C1 Karolinska Hosp, Dept Clin Physiol, S-17176 Stockholm, Sweden. Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Zierath, JR (reprint author), Karolinska Hosp, Dept Clin Physiol, S-17176 Stockholm, Sweden. RI Krook, Anna/K-1192-2015 OI Krook, Anna/0000-0002-0891-0258 NR 59 TC 230 Z9 237 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2000 VL 49 IS 2 BP 284 EP 292 DI 10.2337/diabetes.49.2.284 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 281RD UT WOS:000085173800017 PM 10868945 ER PT J AU Elbein, SC Wegner, K Kahn, SE AF Elbein, SC Wegner, K Kahn, SE TI Reduced beta-cell compensation to the insulin resistance associated with obesity in members of Caucasian familial type 2 diabetic kindreds SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; POLYCYSTIC-OVARY-SYNDROME; PIMA-INDIANS; INTRAVENOUS GLUCOSE; SENSITIVITY; SECRETION; MELLITUS; LEPTIN; NIDDM; HYPERINSULINEMIA AB OBJECTIVE - Both obesity and a family history of diabetes reduce insulin sensitivity but the impact of obesity on insulin secretion among individuals predisposed to diabetes is uncertain. We used a pedigree-based approach to test the hypothesis that p-cell compensation to the insulin resistance associated with obesity is defective among individuals predisposed to diabetes by virtue of a strong family history of type 2 diabetes before the development of diabetes or glucose intolerance. RESEARCH DESIGN AND METHODS - A total of 126 members of 26 families ascertained for at least a sib pair with type 2 diabetes with onset before age 65 years underwent a tolbutamide-modified frequently sampled intravenous glucose tolerance rest (FSIGT). Family members included 26 individuals with impaired glucose tolerance and 100 individuals with normal glucose tolerance (NGT). The acute insulin response to glucose (AIR(glucose)) was determined and insulin sensitivity (S-I) estimated by minimal model analysis of FSIGT data. The beta-cell compensation for insulin sensitivity was estimated from the disposition index (DI), calculated as the product of SI and AIR(glucose). Obesity was measured by BMI. RESULTS - Among all individuals, BMI was a significant predictor of both SI and AIR(glucose), as expected. However, BMI also significantly predicted DI (P = 0.002) after correcting for age, sex, family membership, and glucose tolerance status. The relationship of BMI and DI was confirmed in 85 individuals with NGT who were aged <45 (P = 0.002) but not in 91 unrelated control individuals without a family history of diabetes. When normoglycemic individuals aged <45 were separated into three classes by BMI (less than or equal to 27, 27-30, >30), S-I decreased progressively and significantly with obesity, whereas AIR(glucose) rose significantly from lean to most obese classes. In contrast to the expectation of complete beta-cell compensation with obesity DI fell significantly (P = 0.004) among obese family members. This relationship was not observed in control subjects CONCLUSIONS - Individuals with a genetic predisposition to diabetes show a reduced beta-cell compensatory response to the reduced insulin sensitivity associated with obesity We propose that this impaired compensation may be one manifestation of the underlying genetic defect in susceptible individuals. This finding helps explain the multiplicative effects of family history and obesity on risk of type 2 diabetes. C1 Cent Arkansas Vet Hlthcare Syst, Endocrinol Sect, Little Rock, AR USA. Univ Arkansas Med Sci, Dept Med, Little Rock, AR 72205 USA. Univ Washington, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Elbein, SC (reprint author), John L McClellan Mem Vet Hosp, 4700 W 7th St, Little Rock, AR 72205 USA. FU NIDDK NIH HHS [DK39311, DK17047] NR 32 TC 74 Z9 78 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2000 VL 23 IS 2 BP 221 EP 227 DI 10.2337/diacare.23.2.221 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 279HA UT WOS:000085037300017 PM 10868835 ER PT J AU Whitsel, EA Boyko, EJ Siscovick, DS AF Whitsel, EA Boyko, EJ Siscovick, DS TI Reassessing the role of QT(c) in the diagnosis of autonomic failure among patients with diabetes - A meta-analysis SO DIABETES CARE LA English DT Article ID QT INTERVAL PROLONGATION; Q-T INTERVAL; NERVOUS-SYSTEM; NEUROPATHY; MELLITUS; TESTS; ELECTROCARDIOGRAM; METAANALYSIS; ASSOCIATION; PROPRANOLOL AB OBJECTIVE- A 1992 consensus statement on autonomic testing portrayed Bazett's heart race-corrected QT interval (QT(c)) prolongation as a specific yet insensitive indicator of diabetic autonomic failure. At that time, only a few small studies had evaluated the accuracy of QT(c). To date, even fewer studies have evaluated whether its accuracy is influenced by patient characteristics. RESEARCH DESIGN AND METHODS - We critically appraised 17 studies reporting the sensitivity and specificity of QT(c) for diabetic autonomic failure. The studies represented 4,584 patients with diabetes (mean age 34.9 years, 46% female, 92% with type 1 diabetes, mean duration of diabetes 14.5 years). We summarized the accuracy of QT(c) prolongation for diabetic autonomic failure as an odds ratio (OR) (95% CI) and determined whether patient and study design characteristics influenced the accuracy of QT(c) prolongation by comparing summary receiver operating characteristic curves. RESULTS - Autonomic failure, defined as greater than or equal to 1.2 +/- 0.4 (mean +/- SD) abnormal of 2.0 +/- 1.6 administered cardiovascular reflex tests, was found in 26% (25-28) of patients. The pooled sensitivity and specificity of QT(c) > 441 +/- 8 ms for autonomic failure were 28% (26-29) and 86% (85-87), respectively. Autonomic failure was 2.26 times (1.90-2.70) more likely to be present in patients with than in patients without QT(c) prolongation. At 86% specificity the sensitivity of QT(c) prolongation was 46 vs. 12% for men versus women (P = 0.0077), respectively, and, after adjustment for sex, 66 vs. 17% among patients aged 25 vs. 55 years (P = 0.1902) and 61 vs. 27% at thresholds of >420 vs. >460 ms, respectively (P = 0.2964). CONCLUSIONS - QT(c) prolongation is a specific albeit insensitive indicator of autonomic failure. Although QT(c) prolongation is relatively accurate for men, accuracy may be even greater for young men at low QT(c) thresholds. C1 Vet Affairs Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. Univ Washington, Dept Med & Epidemiol, Seattle, WA 98195 USA. RP Whitsel, EA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 48 TC 56 Z9 59 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2000 VL 23 IS 2 BP 241 EP 247 DI 10.2337/diacare.23.2.241 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 279HA UT WOS:000085037300020 PM 10868838 ER PT J AU Moczulski, DK Scott, L Antonellis, A Rogus, JJ Rich, SS Warram, JH Krolewski, AS AF Moczulski, DK Scott, L Antonellis, A Rogus, JJ Rich, SS Warram, JH Krolewski, AS TI Aldose reductase gene polymorphisms and susceptibility to diabetic nephropathy in Type 1 diabetes mellitus SO DIABETIC MEDICINE LA English DT Article DE aldose reductase gene; diabetic nephropathy; genetic susceptibility; Type 1 diabetes mellitus ID LINKAGE DISEQUILIBRIUM; COMPLICATIONS; EXPRESSION; SORBITOL; 5'-END; REGION; IDDM AB Aims To investigate association and linkage between DNA sequence variants in the aldose reductase (AR) gene on chromosome 7q35 and diabetic nephropathy (DN) in Type 1 diabetes mellitus. Methods By sequencing the promoter region and 10 exons in eight DN cases and eight controls, a frequent bi-allelic polymorphism (C-106T) was discovered. This polymorphism and the known 5'ALR2 dinucleotide repeat polymorphism were genotyped in unrelated cases with advanced nephropathy (n = 221) and unrelated controls with normoalbuminuria (n = 193). For a family based study, 166 case-trios (case and both parents) and 83 control-trios (control and both parents) were also genotyped. Results In the case-control study, carriers of the Z-2 allele of the 5'ALR2 polymorphism had a significantly higher risk of DN than non-carriers (odds ratios: 1.6 for heterozygotes and 2.1 for homozygotes, P < 0.05 for each). The same was true for carriers of the T allele of the C-106T polymorphism (odds ratios: 1.6 for heterozygotes and 1.9 for homozygotes, P < 0.05 for each). Moreover, the haplotype carrying both risk alleles was in excess in DN cases. In the family study, transmission of risk alleles from heterozygous parents was consistent with the case-control study, excess transmission in case-trios and deficient in control-trios. Conclusions Association between DN and two DNA sequence variants in the promoter region of the AR gene implicates the polyol pathway in the development of kidney complications in Type 1 diabetes mellitus. Further examination of the molecular mechanisms underlying these findings may provide insight into the pathogenesis of DN. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK 53534, DK41526] NR 32 TC 54 Z9 58 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD FEB PY 2000 VL 17 IS 2 BP 111 EP 118 DI 10.1046/j.1464-5491.2000.00225.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 300HP UT WOS:000086247500003 PM 10746480 ER PT J AU Kearney, DJ Brousal, A AF Kearney, DJ Brousal, A TI Treatment of Helicobacter pylori infection in clinical practice in the United States - Results from 224 patients SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Helicobacter pylori; peptic ulcer; dyspepsia ID LANSOPRAZOLE TRIPLE THERAPY; METRONIDAZOLE RESISTANCE; TREATMENT REGIMENS; PEPTIC-ULCER; ERADICATION; CLARITHROMYCIN; OMEPRAZOLE; EFFICACY; TRIAL; CURE AB Our objectives were to define treatment success, compliance, and side effects for treatment of Helicobacter pylori in clinical practice. In all, 224 consecutive patients received Helicobacter pylori treatment: 97 received two weeks of bismuth subsalicylate, metronidazole, tetracycline four times a day with a H-2-receptor antagonist twice a day (BMT); 89 received one week of metronidazole, lansoprazole, and clarithromycin twice a day (MLC); and 38 received one week of BMT with lansoprazole twice a day (BMT-PPI). Cure rates were: BMT 81% (95% CI 74-89%), MLC 90% (95% CI 84-96%) BMT-PPI 87% (95% CI 81-92%). More patients prescribed a bismuth-based regimen discontinued medications due to side effects compared to MLC (P = 0.049). Nausea was more common for BMT compared to MLC (P = 0.04). In conclusion, treatment of Helicobacter pylori infection with a one-week course of MLC achieves a high rate of cure in clinical practice. Significantly fewer patients prescribed PPI-based therapy discontinue medications due to side effects as compared to bismuth-based triple therapy. C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Kearney, DJ (reprint author), Vet Adm Med Ctr, 1660 S Columbian Way,111GI, Seattle, WA 98108 USA. NR 40 TC 26 Z9 28 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD FEB PY 2000 VL 45 IS 2 BP 265 EP 271 DI 10.1023/A:1005444006042 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 290YJ UT WOS:000085705200009 PM 10711436 ER PT J AU Singh, B AF Singh, B TI Azimilide - Viewpoint SO DRUGS LA English DT Editorial Material C1 W Los Angeles Vet Affairs Med Ctr, Div Cardiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Singh, B (reprint author), W Los Angeles Vet Affairs Med Ctr, Div Cardiol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PD FEB PY 2000 VL 59 IS 2 BP 278 EP 278 DI 10.2165/00003495-200059020-00017 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 292CY UT WOS:000085777600020 ER PT J AU Mazarati, AM Baldwin, RA Sofia, D Wasterain, CG AF Mazarati, AM Baldwin, RA Sofia, D Wasterain, CG TI Felbamate in experimental model of status epilepticus SO EPILEPSIA LA English DT Article DE self-sustaining status epilepticus; seizures; felbamate; anticonvulsant ID INSENSITIVE GLYCINE RECEPTORS; HUMAN POSTMORTEM BRAIN; PARTIAL SEIZURES; RAT; ANTICONVULSANT; ISCHEMIA AB Purpose: To examine the putative seizure protective properties of felbarnate in an animal model of self-sustaining status epilepticus (SSSE). Methods: SSSE was induced by 30-min stimulation of the perforant path (PPS) through permanently implanted electrodes in free-running male adult Wistar rats. Felbarnate (FBM; 50, 100, and 200 mg/kg), dizepam (DZP; 10 mg/kg), or phenytoin (PHT; 50 mg/kg) were injected i.v. 10 min after SSSE induction. Electrographic manifestations of SSSE and the severity of SSSE-induced neuronal injury were analyzed. Results: Felbamate injected during the early stages of SSSE (10 min after the end of PPS), shortened the duration of seizures in a dose-dependent manner. Total time spent in seizures after FBM and 290 +/- 251 min (50 mg/kg), 15.3 +/- 9 min (100 mg/kg), and 7 +/- 1 min (200 mg/kg), whereas control animals spent 410 +/- 133 min seizing. This effect of FBM was stronger than that of DZP (10 mg/kg, 95 +/- 22 min) and comparable to that of PHT (50 mg/kg, 6.3 +/- 2.5 min). In the applied doses, FBM (200 mg/kg) was more effective than PHT (50 mg/kg) or DZP (10 mg/kg) in shortening seizure duration and decreasing spike frequency, when administered on the pleateau of SSSE (injection 40 min after the end of PPS). Anticonvulsant action of FBM was confirmed by milder neuronal injury compared with control animals. Conclusions: Felbamate, a clinically available AED with a moderate affinity for the glycine site of the NMDA receptor, displayed a potent seizure-protective effect in an animal model of SSSE. These results suggest that FBM might be useful when standard AEDs fail in the treatment of refractory cases of SE. C1 Greater Los Angeles Hlth Care Syst, Sepulveda, CA USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Inst Brain Res, Los Angeles, CA 90024 USA. Wallace Labs, Cranbury, NJ USA. RP Mazarati, AM (reprint author), VA GLAHCS, 111N1 Epilepsy Res,16111 Plummer St, Sepulveda, CA 91343 USA. FU NINDS NIH HHS [NS11315] NR 19 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD FEB PY 2000 VL 41 IS 2 BP 123 EP 127 DI 10.1111/j.1528-1157.2000.tb00130.x PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 282RH UT WOS:000085231900001 PM 10691107 ER PT J AU Dworetzky, BA Hoch, DB Wagner, AK Salmanson, E Shanahan, CW Bromfield, EB AF Dworetzky, BA Hoch, DB Wagner, AK Salmanson, E Shanahan, CW Bromfield, EB TI The impact of a single seizure on health status and health care utilization SO EPILEPSIA LA English DT Article DE seizure; quality of life; health care utilization; impact; health status ID QUALITY-OF-LIFE; WELL-CONTROLLED EPILEPSY; 1ST UNPROVOKED SEIZURE; SURVEY SF-36; PEOPLE; EMERGENCY; RECURRENCE; DIAGNOSIS AB Purpose: To assess the health status of patients after a single seizure. Methods: We compared single-seizure patients (SS) with patients who had well-controlled epilepsy (WC), and uncomplicated hypertension (HT). Patients were adults screened from emergency and outpatient units of two urban teaching hospitals using predefined criteria. The 83 patients (SS, 30; WC, 29; HT, 24) were interviewed by phone about functional status (SF-36), comorbid illness, cause of illness, number of visits to health providers, and drug side effects. Results: No significant differences were found among groups for health status, SF-36 domain, or occurrence of drug side effects. SS patients had significantly lower scores on vitality (p < 0.03) and a trend toward lower role physical function (p < 0.07) compared with age-adjusted population nons. SS reported more visits to health providers than WC or HT, and the number of visits remained high at interview 1 year later. Patient knowledge of the "reason" for the seizure was not associated with health status or number of visits. Conclusions: Health status of patients within 1 year of a single seizure is similar to that of patients with well-controlled epilepsy or hypertension, but SS patients have greater health care utilization. C1 Boston Univ, Sch Med, Boston VAMC, Boston, MA 02118 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Tufts Univ, Sch Med, New England Med Ctr, Boston, MA 02111 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02215 USA. RP Dworetzky, BA (reprint author), 150 S Huntington Ave, Boston, MA 02130 USA. RI Shanahan, Christopher/H-6592-2015; OI Shanahan, Christopher/0000-0001-9067-5922; Hoch, Daniel/0000-0002-4294-024X; Dworetzky, Barbara/0000-0002-3364-2347 NR 25 TC 12 Z9 12 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD FEB PY 2000 VL 41 IS 2 BP 170 EP 176 DI 10.1111/j.1528-1157.2000.tb00136.x PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 282RH UT WOS:000085231900007 PM 10691113 ER PT J AU Krahl, SE Senanayake, SS Handforth, A AF Krahl, SE Senanayake, SS Handforth, A TI Seizure suppression by systemic epinephrine is mediated by the vagus nerve SO EPILEPSY RESEARCH LA English DT Article DE adrenaline; anticonvulsant; epilepsy; pentylenetetrazol; vagus nerve ID STIMULATION AB The present study investigated the seizure-suppressing effects of systemic epinephrine. Rats were injected with epinephrine, and seizures induced with pentylenetetrazol. Seizure severities were significantly reduced 15 min after 1 mg/kg of epinephrine. Severing the subdiaphragmatic vagus nerves abolished this effect, demonstrating that epinephrine-induced seizure suppression is mediated by subdiaphragmatic vagal afferents. The development of novel anti-epileptic drugs that exploit this peripheral pathway may yield new seizure treatments. (C) 2000 Elsevier Science B.V. All rights reserved. C1 W Los Angeles VA Med Ctr, Neurol Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Div Neurosurg, Los Angeles, CA 90095 USA. RP Krahl, SE (reprint author), W Los Angeles VA Med Ctr, Neurol Serv, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM scott.krahl@med.va.gov NR 14 TC 21 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD FEB PY 2000 VL 38 IS 2-3 BP 171 EP 175 DI 10.1016/S0920-1211(99)00089-3 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 273PU UT WOS:000084716700009 PM 10642045 ER PT J AU Hussain, MA AF Hussain, MA TI CD154 for the dragon: a promising development for pancreatic islet transplantation and cure for type 1 diabetes mellitus SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID IMMUNOSUPPRESSION; CD40; CELL C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Mol Endocrinol Lab, Boston, MA 02114 USA. RP Hussain, MA (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Mol Endocrinol Lab, 50 Blossom St, Boston, MA 02114 USA. NR 13 TC 4 Z9 4 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD FEB PY 2000 VL 142 IS 2 BP 111 EP 113 DI 10.1530/eje.0.1420111 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 285UC UT WOS:000085405600002 PM 10664516 ER PT J AU Barr, RG Woodruff, PG Clark, S Camargo, CA AF Barr, RG Woodruff, PG Clark, S Camargo, CA CA Multicenter Airway Res Collaborati TI Sudden-onset asthma exacerbations: clinical features, response to therapy, and 2-week follow-up SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE asthma exacerbation; sudden-onset; triggers ID LIFE-THREATENING ATTACKS; FATAL ASTHMA; PRECIPITATING FACTOR; RESPIRATORY ARREST; DISTINCT ENTITY; SOYBEAN ASTHMA; SALMETEROL; DEATH; OUTBREAKS; BARCELONA AB Sudden-onset asthma exacerbations may have different triggers and responses to treatment than slower-onset exacerbations. The authors studied this hypothesis among patients with severe asthma exacerbations. The Multicenter Airway Research Collaboration prospectively enrolled patients presenting to 64 North American emergency departments with asthma exacerbations. Of 1,847 patients aged 18-54 yrs, 900 had severe exacerbations (peak expiratory flow rate (PEFR) <50% predicted or hospitalized without PEFR), These patients were divided into sudden-onset (less than or equal to 3 h of symptoms) and slower-onset (>3 h of symptoms) groups. Fourteen per cent (95% confidence interval, 11-16%) of patients with severe asthma exacerbations had sudden-onset exacerbations. Sudden-onset patients were similar to slower-onset patients, except triggers of their exacerbations were more often respiratory allergens, exercise or psychosocial stress and less often respiratory infections. Sudden-onset patients were more likely to have used oral beta-agonists and salmeterol in the preceding 1 weeks. Although initial PEFRs and management were similar, sudden-onset patients had a greater improvement in PEFR (35 versus 28% p<0.001), Sudden-onset patients were less often discharged on systemic corticosteroids, but had similar 2-week relapse rates compared with slower-onset patients, Among patients presenting with severe asthma exacerbations, sudden-onset exacerbations had a different pattern of triggers and greater improvement with treatment than slower-onset exacerbations. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA USA. Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA USA. RP Barr, RG (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU BHP HRSA HHS [PE-11001]; NHLBI NIH HHS [HL-07427, HL-03533] NR 36 TC 34 Z9 34 U1 1 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD FEB PY 2000 VL 15 IS 2 BP 266 EP 273 DI 10.1034/j.1399-3003.2000.15b08.x PG 8 WC Respiratory System SC Respiratory System GA 284PR UT WOS:000085341500008 PM 10706490 ER PT J AU Wetter, DW Carmack, CL Anderson, CB Moore, CA De Moor, CA Cinciripini, PM Hirshkowitz, M AF Wetter, DW Carmack, CL Anderson, CB Moore, CA De Moor, CA Cinciripini, PM Hirshkowitz, M TI Tobacco withdrawal signs and symptoms among women with and without a history of depression SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; SMOKING-CESSATION; DAYTIME SLEEPINESS; TRANSDERMAL NICOTINE; DISORDERS; RELAPSE; FRAGMENTATION; INSOMNIA; LATENCY AB A past history of depression is associated with a decreased likelihood of quitting smoking. Tobacco withdrawal may be a mechanism through which depression history impedes smoking cessation. This research examined the influence of depression history on unmedicated tobacco withdrawal signs (polysomnographic measures of sleep) and symptoms (self-reported urge, negative affect, hunger, and sleep) among women (N = 13). Depression history was associated with differential withdrawal-induced changes in several REM sleep parameters. Self-report and other polysomnography (sleep fragmentation, slow-wave sleep) measures displayed statistically significant withdrawal effects but did not discriminate between depression history groups. These results suggest that REM sleep parameters may be sensitive to differential tobacco withdrawal responses that are not readily apparent through self-reported symptoms. C1 Univ Washington, Sch Publ Hlth & Community Med, Ctr Hlth Sci, Grp Hlth Cooperat, Seattle, WA 98101 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Hlth Sci, Seattle, WA 98101 USA. Univ Texas, MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Houston Vet Affairs Hosp, Sleep Disorders & Res Ctr, Houston, TX USA. RP Wetter, DW (reprint author), Univ Washington, Sch Publ Hlth & Community Med, Ctr Hlth Sci, Grp Hlth Cooperat, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. RI Cinciripini, Paul/I-5773-2012; OI Cinciripini, Paul/0000-0003-2877-9928; Wetter, David/0000-0002-6366-0108 FU NIDA NIH HHS [R03 DA10969] NR 52 TC 21 Z9 22 U1 6 U2 8 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD FEB PY 2000 VL 8 IS 1 BP 88 EP 96 DI 10.1037//1064-1297.8.1.88 PG 9 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 293GQ UT WOS:000085844000010 PM 10743908 ER PT J AU Suga, Y Arin, MJ Scott, G Goldsmith, LA Magro, CM Baden, LA Baden, HP Roop, DR AF Suga, Y Arin, MJ Scott, G Goldsmith, LA Magro, CM Baden, LA Baden, HP Roop, DR TI Hot spot mutations in keratin 2e suggest a correlation between genotype and phenotype in patients with ichthyosis bullosa of Siemens SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE keratin 2e; intermediate filaments; genodermatosis; ichthyosis bullosa of Siemens ID ROD DOMAIN; END AB Ichthyosis bullosa of Siemens (IBS) is a rare disorder of cornification characterized by blister formation in the upper suprabasal layers of the epidermis. Molecular analysis of IBS has identified mutations in the keratin 2e (K2e) gene, which is located in the type II keratin gene cluster on chromosome 12q. We have studied two IBS families and have identified heterozygous point mutations in codon 493 of the K2e gene in both families. Whereas a non-conservative amino acid substitution at position 117 of the 2B region of K2e (E117K) was associated with a severe phenotype in family 1, family 2 showed mild clinical features as a result of a conservative substitution (E117D). These data suggest a phenotype-genotype correlation in these families. C1 Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Dermatol, Houston, TX 77030 USA. Univ Rochester, Sch Med, Dept Dermatol, Rochester, NY USA. Univ Rochester, Sch Med, Dept Pathol, Rochester, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. RP Roop, DR (reprint author), Baylor Coll Med, Dept Cell Biol, 1 Baylor Plaza, Houston, TX 77030 USA. FU NICHD NIH HHS [HD25479] NR 12 TC 6 Z9 8 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD FEB PY 2000 VL 9 IS 1 BP 11 EP 15 DI 10.1034/j.1600-0625.2000.009001011.x PG 5 WC Dermatology SC Dermatology GA 283LK UT WOS:000085276900002 PM 10688369 ER PT J AU Wen, Y Sachs, G Athmann, C AF Wen, Y Sachs, G Athmann, C TI A novel lens epithelium gene, LEP503, is highly conserved in different vertebrate species and is developmentally regulated in postnatal rat lens SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE lens epithelial cell; mRNA expression; genome organization; lens protein; confocal microscopy; postnatal development ID FIBROBLAST GROWTH-FACTOR; CELL MESSENGER-RNA; CRYSTALLIN GENES; FIBER DIFFERENTIATION; MOLECULAR-FEATURES; CATARACT FORMATION; FACTOR FGF; EXPLANTS; AGE; EXPRESSION AB The development of the lens is dependent on the proliferation of lens epithelial cells and their differentiation into fiber cells near the lens bow/equator. Identification of genes specifically expressed in the lens epithelial cells and their functions may provide insight into molecular events that regulate the processes of lens epithelial cell differentiation. In this study, a novel lens epithelium gene product. LEP503, identified from rat by a subtractive cDNA cloning strategy was investigated in the genome organization, mRNA expression and protein localization. The genomic sequences for LEP503 isolated from rat, mouse and human span 1754 bp, 1694 bp and 1895 bp regions encompassing the 5'-flanking region, two exons, one intron and 3'-flanking region. All exon-intron junction sequences conform to the GT/AG rule, Both mouse and human LEP503 genes show very high identity (93% for mouse and 79% for human) to rat LEP503 gene in the exon 1 that contains an open reading frame coding for a protein of 61 amino acid residues with a leucine-rich domain. The deduced protein sequences also show high identity (91% between mouse and rat and 77% between human and rat). Western blot shows that LEP503 is present as a specific similar to 6.9 kDa band in the water-insoluble-urea-soluble fraction of lens cortex where lens epithelium is included. Immune-staining shows that LEP503 is localized in the epithelial cells along the entire anterior surface of rat lens. Developmentally, LEP503 is expressed at a low level at newborn, and then the expression level increases by about ten-fold around postnatal day 14 and remains at this high level for about 25 days before it drops back to the low level by postnatal day 84. These data suggest that the LEP 503 may be an important lens epithelial cell gene involving the processes of epithelial cell differentiation. (C) 2000 Academic Press. C1 W Los Angeles Vet Affairs Med Ctr, Membrane Biol Lab, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Wen, Y (reprint author), W Los Angeles Vet Affairs Med Ctr, Membrane Biol Lab, Dept Med, 11301 Wilshire Blvd,Bldg 113,Rm 324, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK41301, DK46917, DK53462] NR 34 TC 6 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD FEB PY 2000 VL 70 IS 2 BP 159 EP 168 DI 10.1006/exer.1999.0770 PG 10 WC Ophthalmology SC Ophthalmology GA 284UZ UT WOS:000085352400004 PM 10655141 ER PT J AU Smith, ER Chiocca, EA AF Smith, ER Chiocca, EA TI Oncolytic viruses as novel anticancer agents: turning one scourge against another SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE brain tumours; gene therapy; neoplasms; replication-conditional viruses ID HERPES-SIMPLEX VIRUS; VACCINIA MELANOMA ONCOLYSATE; EXPERIMENTAL BRAIN-TUMORS; PROTEIN-KINASE PKR; TRANSLATION INITIATION-FACTOR; ACTIVE SPECIFIC IMMUNOTHERAPY; II MALIGNANT-MELANOMA; HUMAN BREAST-CANCER; RIBONUCLEOTIDE REDUCTASE; THYMIDINE KINASE AB Although the use of viruses as oncolytic agents is an historic concept, the use of genetically modified viruses to selectively target tumour cells is relatively novel and recent. The ability of viruses to efficiently infect and lyse cells, combined with the potential augmentation of this effect by progeny viruses throughout the tumour provide justification for exploitation of these agents in cancer therapy. Before application to humans, though, issues related to tumour cell selectivity, lack of toxicity to normal tissues and the effect of the antiviral immune response, will have to be clarified. The more commonly used oncolytic viruses are based on mutant strains of herpes simplex virus, adenovirus and reovirus. The tumour selectivity of each of these strains is discussed, particularly the complementation of the viral defect by cellular pathways involved in tumourigenesis. The combination of oncolytic viruses with radiation, chemotherapy and gene therapy is also reviewed. Further study of the interaction of viral proteins with cellular pathways involved in cell cycle control will provide the rationale for viral mutants with increased selectivity for tumour cells. C1 Massachusetts Gen Hosp, Neurosurg Serv, Mol Neurooncol Lab, Charlestown, MA 02119 USA. RP Chiocca, EA (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Mol Neurooncol Lab, CNY6,13th St, Charlestown, MA 02119 USA. NR 140 TC 39 Z9 42 U1 1 U2 1 PU ASHLEY PUBL LTD PI LONDON PA 1ST FL, THE LIBRARY, 1 SHEPHERDS HILL HIGHGATE, LONDON N6 5QJ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD FEB PY 2000 VL 9 IS 2 BP 311 EP 327 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 344VK UT WOS:000088780000010 PM 11060679 ER PT J AU Yoon, SS Nakamura, H Carroll, NM Bode, BP Chiocca, EA Tanabe, KK AF Yoon, SS Nakamura, H Carroll, NM Bode, BP Chiocca, EA Tanabe, KK TI An oncolytic herpes simplex virus type 1 selectively destroys diffuse liver metastases from colon carcinoma SO FASEB JOURNAL LA English DT Article DE HSV1; gene therapy; ribonucleotide reductase ID EXPERIMENTAL BRAIN-TUMORS; THYMIDINE KINASE GENE; RIBONUCLEOTIDE REDUCTASE; ANTITUMOR-ACTIVITY; MALIGNANT GLIOMAS; VIRAL MUTANT; HEPATITIS-B; P53 STATUS; REPLICATION; THERAPY AB Viruses used for gene therapy are usually genetically modified to deliver therapeutic transgenes and prevent viral replication. in contrast, replication-competent viruses may be used for cancer therapy because replication of some viruses within cancer cells can result in their destruction (oncolysis). Viral ribonucleotide reductase expression is defective in the HSV1 mutant hrR3, Cellular ribonucleotide reductase, which is scarce in normal liver and abundant in liver metastases, can substitute for its viral counterpart to allow hrR3 replication in infected cells. Two or three log orders more of hrR3 virions are produced from infection of colon carcinoma cells than from infection of normal hepatocytes in viral replication assays. This viral replication is oncolytic, A single intravascular administration of hrR3 into immune-competent mice bearing diffuse Liver metastases dramatically reduces tumor burden. hrR3-mediated tumor inhibition is equivalent in immune-competent and immune-incompetent mice, suggesting that viral oncolysis and not the host immune response is the primary mechanism of tumor destruction. HSV1-mediated oncolysis of diffuse liver metastases is effective in mice preimmunized against HSV1, These results indicate that replication-competent HSV1 mutants hold significant promise as cancer therapeutic agents. C1 Massachusetts Gen Hosp, Div Surg Oncol, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Dept Surg, Cox 626,100 Blossom St, Boston, MA 02114 USA. FU NCI NIH HHS [CA64454, CA71345, CA60011] NR 44 TC 93 Z9 96 U1 0 U2 1 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 FEB PY 2000 VL 14 IS 2 BP 301 EP 311 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 281WQ UT WOS:000085184800009 PM 10657986 ER PT J AU Foster, LC Wiesel, P Huggins, GS Panares, R Chin, MT Pellacani, A Perrella, MA AF Foster, LC Wiesel, P Huggins, GS Panares, R Chin, MT Pellacani, A Perrella, MA TI Role of activating protein-1 and high mobility group-I(Y) protein in the induction of CD44 gene expression by interleukin-1 beta in vascular smooth muscle cells SO FASEB JOURNAL LA English DT Article DE inflammation; gene transcription; adhesion molecule; arteriosclerosis ID INTERCELLULAR-ADHESION MOLECULE-1; EPIDERMAL GROWTH-FACTOR; NF-KAPPA-B; TRANSCRIPTION FACTORS; CHROMOSOMAL-PROTEINS; METASTATIC BEHAVIOR; HYALURONAN-BINDING; ENDOTHELIAL-CELLS; GLYCOPROTEIN CD44; DNA-BINDING AB CD44 is a multifunctional cell adhesion molecule that participates in pathological states such as inflammation and tumorigenesis. CD44 is induced on vascular smooth muscle cells after arterial wall injury and may mediate their proliferation and migration into the neointima during arteriosclerosis. We have demonstrated elsewhere that the proinflammatory cytokine interleukin (IL)-1 beta upregulates CD44 mRNA and protein expression in cultured rat aortic smooth muscle cells (RASMC) by increasing gene transcription. By transient transfection of 5'-deletion constructs into RASMC, we show in the present study that a conserved AP-1 site 110 base pairs from the transcription start site of the mouse CD44 promoter is important for basal activity, Mutation of the AP-1 site significantly reduced induction of promoter activity by IL-1 beta, and electrophoretic mobility shift assays demonstrated that Fos and c-Jun were present in the CD44 AP-1 binding complex after IL-1 beta stimulation, in addition, cotransfection of the architectural transcription factor high mobility group (HMG)-I(Y) protein with c-Fos and c-Jun markedly increased trans-activation of the CD44 promoter, Taken together, our studies demonstrate that AP-1 proteins are a central regulatory component used by IL-1 beta to modulate expression of CD44 during an inflammatory response in vascular smooth muscle cells and that transcription of CD44 by AP-1 proteins is enhanced by HMG-1(Y). C1 Brigham & Womens Hosp, Program Dev Cardiovasc Biol, Div Cardiovasc, Boston, MA 02115 USA. Brigham & Womens Hosp, Program Dev Cardiovasc Biol, Div Pulm & Crit Care, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02115 USA. RP Perrella, MA (reprint author), Brigham & Womens Hosp, Program Dev Cardiovasc Biol, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM perrella@cvlab.harvard.edu FU NHLBI NIH HHS [HL03745, HL03194, HL60788] NR 66 TC 41 Z9 47 U1 0 U2 2 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 FEB PY 2000 VL 14 IS 2 BP 368 EP 378 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 281WQ UT WOS:000085184800016 PM 10657993 ER PT J AU Conrad, CC Grabowski, DT Walter, CA Sabia, M Richardson, A AF Conrad, CC Grabowski, DT Walter, CA Sabia, M Richardson, A TI Using MT-/(-) mice to study metallothionein and oxidative stress SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE metallothionein; knockout mice; liver; DNA oxidation; lipid peroxidation; protein oxidation; free radicals ID MANGANESE SUPEROXIDE-DISMUTASE; I-TRANSGENIC MICE; X-IRRADIATION; IONIZING-RADIATION; RAT-LIVER; GLUTAMINE-SYNTHETASE; LIPID-PEROXIDATION; DNA-DAMAGE; ANTIOXIDANT ENZYMES; RENDERED RESISTANT AB Mice with null mutations for metallothionein genes MT-1 and MT-2 were used to study the role that metallothionein plays in protecting cellular targets in vivo from oxidative stress. Wild-type (MT+/+) and MT-null (MT-/-) mice were treated with either saline or zinc and exposed to two types of oxidative stress: gamma-irradiation or 2-nitropropane. There was no alteration in the antioxidant defense system (superoxide dismutase, catalase, or glutathione peroxidase and glutathione levels) to compensate for the lack of the metallothionein in the MT-/- mice. The amount of oxidative damage to liver DNA, lipids, and proteins were similar for the MT-/- and MT+/+ mice even though the levels of metallothionein in the livers of the saline- or zinc-pretreated MT+/+ mice were 5- to 100-fold greater than found in the MT-/- mice. To determine if metallothionein can protect mice from the lethal effects of ionizing radiation, the mean survivals of MT-/- and MT+/+ mice exposed to whole body gamma-irradiation were measured and found to be similar. However, the mean survival increased significantly after zinc pretreatment for both the MT-/- and MT+/+ mice. These results demonstrate that tissue levels of metallothionein do not protect mice in vivo against oxidative stress. (C) 2000 Elsevier Science Inc. C1 S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78284 USA. Univ N Texas, Hlth Sci Ctr, Dept Mol Biol & Immunol, Ft Worth, TX 76107 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78285 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78285 USA. RP Richardson, A (reprint author), S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, GRECC 182,7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NIA NIH HHS [AG15908, AG14674]; NIEHS NIH HHS [ES06277] NR 97 TC 38 Z9 39 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD FEB 1 PY 2000 VL 28 IS 3 BP 447 EP 462 DI 10.1016/S0891-5849(99)00263-4 PG 16 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 289KD UT WOS:000085619000017 PM 10699757 ER PT J AU Sundback, CA Vacanti, JP AF Sundback, CA Vacanti, JP TI Alternatives to liver transplantation: From hepatocyte transplantation to tissue-engineered organs SO GASTROENTEROLOGY LA English DT Editorial Material ID BIODEGRADABLE SPONGES; CLINICAL-EXPERIENCE; ASSIST DEVICE; CRYOPRESERVATION; SURVIVAL; CULTURE; FAILURE; TRIAL C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Warren 1157,55 Fruit St, Boston, MA 02114 USA. NR 30 TC 31 Z9 35 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2000 VL 118 IS 2 BP 438 EP 442 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 277MT UT WOS:000084937900028 PM 10648474 ER PT J AU Graham, DY AF Graham, DY TI Therapy of Helicobacter pylori: Current status and issues SO GASTROENTEROLOGY LA English DT Article ID PEPTIC-ULCER DISEASE; TRIPLE THERAPY; DUODENAL-ULCER; REFLUX ESOPHAGITIS; H-2-RECEPTOR ANTAGONISTS; GASTRIC-CANCER; INFECTION; ERADICATION; OMEPRAZOLE; METRONIDAZOLE C1 Vet Affairs Med Ctr 111D, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Virol, Houston, TX 77030 USA. RP Graham, DY (reprint author), Vet Affairs Med Ctr 111D, Dept Med, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 51 TC 87 Z9 87 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2000 VL 118 IS 2 SU S BP S2 EP S8 DI 10.1016/S0016-5085(00)70003-5 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 284GF UT WOS:000085322600002 PM 10868895 ER PT J AU Podolsky, DK AF Podolsky, DK TI GI Therapeutics 2000 SO GASTROENTEROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 719,32 Fruit St, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2000 VL 118 IS 2 SU S BP S1 EP S1 DI 10.1016/S0016-5085(00)70002-3 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 284GF UT WOS:000085322600001 ER PT J AU Sands, BE AF Sands, BE TI Therapy of inflammatory bowel disease SO GASTROENTEROLOGY LA English DT Review ID ACTIVE CROHNS-DISEASE; PLACEBO-CONTROLLED TRIAL; RECOMBINANT HUMAN INTERLEUKIN-11; CHIMERIC MONOCLONAL-ANTIBODY; INTESTINAL EPITHELIAL-CELLS; SEVERE ULCERATIVE-COLITIS; NECROSIS-FACTOR-ALPHA; ESTABLISHED EXPERIMENTAL COLITIS; HLA-B27 TRANSGENIC RATS; T-HELPER CELL AB In the last decade, substantial gains have been made in the treatment of inflammatory bowel disease (IBD). Refinements in drug formulation have provided the ability to target distinct sites of delivery, enhancing the safety and efficacy of older agents. Immunosuppressive agents beyond corticosteroids have assumed a routine part in the care of patients with IBD. Moreover, as the century closes, we stand at the threshold of unprecedented advances in knowledge of the pathogenesis of ulcerative colitis and Crohn's disease. Simultaneous progress in biotechnology has fostered the development of new agents that strategically target pivotal processes in disease pathogenesis. This review covers agents currently used in the treatment of IBD and seeks to provide an overview of emerging therapies. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sands, BE (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ825A, Boston, MA 02114 USA. NR 142 TC 122 Z9 124 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2000 VL 118 IS 2 SU S BP S68 EP S82 DI 10.1016/S0016-5085(00)70007-2 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 284GF UT WOS:000085322600006 PM 10868899 ER PT J AU Wolfe, MM Sachs, G AF Wolfe, MM Sachs, G TI Acid suppression: Optimizing therapy for gastroduodenal ulcer healing, gastroesophageal reflux disease, and stress-related erosive syndrome SO GASTROENTEROLOGY LA English DT Review ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CRITICALLY ILL PATIENTS; HELICOBACTER-PYLORI INFECTION; PROTON PUMP INHIBITORS; INTENSIVE-CARE UNIT; ANTI-INFLAMMATORY DRUGS; ZOLLINGER-ELLISON SYNDROME; PLACEBO-CONTROLLED TRIAL; ACTIVE DUODENAL-ULCER; CANINE PARIETAL-CELLS C1 Bostn Med Ctr, Gastroenterol Sect, Sch Med, Boston, MA 02118 USA. Boston Med Ctr, Boston, MA USA. Univ Calif Los Angeles, Sch Med, Div Gastroenterol, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Bostn Med Ctr, Gastroenterol Sect, Sch Med, 88 E Newton St, Boston, MA 02118 USA. EM michael.wolfe@bmc.org NR 185 TC 135 Z9 138 U1 2 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2000 VL 118 IS 2 SU S BP S9 EP S31 DI 10.1016/S0016-5085(00)70004-7 PG 23 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 284GF UT WOS:000085322600003 PM 10868896 ER PT J AU Madry, H Trippel, SB AF Madry, H Trippel, SB TI Efficient lipid-mediated gene transfer to articular chondrocytes SO GENE THERAPY LA English DT Article DE gene therapy; cationic liposomes; articular chondrocytes; cell transplantation ID GROWTH-FACTOR-I; DNA-TRANSFECTION; INTIMAL HYPERPLASIA; CARTILAGE EXPLANTS; COLLAGEN GENE; PLASMID DNA; EXPRESSION; VIVO; TRANSPLANTATION; VITRO AB We examined nonviral, lipid-mediated gene transfer methods as potential tools for efficient transfection of articular chondrocytes. Transfection conditions were determined for primary cultures of normal human articular, osteoarthritic human articular and normal bovine articular chondrocytes using a lacZ reporter gene construct with the commercially available cationic liposomes Cellfectin, DMRIE-C, Lipofect-Amine, Lipofectin, LipoTaxi, TransFast and the lipid-based reagent FuGENE 6. Optimized conditions were then evaluated in an ex vivo model of chondrocyte transplantation. FuGENE 6 transfection produced the maximum levels of transgene expression. Transfection efficiency was cell type specific and affected by DNA concentration, lipid/DNA ratio and the presence of hyaluronidase, a matrix-degrading enzyme. Analysis of X-gal staining demonstrated an efficiency of 41.0% in normal bovine articular chondrocytes, 20.7% in normal human articular chondrocytes and 7.8% in osteoarthritic human chondrocytes. Transfected chondrocytes were found to successfully populate the articular cartilage surface in explant cultures. Transplanted genetically modified chondrocytes adhered to the articular cartilage and continued to produce beta-galactosidase for 2 weeks. This evaluation and optimization of lipid-based gene transfer into articular chondrocytes may serve as a useful fool in studies of genes involved in articular cartilage damage and repair and as a potential delivery method for therapeutic genes. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Orthopaed Surg, Orthopaed Res Labs, Boston, MA USA. RP Trippel, SB (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Res Labs, Gray 6th Floor,55 Fruit St, Boston, MA 02114 USA. FU NIAMS NIH HHS [AR45749-01, AR31068] NR 39 TC 107 Z9 114 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD FEB PY 2000 VL 7 IS 4 BP 286 EP 291 DI 10.1038/sj.gt.3301086 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 285FR UT WOS:000085379500004 PM 10694808 ER PT J AU Shafman, TD Levitz, S Nixon, AJ Gibans, LA Nichols, KE Bell, DW Ishioka, C Isselbacher, KJ Gelman, R Garber, J Harris, JR Haber, DA AF Shafman, TD Levitz, S Nixon, AJ Gibans, LA Nichols, KE Bell, DW Ishioka, C Isselbacher, KJ Gelman, R Garber, J Harris, JR Haber, DA TI Prevalence of germline truncating mutations in ATM in women with a second breast cancer after radiation therapy for a contralateral tumor SO GENES CHROMOSOMES & CANCER LA English DT Article ID ATAXIA-TELANGIECTASIA GENE; HETEROZYGOTES; LEUKEMIA; FAMILIES AB Patients treated with conservative surgery and radiation therapy for early-stage breast cancer develop a contralateral breast cancer at a rate of approximately 0.75% per year. Ataxia-telangiectasia (AT) is an autosomal recessive disease that is characterized by increased sensitivity to ionizing radiation (IR) and cancer susceptibility. Epidemiologic studies have suggested that AT carriers, who comprise 1% of the population, may be at an increased risk for developing breast cancer, particularly after exposure to IR. To test this hypothesis, we analyzed blood samples from 57 patients who developed a contralateral breast cancer at least 6 months after completion of radiation therapy for an initial breast tumor. A cDNA-based truncation assay in yeast: was used to test for heterozygous mutations in the ATM gene, which is responsible for AT. No mutations were detected. Our findings fail to support the hypothesis that AT carriers account for a significant fraction of breast cancer cases arising in women after exposure to radiation. Genes Chromosomes Cancer 27:124-129, 2000. (C) 2000 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Canc Ctr CNY7, Ctr Canc Risk Anal, Charlestown, MA 02129 USA. Harvard Univ, Brigham & Womens Hosp,Sch Med, Joint Ctr Radiat Therapy, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Beth Israel Deaconess Med Ctr,Dept Radiat Oncol, Boston, MA 02115 USA. Tohoku Univ, Inst Dev Aging & Canc Genet, Sendai, Miyagi 980, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Genet, Boston, MA 02115 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Canc Ctr CNY7, Ctr Canc Risk Anal, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 32 TC 28 Z9 28 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD FEB PY 2000 VL 27 IS 2 BP 124 EP 129 DI 10.1002/(SICI)1098-2264(200002)27:2<124::AID-GCC2>3.0.CO;2-M PG 6 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 268TQ UT WOS:000084432000002 PM 10612799 ER PT J AU Kung, AL Rebel, VI Bronson, RT Ch'ng, LE Sieff, CA Livingston, DM Yao, TP AF Kung, AL Rebel, VI Bronson, RT Ch'ng, LE Sieff, CA Livingston, DM Yao, TP TI Gene dose-dependent control of hematopoiesis and hematologic tumor suppression by CBP SO GENES & DEVELOPMENT LA English DT Article DE CBP; p300; hematopoiesis; LoH; tumor suppressor ID RUBINSTEIN-TAYBI SYNDROME; ACUTE MYELOID-LEUKEMIA; CREB-BINDING-PROTEIN; TRANSCRIPTIONAL COACTIVATOR; HISTONE ACETYLTRANSFERASE; ADENOVIRUS E1A; P300; TRANSFORMATION; MICE; INDUCTION AB Mice with monoallelic inactivation of the CBP gene develop highly penetrant, multilineage defects in hematopoietic differentiation and, with advancing age, an increased incidence of hematologic malignancies. The latter are characterized, at least in some cases, by loss of heterozygosity (LOH) at the CBP locus. No such pathology was observed in wild-type or p300 heterozygous null mice of the same age and genetic background. Thus, a full complement of CBP, but not p300, is required for normal hematopoietic differentiation. These results also provide the first experimental evidence for the hypothesis that CBP has tumor-suppressing activity. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Vet Med, Boston, MA 02111 USA. Duke Univ, Med Ctr, Dept Pharmacol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Canc Biol, Durham, NC 27710 USA. RP Yao, TP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. OI Kung, Andrew/0000-0002-9091-488X NR 34 TC 291 Z9 295 U1 1 U2 6 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 FEB 1 PY 2000 VL 14 IS 3 BP 272 EP 277 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 285ZC UT WOS:000085417400002 PM 10673499 ER PT J AU Lisi, S Mazzon, I White, K AF Lisi, S Mazzon, I White, K TI Diverse domains of THREAD/DIAP1 are required to inhibit apoptosis induced by REAPER and HID in drosophila SO GENETICS LA English DT Article ID PROGRAMMED CELL-DEATH; BACULOVIRUS INHIBITOR; GENE; PROTEINS; IAP; GRIM; MELANOGASTER; EXPRESSION; SURVIVAL; HOMOLOGS AB Significant amounts of apoptosis take place during Drosophila development. The proapoptotic genes reaper (rpr), grim, and head involution defective (hid) are required for virtually all embryonic apoptosis. The proteins encoded by these genes share a short region of homology at their amino termini. The Drosophila WP homolog THREAD/DIAP1 (TH/DIAP1), encoded by the threat (th) gene, negatively regulates apoptosis during development. It has been proposed that RPR, GRIM, and HID induce apoptosis by binding and inactivating TH/DIAP1. The region of homology between the three proapoptotic proteins has been proposed to bind to the conserved BIR2 domain of TH/DIAP1. Here, we present an analysis of loss-of-function and grain-of-function alleles of th, which indicates that additional domains of TH/DIAP1 are necessary for its ability to inhibit death induced by RPR, GRIM, and HID. In addition, that analysis of loss-of-function mutations demonstrates that th is necessary to block apoptosis very early in embryonic development. This may reflect a requirement to block maternally provided RPR and HID, or it may indicate another function of the TH/DIAP1 protein. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP White, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. RI White, Kristin/D-7936-2013; Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 FU NIGMS NIH HHS [GM-55568] NR 40 TC 158 Z9 160 U1 0 U2 3 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD FEB PY 2000 VL 154 IS 2 BP 669 EP 678 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 281UG UT WOS:000085178700016 PM 10655220 ER PT J AU Oh, J Baksa, K Steward, R AF Oh, J Baksa, K Steward, R TI Functional domains of the Drosophila Bicaudal-D protein SO GENETICS LA English DT Article ID POSTERIOR DETERMINANT NANOS; HELICAL COILED COILS; MELANOGASTER; OOGENESIS; GENE; DIFFERENTIATION; LOCALIZATION; CHROMOSOME; MORPHOLOGY; MUTATIONS AB The localization of oocyte-specific determinants in the form of mRNAs to the pro-oocyte is essential for the establishment of oocyte identity. Localization of the Bicaudal-D (Bic-D) protein to the presumptive oocyte is required for the accumulation of Bic-D and other mRNAs to the pro-oocyte. The Bic-D protein contains four well-defined heptad repeat domains characteristic of intermediate filament proteins, and several of the mutations in Bic-D map to these conserved domains. We have undertaken a structure-function analysis of Bic-D by testing the function of mutant Bic-D transgenes (Bic-DH) deleted for each of the heptad repeat domains in a Bic-D null background. Our transgenic studies indicate that only the C-terminal heptad repeat deletion results in a protein that has lost zygotic and ovarian functions. The three other deletions result in proteins with full zygotic function, but with affected ovarian function. The functional importance of each domain is well correlated with its conservation in evolution. The analysis of females heterozygous for Bic-D-H and the existing alleles Bic-D-PA66 or Bic-D-R26 reveals that Bic-D-R26 as well as some of Bic-DH transgenes have antimorphic effects. The least two-hybrid interaction assay shows that Bic-D forms homodimers. Furthermore, we found that Bic-D exists as a multimeric protein complex consisting of Egl and at least two Bic-D monomers. C1 Rutgers State Univ, Dept Mol Biol & Biochem, Waksman Inst Microbiol, Piscataway, NJ 08854 USA. Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. RP Steward, R (reprint author), Rutgers State Univ, Dept Mol Biol & Biochem, Waksman Inst Microbiol, 190 Frelinghuysen Rd, Piscataway, NJ 08854 USA. NR 24 TC 17 Z9 17 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD FEB PY 2000 VL 154 IS 2 BP 713 EP 724 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 281UG UT WOS:000085178700020 PM 10655224 ER PT J AU O'Donnell, CJ AF O'Donnell, Christopher J. TI Cardiovascular genomics: recent progress, current challenges, future promise SO GENOME BIOLOGY LA English DT Editorial Material AB A report from the second Annual Cardiovascular Genomics Meeting, Sponsored by Cambridge Healthtech, Inc., Miami, January 31-February 1, 2000. C1 [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Framingham, MA 02172 USA. [O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 02172 USA. RP O'Donnell, CJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, 5 Thurber St, Framingham, MA 02172 USA. EM chris@fram.nhlbi.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PD FEB PY 2000 VL 1 IS 1 AR 409 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V34QL UT WOS:000209100800016 ER PT J AU Kuver, R Klinkspoor, JH Osborne, WRA Lee, SP AF Kuver, R Klinkspoor, JH Osborne, WRA Lee, SP TI Mucous granule exocytosis and CFTR expression in gallbladder epithelium SO GLYCOBIOLOGY LA English DT Article DE calcium; chloride channel; cystic fibrosis; mucin ID X-RAY-MICROANALYSIS; MUCIN SECRETION; CYSTIC-FIBROSIS; CHLORIDE TRANSPORT; ZYMOGEN GRANULES; CELLS; MEMBRANE; CALCIUM; GLAND; BILE AB A mechanistic model of mucous granule exocytosis by columnar epithelial cells must take into account the unique physical-chemical properties of mucin glycoproteins and the resultant mucus gel. In particular, any model must explain the intracellular packaging and the kinetics of release of these large, heavily charged species. We studied mucous granule exocytosis in gallbladder epithelium, a model system for mucus secretion by columnar epithelial cells. Mucous granules released mucus by merocrine exocytosis in mouse gallbladder epithelium when examined by transmission electron microscopy. Spherules of secreted mucus larger than intracellular granules were noted on scanning electron microscopy. Electron probe microanalysis demonstrated increased calcium concentrations within mucous granules. Immunofluorescence microscopic studies revealed intracellular colocalization of mucins and the cystic fibrosis transmembrane conductance regulator (CFTR), Confocal laser immunofluorescence microscopy confirmed colocalization, These observations suggest that calcium in mucous secretory granules provides cationic shielding to keep mucus tightly packed. The data also suggests CFTR chloride channels are present in granule membranes. These observations support a model in which influx of chloride ions into the granule disrupts cationic shielding, leading to rapid swelling, exocytosis and hydration of mucus. Such a model explains the physical-chemical mechanisms involved in mucous granule exocytosis. C1 Univ Washington, Sch Med, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98195 USA. RP Kuver, R (reprint author), Univ Washington, Sch Med, Dept Med, Div Gastroenterol, Box 356424, Seattle, WA 98195 USA. RI Lee, Sum Ping/C-4333-2009 FU NIDDK NIH HHS [R01DK50246, DK47754] NR 43 TC 31 Z9 33 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD FEB PY 2000 VL 10 IS 2 BP 149 EP 157 DI 10.1093/glycob/10.2.149 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 281DY UT WOS:000085143700004 PM 10642606 ER PT J AU Contreras, MA Khan, M Smith, BT Cimini, AM Gilg, AG Orak, J Singh, I Singh, AK AF Contreras, MA Khan, M Smith, BT Cimini, AM Gilg, AG Orak, J Singh, I Singh, AK TI Endotoxin induces structure-function alterations of rat liver peroxisomes: Kupffer cells released factors as possible modulators SO HEPATOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; ACUTE-PHASE RESPONSE; BETA-OXIDATION; FACTOR-ALPHA; BACTERIAL-ENDOTOXIN; LIPID-COMPOSITION; GENE-EXPRESSION; FATTY-ACIDS; CACHECTIN; DEGRADATION AB We report that endotoxin treatment results in decreased amounts of peroxisomes as well as changes in structure and function of peroxisomal membranes. Peroxisomes isolated from the liver of control and treated animals showed a marked decrease in total protein, but no significant alteration in the sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) protein profile. However, the Western blot study of the peroxisomal beta-oxidation enzymes and catalase showed an increase in those enzymes in the peroxisomal peak of normal density in endotoxin-treated rats. Disintegration of peroxisomal membranes by carbonate treatment from endotoxin-treated liver and change in the fluidity of peroxisomal membranes suggests alterations in peroxisomal membrane structure. No such alterations were found in mitochondrial or microsomal membranes of endotoxin-treated livers. The lipid analysis of these organelles showed that the only organelle affected was the peroxisome, with a significant decrease in the phospholipid and cholesterol concentrations. To understand the mechanism of endotoxin-mediated alterations in peroxisomes, we studied the possible role of Kupffer cell secreted soluble factors (tumor necrosis factor alpha [TNF-alpha]) on the peroxisomal structure/function. Inactivation/elimination of Kupffer cells by gadolinium chloride before endotoxin treatment did not normalize the overall peroxisomal protein amount and the lipid composition of isolated peroxisomes, However, the levels of individual protein amount in remaining peroxisomes were normalized. Endotoxin also decreased peroxisomal beta-oxidation, and this was partially restored with gadolinium treatment. These results clearly show that peroxisomes are severely affected by endotoxin treatment and suggest that the damage to this organelle may contribute, at least in part, to endotoxin-induced 'hepatic cytotoxicity. C1 Ralph H Johnson Vet Adm Med Ctr, Dept Lab Med, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. RP Singh, AK (reprint author), Ralph H Johnson Vet Adm Med Ctr, Dept Lab Med, 109 Bee St, Charleston, SC 29401 USA. RI Cimini, Annamaria/C-3688-2011 OI Cimini, Annamaria/0000-0002-2737-7970 FU NINDS NIH HHS [NS-37766, NS-22576, NS-34741] NR 59 TC 18 Z9 18 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 FEB PY 2000 VL 31 IS 2 BP 446 EP 455 DI 10.1002/hep.510310226 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 281EB UT WOS:000085144000026 PM 10655269 ER PT J AU Caplan, D Alpert, N Waters, G Olivieri, A AF Caplan, D Alpert, N Waters, G Olivieri, A TI Activation of Broca's area by syntactic processing under conditions of concurrent articulation SO HUMAN BRAIN MAPPING LA English DT Article DE syntactic processing; localization of syntax ID VERBAL WORKING-MEMORY; SENTENCE COMPREHENSION; INDIVIDUAL-DIFFERENCES; SPEECH; DEPENDENCIES; LOCALIZATION; CORTEX; BRAIN AB Regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) when 11 subjects made plausibility judgments about written sentences that varied in their syntactic complexity. While making their judgments, subjects uttered the word "double" aloud at a rate of one utterance per second to inhibit their ability to rehearse the sentences. Blood flow increased in Broca's area when subjects made judgments about the more complex sentences. This result replicates and extends previous findings that blood flow increases in this region when subjects process complex syntax under no interference conditions. The results of this experiment provide strong evidence that the increase in blood flow seen in Broca's area in association with processing syntactically complex structures is not due to subvocal rehearsal of those structures, but rather results from processing syntactic forms themselves. Hum. Brain Mapping 9:65-71, 2000. (C) 2000 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Neuropsychol Lab, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. Boston Univ, Dept Commun Disorders, Boston, MA 02215 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, Dept Neurol, Vincent Burnham 827,Fruit St, Boston, MA 02114 USA. EM Caplan@helix.mgh.harvard.edu FU NIDCD NIH HHS [DC02146] NR 44 TC 185 Z9 185 U1 2 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD FEB PY 2000 VL 9 IS 2 BP 65 EP 71 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 281EA UT WOS:000085143900001 PM 10680763 ER PT J AU Su, M He, CF West, CA Mentzer, SJ AF Su, M He, CF West, CA Mentzer, SJ TI Generation of sheep X (sheep X mouse) heterohybridoma cell line expressing the beta-1 integrin membrane molecule SO HYBRIDOMA LA English DT Article ID LUNG MICROVASCULAR ENDOTHELIUM; BOVINE LEUKEMIA-VIRUS; MONOCLONAL-ANTIBODIES; OVIS-ARIES; HYBRIDOMAS; CULTURE; CLONING; LYMPHOCYTES; SPECIFICITY; KARYOTYPE AB Sheep are an important biological model in such diverse areas as immunology and reproductive biology. The limitation of sheep as an experimental model is the absence of reliable cell lines. To establish cell lines that express functional sheep membrane molecules, we produced a sheep x mouse heterohybridoma by fusion of sheep efferent lymph T cells with the murine myeloma cell line NS1. A cloned heterohybridoma fusion partner was selected by treatment with 8-azaguanine. The resulting cell line HL1/385 was selected for hypoxanthine/aminopterin/thymidine (HAT) sensitivity and growth efficiency. The HL1/385 cell line was used as a back-fusion partner into lectin-stimulated efferent T lymphocytes. The back-fusion approach produced more than 50 heterohybrid cell lines with high growth efficiency. The expression of physiological levels of the sheep beta-1 integrin cell surface molecule on the HT4/6 cell line was stable for months in culture. These results suggest that somatic heterohybrids may provide a reliable source of cell lines for sheep studies in vitro. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Immunophysiol Lab, Boston, MA 02115 USA. RP Mentzer, SJ (reprint author), Dana Farber Canc Inst, Room G09 JFB,44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL47078] NR 50 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD FEB PY 2000 VL 19 IS 1 BP 81 EP 87 DI 10.1089/027245700315824 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA 300ER UT WOS:000086240300009 PM 10768844 ER PT J AU Komers, R Oyama, TT Chapman, JG Allison, KM Anderson, S AF Komers, R Oyama, TT Chapman, JG Allison, KM Anderson, S TI Effects of systemic inhibition of neuronal nitric oxide synthase in diabetic rats SO HYPERTENSION LA English DT Article DE blood pressure; diabetes; S-methyl-L-thiocitrulline; nitric oxide; nitric oxide synthase ID GLOMERULAR CAPILLARY-PRESSURE; ANGIOTENSIN-II; MACULA DENSA; BLOOD-PRESSURE; RENAL HEMODYNAMICS; RESPONSES; HYPERTENSION; EXPRESSION; FEEDBACK; ARGININE AB Diabetes is associated with alterations in nitric oxide-mediated vasomotor function. The role of nitric oxide generated via the neuronal nitric oxide synthase pathway in the control of systemic and renal hemodynamics in diabetes has not been studied. To explore the hypothesis that diabetic vascular dysfunction is in part caused by altered neuronal nitric oxide synthase activity, systemic and renal hemodynamics were assessed before and after acute inhibition of this enzyme with a specific inhibitor, S-methyl-L-thiocitruIline, in control and diabetic rats. The interaction of this pathway and the renin-angiotensin system was studied in separate groups of rats pretreated with the angiotensin II receptor blocker losartan; these rats were compared with rats treated with losartan alone. Diabetic animals demonstrated higher baseline glomerular filtration rates and filtration fractions. At a low dose, the neuronal nitric oxide synthase inhibitor induced similar dose-dependent presser responses in control and diabetic rats. Losartan abolished the presser response in both groups. No changes in renal plasma flow or renal vascular resistance occurred in control rats. In contrast, diabetic rats responded with significant renal vasoconstriction. At a high dose, the renal vasoconstriction was similar in both groups and was not affected by losartan. In conclusion, neuronal nitric oxide synthase-derived nitric oxide plays a role in the control of systemic and renal hemodynamics in normal and diabetic rats. Diabetic rats are more sensitive to the inhibitor, suggesting increased activity of this pathway in the diabetic kidney. Furthermore, renal responses in diabetic rats were attenuated by angiotensin II receptor blockade, whereas losartan alone induced hemodynamic changes that were opposite those seen with neuronal nitric oxide synthase inhibition. This observation implicates angiotensin II as an important modulator of this nitric oxide pathway in diabetes. C1 Oregon Hlth Sci Univ, Div Nephrol & Hypertens, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. RP Anderson, S (reprint author), Oregon Hlth Sci Univ, Div Nephrol, PP262,3314 SW US Vet Hosp Rd, Portland, OR 97201 USA. FU NIA NIH HHS [AG-14699] NR 48 TC 46 Z9 46 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD FEB PY 2000 VL 35 IS 2 BP 655 EP 661 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 285YA UT WOS:000085414900022 PM 10679513 ER PT J AU Gommerman, JL Carroll, MC AF Gommerman, JL Carroll, MC TI Negative selection of B lymphocytes: a novel role for innate immunity SO IMMUNOLOGICAL REVIEWS LA English DT Review ID SYSTEMIC LUPUS-ERYTHEMATOSUS; ANTIGEN-RECEPTOR; COMPLEMENT RECEPTOR; AUTOANTIBODY PRODUCTION; MONOCLONAL-ANTIBODIES; PERIPHERAL TOLERANCE; ACQUIRED-IMMUNITY; CELL REPERTOIRE; SELF-TOLERANCE; DEFICIENT MICE AB Evidence has accumulated that strongly supports a role for innate immunity in B-cell tolerance. Specific recognition proteins, such as natural antibody and collectins, are present in serum that identify highly conserved self-antigens such as nuclear proteins and activate the classical pathway of complement. The direct localization of these types of antigens to the lymphoid compartment in a complement-receptor-dependent manner provides a mechanism to deal with immature, self-reactive B cells developing daily in the bone marrow. Since it would be disadvantageous for the organism to maintain self-reactive B cells, which cross-react with microbial antigens, the innate immune system provides an efficient pathway for their removal or silencing. A possible outcome of a breakdown in this pathway, as found in individuals bearing natural deficiencies in complement C1q or C4, is autoimmunity such as systemic lupus erythematosus. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Carroll, MC (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. NR 79 TC 17 Z9 18 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD FEB PY 2000 VL 173 BP 120 EP 130 DI 10.1034/j.1600-065X.2000.917312.x PG 11 WC Immunology SC Immunology GA 285WL UT WOS:000085411300011 PM 10719673 ER PT J AU Crean, TI John, M Calderwood, SB Ryan, ET AF Crean, TI John, M Calderwood, SB Ryan, ET TI Optimizing the germfree mouse model for in vivo evaluation of oral Vibrio cholerae vaccine and vector strains SO INFECTION AND IMMUNITY LA English DT Article ID ANTIBODY-RESPONSES; B-SUBUNIT; COLONIZATION; IMMUNIZATION; INFECTION; EFFICACY; O139 AB The germfree mouse model of Vibrio cholerae infection can be used to judge immune responses to V. cholerae vaccine and vector strains, In the original model, a single oral inoculation was administered on day 0, a booster oral inoculation was administered on day 14, and immune responses were analyzed with samples collected on day 28, Unfortunately, immune responses in this model frequently were low level, and interanimal variability occurred. In order to improve this model, we evaluated various primary and booster V. cholerae inoculation schedules. The most prominent systemic and mucosal antibody responses were measured in mice that received a multiple primary inoculation series on days 0, 2, 4, and 6 and booster inoculations on days 28 and 42, These modifications result in improved preliminary evaluation of ii. cholerae vaccine and vector strains in mice. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. FU NIAID NIH HHS [AI01332, AI40725, R01 AI040725] NR 21 TC 13 Z9 14 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 2000 VL 68 IS 2 BP 977 EP 981 DI 10.1128/IAI.68.2.977-981.2000 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 275VZ UT WOS:000084842000077 PM 10639476 ER PT J AU Radd, II Hanna, HA Hachem, RY Darouiche, RO AF Radd, II Hanna, HA Hachem, RY Darouiche, RO TI Diagnosis of catheter-related bloodstream infection: Is it necessary to culture the subcutaneous segment? SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Meeting Abstract C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD FEB PY 2000 VL 21 IS 2 BP 97 EP 97 PG 1 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 285XM UT WOS:000085413700077 ER PT J AU Tarazi, FI Baldessarini, RJ AF Tarazi, FI Baldessarini, RJ TI Comparative postnatal development of dopamine D-1, D-2 and D-4 receptors in rat forebrain SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Review DE autoradiography; Caudate-putamen; frontal cortex; hippocampus; nucleus accumbens septi; postnatal development ID NUCLEUS-ACCUMBENS; D-4-LIKE RECEPTORS; DIFFERENTIAL REGULATION; D1-DOPAMINE RECEPTORS; ANTIPEPTIDE ANTISERA; ANTIPSYCHOTIC-DRUGS; PREFRONTAL CORTEX; CEREBRAL-CORTEX; CORPUS STRIATUM; MESSENGER-RNA AB Postnatal development of dopamine D-1, D-2 and D-4 receptors in the caudate-putamen, nucleus accumbens, frontal cortex and hippocampus mas assessed in rat brain between postnatal days 7 and 60. In the caudate-putamen and nucleus accumbens, density of all three receptor subtypes increased to a peak at postnatal day 28, then declined significantly in both regions (postnatal days 35-60) to adult levels. In the frontal cortex and hippocampus, these receptors rose steadily and continuously to stable, maximal adult levels by postnatal day 60. Evidently, D-1, D-2 and D-4 receptors follow a similar course of development in several cortical, limbic and extrapyramidal regions of rat forebrain, with selective elimination of excess dopamine receptors at the time of puberty in the caudate-putamen and accumbens but not other brain regions. (C) 2000 ISDN. Published by Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Consolidated Dept, Boston, MA 02115 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Tarazi, FI (reprint author), Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH-19905, MH-34006, MH-47370] NR 63 TC 185 Z9 187 U1 3 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD FEB PY 2000 VL 18 IS 1 BP 29 EP 37 DI 10.1016/S0736-5748(99)00108-2 PG 9 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 296EQ UT WOS:000086010400002 PM 10708903 ER PT J AU Naliboff, BD AF Naliboff, BD TI Regional brain activity during visceral stimulation in IBS patients SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Greater Los Angeles Vet Affairs Hlth Care Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD FEB PY 2000 VL 35 IS 1 BP 35 EP 35 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 273UY UT WOS:000084727300092 ER PT J AU Sachs, RK Rogoff, A Chen, AM Simpson, PJ Savage, JRK Hahnfeldt, P Hlatky, LR AF Sachs, RK Rogoff, A Chen, AM Simpson, PJ Savage, JRK Hahnfeldt, P Hlatky, LR TI Underprediction of visibly complex chromosome aberrations by a recombinational-repair ('one-hit') model SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article ID IN-SITU HYBRIDIZATION; DOSE-RESPONSE CURVES; DOUBLE-STRAND BREAKS; X-RAY; NOMENCLATURE SYSTEMS; IONIZING-RADIATION; CHARGED-PARTICLES; HUMAN-LYMPHOCYTES; CENTRIC RINGS; EXCHANGES AB Purpose: Published low-LET FISH data were used to test two models of chromosome aberration production based on breakage-and-reunion or recombinational repair. Materials and methods: Randomness of DnTA double strand break induction and misrejoining is analyzed comprehensively and adopted as a working hypothesis. Proximity effects are approximated by using interaction sites. Model results are calculated using CAS (chromosome aberration simulator) Monte Carlo computer software with two adjustable parameters. CAS can emulate the specifics of any experimental painting protocol, allowing very detailed tests of the models. Results: To reasonable approximation, breakage-and-reunion model predictions are consistent with low-LET FISH results. including two large, elaborate, one-paint data sets. An explicitly specified version of the recombinational-repair model severely underpredicts the frequency of the visibly complex aberration patterns most commonly observed with one-paint FISH, and is inconsistent with some observed multi-paint patterns. When high-dose effects (distortion and saturation) are taken into account quantitatively a dose-response relation for apparently simple interchanges slightly favours the breakage-and-re union model over the recombinational-repair model, despite being approximately linear over the dose range 2-6 Gy. Conclusion: The random breakage-and-reunion model gives comprehensive baseline predictions that are sufficiently accurate for the organization of experimental results. The data speak against complex aberrations being formed by the random recombinational repair pathway discussed here. C1 Univ Calif Berkeley, Dept Math, Berkeley, CA 94720 USA. Univ Calif Berkeley, Coll Engn, Berkeley, CA 94720 USA. MRC, Radiat & Genome Stabil Unit, Didcot OX11 0RD, Oxon, England. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sachs, RK (reprint author), Univ Calif Berkeley, Dept Math, Berkeley, CA 94720 USA. FU NIGMS NIH HHS [GM 57245-01] NR 54 TC 26 Z9 26 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD FEB PY 2000 VL 76 IS 2 BP 129 EP 148 PG 20 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 284GM UT WOS:000085323300001 PM 10716635 ER PT J AU Willett, CG AF Willett, CG TI Intraoperative radiation therapy in resected bile duct cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material ID ELECTRON C1 Massachusetts Gen Hosp, Cox Canc Ctr, Dept Radiat Oncol, Boston, MA 02114 USA. RP Willett, CG (reprint author), Massachusetts Gen Hosp, Cox Canc Ctr, Dept Radiat Oncol, Blossom St, Boston, MA 02114 USA. NR 7 TC 1 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 2000 VL 46 IS 3 BP 523 EP 524 DI 10.1016/S0360-3016(99)00471-X PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 285WY UT WOS:000085412400001 PM 10701729 ER PT J AU Levin-Plotnik, D Niemierko, A Akselrod, S AF Levin-Plotnik, D Niemierko, A Akselrod, S TI Effect of incomplete repair on normal tissue complication probability in the spinal cord SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE normal tissue complication probability; radiation myelopathy; incomplete repair; mathematical models ID ACCELERATED RADIOTHERAPY; RADIATION MYELOPATHY; RAT; VOLUME; FRACTIONATION; TOLERANCE; KINETICS; MODEL; IRRADIATION; RESPONSES AB Purpose: To incorporate the effects of repair into a model for normal tissue complication probability (NTCP) in the spinal cord. Methods and Materials: We used an existing model of NTCP for the spinal cord, based on a critical volume concept,into which we incorporated an incomplete repair (IR) scheme. Values for the repair half time were taken from existing experimental data. Repair corrections were expanded to account for the possibility of biphasic repair, namely the existence of long and short components of repair. Results: We found that the model predicts complete repair to occur at approximately 15 hours, consistent with experimental data. The dependence of the model on the value of the dose per fraction was also studied. It was found that there is a sparing effect as the dose per fraction is decreased below 2 Gy, Surface plots of the NTCP as a function of both the interfraction interval (IFI) and the dose per fraction were generated. We investigated "iso-NTCP" curves, which may allow freedom in choice of treatment plans in terms of the optimal IFI and dose per fraction. As for biphasic repair, as the relative weights of the long and short components of repair were varied, the NTCP changed as well. The model showed little difference between mono- and bi exponential repair in the time to complete repair, due to a dominance of the long component at long IFIs. Conclusions: Incorporating IR into NTCP modeling of the spinal cord is consistent with current experimental data-The concept of iso-NTCP curves is an approach which may be clinically useful. (C) 2000 Elsevier Science Inc. C1 Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. Tel Aviv Univ, Sackler Fac Exact Sci, Abramson Inst Med Phys, Ramat Aviv, Israel. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Oncol, Boston, MA USA. RP Levin-Plotnik, D (reprint author), Univ Chicago, Dept Radiat & Cellular Oncol, 5758 S Maryland Ave,MC 9006, Chicago, IL 60637 USA. NR 30 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 2000 VL 46 IS 3 BP 631 EP 638 DI 10.1016/S0360-3016(99)00372-7 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 285WY UT WOS:000085412400014 PM 10701742 ER PT J AU McIntire, GL Bacon, ER Illig, KJ Coffey, SB Singh, B Bessin, G Shore, MT Wolf, GL AF McIntire, GL Bacon, ER Illig, KJ Coffey, SB Singh, B Bessin, G Shore, MT Wolf, GL TI Time course of nodal enhancement with CT x-ray nanoparticle contrast agents - Effect of particle size and chemical structure SO INVESTIGATIVE RADIOLOGY LA English DT Article DE lymph node; computed tomography lymphography; nanoparticles; clearance ID LYMPH-NODES; IODINATED NANOPARTICLES; LYMPHOGRAPHY; EMULSION AB RATIONALE AND OBJECTIVES. Levels of CT enhancement in rabbit lymph nodes were followed with time after subcutaneous injection of four iodinated, insoluble nanoparticle contrast agents to provide experimental support for the hypothesis that clearance of these agents is related to the chemical structure of the agent itself. The impact of particle size was also studied, METHODS. Subcutaneous injections (2 x 0.25 mL) were made in the dorsum of rabbit paws with 15% suspensions of four nanoparticle contrast agents. Images were obtained at 4, 10, 24, 48, and 72 hours and 5, 7, and 14 days after injection. Average attenuation (in Hounsfield units [HU]), node volume, and total iodine uptake were estimated from the CT scans for each lymph node at each time point, RESULTS. All the agents provided adequate enhancement of both the popliteal and axillary lymph nodes of the rabbit (ie, > Delta 100 HU). Lymph node volume appears to be related to the persistence of enhancement, with long-lived agents demonstrating the greatest increase in size. The rate of clearance from the lymph nodes is related to the structure of the agent. CONCLUSIONS. Clearance of insoluble, iodinated nanoparticle contrast agents from lymph nodes can be modulated by changes in the structure of the agent itself. Using the same agent, smaller particles deliver material to the lymph nodes more quickly and clear more quickly. C1 Nycomed Amersham PLC, Wayne, PA USA. Massachusetts Gen Hosp, Ctr Imaging & Pharmaceut Res, Charlestown, MA USA. RP McIntire, GL (reprint author), 113 Piedmont Rd W, Chester, PA 19382 USA. NR 19 TC 18 Z9 19 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD FEB PY 2000 VL 35 IS 2 BP 91 EP 96 DI 10.1097/00004424-200002000-00001 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 280KV UT WOS:000085102700001 PM 10674452 ER PT J AU Litz, BT Orsillo, SM Kaloupek, D Weathers, F AF Litz, BT Orsillo, SM Kaloupek, D Weathers, F TI Emotional processing in posttraumatic stress disorder SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID POST-TRAUMATIC STRESS; VIETNAM VETERANS; SYMPTOM STRUCTURE; COMBAT VETERANS; ANXIETY; AROUSAL; STIMULI; MEMORY; VALIDATION; PICTURES AB The emotional deficits associated with posttraumatic stress disorder (PTSD) are the lease understood and the most understudied aspect of the syndrome. In this study, the connection was evaluated between trauma-context reactivity and subsequent emotional deficits in PTSD. Combat veterans with PTSD and well-adjusted veteran control participants were exposed to reminders of combat, alter which their emotional behavior was assessed in response to a series of emotionally evocative images, Under the neutral condition, both groups exhibited emotional behavior modulated by stimulus valence. Partially consistent with the conceptual model described by B. Litz (1992), the PTSD group exhibited suppressed expressive-motor responses to positively valenced images, in comparison with the control group, only after being exposed to a trauma-related prime. Contrary to expectations, the PTSD group showed no augmentation of emotional response to negatively valenced cues after being exposed to trauma reminders. However, the PTSD group responded to all images, in both prime conditions, with higher heart rate reactivity, suggesting an automatic preparation for demand or threat in any uncertain emotional context. Possible causes and consequences of these results are discussed. C1 Boston Dept Vet Affairs Med Ctr, Natl Ctr PTSD 116B2, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. Oklahoma State Univ, Dept Psychol, Stillwater, OK 74078 USA. Auburn Univ, Dept Psychol, Auburn, AL 36849 USA. RP Litz, BT (reprint author), Boston Dept Vet Affairs Med Ctr, Natl Ctr PTSD 116B2, 150 S Huntington Ave, Boston, MA 02130 USA. OI Kaloupek, Danny/0000-0002-0795-593X NR 50 TC 105 Z9 107 U1 2 U2 8 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD FEB PY 2000 VL 109 IS 1 BP 26 EP 39 DI 10.1037/0021-843X.109.1.26 PG 14 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 293FR UT WOS:000085841400004 PM 10740933 ER PT J AU Finn, PR Sharkansky, EJ Brandt, KM Turcotte, N AF Finn, PR Sharkansky, EJ Brandt, KM Turcotte, N TI The effects of familial risk, personality, and expectancies on alcohol use and abuse SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID CROSS-FOSTERING ANALYSIS; SUBSTANCE USE; AGGRESSIVE-BEHAVIOR; DRINKING BEHAVIOR; EARLY ADOLESCENTS; HISTORY METHOD; SONS; MEN; PSYCHOPATHOLOGY; INHERITANCE AB This study tested a structural model of the association between familial risk, personality risk, alcohol expectancies, and alcohol abuse in a sample of 224 young adult offspring of alcoholics and 209 offspring of nonalcoholics. The results provided support for 2 personality-risk pathways, a social deviance proneness and an excitement/pleasure seeking path, that accounted for a significant portion of the association between a familial alcoholism and alcohol abuse, The path from familial alcoholism to social deviance proneness lead directly to alcohol problems. The path from familial alcoholism to excitement/pleasure seeking was associated with increased drinking, which, in turn, was associated with alcohol problems. Positive alcohol expectancies accounted for part of the association between excitement seeking and alcohol use; The results suggest 2 different biopsychosocial mechanisms that elevate risk for abuse in the offspring of alcoholics. C1 Indiana Univ, Dept Psychol, Bloomington, IN 47405 USA. Boston Vet Affairs Med Ctr, Womens Hlth Sci Div, Boston, MA USA. RP Finn, PR (reprint author), Indiana Univ, Dept Psychol, 1101 E 10th St, Bloomington, IN 47405 USA. FU NIAAA NIH HHS [P50 AA07611] NR 62 TC 118 Z9 118 U1 7 U2 16 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD FEB PY 2000 VL 109 IS 1 BP 122 EP 133 DI 10.1037//0021-843X.109.1.122 PG 12 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 293FR UT WOS:000085841400014 PM 10740943 ER PT J AU Whitfield, KE Fillenbaum, GG Pieper, C Albert, MS Berkman, LF Blazer, DG Rowe, JW Seeman, T AF Whitfield, KE Fillenbaum, GG Pieper, C Albert, MS Berkman, LF Blazer, DG Rowe, JW Seeman, T TI The effect of race and health-related factors on naming and memory - The MacArthur Studies of Successful Aging SO JOURNAL OF AGING AND HEALTH LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Behavioral-Medicine CY 1998 CL NEW ORLEANS, LOUISIANA SP Soc Behav Med, MacArthur Fdn Res Network Successful Aging ID MENTAL-STATE-EXAMINATION; ADULT AGE-DIFFERENCES; ALZHEIMERS-DISEASE; COGNITIVE FUNCTION; DEPRESSIVE SYMPTOMATOLOGY; COMMUNITY POPULATION; AFRICAN-AMERICAN; OLDER PERSONS; WHITE; BLACK AB Objectives: The purpose of the analyses was to examine the impact of health-related variables on race differences in neuropsychological functioning (Boston Naming Task). Methods: Using cross-sectional data from the MacArthur Successful Aging Study, the authors examined the relationship of demographic characteristics, health status, health habits, physical functioning, and speed of performance to naming and incidental recall of items from the Boston Naming Task. Participants were 1,175 healthy African American and European American older persons 70 to 79 years old. Results: Regression analyses indicated that although race differences persisted for confrontational naming after controlling for demographic and health factors, there was no effect due to race for incidental recall scores or for savings scores for recall. Discussion: The racial differences found in test performance may reflect differences in cultural appropriateness of the material rather than differences in ability. C1 Penn State Univ, University Pk, PA 16802 USA. Duke Univ, Durham, NC 27706 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Duke Univ, Durham, NC 27706 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Whitfield, KE (reprint author), Penn State Univ, University Pk, PA 16802 USA. FU NIA NIH HHS [AG08937, AG13662-01A2, AG14263-02] NR 71 TC 47 Z9 47 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0898-2643 J9 J AGING HEALTH JI J. Aging Health PD FEB PY 2000 VL 12 IS 1 BP 69 EP 89 DI 10.1177/089826430001200104 PG 21 WC Gerontology; Health Policy & Services SC Geriatrics & Gerontology; Health Care Sciences & Services GA 280UG UT WOS:000085121700004 PM 10848126 ER PT J AU Simoneau, GG Krebs, DE AF Simoneau, GG Krebs, DE TI Whole-body momentum during gait: A preliminary study of non-fallers and frequent fallers SO JOURNAL OF APPLIED BIOMECHANICS LA English DT Article DE falls; elderly; balance ID SIT-TO-STAND; LOCOMOTOR ACTIVITIES; BIOMECHANICS; KINEMATICS; WALKING; BALANCE AB The importance of momentum in compensating for elderly individuals' strength deficits to achieve activities of daily living, such as rising from a chair has been demonstrated in earlier studies. Here we present a case-control study of three healthy "non-fallers" and two "frequent fallers." All 5 elders were community-living and were tested in the gait laboratory. A four-camera Selspot system was used to obtain whole-body momentum from an Ii-segment kinematic model. Ground reaction forces and kinematics were used to calculate lower extremity joint moments. With the exception of the whole-body's angular momentum about the vertical axis, linear and angular momenta during gait were minimum during mid-single limb support and maximum near heel contact. Whole-body momentum values for individuals with a history of falls were similar to those measured in non-fallers. However, subjects with a history of falls had between 17 and 37% smaller maximum ankle and knee torque values than the subjects without a history of falls during ambulation. A comprehensive description of whole-body linear and angular momenta during steady-state gait in older individuals is presented. While whole-body momentum characteristics and magnitude were similar between fallers and non-fallers, the consequences of the lesser torque values in the fallers' knees and ankles to generate and control this momentum warrant further investigation. C1 Marquette Univ, Dept Phys Therapy, Milwaukee, WI 53201 USA. Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02114 USA. Inst Hlth Profess, Boston, MA 02114 USA. RP Simoneau, GG (reprint author), Marquette Univ, Dept Phys Therapy, Milwaukee, WI 53201 USA. NR 23 TC 21 Z9 21 U1 3 U2 5 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, CHAMPAIGN, IL 61820-2200 USA SN 1065-8483 J9 J APPL BIOMECH JI J. Appl. Biomech. PD FEB PY 2000 VL 16 IS 1 BP 1 EP 13 PG 13 WC Engineering, Biomedical; Sport Sciences SC Engineering; Sport Sciences GA 286LA UT WOS:000085446400001 ER PT J AU Fournier, B Aras, R Hooper, DC AF Fournier, B Aras, R Hooper, DC TI Expression of the multidrug resistance transporter NorA from Staphylococcus aureus is modified by a two-component regulatory system SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; NUCLEOTIDE-SEQUENCE; EFFLUX TRANSPORTER; PHOSPHATE REGULON; GENE REGULATOR; OMPR PROTEIN; VIRULENCE; DNA; IDENTIFICATION; BINDING AB To dissect genetically the regulation of NorA, a multidrug transporter of Staphylococcus aureus, we analyzed the differential expression of the norA promoter using a transcriptional fusion with a P-lactamase reporter gene. Expression studies with an arlS mutant revealed that the norA promoter is ArlS dependent. The arlR-arlS locus was shown to code for a two-component regulatory system. The protein ArlR has strong similarity to response regulators, and ArlS has strong similarity to protein histidine kinases. We have also analyzed the 350-bp region upstream of the Shine-Dalgarno sequence of norA by gel mobility shift experiments. It was shown that only the 115-bp region upstream of the promoter was necessary for multiple binding of an 18-kDa protein. From transcriptional fusions, we have localized four different putative boxes of 6 bp, which appear to play a role in the binding of the 18-kDa protein and in the up-regulation of norA expression in the presence of the arlS mutation. Furthermore, the gel mobility shift of the 18-kDa protein was modified in the presence of the arlS mutation, and the arlS mutation altered the growth-phase regulation of NorA. These results indicate that expression of norA is modified by a two-component regulatory system. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. Inst Pasteur, Unite Biochim Microbienne, F-75724 Paris 15, France. RP Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org FU NIAID NIH HHS [AI23988, R37 AI023988, R01 AI023988] NR 41 TC 60 Z9 66 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD FEB PY 2000 VL 182 IS 3 BP 664 EP 671 DI 10.1128/JB.182.3.664-671.2000 PG 8 WC Microbiology SC Microbiology GA 278RP UT WOS:000085003000013 PM 10633099 ER PT J AU Shanbhag, AS Bailey, HO Hwang, DS Cha, CW Eror, NG Rubash, HE AF Shanbhag, AS Bailey, HO Hwang, DS Cha, CW Eror, NG Rubash, HE TI Quantitative analysis of ultrahigh molecular weight polyethylene (UHMWPE) wear debris associated with total knee replacements SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article DE total knee replacement; UHMWPE; wear debris; retrieval and characterization ID TOTAL HIP REPLACEMENTS; SYNOVIAL-LIKE MEMBRANE; BONE-CEMENT INTERFACE; GENERATED IN-VIVO; FOLLOW-UP; PARTICLES; ARTHROPLASTY; RESORPTION; PROSTHESES AB The size and morphology of particulate near debris retrieved from tissues around 18 failed total knee replacements (TKR) were characterized, Interfacial membranes front nine cemented and nine uncemented TKR mere harvested from below the tibial components during revision surgery. Wear debris were extracted using papain and potassium hydroxide digestion. Ultrahigh molecular weight polyethylene (UHMWPE) particles from around cemented or uncemented TKR were similar in size and morphology, The mean size was 1.7 +/- 0.7 mu m with a range of 0.1-18 mu m. Thirty-sir percent of the particles were less than 1 mu m and 90% were Less than 3 mu m, Morphologically the particles were predominantly spherical with occasional fibrillar attachments and flakes. Particles from TKR were greater than threefold larger than previously characterized particles from total hip replacements, which were 0.5 mu m in mean size, Differences in joint conformity and wear patterns between the hip and knee articulations may explain the disparity in size of the wear debris. Since particle size represents an important variable influencing the magnitude of the biological response, it is possible that in vivo the larger TKR debris results in a diminished mediator release, which in turn may account for the lower incidence of osteolysis and aseptic loosening in some designs of TKR, (C) 2000 John Wiley & Sons, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biomat Lab, Boston, MA 02114 USA. Univ Pittsburgh, Pittsburgh, PA 15213 USA. RP Shanbhag, AS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biomat Lab, GRJ 1115,55 Fruit St, Boston, MA 02114 USA. NR 55 TC 58 Z9 63 U1 1 U2 5 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD FEB PY 2000 VL 53 IS 1 BP 100 EP 110 DI 10.1002/(SICI)1097-4636(2000)53:1<100::AID-JBM14>3.0.CO;2-4 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 276CC UT WOS:000084857200014 PM 10634959 ER PT J AU Menaa, C Barsony, J Reddy, SV Cornish, J Cundy, T Roodman, GD AF Menaa, C Barsony, J Reddy, SV Cornish, J Cundy, T Roodman, GD TI 1,25-dihydroxyvitamin D-3 hypersensitivity of osteoclast precursors from patients with Paget's disease SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE Paget's disease; osteoclasts; precursors; 1,25-(OH)(2)D-3; vitamin D receptor ID VITAMIN-D-RECEPTOR; MARROW CULTURES; IMMUNOCYTOCHEMICAL LOCALIZATION; MULTINUCLEATED CELLS; GENE-EXPRESSION; PHORBOL ESTER; BONE-MARROW; HORMONE; BINDING; LIGAND AB Our previous studies suggested that increased osteoclast formation and activity in Paget's disease may be related in part to increased responsiveness of highly purified osteoclast precursors to 1,25-dihydroxyvitamin D-3 [1,25-(OH)(2)D-3]. However, the basis for this enhanced sensitivity to 1,25-(OH),D3 is unclear To address this question, we examined 24-hydroxylase and 1,25-(OH)(2)D-3 receptor (VDR) messenger RNA (mRNA) expression during human osteoclast differentiation from normal subjects and patients with Paget's disease in response to 1,25-(OH)(2)D-3 as well as VDR content and affinity, Reverse-transcription polymerase chain reaction (RT-PCR) analysis of granulocyte-macrophage colony-forming unit (GM-CFU), the earliest identifiable osteoclast precursor, derived from patients with Paget's disease demonstrated 24-hydroxylase mRNA expression in response to 1,25-(OH)(2)D-3 was induced at concentrations of 1,25-(OH)(2)D-3 that were at least one log less than that required for normal GM-CFU, VDR mRNA and VDR protein were detected in both immature and more differentiated osteoclast precursors, as well as in osteoclast-like multinucleated cells (MNCs), However, VDR expression was lower in MNCs than the mononuclear precursor cells, Osteoclast precursors and MNCs from patients with Paget's disease had levels of VDR expression similar to those of normal subjects but showed increased VDR affinity for 1,25-(OH)(2)D-3. Because the effects of 1,25-(OH)(2)D-3 are in part mediated by induction of expression of RANK ligand on marrow stromal cells, which in turn stimulates osteoclast formation, we examined expression of RANK ligand mRNA by marrow stromal cell lines derived from patients with Paget's disease and normal subjects in response to 1,25-(OH)(2)D-3. RT-PCR analysis showed no difference in sensitivity of marrow stromal cells to 1,25-(OH)(2)D-3 from normal subjects or patients with Paget's disease although the Paget's stromal cells expressed increased basal levels of RANK ligand mRNA, These results show that VDR protein is expressed in early and more differentiated osteoclast precursors, that expression levels of VDR decline with osteoclast differentiation, and that 1,25-(OH)(2)D-3 has direct effects on osteoclast precursors, The enhanced sensitivity to 1,25-(OH)(2)D-3 is an intrinsic property of osteoclast precursors from patients with Paget's disease that distinguishes them from normal osteoclast precursors, Furthermore, our results suggest that an increased affinity of VDR for 1,25-(OH)(2)D-3 may be responsible for the enhanced 1,25-(OH)(2)D-3 sensitivity of osteoclast precursors in patients with Paget's disease compared with normal subjects. C1 Univ Texas, Hlth Sci Ctr, Dept Med Hematol, San Antonio, TX 78284 USA. NIH, Bethesda, MD 20892 USA. Univ Auckland, Auckland 1, New Zealand. Audie Murphy Vet Adm Hosp, San Antonio, TX USA. RP Roodman, GD (reprint author), Res Hematol 151, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NIA NIH HHS [AG13625]; NIAMS NIH HHS [AR41336, AR44603] NR 27 TC 52 Z9 54 U1 0 U2 3 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2000 VL 15 IS 2 BP 228 EP 236 DI 10.1359/jbmr.2000.15.2.228 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 282HR UT WOS:000085212800006 PM 10703924 ER PT J AU Koski, G AF Koski, G TI Internal mammary artery spasm: Is calcium the culprit? SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Cardiovasc Anesthesia Grp, Dept Anesthesia & Crit Care Med, Boston, MA 02114 USA. RP Koski, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Cardiovasc Anesthesia Grp, Dept Anesthesia & Crit Care Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD FEB PY 2000 VL 14 IS 1 BP 1 EP 3 DI 10.1016/S1053-0770(00)90045-4 PG 3 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 283RV UT WOS:000085290200001 PM 10698382 ER PT J AU Hinkin, CH Castellon, SA Hardy, DJ AF Hinkin, CH Castellon, SA Hardy, DJ TI Dual task performance in HIV-1 infection SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article; Proceedings Paper CT 25th Meeting of the International-Neuropsychological-Society CY FEB 05-08, 1997 CL ORLANDO, FLORIDA SP Int Neuropsychol Soc ID IMMUNODEFICIENCY-VIRUS-INFECTION; WORKING-MEMORY; REACTION-TIME; HIV-1-INFECTED INDIVIDUALS; QUINOLINIC ACID; ATTENTION; DEMENTIA; DEFICITS; DISEASE AB Fifty HIV-infected individuals and 20 uninfected controls participated in an investigation of dual task performance in HIV-1 infection. Participants first engaged in a simple auditory reaction time (RT) task followed by a visual choice RT task (single task condition), and then they simultaneously engaged in both tasks (dual task condition). Under single task conditions, the HIV+ participants did not significantly differ from controls on either simple or choice RT (though a trend was evident on single task choice RT). In contrast, under dual task conditions the HIV+ group's performance decrement, relative to controls, was significantly greater on both simple and choice RT. This dual task decrement was also significantly associated with slower performance on the interference condition of the Stroop. Patients with AIDS tended to have greater dual task decrements than did the pre-AIDS group, though this fell short of statistical significance. These results suggest that HIV-1 infection leads to deficits in divided attention and the simultaneous processing of competing stimuli, deficits which have been linked to disruption of the anterior attentional system. C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, ABPP, Los Angeles, CA 90024 USA. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Hinkin, CH (reprint author), Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, ABPP, 760 Westwood Plaza,Room C8-747, Los Angeles, CA 90024 USA. FU NIMH NIH HHS [R03MH54465] NR 32 TC 28 Z9 29 U1 2 U2 5 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD FEB PY 2000 VL 22 IS 1 BP 16 EP 24 DI 10.1076/1380-3395(200002)22:1;1-8;FT016 PG 9 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 287BE UT WOS:000085484000002 PM 10649542 ER PT J AU Seminara, SB Beranova, M Oliveira, LMB Martin, KA Crowley, WF Hall, JE AF Seminara, SB Beranova, M Oliveira, LMB Martin, KA Crowley, WF Hall, JE TI Successful use of pulsatile gonadotropin-releasing hormone (GnRH) for ovulation induction and pregnancy in a patient with GnRH receptor mutations SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FREE ALPHA-SUBUNIT; HYPOGONADOTROPIC HYPOGONADISM; LUTEINIZING-HORMONE; CORPUS-LUTEUM; HYPOTHALAMIC AMENORRHEA; PROGESTERONE SECRETION; MENSTRUAL-CYCLE; WOMEN; GENE; FOLLICLE AB GnRH receptor mutations have recently been identified in a small number of familial cases of nonanosmic hypogonadotropic hypogonadism. In the present report we studied a kindred in which two sisters with primary amenorrhea were affected with GnRH deficiency due to a compound heterozygote mutation (Gln(106)Arg, Arg(262)Gln) and performed extensive phenotyping studies. Baseline patterns of gonadotropin secretion and gonadotropin responsiveness to exogenous pulsatile GnRH were examined in the proband. Low amplitude pulses of both LH and free alpha-subunit (FAS) were detected during 24 h of every 10 min blood sampling. The proband then received exogenous pulsatile GnRH iv for ovulation induction, and daily blood samples for gonadotropins and sex steroids were monitored. At the conventional GnRH replacement dose for women with hypogonadotropic hypogonadism (75 ng/kg), no follicular development occurred. At a GnRH dose of 100 ng/kg, the level and pattern of gonadotropin secretion more closely mimicked the follicular phase of normal women; a single dominant follicle was recruited, and an endogenous LH surge was elicited. However, the luteal phase was inadequate, as assessed by progesterone levels. At a GnRH dose of 250 ng/kg, the gonadotropin and sex steroid dynamics reproduced those of normal ovulatory women in both the follicular and luteal phases, and the proband conceived. The FAS responses to both conventional and high dose GnRH were within the normal range. The following conclusions were made: 1) Increased doses of GnRH may be used effectively for ovulation induction in same patients with GnRH receptor mutations. 2) Higher doses of GnRH are required for normal luteal phase dynamics than for normal follicular phase function. 3) Hypersecretion of FAS in response to exogenous GnRH, which is a feature of congenital hypogonadotropic hypogonadism, was not seen in this patient with a GnRH receptor mutation. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Bartlett Hall Extens 505,55 Fruit St, Boston, MA 02114 USA. EM seminara.stephanie@mgh.harvard.edu FU NICHD NIH HHS [P30 HD028138, P30-HD-28138, U54-HD29164, U54 HD028138, U54 HD029164] NR 35 TC 65 Z9 68 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 2000 VL 85 IS 2 BP 556 EP 562 DI 10.1210/jc.85.2.556 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 285EX UT WOS:000085377700018 PM 10690855 ER PT J AU Cusi, K Maezono, K Osman, A Pendergrass, M Patti, ME Pratipanawatr, T DeFronzo, RA Kahn, CR Mandarino, LJ AF Cusi, K Maezono, K Osman, A Pendergrass, M Patti, ME Pratipanawatr, T DeFronzo, RA Kahn, CR Mandarino, LJ TI Insulin resistance differentially affects the PI3-kinase- and MAP kinase-mediated signaling in human muscle SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HUMAN SKELETAL-MUSCLE; ACTIVATED PROTEIN-KINASE; DEPENDENT DIABETES-MELLITUS; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; RECEPTOR SUBSTRATE-1 PHOSPHORYLATION; GLYCOGEN-SYNTHASE ACTIVATION; GLUCOSE-TRANSPORT; GLUT4 TRANSLOCATION; TYROSINE KINASE; IN-VIVO AB The broad nature of insulin resistant glucose metabolism in skeletal muscle of patients with type 2 diabetes suggests a defect in the proximal part of the insulin signaling network. We sought to identify the pathways compromised in insulin resistance and to test the effect of moderate exercise on whole-body and cellular insulin action. We conducted euglycemic clamps and muscle biopsies on type 2 diabetic patients, obese nondiabetics and lean controls, with and without a single bout of exercise. Insulin stimulation of the phosphatidylinositol 3-kinase (PI 3-kinase) pathway, as measured by phosphorylation of the insulin receptor and IRS-1 and by IRS protein association with p85 and with PI 3-kinase, was dramatically reduced in obese nondiabetics and virtually absent in type 2 diabetic patients. Insulin stimulation of the MAP kinase pathway was normal in obese and diabetic subjects. Insulin stimulation of glucose-disposal correlated with association of p85 with IRS-1. Exercise 24 hours before the euglycemic clamp increased phosphorylation of insulin receptor and IRS-1 in obese and diabetic subjects but did not increase glucose uptake or PI S-kinase association with IRS-1 upon insulin stimulation. Thus, insulin resistance differentially affects the PI 3-kinase and MAP kinase signaling pathways, and insulin-stimulated IRS-l-association with PI 3-kinase defines a key step in insulin resistance. C1 Univ Texas, Hlth Sci Ctr, Div Diabet, Dept Med, San Antonio, TX 78229 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Mandarino, LJ (reprint author), Univ Texas, Hlth Sci Ctr, Div Diabet, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NCRR NIH HHS [M01 RR001346]; NIDDK NIH HHS [DK02526, R01 DK024092, R01 DK033201, R01 DK047936, R01DK24092, R01DK47936] NR 47 TC 639 Z9 672 U1 3 U2 33 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 2000 VL 105 IS 3 BP 311 EP 320 DI 10.1172/JCI7535 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 282FP UT WOS:000085207600010 PM 10675357 ER PT J AU Tomasson, MH Sternberg, DW Williams, IR Carroll, M Cain, D Aster, JC Ilaria, RL Van Etten, RA Gilliland, DG AF Tomasson, MH Sternberg, DW Williams, IR Carroll, M Cain, D Aster, JC Ilaria, RL Van Etten, RA Gilliland, DG TI Fatal myeloproliferation, induced in mice by TEL/PDGF beta R expression, depends on PDGF beta R tyrosines 579/581 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CHRONIC MYELOMONOCYTIC LEUKEMIA; HEMATOPOIETIC-CELL LINES; RETROVIRAL VECTORS; RECEPTOR-BETA; KINASE; FUSION; GENE; SIGNAL; PHOSPHORYLATION; TRANSFORMATION AB The t(5;12)(q33;p13) translocation associated with chronic myelomonocytic leukemia (CMML) generates a TEL/PDGF beta R fusion gene. Here, we used a murine bone marrow transplant (BMT) assay to test the transforming properties of TEL/PDGF beta R in vivo. TEL/PDGF beta R, introduced into whole bone marrow by retroviral transduction, caused a rapidly fatal myeloproliferative disease that closely recapitulated human CMML. TEL/PDGF beta R transplanted mice developed leukocytosis with Gr-1(+) granulocytes, splenomegaly, evidence of extramedullary hematopoiesis, and bone marrow fibrosis, but no lymphoproliferative disease. We assayed mutant forms of the TEL/PDGF beta R fusion protein - including 8 tyrosine to phenylalanine substitutions at phosphorylated PDGF beta R sites to which various SH2 domain-containing signaling intermediates bind - for ability to transform hematopoietic cells. All of the phenylalanine (F-) mutants tested conferred IL-3-independence to a cultured murine hematopoietic cell line, but, in the BMT assay, different P-mutants displayed distinct transforming properties. In transplanted animals, tyrosines 579/581 proved critical for the development of myeloproliferative phenotype. F-mutants with these residues mutated showed no sign of myeloproliferation but instead developed T-cell lymphomas. In summary, TEL/PDGF beta R is necessary and sufficient to induce a myeloproliferative disease in a murine BMT model, and PDGF beta R residues Y579/581 are required for this phenotype. C1 Harvard Univ, Brigham & Womens Hosp, Inst Med, Dept Med, Boston, MA 02115 USA. Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. Univ Penn, Div Hematol & Oncol, Philadelphia, PA 19104 USA. Univ Texas, SW Med Ctr, Simmons Canc Ctr, Dallas, TX 75235 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Gilliland, DG (reprint author), Harvard Univ, Inst Med, 4 Blackfan Circle,Room 421, Boston, MA 02115 USA. RI Williams, Ifor/D-3648-2011 OI Williams, Ifor/0000-0002-8810-2911 FU NCI NIH HHS [K08CA81197-01, P01 CA066996, P01CA66996-01]; PHS HHS [P01OK50654] NR 30 TC 88 Z9 90 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 2000 VL 105 IS 4 BP 423 EP 432 DI 10.1172/JCI8902 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 286LD UT WOS:000085446700005 PM 10683371 ER PT J AU Lien, E Means, TK Heine, H Yoshimura, A Kusumoto, S Fukase, K Fenton, MJ Oikawa, M Qureshi, N Monks, B Finberg, RW Ingalls, RR Golenbock, DT AF Lien, E Means, TK Heine, H Yoshimura, A Kusumoto, S Fukase, K Fenton, MJ Oikawa, M Qureshi, N Monks, B Finberg, RW Ingalls, RR Golenbock, DT TI Toll-like receptor 4 imparts ligand-specific recognition of bacterial lipopolysaccharide SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID DROSOPHILA TOLL; SIGNAL-TRANSDUCTION; HUMAN-MONOCYTES; CELL-LINE; ENDOTOXIN; GENE; PATHWAY; LPS; EXPRESSION; RESPONSIVENESS AB Lipopolysaccharide (LPS) is the main inducer of shock and death in Gram-negative sepsis. Recent evidence suggests that LPS-induced signal transduction begins with CD14-mediated activation of 1 or more Toll-like receptors (TLRs). The lipid A analogues lipid IVa and Rhodobacter sphaeroides lipid A (RSLA) exhibit an uncommon species-specific pharmacology Both compounds inhibit the effects of LPS in human cells but display LPS-mimetic activity in hamster cells. We transfected human TLR4 or human TLR2 into hamster fibroblasts to determine if either of these LPS signal transducers is responsible for the species-specific pharmacology RSLA and lipid IVa strongly induced NF-KB activity and IL-6 release in Chinese hamster ovary fibroblasts expressing CD14 (CHO/CD14), but these compounds antagonized LPS antagonists in CHO/CD14 fibroblasts that overexpressed human TLR4. No such antagonism occurred in cells overexpressing human TLR2. We cloned TLR4 from hamster macrophages and found that human THP-1 cells expressing the hamster TLR4 responded to Lipid IVa as an LPS mimetic, as if they were hamster in origin. Hence, cells heterologously overexpressing TLR4 from different species acquired a pharmacological phenotype with respect to recognition of lipid A substructures that corresponded to the species from which the TLR4 transgene originated. These data suggest that TLR4 is the central lipid A-recognition protein in the LPS receptor complex. C1 Boston Med Ctr, Maxwell Finland Lab Infect Dis, Boston, MA 02118 USA. Norwegian Univ Sci & Technol, Inst Canc Res & Mol Biol, N-7034 Trondheim, Norway. Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. Osaka Univ, Grad Sch Sci, Dept Chem, Toyonaka, Osaka 5600043, Japan. William S Middleton Mem Vet Hosp, Madison, WI 53705 USA. Dana Farber Canc Inst, Infect Dis Lab, Boston, MA 02115 USA. RP Golenbock, DT (reprint author), Boston Med Ctr, Maxwell Finland Lab Infect Dis, 774 Albany St, Boston, MA 02118 USA. RI Finberg, Robert/E-3323-2010; Oikawa, Masato/E-9411-2010; Monks, Brian/B-8362-2015 OI Oikawa, Masato/0000-0002-3919-811X; Monks, Brian/0000-0003-4008-3093 FU NIAID NIH HHS [AI-01476, AI-38505]; NIGMS NIH HHS [GM-56060, R01 GM050870, R01 GM054060, R37 GM054060] NR 42 TC 578 Z9 594 U1 4 U2 35 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 2000 VL 105 IS 4 BP 497 EP 504 DI 10.1172/JCI8541 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 286LD UT WOS:000085446700013 PM 10683379 ER PT J AU Kirkpatrick, WR Lopez-Ribot, JL Mcatee, RK Patterson, TF AF Kirkpatrick, WR Lopez-Ribot, JL Mcatee, RK Patterson, TF TI Growth competition between Candida dubliniensis and Candida albicans under broth and biofilm growing conditions SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID VIRUS-INFECTED PATIENTS; CELL-SURFACE HYDROPHOBICITY; DENTURE ACRYLIC SURFACES; FLUCONAZOLE RESISTANCE; IN-VITRO; OROPHARYNGEAL CANDIDIASIS; IDENTIFICATION; SUSCEPTIBILITY; EXPRESSION; MACRODILUTION AB Seven isolates each of Candida albicans and Candida dubliniensis were paired (11 pairs) and examined for competitive interaction. Equal numbers of CFU of each competitor Here inoculated into Sabouraud dextrose broth and incubated at 37 degrees C with vigorous shaking under conditions favorable to either broth or biofilm growth. Surviving proportions of each competitor were calculated from the broth culture at 24 and 96 h and the biofilm culture at 96 h, with species differentiation done on CHROMagar Candida medium. C. albicans had a competitive advantage ol er C. dubliniensis in broth culture and under biofilm growing conditions; however, with the presence of a supporting structure for biofilm formation, C. dubliniensis was able to better withstand the competitive pressures from C. albicans. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX 78284 USA. RP Kirkpatrick, WR (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. RI Lopez-Ribot, Jose/D-2048-2010 FU NCRR NIH HHS [M01 RR001346, M01RR01346]; NIAID NIH HHS [1R29AI42401]; NIDCR NIH HHS [5RO1DE11381, R01 DE011381] NR 30 TC 25 Z9 26 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD FEB PY 2000 VL 38 IS 2 BP 902 EP 904 PG 3 WC Microbiology SC Microbiology GA 281XR UT WOS:000085187200083 PM 10655413 ER PT J AU Colleoni, M Bonetti, M Coates, AS Castiglione-Gertsch, M Gelber, RD Price, K Rudenstam, CM Lindtner, J Collins, J Thurlimann, B Holmberg, S Veronesi, A Marini, G Goldhirsch, A AF Colleoni, M Bonetti, M Coates, AS Castiglione-Gertsch, M Gelber, RD Price, K Rudenstam, CM Lindtner, J Collins, J Thurlimann, B Holmberg, S Veronesi, A Marini, G Goldhirsch, A CA Int Breast Canc Study Grp TI Early start of adjuvant chemotherapy may improve treatment outcome for premenopausal breast cancer patients with tumors not expressing estrogen receptors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GROWTH; ANGIOGENESIS; CARCINOMA; THERAPY; REMOVAL; CYCLOPHOSPHAMIDE; METHOTREXATE; ASSOCIATION; KINETICS; IMPACT AB purpose: The proper time to commence adjuvant chemotherapy after primary surgery for breast cancer is unknown. An analysis of the International (Ludwig) Breast Cancer Study Group (IBCSG) Trial V at a median follow-up of 11 years suggested that early initiation of adjuvant chemotherapy might improve outcome for premenopausal, node-positive patients whose turners did not express any estrogen receptor (ER). Patients and Methods: We investigated the relationship between early initiation of adjuvant chemotherapy, ER status, and prognosis in 1,788 premenopausal, node-positive patients treated on IBCSG trials I, II, and VI. The disease-free survival for 599 patients (84 with ER-absent tumors) who commenced adjuvant chemotherapy within 20 days (early initiation) was compared with the disease-free survival for 1,189 patients (142 with ER-absent tumors) who started chemotherapy 21 to 86 days after surgery (conventional initiation). The median follow-up was 7.7 years. Results: Among patients with ER-absent tumors, the 10-year disease-free survival was 60% for the early initiation group compared with 34% for the conventional initiation group (226 patients; hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.33 to 0.72; P = .0003). This difference remained statistically significant in a Cox multiple regression analysis controlling for study group, number of positive nodes, tumor size, age, vessel invasion, and institution (HR, 0.60; 95% CI, 0.39 to 0.92; P = .019). Conversely, early initiation of chemotherapy did not significantly improve disease-free survival for patients with tumors expressing ER(1,562 patients; multiple regression HR, 0.93; 95% CI, 0.79 to 1.10; P = .40). Conclusion: In premenopausal patients with ER-absent tumors, early initiation of systemic chemotherapy after primary surgery might improve outcome. Further confirmatory studies are required before any widespread modification of current clinical practice. In premenopausal patients with tumors expressing some ER, gains from early initiation are unlikely to be clinically significant. J Clin Oncol 18:584-590. (C) 2000 by American Society of Clinical Oncology. C1 European Inst Oncol, Div Med Oncol, I-20141 Milan, Italy. Ctr Riferimento Oncol, I-33081 Aviano, Italy. Spedali Civili, Oncol Med & Fdn Beretta, I-25125 Brescia, Italy. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Int Breast Canc Study Grp Stat Ctr, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn, Boston, MA 02115 USA. Univ Sydney, Sydney, NSW 2006, Australia. Australian Canc Soc, Sydney, NSW, Australia. Anticanc Council Victoria, Melbourne, Vic, Australia. Canc Study Grp Coordinat Ctr, Bern, Switzerland. Osped Civico, Lugano, Switzerland. Kantonsspital, St Gallen, Switzerland. Sahlgrens Univ Hosp, W Swedish Breast Canc Study Grp, Gothenburg, Sweden. Inst Oncol, Ljubljana, Slovenia. RP Colleoni, M (reprint author), European Inst Oncol, Div Med Oncol, Via Ripamonti 435, I-20141 Milan, Italy. OI Bonetti, Marco/0000-0003-2304-4180 FU NCI NIH HHS [CA75362] NR 43 TC 125 Z9 127 U1 3 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 2000 VL 18 IS 3 BP 584 EP 590 PG 7 WC Oncology SC Oncology GA 281ZX UT WOS:000085192300015 PM 10653873 ER PT J AU Bonomi, P Kim, KM Fairclough, D Cella, D Kugler, J Rowinsky, E Jiroutek, M Johnson, D AF Bonomi, P Kim, KM Fairclough, D Cella, D Kugler, J Rowinsky, E Jiroutek, M Johnson, D TI Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: Results of an eastern cooperative oncology group trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CLINICAL-TRIALS; RANDOMIZED TRIAL; PHASE-II; CHEMOTHERAPY; REGIMENS; TAXOL AB purpose: Treatment with cisplatin-based chemotherapy provides a modest survival advantage over supportive care alone in advanced non-small-cell lung cancer (NSCLC). To determine whether a new agent, paclitaxel, would further improve survival in NSCLC, the Eastern Cooperative Oncology Group conducted a randomized trial comparing paclitaxel plus cisplatin to a standard chemotherapy regimen consisting of cisplatin and etoposide. Patients and Methods: The study was carried out by a multi-institutional cooperative group in chemotherapy-naive stage IIIB to IV NSCLC patients randomized to receive paclitaxel plus cisplatin or etoposide plus cisplatin. Paclitaxel was administered at two different dose levels (135 mg/m(2) and 250 mg/m(2)), and etoposide was given at a dose of 100 mg/m(2) daily on days 1 to 3. Each regimen was repeated every 21 days and each included cisplatin (75 mg/m(2)). Results: The characteristics of the 599 patients were well-balanced across the three treatment groups. Superior survival was observed with the combined paclitaxel regimens (median survival time, 9.9 months; 1-year survival rate, 38.9%) compared with etoposide plus cisplatin (median survival time, 7.6 months; 1-year survival rate, 31.8%; P = .048). Comparing survival for the two dose levels of paclitaxel revealed no significant difference. The median survival duration for the stage IIIB subgroup was 7.9 months for etoposide plus cisplatin patients versus 13.1 months for all paclitaxel patients (P = .152). For the stage N subgroup, the median survival time for etoposide plus cisplatin was 7.6 months compared with 8.9 months for paclitaxel (P = .246). With the exceptions of increased granulocytopenia on the low-dose paclitaxel regimen and increased myalgias, neurotoxicity, and, possibly, increased treatment-related cardiac events with high-dose paclitaxel, toxicity was similar across all three arms. Quality of life (QOL) declined significantly over the 6 months. However, QOL scores were not significantly different among the regimens. Conclusion: As a result of these observations, paclitaxel (135 mg/m(2)) combined with cisplatin has replaced etoposide plus cisplatin as the reference regimen in our recently completed phase III trial. J Clin Oncol 18:623-631. (C) 2000 by American Society of Clinical Oncology. C1 Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Illinois Oncol Res Assoc, Peoria, IL USA. Northwestern Univ, Evanston Northwestern Hlth Care, Evanston, IL USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. Amer Med Ctr, Canc Res Ctr, Denver, CO USA. Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. Dana Farber Canc Ctr, Boston, MA USA. Vanderbilt Univ, Nashville, TN USA. RP Bonomi, P (reprint author), Rush Med Coll, 1725 W Harrison St,Ste 821, Chicago, IL 60612 USA. FU NCI NIH HHS [CA49957, CA23318, CA25988] NR 30 TC 390 Z9 405 U1 0 U2 20 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 2000 VL 18 IS 3 BP 623 EP 631 PG 9 WC Oncology SC Oncology GA 281ZX UT WOS:000085192300019 PM 10653877 ER PT J AU Burstein, HJ AF Burstein, HJ TI Diagnosis in oncology - Side effects of chemotherapy - Case 1. Radiation recall dermatitis from gemcitabine SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID IMMUNE-DEFICIENCY-SYNDROME; PATIENT; RADIOTHERAPY; AGENTS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 15 TC 38 Z9 39 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 2000 VL 18 IS 3 BP 693 EP 694 PG 2 WC Oncology SC Oncology GA 281ZX UT WOS:000085192300027 PM 10653885 ER PT J AU Attar, EC Ervin, T Janicek, M Deykin, A Godleski, J AF Attar, EC Ervin, T Janicek, M Deykin, A Godleski, J TI Diagnosis in oncology - Side effects of chemotherapy - Case 3. Acute interstitial pneumonitis related to gemcitabine SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PULMONARY C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Attar, EC (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 4 TC 23 Z9 25 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 2000 VL 18 IS 3 BP 697 EP 698 PG 2 WC Oncology SC Oncology GA 281ZX UT WOS:000085192300029 PM 10653887 ER PT J AU Fine, HA Figg, WD Jaeckle, K Wen, PY Kyritsis, AP Loeffler, JS Levin, VA Black, PM Kaplan, R Pluda, JM Yung, WKA AF Fine, HA Figg, WD Jaeckle, K Wen, PY Kyritsis, AP Loeffler, JS Levin, VA Black, PM Kaplan, R Pluda, JM Yung, WKA TI Phase II trial of the antiangiogenic agent thalidomide in patients with recurrent high-grade gliomas SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TUMOR ANGIOGENESIS; FACTOR EXPRESSION; INHIBITION; CHEMOTHERAPY; ASTROCYTOMAS; THERAPIES; LYMPHOMA; CRITERIA; DISEASE AB Purpose: Little progress has been made in the treatment of adult high-grade gliomas over the last two decades, thus necessitating a search for novel therapeutic strategies. Malignant gliomas are vascular or angiogenic tumors, which leads to the supposition that angiogenesis inhibition may represent a potentially promising strategy in the treatment of these tumors. We present the results of a phase II trial of thalidomide, a putative inhibitor of angiogenesis, in the treatment of adults with previously irradiated, recurrent high-grade gliomas. Patients and Methods: Patients with a histologic diagnosis of anaplastic mixed glioma, anaplastic astrocytoma, or glioblastoma multiforme who had radiographic demonstration of tumor progression after standard external-beam radiotherapy with or without chemotherapy were eligible. Patients were initially treated with thalidomide 800 mg/d with increases in dose by 200 mg/d every 2 weeks until a final daily dose of 1,200 mg was achieved. Patients were evaluated every 8 weeks for response by both clinical and radiographic criteria. Results: A total of 39 patients were accrued, with 36 patients being assessable for both toxicity and response. Thalidomide was well tolerated, with constipation and sedation being the major toxicities. One patient developed a grade 2 peripheral neuropathy after treatment with thalidomide for nearly a year. There were two objective radiographic partial responses (6%), two minor responses (6%), and 12 patients with stable disease (33%). Eight patients were alive more than 1 year after starting thalidomide, although almost all with tumor progression. Changes in serum levels of basic fibroblastic growth factor (bFGF) were correlated with time to tumor progression and overall survival. Conclusion: Thalidomide is a generally well-tolerated drug that may have antitumor activity in a minority of patients with recurrent high-grade gliomas. Future studies will better define the usefulness of thalidomide in newly diagnosed patients with malignant gliomas and in combination with radiotherapy and chemotherapy. Additionally, studies will be needed to confirm the potential utility of changes in serum bFGF as a marker of antiangiogenic activity and/or glioma growth. (C) 2000 by American Society of Clinical Oncology. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurooncol,Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. Natl Cent Nervous Syst Consortium, Houston, TX USA. NCI, Canc Treatment & Evaluat Program, Investigat Drug Branch, Div Canc Therapy & Diagnosis, Bethesda, MD 20892 USA. RP Fine, HA (reprint author), NINDS, NCI, Neurooncol Branch, NIH, Bldg 10,Rm 12W253,10 Ctr Dr, Bethesda, MD 20892 USA. RI Ain, Kenneth/A-5179-2012; Figg Sr, William/M-2411-2016 OI Ain, Kenneth/0000-0002-2668-934X; NR 34 TC 331 Z9 341 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 2000 VL 18 IS 4 BP 708 EP 715 PG 8 WC Oncology SC Oncology GA 285RL UT WOS:000085401800002 PM 10673511 ER PT J AU Tulpule, A Scadden, DT Espina, BM Cabriales, S Howard, W Shea, K Gill, PS AF Tulpule, A Scadden, DT Espina, BM Cabriales, S Howard, W Shea, K Gill, PS TI Results of a randomized study of IM862 nasal solution in the treatment of AIDS-related Kaposi's sarcoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PENTOSAN POLYSULFATE; GROWTH-FACTOR; TRIAL; DOXORUBICIN; BLEOMYCIN; VINCRISTINE; INHIBITOR; CRITERIA; CELLS AB Purpose: Although advances have been made in the treatment of AIDS-related Kaposi's sarcoma (AIDS-KS) with systemic chemotherapy, less toxic therapies are needed. lM862 is a naturally occurring peptide with antiangiogenic properties and was thus studied in patients with AIDS-KS. Patients and Methods: lM862 was given as intranasal drops at a dose of 5 mg. patients were randomized to two dosing schedules given in repeated cycles until disease progression or unacceptable toxicity: 5 days of therapy followed by 5 days off (n = 18) and every other day dosing (n = 26). Results: Forty-two male patients and two female patients with a median age of 38 years (range, 22 to 53 years) were accrued. Twenty-one patients (47%) had more than 50 mucocutaneous lesions, 14 (32%) had lymphedema, and none had visceral involvement. Thirty-three patients (75%) had received prior systemic chemotherapy. Twenty-four patients (55%) had CD4(+) lymphocyte count less than or equal to 200/mm(3). All but five patients were being treated with concurrent protease inhibitor(s), for a median of 10 months (range, 0 to 24 months). Major responses were documented in 36%, with five complete and 11 partial remissions, occurring after a median of 6 weeks (range, 3 to 26 weeks) and lasting a median of 33+ weeks (range, 12+ to 95+ weeks). Twenty one patients had stable disease for periods of 7 to 72+ weeks. Adverse effects to IM862 were limited to mild and transient headache, fatigue, tingling, and nausea. No hematologic adverse effects attributed to treatment were reported. Conclusion: lM862 given as intranasal drops is well tolerated and has antitumor activity in patients with AIDS-KS. A randomized double-blinded study to define the activity of lM862 in patients with AIDS-KS is in progress. (C) 2000 by American Society of Clinical Oncology. C1 Univ So Calif, Sch Med, Kenneth Norris Canc Hosp & Res Inst, Div Hematol,Dept Med, Los Angeles, CA 90033 USA. Harvard Univ, Med Ctr, Massachusetts Gen Hosp, Dept Med,Div Hematol, Boston, MA 02115 USA. RP Gill, PS (reprint author), Univ So Calif, Sch Med, Kenneth Norris Canc Hosp & Res Inst, Div Hematol,Dept Med, 1441 Eastlake Ave,MS-34, Los Angeles, CA 90033 USA. NR 31 TC 48 Z9 49 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 2000 VL 18 IS 4 BP 716 EP 723 PG 8 WC Oncology SC Oncology GA 285RL UT WOS:000085401800003 PM 10673512 ER PT J AU Raskind, MA Dobie, DJ Kanter, ED Petrie, EC Thompson, CE Peskind, ER AF Raskind, MA Dobie, DJ Kanter, ED Petrie, EC Thompson, CE Peskind, ER TI The alpha(1)-adrenergic antagonist prazosin ameliorates combat trauma nightmares in veterans with posttraumatic stress disorder: A report of 4 cases SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID ADRENERGIC-RECEPTORS; HUMAN-BRAIN; SLEEP; PTSD; ALPHA-1-ADRENOCEPTORS; PHARMACOLOGY; MECHANISMS; MANAGEMENT; SECRETION; NEURONS AB Background: Central nervous system (CNS) adrenergic hyperresponsiveness may be involved in the pathophysiology of posttraumatic stress disorder (PTSD). Two Vietnam combat veterans with PTSD prescribed the centrally active alpha(1)-adrenergic antagonist prazosin for symptoms of benign prostatic hypertrophy unexpectedly reported elimination of combat trauma nightmares. This observation prompted an open-label feasibility trial of prazosin for combat trauma nightmares in chronic combat-induced PTSD. Method: Four consecutively identified combat veterans with chronic DSM-IV PTSD and severe intractable combat trauma nightmares participated in an 8-week open trial of escalating-dose prazosin. Nightmare severity response was rated using the nightmare item of the Clinician Administered PTSD Scale and the Clinical Global Impressions-Change scale. Results: The 2 patients who achieved a daily prazosin dose of at lease 5 mg were markedly improved, with complete elimination of trauma nightmares and resumption of normal dreaming. The 2 subjects limited to 2 mg of prazosin to avoid excessive blood pressure reduction were moderately improved with at least 50% reduction in nightmare severity. Conclusion: These clinical observations, together with neurobiological evidence for alpha(1)-adrenergic regulation of CNS neurobiological systems relevant to PTSD, provide rationale for placebo-controlled trials of prazosin for PTSD combat trauma nightmares. C1 Vet Affairs NW Network Mental Illness Res Educ &, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Raskind, MA (reprint author), VA Puget Sound Hlth Care Syst, Mental Hlth Serv 116, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 32 TC 77 Z9 79 U1 1 U2 6 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 FEB PY 2000 VL 61 IS 2 BP 129 EP 133 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 293BC UT WOS:000085830800008 PM 10732660 ER PT J AU Miguel, EC do Rosario-Campos, MC Prado, HD do Valle, R Rauch, SL Coffey, BJ Baer, L Savage, CR O'Sullivan, RL Jenike, MA Leckman, JF AF Miguel, EC do Rosario-Campos, MC Prado, HD do Valle, R Rauch, SL Coffey, BJ Baer, L Savage, CR O'Sullivan, RL Jenike, MA Leckman, JF TI Sensory phenomena in obsessive-compulsive disorder and Tourette's disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 3rd IOCD Annual meeting CY SEP 10-11, 1998 CL MADEIRA, PORTUGAL SP IOCD ID BASAL GANGLIA; REPETITIVE BEHAVIORS; GILLES; SCALE; SYMPTOMS; FAMILY; TICS AB Background: Recent studies have suggested that obsessive-compulsive disorder (OCD) is a heterogeneous disorder with some forms related to ties and Tourette's disorder. The present study was undertaken to investigate the sensory phenomena in patients with OCD and/or Tourette's disorder to determine if these phenotypic features represent valid clinical indices for differentiating tie-related OCD from non-tie-related OCD. Method: We evaluated 20 adult outpatients with OCD, 20 with OCD plus Tourette's disorder, and 21 with Tourette's disorder, using a semistructured interview designed to assess several definitions of sensory phenomena reported in the literature. DSM-III-R criteria were used for the OCD and Tourette's disorder diagnoses. Results: Sensory phenomena including bodily sensations, mental urges, and a sense of inner tension were significantly more frequent in the 2 Tourette's disorder groups when compared with the OCD alone group. Feelings of incompleteness and a need for things to be "just right" were reported more frequently in the OCD plus Tourette's disorder group compared with the other 2 groups. Conclusion: Sensory phenomena may be an important phenotypic measure for grouping patients along the OCD-Tourette's disorder spectrum. Sensory phenomena include bodily and mental sensations. Bodily sensations include focal or generalized body sensations (usually tactile, muscular-skeletal/visceral, or both) occurring either before or during the patient's performance of the repetitive behaviors. These sensations are more frequently found in patients with OCD plus Tourette's disorder than in patients with OCD alone. Mental sensations include urge only, energy release (mental energy that builds up and needs to be discharged), incompleteness, and just-right perceptions. They are all more frequently found in patients with OCD plus Tourette's disorder than in patients with OCD alone. C1 Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Santa Casa Med Sch, Dept Psychiat, Sao Paulo, Brazil. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. McLean Hosp, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Boston, MA USA. Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. RP Miguel, EC (reprint author), USP, Fac Med, Hosp Clin, Inst Psiquiat, Rua Ovidio Pires Campos S-N, BR-05430010 Sao Paulo, Brazil. RI Miguel, Euripedes/B-2871-2008; OI Rosario, Maria Conceicao/0000-0002-9687-0072 NR 41 TC 133 Z9 137 U1 1 U2 12 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 FEB PY 2000 VL 61 IS 2 BP 150 EP 156 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 293BC UT WOS:000085830800019 PM 10732667 ER PT J AU Rothschild, AJ Shindul-Rothschild, JA Viguera, A Murray, M Brewster, S AF Rothschild, AJ Shindul-Rothschild, JA Viguera, A Murray, M Brewster, S TI Comparison of the frequency of behavioral disinhibition on alprazolam, clonazepam, or no benzodiazepine in hospitalized psychiatric patients SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID BORDERLINE PERSONALITY-DISORDER; HOSTILITY; DYSCONTROL; DEPRESSION; ANXIETY AB Several case reports have suggested that treatment with the benzodiazepine alprazolam can result in behavioral disinhibition. To address this question, the authors reviewed the medical records (blinded to all pharmacologic treatments the patients received) of 323 psychiatric inpatients treated with alprazolam (108 patients), clonazepam (111 patients), or no benzodiazepine (104 patients) between January 1989 and June 1990, During benzodiazepine treatment, there were no significant differences among the three groups on the following measures: (I) acts of self-injury (alprazolam, 1.9%; clonazepam, 1.8%; no benzodiazepine, 2.9%); (2) assaults on staff or other patients (alprazolam, 0%; clonazepam, 0.9%; no benzodiazepine, 1.0%); (3) need for seclusion or restraints (alprazolam, 3.7%; clonazepam, 6.3%; no benzodiazepine, 4.8%); (4) increased need for observation by hospital staff (alprazolam, 8.3%; clonazepam, 7.2%; no benzodiazepine, 6.7%); and (5) decrease in patient privileges (alprazolam, 11.1%; clonazepam, 12.6%; no benzodiazepine, 11.5%), The results indicate that in an inpatient psychiatric population, the frequency of behavioral disturbances with alprazolam, clonazepam, or no benzodiazepine does not differ. This suggests that alprazolam does not possess unique disinhibitory activity. Second, these data suggest that disinhibition may not be an important clinical problem associated with benzodiazepine use. The design of the study does not allow one to establish a relationship between the prescription of the benzodiazepine and worsening behaviors, and the findings need to be interpreted conservatively because it was a retrospective review of a heterogeneous population. However, it is noteworthy that the incidence of adverse events was low even in this high-risk population, and because the patients were in the hospital and under constant observation, the objective assessment of so-called paradoxical reactions was undertaken in a controlled setting. C1 Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. McLean Hosp, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Boston Coll, Sch Nursing, Chestnut Hill, MA 02167 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Rothschild, AJ (reprint author), Univ Massachusetts, Sch Med, Dept Psychiat, 361 Plantat St, Worcester, MA 01655 USA. NR 29 TC 23 Z9 23 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 2000 VL 20 IS 1 BP 7 EP 11 DI 10.1097/00004714-200002000-00003 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 275TM UT WOS:000084836300003 PM 10653202 ER PT J AU McDermott, PA Alterman, AI Cacciola, JS Rutherford, MJ Newman, JP Mulholland, EM AF McDermott, PA Alterman, AI Cacciola, JS Rutherford, MJ Newman, JP Mulholland, EM TI Generality of Psychopathy Checklist - Revised factors over prisoners and substance-dependent patients SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID ANTISOCIAL PERSONALITY-DISORDER; REFINEMENT; ALCOHOLISM; ROTATION; ABUSE AB The Psychopathy Checklist-Revised (PCL-R; R. D. Hare, 1991) is an often-used device for assessment of adult antisociality. This research examined generalizability by replicating the 2-factor model for a sample of 326 male prisoners and assessing its congruence and relative reliability and specificity among 620 substance-dependent patients. Generality was assessed also across addiction subtypes (opioid, cocaine, and alcohol), age, gender, and ethnicity. The 2-factor model was found inappropriate for the substance-dependent samples, whereas a unidimensional model represented by the PCL-R total score was found generalizable across prison and substance-dependent samples. C1 Univ Penn, Grad Sch Educ, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Washington, Alcohol & Drug Inst, Seattle, WA 98195 USA. Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA. RP McDermott, PA (reprint author), Univ Penn, Grad Sch Educ, 3700 Walnut St, Philadelphia, PA 19104 USA. NR 33 TC 28 Z9 29 U1 2 U2 4 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 FEB PY 2000 VL 68 IS 1 BP 181 EP 186 DI 10.1037//0022-006X.68.1.181 PG 6 WC Psychology, Clinical SC Psychology GA 287FJ UT WOS:000085495600021 PM 10710854 ER PT J AU Lingstrom, P van Ruyven, FOJ van Houte, J Kent, R AF Lingstrom, P van Ruyven, FOJ van Houte, J Kent, R TI The pH of dental plaque in its relation to early enamel caries and dental plaque flora in humans SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE dental plaque; pH; mutans streptococci; caries ID MUTANS STREPTOCOCCI; SUCROSE CONCENTRATION; ROOT SURFACES; SOUND; ACIDOGENESIS; DENTITION; ETIOLOGY; LESIONS; SALIVA AB Dental caries appears to result from the action of multiple, interrelated factors. A companion study dealt: with the plaque-flora/caries relationship (van Ruyven ed al., 2000). The plaque-pH/caries relationship is the subject of this study. Since both studies involve the same subjects, plaques, and tooth surfaces, data on the examined factors have also been integrated. In vivo plaque pH determinations (microelectrode) were done on buccal sound (s) and "white-spot" (ws) caries surfaces in a selected dentition area in a low-caries (no ws) and higher caries subject group. The pH response to sugar was evaluated before and after a sugar rinse, a local sugar application, or sucking on a sugary lozenge. pH pro files with sugar rinsing and normal or limited salivary flow conditions, showed progressively decreasing plaque pH values at various time points in the order of low-caries subjects (s sites), higher-caries subjects (s sites), higher-caries subjects (s + ws sites), and higher-caries subjects (ws sites). The minimum pH values showed the same trend. Analyses of all data indicated only a statistical difference for minimum values for s sites in low-caries subjects vs. ws sites in higher-caries subjects, and for s and ws sites in the latter. Local sugar application and sucking on a sugary lozenge induced smaller pH drops than sugar rinsing; such suboptimal sugar exposure caused a disappearance of the difference between the minimum pH values for s and WS sites observed with sugar rinsing in the higher-caries subjects. Initial plaque pH values were similar regardless of subject or tooth caries status. The values were also not correlated with the plaque levels of strongly iodophilic polysaccharide-storing bacteria. Collectively, both studies indicate that increasing subject caries status is characterized by increasing plaque levels of highly-acid-tolerant, acidogenic bacteria and an increasing plaque-pH-lowering potential and support the dynamic relationship between these parameters. C1 Univ Gothenburg, Fac Odontol, Dept Cariol, SE-40530 Gothenburg, Sweden. Forsyth Inst, Dept Oral Microbiol, Boston, MA 02115 USA. Forsyth Inst, Dept Clin Trials & Human Experimentat, Boston, MA 02115 USA. RP Lingstrom, P (reprint author), Univ Gothenburg, Fac Odontol, Dept Cariol, POB 450, SE-40530 Gothenburg, Sweden. FU NIDCR NIH HHS [DE 07009, DE 07493] NR 33 TC 43 Z9 53 U1 6 U2 18 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD FEB PY 2000 VL 79 IS 2 BP 770 EP 777 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 287FF UT WOS:000085495300011 PM 10728979 ER PT J AU Macuch, PJ Tanner, ACR AF Macuch, PJ Tanner, ACR TI Campylobacter species in health, gingivitis, and periodontitis SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE Campylobacter; health; gingivitis; periodontal disease; microbiology ID BACTEROIDES-GRACILIS; EIKENELLA-CORRODENS; WOLINELLA-RECTA; SP-NOV; MICROBIOTA; CONCISUS; LESIONS; BACTERIOLOGY; UREOLYTICUS; IDENTIFICATION AB At least seven Campylobacter species have been identified from subgingival sites. Campylobacter rectus has been implicated as a periodontal pathogen; however, association with periodontal infections of other Campylobacter species, especially the newly described Campylobacter showae, is unclear. This study examined which Campylobacter species were associated with periodontal health and disease. Subgingival Campylobacter species from initial and established periodontitis were compared with species from periodontally healthy subjects, including subjects with gingivitis. Campylobacter species were isolated on selective media and identified by whole-cell protein profiles (SDS-PAGE). Except for C. rectus, Campylobacter levels were frequently below the detection limit (2-5% of the microbiota) of non-selective culture methods. C. rectus and C. showae, including Campylobacter X, were found more frequently and in higher levels from diseased than from healthy periodontal sites. C. gracilis was the dominant Campylobacter species found in relatively shallow pockets; however, its presence was unrelated to periodontal health or disease. C. concisus was isolated in higher proportions from relatively shallow and healthy sites, compared with deeper pockets. C. curvus was unrelated to periodontal health or disease. Analysis of the study data confirmed the relationship of C. rectus with diseased subgingival sites and indicated that C. showae may also be associated with periodontal disease. C1 Altran Corp, Boston, MA USA. Forsyth Inst, Boston, MA 02115 USA. RP Tanner, ACR (reprint author), Altran Corp, Boston, MA USA. FU NIDCR NIH HHS [DE 09513] NR 40 TC 63 Z9 64 U1 0 U2 2 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD FEB PY 2000 VL 79 IS 2 BP 785 EP 792 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 287FF UT WOS:000085495300013 PM 10728981 ER PT J AU Biddinger, PD Nadel, ES Brown, DFM AF Biddinger, PD Nadel, ES Brown, DFM TI Blunt trauma with a medical twist SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID CARDIAC TROPONIN-I; CONTUSION C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Biddinger, PD (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD FEB PY 2000 VL 18 IS 2 BP 247 EP 251 DI 10.1016/S0736-4679(99)00203-6 PG 5 WC Emergency Medicine SC Emergency Medicine GA 286ZL UT WOS:000085478700019 PM 10699531 ER PT J AU Romero, AD Green, DB Wucherpfennig, AL AF Romero, AD Green, DB Wucherpfennig, AL TI Heat transfer to the periodontal ligament during root obturation procedures using an in vitro model SO JOURNAL OF ENDODONTICS LA English DT Article ID THERMOMECHANICAL COMPACTION; CANAL OBTURATION; TEMPERATURES; SURFACE AB It appears to be important to avoid thermal injury to the periodontal ligament when using heated gutta-percha techniques such as "System B," An in vitro model was developed, consisting of an extracted human tooth rooted in an artificial periodontal ligament (PDL) and alveolar socket, which allowed us to measure the temperature transferred to the root surface. The teeth were instrumented and subsequently embedded in alginate to simulate the PDL, Medium gutta-percha points were fit, sealer was applied, and a fine Buchanan plugger was used for condensation. Temperature measurements were taken simultaneously at the apex and 5 mm from the apex during obturation with two fine gauge thermocouples connected to a digital thermometer, The average temperature increase was similar to 1 degrees C at the apex and similar to 2 degrees C at the 5 mm mark. The resulting temperature increases appear to be lower than previously reported by other investigators (Hardie, 1986, 1987; Barkhordar et at., 1990; Weller et at., 1991; Lee et al,, 1998), who did not allow for the heat disseminating effect of the PDL. C1 Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA. Forsyth Dent Ctr, Boston, MA 02115 USA. RP Wucherpfennig, AL (reprint author), Tufts Univ, Sch Dent Med, Dept Endodont, 1 Kneeland St, Boston, MA 02111 USA. NR 14 TC 17 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0099-2399 J9 J ENDODONT JI J. Endod. PD FEB PY 2000 VL 26 IS 2 BP 85 EP 87 DI 10.1097/00004770-200002000-00006 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 279EV UT WOS:000085032200006 PM 11194378 ER PT J AU Collins, MM Stafford, RS Barry, MJ AF Collins, MM Stafford, RS Barry, MJ TI Age-specific patterns of prostate-specific antigen testing among primary care physician visits SO JOURNAL OF FAMILY PRACTICE LA English DT Article; Proceedings Paper CT Meeting of the National-Society-of-General-Internal-Medicine CY APR, 1998 CL CHICAGO, ILLINOIS SP Natl Soc Gen Internal Med DE prostate; prostate-specific antigen; physicians; family ID CANCER; BENEFITS; RISKS AB BACKGROUND Early detection of prostate cancer is thought to effective, and indirect evidence suggests that men aged 50 to G9 years will benefit most while those aged 70 and older will benefit least from it. The goal of our study was to describe usual care patterns for prostate-specific antigen (PSA) testing by primary; care physicians in the United States, METHODS We analyzed office visits made by adult men to family physicians, general internists, general practitioners, and geriatricians recorded by thr 1995 and 1996 National Ambulatory Medical Care Surveys. Our outcome measure a as the probability of a primary care physician ordering a PSA tent during a visit. RESULTS Seventeen percent of the tests reported were among men aged younger than 50 years, 50% were for men aged 50 to 69 years, and 33% were for men aged 70 years and older. The frequency of PSA testing was highest during visits by men aged 60 to 64 years (7.1%), 65 to 69 years (7.0%), 70 to 74 years (7.0%), and 75 to 79 years (6.3%) but lower for men aged older than 80 years (3.1%). CONCLUSIONS Our findings suggest that during the mid-1990s prostate cancer screening decisions by primary care physicians were not sensitive to patients' ages. C1 Massachusetts Gen Hosp, Div Gen Med, Med Serv, Boston, MA 02114 USA. RP Collins, MM (reprint author), Massachusetts Gen Hosp, Div Gen Med, Med Serv, 50 Staniford St, Boston, MA 02114 USA. NR 23 TC 24 Z9 24 U1 1 U2 1 PU DOWDEN PUBLISHING CORP PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD FEB PY 2000 VL 49 IS 2 BP 169 EP 172 PG 4 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 314VH UT WOS:000087077900009 ER PT J AU Kiertscher, SM Luo, J Dubinett, SM Roth, MD AF Kiertscher, SM Luo, J Dubinett, SM Roth, MD TI Tumors promote altered maturation and early apoptosis of monocyte-derived dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; ANTIGEN-PRESENTING FUNCTION; T-HELPER CELLS; HUMAN BLOOD; DOWN-REGULATION; UP-REGULATION; CUTTING EDGE; IN-VIVO; CANCER; ACTIVATION AB Tumors produce a number of immunosuppressive factors that block the maturation of CD34(+) stem cells into dendritic cells (DC), We hypothesized that tumors might also interfere with the maturation and/or function of human monocyte-derived DC. In contrast to stem cells, we found that CD14(+) cells responded to tumor culture supernatant (TSN) by increasing expression of APC surface markers, up-regulating nuclear translocation of RelB, and developing allostimulatory activity. Although displaying these characteristics of mature DC, TSN-exposed DC lacked the capacity to produce IL-12, did not acquire full allostimulatory activity, and rapidly underwent apoptosis. The effects of TSN appeared to be specific for maturing DC, and were not reversed by Abs against known DC regulatory factors including IL-10, vascular endothelial growth factor, TGF-beta, or PGE(2). Supernatants collected from nonmalignant cell sources had no effect on DC maturation. The altered maturation and early apoptosis of monocyte-derived DC may represent another mechanism by which tumors evade immune detection. C1 Univ Calif Los Angeles, Sch Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Kiertscher, SM (reprint author), Univ Calif Los Angeles, Sch Med, Div Pulm & Crit Care Med, 37-131 CHS, Los Angeles, CA 90095 USA. FU NCI NIH HHS [R01 CA71818] NR 50 TC 172 Z9 192 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2000 VL 164 IS 3 BP 1269 EP 1276 PG 8 WC Immunology SC Immunology GA 277AJ UT WOS:000084910300018 PM 10640740 ER PT J AU Reilly, CM Oates, JC Cook, JA Morrow, JD Halushka, PV Gilkeson, GS AF Reilly, CM Oates, JC Cook, JA Morrow, JD Halushka, PV Gilkeson, GS TI Inhibition of mesangial cell nitric oxide in MRL/lpr mice by prostaglandin J(2) and proliferator activation receptor-gamma agonists SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MURINE LUPUS NEPHRITIS; RENAL THROMBOXANE PRODUCTION; SQUAMOUS CARCINOMA-CELLS; MRL/MP-LPR/LPR MICE; DELTA(12)-PROSTAGLANDIN J(2); PERITONEAL-MACROPHAGES; AUTOIMMUNE-DISEASE; INDUCTION; SYNTHASE; EXPRESSION AB MRL/Mp-lpr/lpr (MRL/lpr) mice develop immune complex glomerulonephritis similar to human lupus, Glomerular mesangial cells are key modulators of the inflammatory response in lupus nephritis, When activated, these cells secrete inflammatory mediators including NO and products of cyclooxygenase perpetuating the local inflammatory response. P6J(2), a product of cyclooxygenase, is a potent in vitro inhibitor of macrophage inflammatory functions and is postulated to function as an in vivo inhibitor of macrophage-mediated inflammatory responses, We hypothesized that in lupus, a defect in PGJ(2), production allows the inflammatory response to continue unchecked. To test this hypothesis, mesangial cells were isolated from MRL/lpr and BALB/c mice and stimulated with IL-1 beta or LPS plus IFN-gamma, In contrast to the 2.- to 3-fold increase in PGJ(2) production by stimulated BALB/c mesangial cells, supernatant PGJ(2) did not increase in MRL/lpr mesangial cell cultures. NO production in stimulated MRL/lpr and BALB/c mesangial cells, was blocked by PGJ(2) and pioglitazone, These studies suggest that abnormalities in PGJ(2) production are present in MRL/lpr mice and may be linked to the heightened activation state of mesangial cells in these mice. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pharmacol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Physiol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Med Res Serv, Charleston, SC 29403 USA. Vanderbilt Univ, Sch Med, Nashville, TN 37232 USA. RP Gilkeson, GS (reprint author), Med Univ S Carolina, Dept Med, 912 Clin Sci Bldg,171 Ashley Ave, Charleston, SC 29425 USA. FU NIAMS NIH HHS [K08 AR002193]; NIDDK NIH HHS [DK 48831]; NIGMS NIH HHS [GM 15431, GM 42056] NR 44 TC 60 Z9 64 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 FEB 1 PY 2000 VL 164 IS 3 BP 1498 EP 1504 PG 7 WC Immunology SC Immunology GA 277AJ UT WOS:000084910300045 PM 10640767 ER PT J AU Tsoukas, MM Gonzalez, S Flotte, TJ Anderson, RR Sherwood, ME Kollias, N AF Tsoukas, MM Gonzalez, S Flotte, TJ Anderson, RR Sherwood, ME Kollias, N TI Wavelength and fluence effect on vascular damage with photodynamic therapy on skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE benzoporphyrin derivative monoacid ring A photoxicity; skin histology ID LIGHT-DOSE DEPENDENCE; BENZOPORPHYRIN DERIVATIVES; TUMOR; PHOTOSENSITIVITY; DRUG; MICE AB Normal skin phototoxicity is clinically predictable during photodynamic therapy with light at 690 and 458 nm wavelengths, in the first 5 h after intravenous bolus infusion of benzoporphyrin derivative monoacid ring A. This study goal was to determine histologic milestones that lead to tissue necrosis with exposure to red (690 nm) and blue (458 nm) light. The threshold doses for skin necrosis on rabbits were equal at both wavelengths. Lower, equal to, and higher than threshold fluences were delivered in duplicates at hourly intervals, with 40% increments, at constant irradiance. Pathology specimens from irradiated and control sites, were collected at 0, 2, 7, 24, 48 h, and 2 wk after treatment and were paired to equivalent treated sites for clinical evaluation. Immediately after irradiation, at 690 and 458 nm thresholds, light microscopy showed stasis and inflammatory infiltrate in the papillary dermis, respectively; electron microscopy demonstrated pericyte and endothelial cell damage - greater at 690 than 458 nm, At day 1, vascular stasis in the dermis showed a steeper dose-response with red than blue light, and led to necrosis of skin appendages (day 1) and epidermis (days 1-2) at both wavelengths. Subthreshold fluences induced similar, but significantly milder (p < 0.05) changes and epidermis recovered, Skin necrosis, at threshold fluences in photodynamic therapy with benzoporphyrin derivative mono-acid ring A, was primarily due to vascular compromise to a depth potentially reaching the subcutaneous muscle at 690 nm, whereas at 458 nm vascular damage was confined to upper dermis, This system facilitates selective destruction of skin vasculature, sparing normal epidermis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. RP Kollias, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. NR 20 TC 18 Z9 20 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 2000 VL 114 IS 2 BP 303 EP 308 DI 10.1046/j.1523-1747.2000.00872.x PG 6 WC Dermatology SC Dermatology GA 285AN UT WOS:000085366100010 PM 10651990 ER PT J AU Kalume, DE Stenflo, J Czerwiec, E Hambe, B Furie, BC Furie, B Roepstorff, P AF Kalume, DE Stenflo, J Czerwiec, E Hambe, B Furie, BC Furie, B Roepstorff, P TI Structure determination of two conotoxins from Conus textile by a combination of matrix-assisted laser desorption/ionization time-of-flight and electrospray ionization mass spectrometry and biochemical methods SO JOURNAL OF MASS SPECTROMETRY LA English DT Article; Proceedings Paper CT 46th ASMS Conference CY MAY 31-JUN 04, 1998 CL ORLANDO, FLORIDA SP ASMS DE conotoxin; Conus textile; bromotryptophan; matrix-assisted laser desorption/ionization mass spectrometry; electrospray ionization mass spectrometry ID GAMMA-CARBOXYGLUTAMIC ACID; VITAMIN-K; ACETYLCHOLINE-RECEPTORS; PSEUDOMONAS-FRAGI; PEPTIDE TOXIN; ION-CHANNEL; VENOM; GLYCOPROTEINS; TRYPTOPHAN; GEOGRAPHUS AB Two highly modified conotoxins from the mollusc Conus textile, epsilon-TxIX and Gla(1)-TxVI, were characterized by matrix-assisted laser desorption/ionization and electrospray mass spectrometry and also by electrospray ionization tandem and triple mass spectrometry in combination with enzymatic cleavage and chemical modification reactions. The mass spectrometric studies allowed the confirmation of the sequence determined by Edman degradation and assignment of unidentified amino acid residues, among which bromotryptophan residues and an O-glycosylated threonine residue were observed. Methyl esterification was found necessary for the site-specific assignment of the Gla residues in the peptides, Copyright (C) 2000 John Wiley & Sons, Ltd. C1 Odense Univ, Dept Mol Biol, Univ So Denmark, DK-5230 Odense M, Denmark. Univ Brasilia, Ctr Brasileiro Sequenciamento Prot, Lab Bioquim & Quim Prot, Dept Biol Celular, BR-70910900 Brasilia, DF, Brazil. Malmo Univ Hosp, Dept Clin Chem, Univ Lund, S-20502 Malmo, Sweden. Marine Biol Lab, Woods Hole, MA 02543 USA. Harvard Univ, Sch Med, Ctr Hemostasis & Thrombosis Res, BIDMC, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Roepstorff, P (reprint author), Odense Univ, Dept Mol Biol, Univ So Denmark, Campusvej 55, DK-5230 Odense M, Denmark. NR 43 TC 43 Z9 47 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1076-5174 J9 J MASS SPECTROM JI J. Mass Spectrom. PD FEB PY 2000 VL 35 IS 2 BP 145 EP 156 DI 10.1002/(SICI)1096-9888(200002)35:2<145::AID-JMS922>3.3.CO;2-9 PG 12 WC Biophysics; Chemistry, Organic; Spectroscopy SC Biophysics; Chemistry; Spectroscopy GA 282MN UT WOS:000085222800005 PM 10679974 ER PT J AU Sturm, S Koch, M White, FA AF Sturm, S Koch, M White, FA TI Cloning and analysis of a murine PIAS family member, PIAS gamma, in developing skin and neurons SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE PIAS gamma; PIAS family; murine homolog; tissue-specific expression; mouse development; neurons; skin; in situ hybridization ID TARGETED DISRUPTION; TYROSINE-PHOSPHATASE; GENE-EXPRESSION; PROTEIN; STAT1; INTERFERON; PATHWAY; INHIBITION; RESPONSES; ENCODES AB Signal transducer and activator of transcription (STAT) proteins are latent cytoplasmic transcription factors that become activated in response to stimulation by various cytokines. Recently a new family of five structurally related proteins, called PIAS (Protein Inhibitor of Activated STAT) has been identified as potentially important downregulators of this pathway. Members of the PIAS family of STAT inhibitors may play a prominent role in the downregulation of STAT-mediated signaling processes. In this article we describe the isolation of the cDNA and expression of the gene for the murine homologue of the human STAT inhibitor family member PIAS gamma. The cDNA for mPIAS gamma encodes a protein of 507 amino acids that is highly homologous to the human protein and is expressed in the mouse as early as d 7.5 of gestation. In situ hybridizations of staged mouse embryos localized the transcript for the PIAS gamma gene to the limbs, neuroepithelium, and the inner root sheath of the hair follicle, suggesting a role in the development of these structures. Immunostaining studies with a polyclonal antibody (PAb) recognizing human PIAS gamma localized the protein in the hair follicle of human scalp hair and in monkey neuronal cells. Thus PIAS gamma exhibits a highly selective pattern of expression, suggesting that it modulates the response of cells to developmental cues. C1 Vet Affairs Med Ctr, Neurosci Res Ctr, West Haven, CT 06516 USA. Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Wyeth Ayerst Res, Dept Oncol, Pearl River, NY 10965 USA. RP White, FA (reprint author), Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. RI White, Fletcher/F-2895-2012 NR 42 TC 14 Z9 17 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD FEB-APR PY 2000 VL 14 IS 1-2 BP 107 EP 121 DI 10.1385/JMN:14:1-2:107 PG 15 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 319EM UT WOS:000087328600012 PM 10854042 ER PT J AU Gao, QS Memmott, J Lafyatis, R Stamm, S Screaton, G Andreadis, A AF Gao, QS Memmott, J Lafyatis, R Stamm, S Screaton, G Andreadis, A TI Complex regulation of tau exon 10, whose missplicing causes frontotemporal dementia SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE microtubule-associated protein tau; expression pattern of regulated isoforms; microtubule binding domain; regulation of alternative splicing; frontotemporal dementia ID PRE-MESSENGER-RNA; IMMUNODEFICIENCY-VIRUS TYPE-1; PERIPHERAL NERVOUS-SYSTEM; FIBRONECTIN EDA EXON; OF-WHITE-APRICOT; PROTEIN-TAU; SR PROTEINS; SPLICING ENHANCER; CHROMOSOMAL LOCALIZATION; FRASIER-SYNDROME AB Tau is a microtubule-associated protein whose transcript undergoes complex regulated splicing in the mammalian nervous system. Exon 10 of the gene is an alternatively spliced cassette that is adult-specific and that codes for a microtubule binding domain. Recently, mutations that affect splicing of exon 10 have been shown to cause inherited frontotemporal dementia (FTDP), In this study, we establish the endogenous expression patterns of exon 10 in human tissue; by reconstituting naturally occurring FTDP mutants in the homologous context of exon 10, we show that the cis determinants of exon 10 splicing regulation include an exonic silencer within the exon, its 5' splice site, and the relative affinities of its flanking exons to it. By cotransfections in vivo, we demonstrate that several splicing regulators affect the ratio of tau isoforms by inhibiting exon 10 inclusion. C1 EK Shriver Ctr Mental Retardat, Dept Biomed Sci, Waltham, MA 02454 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Med, Arthrit Ctr, Boston, MA USA. Max Planck Inst Neurobiol, Martinsried, Germany. John Radcliffe Hosp, Inst Mol Med, Human Immunol Grp, Oxford, England. RP Andreadis, A (reprint author), EK Shriver Ctr Mental Retardat, Dept Biomed Sci, 200 Trapelo Rd, Waltham, MA 02454 USA. FU NICHD NIH HHS [P01 HD05515] NR 88 TC 65 Z9 65 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 2000 VL 74 IS 2 BP 490 EP 500 DI 10.1046/j.1471-4159.2000.740490.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 274KU UT WOS:000084765700005 PM 10646499 ER PT J AU Nakai, M Qin, ZH Chen, JF Wang, YM Chase, TN AF Nakai, M Qin, ZH Chen, JF Wang, YM Chase, TN TI Kainic acid-induced apoptosis in rat striatum is associated with nuclear factor-kappa B activation SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE kainic acid; apoptosis; neurodegeneration; nuclear transcription factor-kappa B (NF-kappa B); I kappa B-alpha; NF-kappa B p65; c-Myc; p53 ID METHYL-D-ASPARTATE; CEREBELLAR GRANULE NEURONS; CEREBRAL-ARTERY OCCLUSION; MESSENGER-RNA EXPRESSION; BETA-AMYLOID PRECURSOR; CORTICAL CELL-CULTURES; DNA FRAGMENTATION; TUMOR-SUPPRESSOR; QUINOLINIC ACID; HUNTINGTONS-DISEASE AB The present study evaluated whether nuclear factor-kappa B (NF-kappa B) activation contributes to the apoptotic-like death of striatal neurons induced by kainic acid (KA) receptor stimulation. Intrastriatally infused KA (1.25-5.0 nmol) produced substantial neuronal loss as indicated by an 8-73% decrease in 67-kDa glutamic acid decarboxylase (p < 0.05), KA (1.25-5.0 nmol) elicited internucleosomal DNA fragmentation that was inhibited by the AMPA/KA receptor antagonist NBQX (1,2,3,4-tetrahydro-6-nitro-2,3-dibenzo[f]quinoxaline-7-sulfonamide) but not by the NMDA receptor antagonist MK-801. A decrease in I kappa B-alpha. protein levels, which was accompanied by an increase in NF-kappa B binding activity, was found from 6 to 72 h after KA (2.5 nmol) infusion. NF-kappa B was composed mainly of p65 and c-Rel as revealed by supershift assay. In addition, c-Myc and p53 increased from five- to sevenfold from 24 to 72 h after KA (2.5 nmol) administration. Immunohistochemistry revealed high levels of c-Myc and p53 immunoreactivity, mainly in medium-sized striatal neurons. Pretreatment with the cell-permeable recombinant peptide NF-kappa B SN50 (5-20 mu g) blocked NF-kappa B nuclear translocation, but had no effect on AP-I binding. NF-kappa B SN50 also inhibited the KA-induced up-regulation of c-Myc and p53, as well as internucleosomal DNA fragmentation. The apoptotic-like destruction of rat striatal neurons induced by KA receptor stimulation thus appears to involve biochemical mechanisms similar to those mediating: the excitotoxic response to NMDA receptor stimulation. The present results provide additional support for the view that NF-kappa B activation contributes to c-Myc and p53 induction and subsequent apoptosis in an excitotoxic model of Huntington's disease. C1 NINCDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Mol Neurobiol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Chase, TN (reprint author), NINCDS, Expt Therapeut Branch, NIH, Bldg 10,Rm 5C103,10 Ctr Dr,MSC 1406, Bethesda, MD 20892 USA. NR 72 TC 91 Z9 96 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 2000 VL 74 IS 2 BP 647 EP 658 DI 10.1046/j.1471-4159.2000.740647.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 274KU UT WOS:000084765700022 PM 10646516 ER PT J AU Clark, RSB Kochanek, PM Watkins, SC Chen, MZ Dixon, CE Seidberg, NA Melick, J Loeffert, JE Nathaniel, PD Jin, KL Graham, SH AF Clark, RSB Kochanek, PM Watkins, SC Chen, MZ Dixon, CE Seidberg, NA Melick, J Loeffert, JE Nathaniel, PD Jin, KL Graham, SH TI Caspase-3 mediated neuronal death after traumatic brain injury in rats SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE apoptosis; cysteine protease; N-benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethyl ketone; programmed cell death ID CONTROLLED CORTICAL IMPACT; APOPTOTIC CELL-DEATH; INTERLEUKIN-1-BETA CONVERTING-ENZYME; COGNITIVE DEFICITS; CEREBRAL-ISCHEMIA; TRANSGENIC MICE; MESSENGER-RNA; EXPRESSION; INHIBITION; PROTEIN AB During programmed cell death, activation of caspase-3 leads to proteolysis of DNA repair proteins, cytoskeletal proteins, and the inhibitor of caspase-activated deoxyribonuclease, culminating in morphologic changes and DNA damage defining apoptosis, The participation of caspase-3 activation in the evolution of neuronal death after traumatic brain injury in rats was examined. Cleavage of pro-caspase-3 in cytosolic cellular fractions and an increase in caspase-3-like enzyme activity were seen in injured brain versus control. Cleavage of the caspase-3 substrates DNA-dependent protein kinase and inhibitor of caspase-activated deoxyribonuclease and co-localization of cytosolic caspase-3 in neurons with evidence of DNA fragmentation were also identified. Intracerebral administration of the caspase-3 inhibitor N-benzyloxycarbonyl-Asp-Glu-Val-Asp-fluomethyl ketone (480 ng) after trauma reduced caspase-3-like activity and DNA fragmentation in injured brain versus vehicle at 24 h. Treatment with N-benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethyl ketone for 72 h (480 ng/day) reduced contusion size and ipsilateral dorsal hippocampal tissue loss at 3 weeks but had no effect on functional outcome versus vehicle. These data demonstrate that caspase-3 activation contributes to brain tissue loss and downstream biochemical events that execute programmed cell death after traumatic brain injury. Caspase inhibition may prove efficacious in the treatment of certain types of brain injury where programmed cell death occurs. C1 Univ Pittsburgh, Brain Trauma Res Ctr, Safar Ctr Resuscitat Res, Dept Anesthesiol & Crit Care Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Brain Trauma Res Ctr, Safar Ctr Resuscitat Res, Dept Pediat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Brain Trauma Res Ctr, Safar Ctr Resuscitat Res, Dept Cell Biol & Physiol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Brain Trauma Res Ctr, Safar Ctr Resuscitat Res, Dept Neurol Surg, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Brain Trauma Res Ctr, Safar Ctr Resuscitat Res, Dept Neurol, Pittsburgh, PA 15260 USA. VA Pittsburgh Hlth Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Clark, RSB (reprint author), Univ Pittsburgh, Brain Trauma Res Ctr, Safar Ctr Resuscitat Res, Dept Anesthesiol & Crit Care Med, 3434 5th Ave, Pittsburgh, PA 15260 USA. RI Kochanek, Patrick/D-2371-2015 OI Kochanek, Patrick/0000-0002-2627-913X FU NINDS NIH HHS [P50 NS30318, KO8 NS01946, R01 NS38620] NR 53 TC 233 Z9 246 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 2000 VL 74 IS 2 BP 740 EP 753 DI 10.1046/j.1471-4159.2000.740740.x PG 14 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 274KU UT WOS:000084765700032 PM 10646526 ER PT J AU Albers, DS Augood, SJ Park, LCH Browne, SE Martin, DM Adamson, J Hutton, M Standaert, DG Vonsattel, JPG Gibson, GE Beal, MF AF Albers, DS Augood, SJ Park, LCH Browne, SE Martin, DM Adamson, J Hutton, M Standaert, DG Vonsattel, JPG Gibson, GE Beal, MF TI Frontal lobe dysfunction in progressive supranuclear palsy: Evidence for oxidative stress and mitochondrial impairment SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE tauopathy; lipid peroxidation; mitochondrial dysfunction; malondialdehyde ID ALPHA-KETOGLUTARATE DEHYDROGENASE; POSITRON EMISSION TOMOGRAPHY; PROTEIN-TAU; NEUROFIBRILLARY TANGLES; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; COENZYME Q(10); HUMAN-BRAIN; DEMENTIA; HYPOMETABOLISM AB Recent data from our laboratory have shown a regionally specific increase in lipid peroxidation in postmortem progressive supranuclear palsy (PSP) brain. To extend this finding, we measured activities of mitochondrial enzymes as well as tissue malondialdehyde (MDA) levels in postmortem superior frontal cortex (Brodmann's area 9; SFC) from 14 pathologically confirmed cases of PSP and 13 age-matched control brains. Significant decreases (-39%) in alpha-ketoglutarate dehydrogenase complex/glutamate dehydrogenase ratio and significant increases (+36%) in tissue MDA levels were observed in the SFC in PSP; no differences in complex I or complex IV activities were detected. Together, these results suggest that mitochondrial dysfunction and lipid peroxidation may underlie the frontal metabolic and functional deficits observed in PSP. C1 Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. Cornell Univ, Coll Med, Burke Med Res Inst, White Plains, NY 10605 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. RP Albers, DS (reprint author), Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, Room A503,525 E 68th St, New York, NY 10021 USA. OI Standaert, David/0000-0003-2921-8348 FU NIMH NIH HHS [MH/NS 31862] NR 38 TC 71 Z9 71 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 2000 VL 74 IS 2 BP 878 EP 881 DI 10.1046/j.1471-4159.2000.740878.x PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 274KU UT WOS:000084765700047 PM 10646541 ER PT J AU Heimberger, AB Crotty, LE Archer, GE McLendon, RE Friedman, A Dranoff, G Bigner, DD Sampson, JH AF Heimberger, AB Crotty, LE Archer, GE McLendon, RE Friedman, A Dranoff, G Bigner, DD Sampson, JH TI Bone marrow-derived dendritic cells pulsed with tumor homogenate induce immunity against syngeneic intracerebral glioma SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE dendritic cells; glioma; central nervous system (CNS); encephalomyelitis ID GROWTH-FACTOR RECEPTOR; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; COLONY-STIMULATING FACTOR; CYTOTOXIC T-LYMPHOCYTES; CENTRAL-NERVOUS-SYSTEM; MONOCLONAL-ANTIBODIES; IN-VIVO; ANTITUMOR IMMUNITY; GLIOBLASTOMA CELLS; GENETIC-CONTROL AB To evaluate the efficacy and toxicity of dendritic cell (DC) based therapy for intracerebral gliomas, we utilized a cell Line derived from an astrocytoma that arose spontaneously in a VM/Dk mouse. This astrocytoma mirrors human gliomas phenotypically, morphologically and secretes transforming growth factor (TGF)-beta s, immunosuppressive cytokines secreted by human gliomas. Systemic vaccination of mice with DCs pulsed with tumor homogenate followed by intracranial tumor challenge produced a > 160% increase in median survival (p = 0.016) compared with mice vaccinated with PBS or unpulsed DCs (p = 0.083). Fifty percent of mice treated with pulsed DCs survived long-term. Immunologic memory was demonstrated by survival of mice rechallenged with tumor. Both cell-mediated and humoral immunity was induced. On histological examination only focal areas of demyelination at the tumor implantation site were present. There was no evidence that autoimmune encephalomyelitis was induced by DC vaccination. Therefore, in a murine model, vaccination with DCs pulsed with glioma tumor homogenate is a safe and effective therapy against a syngeneic glioma located in the immunologically privileged central nervous system (CNS). (C) 2000 Elsevier Science B.V. All rights reserved. C1 Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Div Neurosurg, Durham, NC 27710 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02215 USA. RP Sampson, JH (reprint author), Duke Univ, Med Ctr, Dept Pathol, Box 3807, Durham, NC 27710 USA. FU NCI NIH HHS [CA11898]; NINDS NIH HHS [NS20023] NR 52 TC 77 Z9 81 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD FEB 1 PY 2000 VL 103 IS 1 BP 16 EP 25 DI 10.1016/S0165-5728(99)00172-1 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 277MM UT WOS:000084937400003 PM 10674985 ER PT J AU Baba, H Doubell, TP Moore, KA Woolf, CJ AF Baba, H Doubell, TP Moore, KA Woolf, CJ TI Silent NMDA receptor-mediated synapses are developmentally regulated in the dorsal horn of the rat spinal cord SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SUBSTANTIA-GELATINOSA NEURONS; ACTION-POTENTIAL PROPAGATION; GLUTAMATERGIC SYNAPSES; PRIMARY AFFERENTS; MYELINATED AFFERENTS; NERVE INJURY; SENSITIZATION; HYPERALGESIA; HIPPOCAMPUS; CONDUCTANCE AB Silent NMDA receptor-mediated synapses are developmentally regulated in the dorsal horn of the rat spinal cord. J. Neurophysiol. 83: 955-962, 2000. In vitro whole cell patch-clamp recording techniques were utilized to study silent pure-N-methyl-D-aspartate (NMDA) receptor-mediated synaptic responses in lamina II (substantia gelatinosa, SG) and lamina III of the spinal dorsal hem. To clarify whether these synapses are present in the adult and contribute to neuropathic pain, transverse lumbar spinal cord slices were prepared from neonatal, naive adult and adult sciatic nerve transected rats. In neonatal rats, pure-NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) were elicited in SG neurons either by focal intraspinal stimulation (n = 15 of 20 neurons) or focal stimulation of the dorsal root (n = 2 of 7 neurons). In contrast, in slices from naive adult rats, no silent pure-NMDA EPSCs were recorded in SG neurons following focal intraspinal stimulation (n = 27), and only one pure-NMDA EPSC was observed in lamina III (n = 23). Furthermore, in rats with chronic sciatic nerve transection, pure-NMDA EPSCs were elicited by focal intraspinal stimulation in only 2 of 45 SG neurons. Although a large increase in A beta fiber evoked mixed alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA receptor-mediated synapses was detected after sciatic nerve injury, A beta fiber-mediated pure-NMDA EPSCs were not evoked in SG neurons by dorsal root stimulation. Pure-NMDA receptor-mediated EPSCs are therefore a transient, developmentally regulated phenomenon, and, although they may have a role in synaptic refinement in the immature dorsal horn, they are unlikely to be involved in receptive field plasticity in the adult. C1 Harvard Univ, Sch Med, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. RP Baba, H (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, Neural Plast Res Grp, MGH-E 4th Floor,149 13th St, Charlestown, MA 02129 USA. OI doubell, timothy/0000-0003-1054-5592 FU NINDS NIH HHS [NS-38253-01] NR 41 TC 54 Z9 56 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 2000 VL 83 IS 2 BP 955 EP 962 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 285TJ UT WOS:000085403900028 PM 10669507 ER PT J AU Melcher, JR Sigalovsky, IS Guinan, JJ Levine, RA AF Melcher, JR Sigalovsky, IS Guinan, JJ Levine, RA TI Lateralized tinnitus studied with functional magnetic resonance imaging: Abnormal inferior colliculus activation SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Review ID DORSAL COCHLEAR NUCLEUS; SALICYLATE-INDUCED CHANGES; EVENT-RELATED POTENTIALS; PRIMARY AUDITORY-CORTEX; NOISE-INDUCED TINNITUS; STEM-EVOKED-RESPONSES; HIGH-INTENSITY SOUND; BRAIN-STEM; NEURAL ACTIVITY; HEARING-LOSS AB Lateralized tinnitus studied with functional magnetic resonance imaging: abnormal inferior colliculus activation. J. Neurophysiol. 83. 1058-1072, 2000. Tinnitus, the perception of sound in the absence of external stimuli, is a common and often disturbing symptom that is not understood physiologically. This paper presents an approach for using functional magnetic resonance imaging (fMRI) to investigate the physiology of tinnitus and demonstrates that the approach is effective in revealing tinnitus-related abnormalities in brain function. Our approach as applied here included 1) using a masking noise stimulus to change tinnitus loudness and examining the inferior colliculus (IC) for corresponding changes in activity, 2) separately considering subpopulations with particular tinnitus characteristics, in this case tinnitus lateralized to one ear, 3) controlling for intersubject differences in hearing loss by considering only subjects with normal or near-normal audiograms, and 4) tailoring the experimental design to the characteristics of the tinnitus subpopulation under study. For lateralized tinnitus subjects, we hypothesized that sound-evoked activation would be abnormally asymmetric because of the asymmetry of the tinnitus percept. This was tested using two reference groups for comparison. nontinnitus subjects and nonlateralized tinnitus subjects. Binaural noise produced abnormally asymmetric IC activation in every lateralized tinnitus subject (n = 4). In reference subjects (n = 9), activation (i.e., percent change in image signal) in the right versus left IC did not differ significantly. Compared with reference subjects, lateralized tinnitus subjects showed abnormally low percent signal change in the IC contralateral, but not ipsilateral, to the tinnitus percept. Consequently, activation asymmetry (i.e., the ratio of percent signal change in the IC ipsilateral versus contralateral to the tinnitus percept) was significantly greater in lateralized tinnitus subjects as compared with reference subjects. Monaural noise also produced abnormally asymmetric IC activation in lateralized tinnitus subjects. Two possible models are presented to explain why IC activation was abnormally low contralateral to the tinnitus percept in lateralized tinnitus subjects. Both assume that the percept is associated with abnormally high ("tinnitus-related'') neural activity in the contralateral IC. Additionally, they assume that either 1) additional activity evoked by sound was limited by saturation or 2) sound stimulation reduced the level of tinnitus-related activity as it reduced the loudness of (i.e., masked) the tinnitus percept. In summary, this work demonstrates that fMRI can provide objective measures of lateralized tinnitus and tinnitus-related activation can be interpreted at a neural level. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Speech & Hearing Sci Program, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Melcher, JR (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [P01 DC000119-24, P01DC-00119, R21 DC003255-02, R21DC-03255, T32 DC000038-12, T32DC-00038] NR 119 TC 167 Z9 176 U1 0 U2 10 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 2000 VL 83 IS 2 BP 1058 EP 1072 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 285TJ UT WOS:000085403900038 PM 10669517 ER PT J AU Frohlich, DEC Chen, JL Neuberg, D Kehoe, KM Van den Abbeele, AD AF Frohlich, DEC Chen, JL Neuberg, D Kehoe, KM Van den Abbeele, AD TI When is hilar uptake of Ga-67-citrate indicative of residual disease after CHOP chemotherapy? SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE hilar uptake; Ga-67; non-Hodgkin's lymphoma; CHOP chemotherapy; radionuclide imaging ID NON-HODGKINS-LYMPHOMA; EMISSION COMPUTED-TOMOGRAPHY; LARGE-CELL LYMPHOMA; GA-67 SCINTIGRAPHY; MALIGNANT-LYMPHOMA; MASS; RECURRENCE; MANAGEMENT; PROGNOSIS; THERAPY AB The purpose of this study was to evaluate the prevalence and characterize the patterns of hilar uptake (HU) on Ga-67-citrate imaging after cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy regimens for non-Hodgkin's lymphoma (NHL), to differentiate hilar lymphoma (HL) from HU of benign etiology. Methods: A total of 930 studies (698 planar, 232 thoracic SPECT) was reviewed retrospectively in 100 NHL patients (29 low-grade, 60 intermediate-grade, and 11 high-grade) treated with CHOP and followed up longitudinally with serial gallium studies (planar: median, 7; range, 3-16 studies in 100 patients; SPECT: median, 1; range, 0-11 studies in 72 patients) over a median duration of 36 mo (range, 6-112 mo) from diagnosis. Clinical outcome and size changes over time on correlative CT and/or radiographs were used to evaluate benign versus malignant changes within the hila. Results: HU after CHOP was present in 79% of patients (90% confidence interval [CI], 71%-85%), with 33% showing HU on SPECT alone. Once present, HU persisted for a median of 27 mo (range, 2-84 mo) from onset. The prevalence of HU and HL at various time points was as follows: baseline HU, 52% with HL 60%; mid-CHOP HU, 59% with HL 2%; post-CHOP HU, 52% with HL 6%; follow-up HU, 76% with HL 9%. HU of benign etiology was not significantly correlated with CHOP dosage. HU was symmetric in 90% of patients (90% CI, 82%-95%) and less intense than the original disease in 89% of patients (90% CI, 80%-95%), and these features were highly predictive of benign etiology (negative predictive value [NPV], 98.6% if symmetric; NPV, 96.5% if less than original disease; NPV, 100% if both present). Asymmetric HU equal in intensity to the original disease, however, was highly predictive of HL (positive predictive Value [PPV], 87.5% if asymmetric; PPV, 85.7% if equal to original disease; PPV, 100% if both present). Conclusion: HU after CHOP is common (overall incidence, 79%), often seen only on SPECT, and most likely of benign etiology when symmetric and less intense than the original disease. Asymmetric HU that equals the intensity of the original disease, however, is a possible indicator for HL. C1 Harvard Univ, Div Nucl Med, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Div Biostat, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Van den Abbeele, AD (reprint author), Harvard Univ, Div Nucl Med, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 29 TC 4 Z9 4 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD FEB PY 2000 VL 41 IS 2 BP 269 EP 274 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 283CX UT WOS:000085259500015 PM 10688110 ER PT J AU Shah, U Walker, WA AF Shah, U Walker, WA TI Adverse host responses to bacterial toxins in human infants SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-for-Nutritional-Sciences CY APR 17-21, 1999 CL WASHINGTON, D.C. SP Amer Soc Nutr Sci DE bacterial toxin; enterocyte; developmental regulation ID RAT SMALL-INTESTINE; NEONATAL NECROTIZING ENTEROCOLITIS; STABLE ENTERO-TOXIN; ESCHERICHIA-COLI; CLOSTRIDIUM-DIFFICILE; CHOLERA-TOXIN; HUMAN-MILK; DEVELOPMENTAL REGULATION; ELECTROLYTE TRANSPORT; MICROVILLUS MEMBRANES AB Bacterial toxin interaction with the intestinal epithelium is regulated developmentally as well as by nutritional factors. II is the binding of bacterial toxins to the epithelium followed by several events that forms the basis of infantile diarrhea, a leading cause of morbidity and mortality world-wide. There has been increasing interest in bacterial toxin interaction with the enterocyte, postreceptor events that follow and the effect of developmental regulation on necrotizing enterocolitis. Diet and environmental factors can provide a major influence on bacterial-enterocyte interaction. Particularly important is the role of breast milk and its constituents, as well as probiotics, in this regard. The purpose of this review is to provide a brief overview on this complex interaction. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. RP Walker, WA (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 81 TC 10 Z9 10 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD FEB PY 2000 VL 130 IS 2 SU S BP 420S EP 425S PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 282MF UT WOS:000085221300039 PM 10721919 ER PT J AU Petropoulos, AE Cheney, ML AF Petropoulos, AE Cheney, ML TI Induction of facial muscle neurotization by temporalis muscle transposition: Literature review and animal model evaluation using horseradish peroxidase uptake SO JOURNAL OF OTOLARYNGOLOGY LA English DT Article DE facial; neurotization; paralysis; reinnervation; temporalis transposition; trigeminal ID SKELETAL-MUSCLE; PARALYZED FACE; NERVE; REHABILITATION; REINNERVATION; RABBIT AB Objective: To study the concept of facial muscle reinnervation from the trigeminal pathway following facial nerve paralysis. Design and Methods: We studied this phenomenon in an animal model using the neuronal marker, horseradish peroxidase (HRP). The temporalis transposition procedure was performed at varying intervals post facial nerve transection. To evaluate the trigeminal-facial reinnervation process and its timing, the zygomaricus major muscle was injected with HRP at varied periods after temporalis transposition, and histologic sections of the brainstem nuclei were examined for the final location of the MRP. Results: The presence of HRP in the trigeminal nucleus provided evidence of trigeminal-facial neurotization in those animals that underwent temporalis transposition up to 2 months following facial denervation and in which the HRP injection was performed 4 months after temporalis transposition. Conclusions: The findings of our pilot study are strongly supportive of the trigeminal-facial neurotization hypothesis in those animals that underwent temporalis transposition up to 2 months post facial denervation and in which 4 months were allowed thereafter for adequate neurite ingrowth and neurotization to occur. This suggests that the neurotrophic signals are greatest up to 2 months post denervation and denotes the optimal time for performance of reconstructive procedures. Future studies with a larger number of animals in each group will be necessary to ensure more potent statistical significance and to augment our experimental evidence that trigeminal-facial crossover does occur and can be used as an adjunctive concept to maximize early rehabilitation of the paralyzed face. C1 Harvard Univ, Massachusetts Eye & Ear Infirm,Sch Med, Dept Otolaryngol Head & Neck Surg, Div Facial Plast & Reconstruct Surg, Boston, MA 02114 USA. RP Cheney, ML (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm,Sch Med, Dept Otolaryngol Head & Neck Surg, Div Facial Plast & Reconstruct Surg, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [T32-DC00020] NR 54 TC 3 Z9 6 U1 0 U2 1 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0381-6605 J9 J OTOLARYNGOL JI J. Otolaryngol. PD FEB PY 2000 VL 29 IS 1 BP 40 EP 46 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 288BK UT WOS:000085541800009 PM 10709171 ER PT J AU Stark, LJ Jelalian, E Powers, SW Mulvihill, MM Opipari, LC Bowen, A Harwood, I Passero, MA Lapey, A Light, M Hovell, MF AF Stark, LJ Jelalian, E Powers, SW Mulvihill, MM Opipari, LC Bowen, A Harwood, I Passero, MA Lapey, A Light, M Hovell, MF TI Parent and child mealtime behavior in families of children with cystic fibrosis SO JOURNAL OF PEDIATRICS LA English DT Article ID INCREASING CALORIE CONSUMPTION; GROWTH AB Objectives: We investigated the hypothesis thai children with cystic fibrosis (CF) and their parents would show more maladaptive behaviors during dinner than children without CF and their parents. Study design: Children with CF (n = 32) and their parents were compared with 29 children without CF and their parents on the rate and frequency of parent-child behaviors during a typical dinner in the families' homes by using multivariate analyses of variance. Results: When the rate of behavior controlling for meal length, was examined, no differences were found between groups. However, parents of children with CF were found to differ from parents of control subjects in the frequency of direct and indirect commands (P<.05), coaxes (P<.01), physical prompts (P<.01), and feeding their child (P<.05). Children with CF were found to engage in more talk, spend more time away from the table, refuse food, and exhibit more noncompliance toward commands to eat than control children (P<.05 for all child variables). When behaviors were examined as a function of meal phase, parents of children with and without CF both showed an increase in commands (P<.01), coaxes (P<.05), feeds (P<.01), and physical prompts (P<.01) in the second half of the meal as compared with the first. Children with CF and the control children showed an increase in behaviors incompatible with eating during the second half of the meal compared tv;th the first (P<.01). When faster eaters were compared with slower eaters, faster eaters consumed a higher percentage of the recommended daily allowance of energy (P<.01) than slower eaters and showed a trend to be at higher weight percentiles for age and sex (P=.08) regardless of group (CF or control). Conclusions: Children with CF and their parents do not differ from children without CF and their parents in the rate of behaviors exhibited or types of strategies used to encourage:eating. However, children with CF and their parents engage in these behaviors more frequently. Our data do not support typical parenting behaviors as effective in meeting the CF dietary requirements. Additional support in the form of child behavior management training may be needed to assist parents in meeting their child's caloric requirements. C1 Univ Cincinnati, Coll Med,Childrens Hosp, Med Ctr, Div Psychol OSB4, Cincinnati, OH 45229 USA. Brown Univ, Sch Med, Dept Psychiat & Human Behav, Providence, RI 02912 USA. Brown Univ, Sch Med, Dept Pediat, Providence, RI 02912 USA. Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA USA. San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA. RP Stark, LJ (reprint author), Univ Cincinnati, Coll Med,Childrens Hosp, Med Ctr, Div Psychol OSB4, 3333 Burnet Ave, Cincinnati, OH 45229 USA. NR 21 TC 61 Z9 62 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 FEB PY 2000 VL 136 IS 2 BP 195 EP 200 DI 10.1016/S0022-3476(00)70101-6 PG 6 WC Pediatrics SC Pediatrics GA 283RP UT WOS:000085289400015 PM 10657825 ER PT J AU Lahorra, JA Torchiana, DF Hahn, C Bashour, CA Denenberg, AG Titus, JS Daggett, WM Geffin, GA AF Lahorra, JA Torchiana, DF Hahn, C Bashour, CA Denenberg, AG Titus, JS Daggett, WM Geffin, GA TI Recovery after cardioplegia in the hypertrophic rat heart SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE cardioplegia; glycogen; hyperthyroidism; hypertrophy; hypothyroidism; isomyosin; myocardial efficiency; myocardial oxygen consumption; pressure overload; stunning ID LEFT-VENTRICULAR HYPERTROPHY; CARDIAC-HYPERTROPHY; ENERGY-METABOLISM; PRESSURE-OVERLOAD; MYOSIN ISOENZYMES; ISCHEMIC-INJURY; AORTIC-STENOSIS; RABBIT HEART; MYOCARDIUM; EXPRESSION AB Background. Enhanced recovery after cardioplegic arrest has been observed in rat hearts with hypertrophy induced by hemodynamic overload. We hypothesize that this is related to altered characteristics of hypertrophied myocardium-reflected by increased V-3 isomyosin and glycolytic potential-other than increased left ventricular mass. Materials and methods. Isolated hearts from age-matched nonoperated and sham-operated control rats and from aortic-banded, hyperthyroid, and hypothyroid rats-groups in which hypertrophy and V-3 as a percentage of left ventricular myosin vary independently-underwent 2 h of multidose cardioplegic arrest at 8 degrees C followed by reperfusion at 37 degrees C, Left ventricular V-3 isomyosin was evaluated after separation by gel electrophoresis. Results. Moderate left ventricular hypertrophy was produced by aortic banding or hyperthyroidism and atrophy by hypothyroidism. V-3 isomyosin was increased in banded (28%) and hypothyroid (75%) rats compared to control (12%) and hyperthyroid rats (7%). Myocardial glycogen content closely paralleled %V-3. At 30 min of working reperfusion, functional recovery (assessed as percentage prearrest cardiac output) was 66 +/- 4 and 68 +/- 5% in control and hyperthyroid hearts and 81 +/- 2 and 80 +/- 5% in hearts from banded and hypothyroid rats (each P < 0.05 vs controls), respectively. At 30 min, hearts from banded and hypothyroid rats were also more efficient (as indexed by cardiac output at constant mean aortic pressure/myocardial oxygen consumption) than control and hyperthyroid hearts. Conclusions. The data suggest that recovery is related not to increased mass but to other changes in overload hypertrophy, Increased percentage V-3 isomyosin and glycogen reflect these changes and may themselves contribute to improved functional recovery after cardioplegic arrest, as may increased postischemic efficiency. (C) 2000 Academic Press. C1 Massachusetts Gen Hosp, Dept Surg, Surg Cardiovasc Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Geffin, GA (reprint author), Massachusetts Gen Hosp, Dept Surg, Surg Cardiovasc Unit, BUL-119,Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL12322, HL12777] NR 47 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC 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 FEB PY 2000 VL 88 IS 2 BP 88 EP 96 DI 10.1006/jsre.1999.5780 PG 9 WC Surgery SC Surgery GA 279VH UT WOS:000085065400004 PM 10644472 ER PT J AU Xu, XJ LoCicero, J Macri, E Loda, M Ellis, FH AF Xu, XJ LoCicero, J Macri, E Loda, M Ellis, FH TI Barrett's esophagus and associated adenocarcinoma in a mouse surgical model SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Barrett's esophagus; adenocarcinoma; experimental reflux ID REFLUX; RATS; CARCINOMA; JUICE AB Background The development of Barrett's esophagus (BE) and Barrett's associated adenocarcinoma (BAA) in the rat after experimental inducement of esophageal reflux of gastric, bile, and pancreatic juice has been reported by others. The purpose of this study was to determine whether similar results could be demonstrated in the mouse model. Materials and methods. One hundred eight Swiss-Webster mice were used in this study and were divided into three groups: Group I, 37 mice with esophagojejunostomy; Group II, 39 mice with esophagojejunostomy and the carcinogen N-methyl-N-benzylnitrosamine (MBN); and Group III, 32 mice with MBN alone. The animals were sacrificed after 19 weeks. Macroscopic and histopathologic examinations were performed. Results. One hundred mice survived and were available for pathologic study. Macroscopic evidence suggested esophagitis in 60.6% of mice in Group I, 62.8% of mice in Group II, and 9% of mice in Group III and suggested tumor in 3% of mice in Group I, 51.4% of mice in Group II, and 53.1% of mice in Group III. Histopathologic analysis disclosed BE in 42.4% of mice in Group I, 20% of mice in Group II, and 12.5% of mice in Group III. Cancer was present in 12.2% of mice in Group I, 54.3% of mice in Group II, and 46.9% of mice in Group III. Adenocarcinoma with or without squamous cell carcinoma was present in 6.1% of mice in Group I, 37.1% of mice in Group II, and 12.5% of mice in Group III. Conclusions, Esophagojejunostomy plus MBN in the mouse results in BE, BAA, or both in 57.1% of animals, consistent with findings in the rat model after similar interventions. (C) 2000 Academic Press. C1 Beth Israel Deaconess Med Ctr, Div Cardiothorac Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Xu, XJ (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiothorac Surg, Boston, MA 02115 USA. NR 16 TC 31 Z9 31 U1 0 U2 1 PU ACADEMIC PRESS INC 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 FEB PY 2000 VL 88 IS 2 BP 120 EP 124 DI 10.1006/jsre.1999.5774 PG 5 WC Surgery SC Surgery GA 279VH UT WOS:000085065400008 PM 10644476 ER PT J AU Hongcharu, W Dwyer, P Gonzalez, S Anderson, RR AF Hongcharu, W Dwyer, P Gonzalez, S Anderson, RR TI Confirmation of onychomycosis by in vivo confocal microscopy SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article AB Onychomycosis is common in adults and constitutes 20% of all nail disease. Widely used methods to confirm a clinical diagnosis of onychomycosis often yield negative results (ie, potassium hydroxide [KOH] preparation) or are slow (ie, dermatophyte cultures). We report a case of onychomycosis in which we used in vivo confocal microscopy to diagnose the disease; we also correlated our findings with results from routine KOH preparations. On the basis of our findings, we hypothesize that in vivo confocal microscopy may be faster and more accurate than the conventional microscope used in KOH preparations in the diagnosis of onychomycosis. C1 Massachusetts Gen Hosp, Dept Dermatol, Wellman Labs Photomed, Boston, MA 02114 USA. RP Anderson, RR (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Wellman Labs Photomed, 50 Blossom St,Bartlett Extens 6, Boston, MA 02114 USA. NR 6 TC 50 Z9 57 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 2000 VL 42 IS 2 BP 214 EP 216 DI 10.1016/S0190-9622(00)90128-2 PN 1 PG 3 WC Dermatology SC Dermatology GA 281ER UT WOS:000085145400007 PM 10642675 ER PT J AU Shapiro, M Jimenez, S Werth, VP AF Shapiro, M Jimenez, S Werth, VP TI Pemphigus vulgaris induced by D-penicillamine therapy in a patient with systemic sclerosis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID DRUG-INDUCED PEMPHIGUS; AUTOANTIBODIES AB D-Penicillamine-induced pemphigus occurs infrequently, typically in patients with rheumatoid arthritis. We describe a patient with systemic sclerosis who experienced this complication 3 months after starting D-penicillamine therapy. Nikolsky's sign, histopathologic findings, and direct immunofluorescence all confirmed the diagnosis. Termination of disease progression required intravenous pulse glucocorticoids, azathioprine, and 3 courses of plasmapheresis. The presentation, treatment, and etiology of D-penicillamine-induced pemphigus are reviewed, and the incidence of this complication in scleroderma patients is examined. C1 Univ Penn, Med Ctr, Dept Dermatol & Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Penn Hosp, Dept Med, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Dept Rheumatol, Philadelphia, PA 19107 USA. RP Werth, VP (reprint author), Univ Penn, Med Ctr, Dept Dermatol & Med, 36th & Spruce, Philadelphia, PA 19104 USA. NR 19 TC 19 Z9 19 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 2000 VL 42 IS 2 BP 297 EP 299 DI 10.1016/S0190-9622(00)90146-4 PN 1 PG 3 WC Dermatology SC Dermatology GA 281ER UT WOS:000085145400026 PM 10642693 ER PT J AU Laham, RJ Rezaee, M Garcia, L Post, M Sellke, FW Baim, DS Simons, M AF Laham, RJ Rezaee, M Garcia, L Post, M Sellke, FW Baim, DS Simons, M TI Tissue and myocardial distribution of intracoronary, intravenous, intrapericardial, and intramyocardial I-125-labeled basic fibroblast growth factor (bFGF) favor intramyocardial delivery SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 14 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 10A EP 10A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209700037 ER PT J AU Charash, WE Lodder, RA Moreno, PR Purushothaman, KR Swain, JA O'Connor, WN Muller, JE AF Charash, WE Lodder, RA Moreno, PR Purushothaman, KR Swain, JA O'Connor, WN Muller, JE TI Detection of simulated vulnerable plaque using a novel near infrared spectroscopy catheter SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Univ Kentucky, Gill Heart Inst, Lexington, KY 40506 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 4 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 38A EP 38A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209700147 ER PT J AU Tearney, GJ Jang, IK Kang, DH Aretz, HT Houser, SL Brady, TJ Schlendorf, K Shishkov, M Bouma, BE AF Tearney, GJ Jang, IK Kang, DH Aretz, HT Houser, SL Brady, TJ Schlendorf, K Shishkov, M Bouma, BE TI Optical coherence tomography of human coronary arteries: A new imaging modality to visualize different components of plaques SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 52A EP 53A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209700201 ER PT J AU Oesterle, SN Yeung, AC Lo, S Virmani, R Van Bibber, R Flaherty, JC Lamson, TC Kim, SW Garibotto, JT Tumas, MW Makower, J AF Oesterle, SN Yeung, AC Lo, S Virmani, R Van Bibber, R Flaherty, JC Lamson, TC Kim, SW Garibotto, JT Tumas, MW Makower, J TI Percutaneous in-situ coronary venous arterialization (PICVA) improves survival in response to acute ischemia in the porcine model SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Stanford Univ, Ctr Med, Stanford, CA 94305 USA. USAF, Inst Pathol, Washington, DC 20330 USA. SNBL USA Inc, Redmond, WA USA. TransVasc Inc, Menlo Park, CA USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 61A EP 61A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209700235 ER PT J AU Pearlman, JD Wu, Y Simons, M Balm, DS Laham, RJ AF Pearlman, JD Wu, Y Simons, M Balm, DS Laham, RJ TI Correspondence of BIOSENSE-Guided endocardial catheter maps with MRI: Influence of number of locations sampled SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 81A EP 81A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209700312 ER PT J AU Sun, W Chen, F Sarma, JSM Singh, BN AF Sun, W Chen, F Sarma, JSM Singh, BN TI Acute effects of dronedarone on potassium currents in isolated rabbit ventricular myocytes. Comparison with amiodarone SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Sect Cardiol,Cardiovasc Res Labs, Los Angeles, CA 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 98A EP 98A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209700374 ER PT J AU Keane, D Houghtaling, C Qin, H Aretz, T Ruskin, JN AF Keane, D Houghtaling, C Qin, H Aretz, T Ruskin, JN TI Linear cryo ablation of the cave tricuspid isthmus under guidance by phased array intracardiac echocardiography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 126A EP 126A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209700485 ER PT J AU Pratt, CM Ruskin, JN Friedrich, T AF Pratt, CM Ruskin, JN Friedrich, T TI Dofetilide use in atrial fibrillation: A treatment strategy to minimize proarrhythmic risk SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Pfizer Inc, New York, NY USA. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 154A EP 154A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209700595 ER PT J AU Bocker, W Grazette, L Haq, S Rosenzweig, A Force, T Hajjar, RJ AF Bocker, W Grazette, L Haq, S Rosenzweig, A Force, T Hajjar, RJ TI Anti-ErbB-2-Antibody and doxorubicin induce cardiomyocyte apoptosis accompanied by a decreased phosphorylation of AM and ERK 1/2 SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 169A EP 169A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209700650 ER PT J AU Januzzi, JL Davidoff, R Mendes, LA Thompson, CR Sleeper, LA Steingart, R Gin, K Dzavik, V Goldberger, M Hochman, JS Picard, MH AF Januzzi, JL Davidoff, R Mendes, LA Thompson, CR Sleeper, LA Steingart, R Gin, K Dzavik, V Goldberger, M Hochman, JS Picard, MH CA SHOCK Investigators TI Explaining the relationship between age, cardiogenic shock and outcomes: Echocardiographic observations from the SHOCK trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Thompson, Christopher/F-3967-2010 OI Thompson, Christopher/0000-0001-9206-376X 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 219A EP 220A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209700845 ER PT J AU Chow, CM Davidoff, R Mendes, LA Thompson, CR Sleeper, LA Steingart, R Gin, K Dzavik, V Hochman, JS Picard, MH AF Chow, CM Davidoff, R Mendes, LA Thompson, CR Sleeper, LA Steingart, R Gin, K Dzavik, V Hochman, JS Picard, MH CA SHOCK Trial TI Early echo-Doppler findings in shock complicating acute MI SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Thompson, Christopher/F-3967-2010 OI Thompson, Christopher/0000-0001-9206-376X 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 228A EP 228A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209700881 ER PT J AU Prabhu, SD Chandrasekar, B Murray, DR Freeman, GL AF Prabhu, SD Chandrasekar, B Murray, DR Freeman, GL TI beta-adrenergic blockade in developing heart failure: Effects on myocardial inflammatory cytokines, nitric oxide, and remodeling SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 231A EP 231A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209700891 ER PT J AU Prabhu, SD Freeman, GL AF Prabhu, SD Freeman, GL TI Altered left ventricular inotropic reserve and mechanoenergetics early in the development of heart failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 233A EP 233A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209700900 ER PT J AU Min, JY Morgan, JP Meissner, A Simon, R AF Min, JY Morgan, JP Meissner, A Simon, R TI Effects of candesartan and enalapril on contractility, intracellular Ca2+ handling and myofibrillar Ca2+ responsiveness in failing myocardium of postinfarction rats SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, BIDMC, Sch Med, Boston, MA 02115 USA. Univ Kiel, D-24098 Kiel, Germany. 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 235A EP 235A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209700908 ER PT J AU Moreno, PR Purushothaman, KR O'Connor, WN Booth, DC Fuster, V Muller, JE AF Moreno, PR Purushothaman, KR O'Connor, WN Booth, DC Fuster, V Muller, JE TI Increased neovascularization in disrupted human atherosclerotic plaques SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Univ Kentucky, Gill Heart Inst, Lexington, KY USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 275A EP 275A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209701057 ER PT J AU Kinlay, S Burgess, B Rizzo, R Cordelia, N Cabral, V O'Donnell, C Plutzky, J AF Kinlay, S Burgess, B Rizzo, R Cordelia, N Cabral, V O'Donnell, C Plutzky, J TI Conventional coronary risk factors are more frequent in coronary artery bypass recipients with premature atherosclerosis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Partners Premature Atherosclerosis Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 300A EP 300A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209701157 ER PT J AU Moreno, PR Purushothaman, KR O'Connor, WN Fuster, V Muller, JE AF Moreno, PR Purushothaman, KR O'Connor, WN Fuster, V Muller, JE TI Lack of association between calcification and vulnerability in human atherosclerotic plaques SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Univ Kentucky, Gill Heart Inst, Lexington, KY USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 303A EP 303A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209701171 ER PT J AU Min, JY Hampton, TG Wang, JF DeAngelis, J Morgan, JP AF Min, JY Hampton, TG Wang, JF DeAngelis, J Morgan, JP TI Depressed tolerance to fluorocarbon-simulated ischemia in failing rat myocardium due to impaired intracellular Ca2+ modulation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 379A EP 379A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209701455 ER PT J AU Kloner, RA Das, S Poole, WK Muller, J Cannon, CP Braunwald, E AF Kloner, RA Das, S Poole, WK Muller, J Cannon, CP Braunwald, E TI Seasonal variation of myocardial infarct size in humans SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Univ So Calif, Good Samaritan Hosp, Los Angeles, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RI Kloner, Robert/B-2971-2012 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 389A EP 390A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209701496 ER PT J AU Sabatine, MS Snapinn, S Theroux, P Jang, IK AF Sabatine, MS Snapinn, S Theroux, P Jang, IK TI Factors influencing outcome and degree of benefit with GP IIb/IIIa inhibition in patients with non-ST-elevation acute coronary syndromes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Merck Res Labs, W Point, PA USA. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 392A EP 393A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209701508 ER PT J AU Vancon, AC Chow, CM Fox, ER Hill, J Picard, MH Scherrer-Crosbie, M AF Vancon, AC Chow, CM Fox, ER Hill, J Picard, MH Scherrer-Crosbie, M TI Pulse inversion harmonic imaging: Does it improve the endocardial border definition? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 439A EP 440A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209701682 ER PT J AU Chow, CM Vancon, AC Hoy, MJ Scherrer-Crosbie, M Picard, MH AF Chow, CM Vancon, AC Hoy, MJ Scherrer-Crosbie, M Picard, MH TI Now much does harmonic imaging affect cardiac dimensions? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 440A EP 440A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209701683 ER PT J AU Buck, T Mucci, R Guerrero, JL Holmvang, G Handschumacher, MD Levine, RA AF Buck, T Mucci, R Guerrero, JL Holmvang, G Handschumacher, MD Levine, RA TI The backscattered Doppler power times velocity integral at the vena contracta for direct quantification of regurgitant volume flow: Clinical validation versus MRI SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 471A EP 471A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209701801 ER PT J AU Januzzi, JL Church, CC Gosselin, JA Zamejtis, AL Fetterman, RC Walovitch, RC Picard, MH AF Januzzi, JL Church, CC Gosselin, JA Zamejtis, AL Fetterman, RC Walovitch, RC Picard, MH TI Quantifying in vivo kinetics of ultrasound contrast agents using peripheral artery Doppler power SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Acusphere Inc, Boston, MA 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 478A EP 478A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209701827 ER PT J AU Mele, D Olstad, B Donateo, M Pedini, I Alboni, P Levine, RA AF Mele, D Olstad, B Donateo, M Pedini, I Alboni, P Levine, RA TI Strain rate imaging can accurately identity infarct segments in patients with myocardial infection: A clinical study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Osped Civile, Div Cardiol, Cento, Italy. Norwegian Biomed Univ, Trondheim, Norway. Massachusetts Gen Hosp, Noninvas Cardiac Lab, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 494A EP 494A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209701886 ER PT J AU Haq, S Choukroun, G Kang, Z Alessandrini, A Boecker, W Terao, Y Matsui, T Rosenweig, A Hajar, R Woodgett, J Force, T AF Haq, S Choukroun, G Kang, Z Alessandrini, A Boecker, W Terao, Y Matsui, T Rosenweig, A Hajar, R Woodgett, J Force, T TI Role of glycogen synthase kinase-3 beta in cardiomyocyte hypertrophy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Div Cardiovasc, Charlestown, MA 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 521A EP 521A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209701983 ER PT J AU Hung, J Handschumacher, MD Guerrero, JL Levine, RA AF Hung, J Handschumacher, MD Guerrero, JL Levine, RA TI Determinants of ischemic mitral regurgitation: Are the papillary muscles in or out of the ring? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Cardiac Unit, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 523A EP 523A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209701988 ER PT J AU Buck, T Guerrero, JL Handschumacher, MD Levine, RA AF Buck, T Guerrero, JL Handschumacher, MD Levine, RA TI A new in vivo model providing a direct gold standard for mitral regurgitant flow quantification. Application to validate a new Doppler method SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 524A EP 524A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209701992 ER PT J AU Law, AV Lapuerta, P Asch, SM AF Law, AV Lapuerta, P Asch, SM TI Development and testing of a clinically-detailed tool to assess quality of care in hypertension SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 RAND Hlth, Santa Monica, CA USA. Bristol Myers Squibb Pharmaceut Res Inst, Princeton, NJ 08543 USA. W Los Angeles Vet Adm, W Los Angeles, CA 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 2000 VL 35 IS 2 SU A BP 558A EP 558A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282GL UT WOS:000085209702116 ER PT J AU Saliba, D Kington, R Buchanan, J Bell, R Wang, MM Lee, M Herbst, M Lee, D Sur, D Rubenstein, L AF Saliba, D Kington, R Buchanan, J Bell, R Wang, MM Lee, M Herbst, M Lee, D Sur, D Rubenstein, L TI Appropriateness of the decision to transfer nursing facility residents to the hospital SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE appropriateness; transfers; hospitalization; emergency department; nursing facility ID PROSPECTIVE PAYMENT SYSTEM; ACUTE-CARE FACILITIES; LONG-TERM; HOME RESIDENTS; EVALUATION PROTOCOL; MEDICAL-CARE; ADVANCE DIRECTIVES; INAPPROPRIATE USE; PATIENT TRANSFER; HEALTH-CARE AB OBJECTIVES: To develop and test a standardized instrument, the purpose of which is to assess (1) whether skilled nursing facilities (SNFs) transfer residents to emergency departments (ED) inappropriately, (2) whether residents are admitted to hospitals inappropriately, (3) and factors associated with inappropriate transfers. DESIGN: A structured implicit review (SIR) of medical records. SETTING AND PARTICIPANTS: Using nested random sampling in eight community SNFs, we identified SNF and hospital records of 100 unscheduled transfers to one of 10 hospitals. MEASUREMENTS: Seven trained physician reviewers assessed appropriateness using a SIR form designed for this study (2 independent reviews per record, 200 total reviews). We measured interrater reliability with kappa statistics and used bivariate analysis to identify factors associated with assessment that transfer was inappropriate. RESULTS: In 36% of ED transfers and 40% of hospital admissions, both reviewers agreed that transfer/admit was inappropriate, meaning the resident could have been cared for safely at a lower level of care. Agreement was high for both ED (percent agreement 84%, kappa .678) and hospital (percent agreement 89%, kappa .779). When advance directives were considered, both reviewers rated 44% of ED transfers and 45% of admissions inappropriate. Factors associated with inappropriateness included the perceptions that: (1) poor quality of care contributed to transfer need, (2) needed services would typically be available in outpatient settings, and (3) the chief complaint did not warrant hospitalization. CONCLUSIONS: Inappropriate transfers are a potentially large problem. Some inappropriate transfers may be associated with poor quality of care in SNFs. This study demonstrates that structured implicit review meets criteria for reliable assessment of inappropriate transfer rates. Structured implicit review may be a valuable tool for identifying inappropriate transfers from SNFs to EDs and hospitals. C1 RAND Corp, Santa Monica, CA 90407 USA. VA Greater Los Angeles Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. AT&T Labs, Murray Hill, NJ 07974 USA. Univ Calif Los Angeles, Family Practice Residency Program, Santa Monica, CA USA. RP Saliba, D (reprint author), RAND Corp, 1700 Main St, Santa Monica, CA 90407 USA. FU NIA NIH HHS [AG10415] NR 76 TC 177 Z9 177 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD FEB PY 2000 VL 48 IS 2 BP 154 EP 163 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 284BT UT WOS:000085311400006 PM 10682944 ER PT J AU Brown, D AF Brown, D TI Vasopressin: Induced structural change in toad bladder luminal membrane - Commentary SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID URINARY-BLADDER C1 Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. RP Brown, D (reprint author), Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 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 FEB PY 2000 VL 11 IS 2 BP 379 EP 380 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 280JK UT WOS:000085099500023 ER PT J AU Llevadot, J Coulter, SA Giugliano, RP AF Llevadot, J Coulter, SA Giugliano, RP TI A practical approach to the diagnosis and management of thrombocytopenia associated with glycoprotein IIb/IIIa receptor inhibitors SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE thrombocytopenia; platelet aggregation inhibitors; platelet glycoprotein GP IIb-IIIa complex; antiplatelet; diagnosis; management ID HEPARIN-INDUCED THROMBOCYTOPENIA; ACUTE MYOCARDIAL-INFARCTION; THERAPY; ANTIBODIES; PHASE AB The introduction of drugs that inhibit the GP IIb/IIIa receptor represents one of the most important new developments in the field of cardiovascular pharmacotherapeutics of the past decade. Thrombocytopenia associated with a GP IIb/IIIa inhibitor can occur in up to 5% of patients and is associated with poor clinical outcomes. Monitoring of the platelet count early after administration of these drugs is recommended and further assessment of the platelet count should be performed with long-term oral administration. Confirmation of true thrombocytopenia and an investigation of other potential etiologies are crucial initial diagnostic steps that should be taken when a platelet count of < 100,000/cm(3) is encountered. In patients receiving concomitant heparin, identification of heparin-induced thrombocytopenia using an enzyme-linked immunosorbent assay to detect anti-heparin-PF4 antibodies is preferred. Treatment recommendations depend upon the severity of thrombocytopenia and presence of bleeding. In general, GP IIb/IIIa inhibitor therapy should be stopped; conventional critical care instituted; and platelet transfusions considered if the platelet count is < 10,000/cm(3), if there is severe bleeding, or if an emergency invasive procedure is required. Readministration of GP IIb/IIIa inhibitors may be associated with an increased risk of thrombocytopenia in selected circumstances, and caution is advised if the patient had previously experienced a significant decline in the platelet count or developed drug-induced antibodies following prior use. Future areas of research should target the mechanism(s) of thrombocytopenia, more accurate diagnostic methods, and the risk of thrombocytopenia when these drugs are combined with other antiplatelet and anticoagulant agents. C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Giugliano, RP (reprint author), TIMI Study Off, 333 Longwood Ave,Suite 402, Boston, MA 02115 USA. NR 24 TC 16 Z9 17 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD FEB PY 2000 VL 9 IS 2 BP 175 EP 180 DI 10.1023/A:1018779116791 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 269VZ UT WOS:000084499400006 PM 10613999 ER PT J AU Kennedy, JG Soffe, KE Rogers, BW Kumar, S Griffen, DR Vedova, PAD Sullivan, RJ Sheehan, LJ AF Kennedy, JG Soffe, KE Rogers, BW Kumar, S Griffen, DR Vedova, PAD Sullivan, RJ Sheehan, LJ TI Deep vein thrombosis prophylaxis in hip fractures: A comparison of the arteriovenous impulse system and aspirin SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE DVT; aspirin; AV pump; hemiarthroplasty ID TOTAL KNEE REPLACEMENT; VENOUS THROMBOEMBOLISM; METAANALYSIS; HEPARIN; DISEASE; FOOT AB Background: A prospective, randomized controlled trial was used to compare the efficacy of the arteriovenous (AV) impulse system and aspirin in reducing venous thrombosis after fracture to the femoral neck. Methods: A total of 143 patients underwent hemiarthroplasty, after which 70 patients were treated with the AV pump and a second group of 73 patients were commenced on 325 mg of aspirin. Duplex ultrasound was used to assess both proximal and distal venous thrombi on days 7 to 10. Calf and thigh circumferences were also measured. Results: Thrombi developed in seven of the patients treated with aspirin and in four patients treated with the AV pump. No statistically significant difference could be established (p = 0.109). There was a significant reduction in both calf (p = 0.003) and thigh (p = 0.003) swelling in the group treated with the AV pump. Neither treatment group was a significant predictor of a poorer outcome by using logistical regression analysis (p = 0.258). Conclusions: Both aspirin and the AV pump are effective in reducing thromboembolic events after hemiarthroplasty of the hip. C1 Univ Coll Dublin, Dept Orthopaed Surg, Mater Misericordiae Hosp, Dublin 2, Ireland. Massachusetts Gen Hosp, Joint Replacement Serv, Boston, MA 02114 USA. St Elizabeths Med Ctr, Joint Replacement Serv, Div Orthopaed Surg, Boston, MA USA. Univ La Sapienza, Clin Ortoped 2, Rome, Italy. RP Kennedy, JG (reprint author), Univ Coll Dublin, Dept Surg, Mater Misericordiae Hosp, Dublin 2, Ireland. NR 33 TC 7 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD FEB PY 2000 VL 48 IS 2 BP 268 EP 272 DI 10.1097/00005373-200002000-00012 PG 5 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 284MH UT WOS:000085335800014 PM 10697085 ER PT J AU Abou-Zamzam, AM Moneta, GL Edwards, JM Yeager, RA Taylor, LM Porter, JM AF Abou-Zamzam, AM Moneta, GL Edwards, JM Yeager, RA Taylor, LM Porter, JM TI Is a single preoperative duplex scan sufficient for planning bilateral carotid endarterectomy? SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the Society-for-Vascular-Surgery CY JUN 06-09, 1999 CL WASHINGTON, D.C. SP Soc Vasc Surg ID ARTERY STENOSIS; FOLLOW-UP; ARTERIOGRAPHY; OCCLUSION; CRITERIA; OVERESTIMATION; 60-PERCENT; SYMPTOMS; FLOW AB Purpose: Duplex scanning is often the sole imaging study before carotid endarterectomy (CEA). Patients with bilateral severe internal carotid artery (ICA) stenosis may be considered for bilateral CEA. High-grade ICA stenosis, however, may artifactually elevate velocity measurements used to quantify stenosis in the contralateral ICA. It is unknown whether ipsilateral CEA will influence duplex determination of the presence of a contralateral 60% to 99% ICA stenosis. This study was performed to determine whether a single preoperative duplex scan is sufficient to plan bilateral CEA. Methods: Preoperative and early postoperative carotid duplex scans in patients with bilateral ICA stenosis who underwent unilateral CEA were reviewed. Changes in duplex scans that determined stenosis in the ICA contralateral to the CEA were analyzed. Previously validated criteria used to determine 60% to 99% ICA stenosis were a peak systolic velocity (PSV) of 260 cm/sec or more combined with an end diastolic velocity (EDV) of 70 cm/sec or more. Results: Over an 8-year period, 460 patients underwent CEA; 107 patients (23.3%) had an asymptomatic 50% to 99% contralateral ICA stenosis by standard criteria (PSV, >125 cm/sec) and an early postoperative duplex scan examination. Of these 107 patients, 38 patients (35.5%) had duplex scan criteria for 60% to 99% contralateral ICA stenosis. In these 38 patients, there was a mean postoperative PSV decrease of 47.7 cm/sec (10.1%) and a mean EDV decrease of 36.0 cm/sec (19.3%) in the ICA contralateral to the CEA. Eight of 38 (21.1%) preoperative contralateral 60% to 99% ICA lesions were reclassified as less than 60% on postoperative duplex scanning. Six of 69 (8.7%) preoperative lesions of less than 60% were reclassified as 60% to 99% on postoperative duplex scan. These six preoperative examinations were all close to the criteria for 60% to 99% stenosis (mean PSV, 232.5 cm/sec; mean EDV, 62.5 cm/sec). Conclusion: One-fifth of patients with apparent 60% to 99% contralateral ICA lesions before the operation have less than 60% stenosis when restudied with duplex scan after unilateral CEA. Lesions below but near the cutoff for 60% to 99% may be reclassified as 60% to 99% on the postoperative duplex scan. These findings mandate that when duplex scanning is used as the sole imaging modality before CEA, patients with severe bilateral carotid stenosis must have an additional carotid duplex examination before operation on the second side. C1 Oregon Hlth Sci Univ, Div Vasc Surg, Dept Surg, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Moneta, GL (reprint author), Oregon Hlth Sci Univ, Div Vasc Surg, Dept Surg, OP-11,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. NR 19 TC 15 Z9 16 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD FEB PY 2000 VL 31 IS 2 BP 282 EP 287 DI 10.1016/S0741-5214(00)90159-9 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 283VE UT WOS:000085296100014 PM 10664497 ER PT J AU LaMuraglia, GM O'Hara, PJ Baker, WH Naslund, TC Norris, EJ Li, J Vandermeersch, E AF LaMuraglia, GM O'Hara, PJ Baker, WH Naslund, TC Norris, EJ Li, J Vandermeersch, E TI The reduction of the allogenic transfusion requirement in aortic surgery with a hemoglobin-based solution SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the Society-for-Vascular-Surgery CY JUN 06-09, 1999 CL WASHINGTON, D.C. SP Soc Vasc Surg ID OXYGEN-TRANSPORT; BOVINE HEMOGLOBIN; BLOOD SUBSTITUTE; CARRIER; HEMODILUTION; ANEURYSM; MODEL AB Objective: Because of allogenic red blood cell (RBC) availability and infection problems, novel alternatives, including hemoglobin-based oxygen-carrying solutions (HBOC), are being explored to minimize the perioperative requirement of RBC transfusions. This study evaluated HBOC-201, a room-temperature stable, polymerized, bovine-HBOC, as a substitute for allogenic RBC transfusion in patients undergoing elective infrarenal aortic operations. Methods: In a single blind, multicenter trial, 72 patients were prospectively randomized two-to-one to HBOC (n = 48) or allogenic RBC (n = 24) at the time of the first transfusion decision, either during or after elective infrarenal aortic reconstruction. Patients randomized to the HBOC group received 60 g of HBOC for the initial transfusion and had the option to receive three more doses (30 g each) within 96 hours. In this group, any further blood requirement was met with allogenic RBCs. Patients randomized to the allogenic RBC group received only standard RBC transfusions, The efficacy analysis was a means of assessing the ability of HBOC to eliminate the requirement for any allogenic RBC transfusions from the time of randomization through 28 days. Safety was evaluated by means of standard clinical trial methods. Results: The two treatment groups were comparable for all baseline characteristics. Although all patients in the allogenic RBC group required at least one allogenic RBC transfusion, 13 of 48 patients (27%; 95% CI, 15% to 42%) in the HBOC group did not require any allogenic RBC transfusions. The only significant changes documented were a 15% increase in mean arterial pressure and a three-fold peak increase in serum urea nitrogen concentration after HBOC. The complications were similar in both groups, with no allergic reactions. There were two perioperative deaths (8%) in the allogenic RBC group and three perioperative deaths (6%) in the:HBOC group (P = 1.0). Conclusion: HBOC significantly eliminated the need for any-allogenic RBC transfusion in 27% of patients undergoing infrarenal aortic reconstruction, but did not reduce the median allogenic RBC requirement. HBOC transfusion was well tolerated and did not influence morbidity or mortality rates. C1 Harvard Univ, Div Vasc Surg, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Cleveland Clin Fdn, Div Vasc Surg, Cleveland, OH USA. Johns Hopkins Med Inst, Dept Anesthesiol & Crit Care Med, Boston, MA USA. Loyola Univ, Div Vasc Surg, Med Ctr, Maywood, IL 60153 USA. Vanderbilt Univ, Med Ctr, Div Vasc Surg, Nashville, TN 37240 USA. Katholieke Univ Leuven Hosp, Dept Anesthesia, Louvain, Belgium. RP LaMuraglia, GM (reprint author), Harvard Univ, Div Vasc Surg, Sch Med, Massachusetts Gen Hosp, 15 Parkman St, Boston, MA 02114 USA. NR 20 TC 85 Z9 88 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD FEB PY 2000 VL 31 IS 2 BP 299 EP 306 DI 10.1016/S0741-5214(00)90161-7 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 283VE UT WOS:000085296100018 PM 10664499 ER PT J AU Andreadis, S Lavery, T Davis, HE le Doux, JM Yarmush, ML Morgan, JR AF Andreadis, S Lavery, T Davis, HE le Doux, JM Yarmush, ML Morgan, JR TI Toward a more accurate quantitation of the activity of recombinant retroviruses: Alternatives to titer and multiplicity of infection SO JOURNAL OF VIROLOGY LA English DT Article ID MEDIATED GENE-TRANSFER; HALF-LIFE; TRANSDUCTION; VECTOR; CELLS; TIME; EFFICIENCY; KINETICS; RANGE; LINES AB In this paper, we present a mathematical model with experimental support of how several key parameters govern the adsorption of active retro-virus particles onto the surface of adherent cells, These parameters, including time of adsorption, volume of virus, and the number, size, and type of target cells, as well as the intrinsic properties of the virus, diffusion coefficient, and half-life (t(1/2)), have been incorporated into a mathematical expression that describes the rate at which active virus particles adsorb to the cell sm face. From this expression, we have obtained estimates of C-vo. the starting concentration of active retrovirus particles. In contrast to titer, C-vo is independent of the specific conditions of the assay. The relatively slow diffusion (D = 2 x 10(-8) cm(2)/s) and rapid decay (t(1/2) = 6 to 7 h) of retrovirus particles explain why C-vo values are significantly higher than titer values. Values of C-vo also indicate that the number of defective particles in a retrovirus stock is much lower than previously thought, which has implications especially for the use of retroviruses for in vivo gene therapy. With this expression, we have also computed AVC (active viruses/cell), the number of active retrovirus particles that would adsorb per cell during a gives adsorption time. In contrast to multiplicity of infection, which is based an titer and is subject to the same inaccuracies, AVC is based on the physicochemical parameters of the transduction assay and so is a more reliable alternative. C1 Shriners Hosp Crippled Children, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. RP Morgan, JR (reprint author), Shriners Hosp Crippled Children, 51 Blossom St, Boston, MA 02114 USA. OI Morgan, Jeffrey/0000-0002-7546-3443 FU NICHD NIH HHS [HD-28528] NR 24 TC 23 Z9 23 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2000 VL 74 IS 3 BP 1258 EP 1266 DI 10.1128/JVI.74.3.1258-1266.2000 PG 9 WC Virology SC Virology GA 273YZ UT WOS:000084738100022 PM 10627536 ER PT J AU Moulard, M Lortat-Jacob, H Mondor, I Roca, G Wyatt, R Sodroski, J Lu, Z Olson, W Kwong, PD Sattentau, QJ AF Moulard, M Lortat-Jacob, H Mondor, I Roca, G Wyatt, R Sodroski, J Lu, Z Olson, W Kwong, PD Sattentau, QJ TI Selective interactions of polyanions with basic surfaces on human immunodeficiency virus type 1 gp120 SO JOURNAL OF VIROLOGY LA English DT Article ID HEPARAN-SULFATE PROTEOGLYCAN; HUMAN MONOCLONAL-ANTIBODY; DEXTRAN SULFATE; ENVELOPE GLYCOPROTEIN; HIV-1 INFECTION; V3 LOOP; CHEMOKINE RECEPTORS; CORECEPTOR USAGE; HUMAN LIVER; BINDING AB It is well established that the gp120 V3 loop of T-cell-line-adapted human immunodeficiency virus type 1 (HIV-1) binds both cell-associated and soluble polyanions, Virus infectivity is increased by interactions between HIV-1 and heparan sulfate proteoglycans on some cell types, and soluble polyanions such as heparin and dextran sulfate neutralize HIV-1 in vitro. However, the analysis of gp120-polyanion interactions has been limited to T-cell-line-adapted, CXCR4-using virus and virus-derived gp120, and the polyanion binding ability of gp120 regions other than the V3 loop has not been addressed. Here we demonstrate by monoclonal-antibody inhibition, labeled heparin binding, and surface plasmon resonance studies that a second site, most probably corresponding to the newly defined, highly conserved coreceptor binding region on gp120, forms part of the polyanion binding surface. Consistent with the binding of polyanions to the coreceptor binding surface, dextran sulfate interfered with the gp120-CXCR4 association while having no detectable effect on the gp120-CD4 interaction. The interaction between polyanions and X4 or R5X4 gp120 was readily detectable, whereas weak or undetectable binding was observed with R5 gp120. Analysis of mutated forms of X4 gp120 demonstrated that the V3 loop is the major determinant for polyanion binding whereas other regions, including the V1/V2 loop structure and the NH2 and COOH termini, exert a more subtle influence. A molecular model of the electrostatic potential of the conserved coreceptor binding region confirmed that it is basic but that the overall charge on this surface is dominated by the V3 loop. These results demonstrate a selective interaction of gp120 with polyanions and suggest that the conserved coreceptor binding surface may present a novel and conserved target for therapeutic intervention. C1 Ctr Immunol Marseille Luminy, F-13288 Marseille 9, France. Inst Biol Struct, F-38027 Grenoble, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Progen Pharmaceut Inc, Tarrytown, NY 10591 USA. Columbia Univ Coll Phys & Surg, Dept Biochem & Mol Biophys, New York, NY 10032 USA. RP Sattentau, QJ (reprint author), Univ London Imperial Coll Sci Technol & Med, Jefferiss Res Trust Labs, Norfolk Pl, London W2 1PG, England. NR 91 TC 252 Z9 260 U1 3 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2000 VL 74 IS 4 BP 1948 EP 1960 DI 10.1128/JVI.74.4.1948-1960.2000 PG 13 WC Virology SC Virology GA 277XC UT WOS:000084958000041 PM 10644368 ER PT J AU Kwong, PD Wyatt, R Sattentau, QJ Sodroski, J Hendrickson, WA AF Kwong, PD Wyatt, R Sattentau, QJ Sodroski, J Hendrickson, WA TI Oligomeric modeling and electrostatic analysis of the gp120 envelope glycoprotein of human immunodeficiency virus SO JOURNAL OF VIROLOGY LA English DT Article ID V3 LOOP; NEUTRALIZING ANTIBODIES; MEMBRANE ASSOCIATION; RECEPTOR-BINDING; ATOMIC-STRUCTURE; TYPE-1 ENTRY; HIV-1 GP120; CD4 BINDING; SOLUBLE CD4; IN-VITRO AB The human immunodeficiency virus envelope glycoproteins, gp120 and gp41, function in cell entry by binding to CD4 and a chemokine receptor on the cell surface and orchestrating the direct fusion of the viral and target cell membranes. On the virion surface, three gp120 molecules associate noncovalently with the ectodomain of the gp41 trimer to form the envelope oligomer. Although an atomic-level structure of a monomeric gp120 core has been determined, the structure of the oligomer is unknown. Here, the orientation of gp120 in the oligomer is modeled by using quantifiable criteria of carbohydrate exposure, occlusion of conserved residues, and steric considerations with regard to the binding of the neutralizing antibody 17b. Applying similar modeling techniques to influenza virus hemagglutinin suggests a rotational accuracy for the oriented gp120 of better than 10 degrees. The model shows that CD4 binds obliquely, such that multiple CD4 molecules bound to the same oligomer have their membrane-spanning portions separated by at least 190 Angstrom. The chemokine receptor, in contrast, binds to a sterically restricted surface close to the trimer axis. Electrostatic analyses reveal a basic region which faces away from the virus, toward the target cell membrane, and is conserved on core gp120. The electrostatic potentials of this region are strongly influenced by the overall charge, but not the precise structure, of the third variable (V3) loop. This dependence on charge and not structure may make electrostatic interactions between this basic region and the cell difficult to target therapeutically and may also provide a means of viral escape from immune system surveillance. C1 Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Ctr Immunol Marseille Luminy, F-13288 Marseille 9, France. RP Kwong, PD (reprint author), Columbia Univ, Dept Biochem & Mol Biophys, Black Bldg,Room 204,650 W 168th St, New York, NY 10032 USA. FU NCI NIH HHS [P30 CA006516]; NIAID NIH HHS [AI 28691, AI 31783, AI 39420, R01 AI031783, P30 AI042848, P30 AI028691, R01 AI039420] NR 64 TC 225 Z9 229 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2000 VL 74 IS 4 BP 1961 EP 1972 DI 10.1128/JVI.74.4.1961-1972.2000 PG 12 WC Virology SC Virology GA 277XC UT WOS:000084958000042 PM 10644369 ER PT J AU Zanchi, A Moczulski, DK Hanna, LS Wantman, M Warram, JH Krolewski, AS AF Zanchi, A Moczulski, DK Hanna, LS Wantman, M Warram, JH Krolewski, AS TI Risk of advanced diabetic nephropathy in type 1 diabetes is associated with endothelial nitric oxide synthase gene polymorphism SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 58th Annual Meeting of the American-Diabetes-Association CY JUN 13-16, 1998 CL CHICAGO, ILLINOIS SP Amer Diabet Assoc DE gene for NOS; IDDM; DNA sequence; eNOS polymorphism; diabetes; endothelium ID MISSENSE GLU298ASP VARIANT; ESSENTIAL-HYPERTENSION; LINKAGE ANALYSIS; MICROALBUMINURIA; MELLITUS; DYSFUNCTION; DISEASE; JAPANESE; IDDM; SUSCEPTIBILITY AB Background. Polymorphisms in the endothelial nitric oxide synthase gene (eNOS) may be implicated in the development of nephropathy in patients with type 1 or insulin-dependent diabetes mellitus (IDDM). Methods. Three groups of IDDM patients were selected to study this hypothesis: cases with advanced diabetic nephropathy (N = 78), cases with overt proteinuria but normal serum creatinine (N = 74), and controls with normoalbuminuria despite 15 years of diabetes (N = 195). Parents of 132 cases and 53 controls were also examined and were used for the transmission disequilibrium test, a family-based study design to test association. Results. We examined four eNOS polymorphisms, and two were associated with diabetic nephropathy in the case-control comparisons: a T to C substitution in the promoter at position -786 and the a-deletion/b-insertion in intron 4. For the former, the risk of developing advanced nephropathy was higher for C allele homozygotes than for the other two genotypes (odds ratio 2.8, 95% CI, 1.4 to 5.6). For the latter polymorphism, it was the a-deletion carriers that had the higher risk (odds ratio 2.3, 95% CI, 1.3 to 4.0) in comparison with noncarriers. Both polymorphisms were analyzed together as haplotypes in a family-based study using the transmission disequilibrium test. The C/a-deletion haplotype was transmitted from heterozygous parents to cases with advanced diabetic nephropathy with a significantly higher frequency than expected (P = 0.004). Conclusion. The findings of the case-control and family-based studies demonstrate clearly that DNA sequence differences in eNOS influence the risk of advanced nephropathy in type 1 diabetes. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol,Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Krolewski, AS (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol,Div Res, 1 Joslin Pl,Room 305, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK41526, DK53534] NR 43 TC 150 Z9 161 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 2000 VL 57 IS 2 BP 405 EP 413 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 282WG UT WOS:000085243000004 PM 10652017 ER PT J AU Stehman-Breen, CO Sherrard, DJ Gillen, D Caps, M AF Stehman-Breen, CO Sherrard, DJ Gillen, D Caps, M TI Determinants of type and timing of initial permanent hemodialysis vascular access SO KIDNEY INTERNATIONAL LA English DT Article DE arteriovenous fistula; PTFE graft; veins for dialysis; hemodialysis AB Background. We undertook a population-based study of hemodialysis (HD) patients to determine which factors are important in predicting the type of permanent access initially placed and if a functional permanent access is in place at the start of HD. Methods. Selected characteristics were abstracted from the United States Renal Data System (USRDS) Dialysis Morbidity and Mortality Study (DMMS) Wave 2. Logistic regression was used to estimate the independent contribution of specific characteristics in predicting whether the initial permanent access placed was an arteriovenous (AV) fistula compared with a polytetrafluoroethylene (PTFE) graft, and in predicting whether permanent access (fistula or graft) was in place at the initiation of dialysis. Results. Sixty seven percent of the patients had an AV graft placed as their first permanent access. Characteristics important in predicting if a fistula was initially placed included age (per decade; aOR = 0.84, P < 0.001), female gender (aOR = 0.52, P < 0.001), body mass index (per standard deviation; aOR = 0.70, P = 0.09), avoiding blood draws (aOR = 1.96, P < 0.001), ability to ambulate (aOR = 2.24, P = 0.008), underlying renal disease (glomerular compared with diabetes, aOR = 2.19, P = 0.009), college education (aOR = 1.72, P = 0.002), and sharing in decision making (aOR = 1.50, P = 0.02). Thirty-four percent of patients (34.4%) had functional permanent access at the start of HD. Characteristics important in predicting which patients had functional permanent access included serum albumin (per 1 mg/dL increase, aOR = 1.55, P = 0.003), erythropoietin prior to starting HD (aOR = 1.79, P = 0.002), fewer predialysis nephrologist visits (aOR = 0.21, P < 0.001), and when the patient was told they had renal disease (aOR = 0.33, P = 0.002). Conclusions. PTFE grafts were the most common initial permanent access. The majority of patients did not have permanent access at the start of dialysis. Factors that are thought to compromise identification of adequate veins were important predictors of PTFE graft placement. Permanent access at the start of HD was largely a function of early patient education and early referral to a nephrologist. C1 Vet Affairs Puget Sound Hlth Care Syst, Div Nephrol, Dept Med, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Surg, Div Vasc Surg, Seattle, WA 98108 USA. Univ Washington, Dept Biostat, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. RP Stehman-Breen, CO (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Nephrol, Dept Med, 1660 S Columbian Way,Mailstop 111A, Seattle, WA 98108 USA. NR 11 TC 158 Z9 167 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 2000 VL 57 IS 2 BP 639 EP 645 DI 10.1046/j.1523-1755.2000.00885.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 282WG UT WOS:000085243000029 PM 10652042 ER PT J AU Schaefer, L Engman, A Miller, JB AF Schaefer, L Engman, A Miller, JB TI Coding sequence, chromosomal localization, and expression pattern of Nrf1: the mouse homolog of Drosophila erect wing SO MAMMALIAN GENOME LA English DT Article ID NUCLEAR RESPIRATORY FACTOR-1; PROTEIN SECONDARY STRUCTURE; GENE REGULATORY FACTORS; DNA-BINDING PROTEIN; SEA-URCHIN EMBRYO; MITOCHONDRIAL INTERACTIONS; MUSCLE DEVELOPMENT; TRANSCRIPTION; P3A2; MELANOGASTER AB In Drosophila. the erect wine (ewg) protein is required for proper development of the central nervous system and the indirect flight muscles. The fly ewg gene encodes a novel DNA-binding domain that is also found in four genes previously identified in sea urchin, chicken, zebrafish, and human. To identify mouse ewg homologs, we designed degenerate primers to the conserved DNA-binding domain. The RT-PCR product obtained from mRNA of the mouse muscle cell line C2C12 was used to screen cDNA libraries; a single gene was identified which encodes a predicted 503 amino acid protein. The mouse ewg homolog, termed Nrf1, was mapped to proximal Chr 6. By RT-PCR and Northern analysis, Nrf1 was expressed in all tissues examined, and Northern analysis on adult tissues revealed a complex banding pattern suggesting extensive alternative splicing. Nrf1 hybridized to mRNA transcripts at approximately 2.2 kb, 4.0 kb, 4.4 kb, and 5.0 kb, with additional tissue-specific transcripts at 1.5 kb in testis, 1.9 kb in lung, and 3.7 kb in skeletal muscle. In situ hybridization an whole-mount E9-10.5 embryos showed a broad pattern of expression, with the highest levels of expression in the central nervous system, somites, first branchial arch. optic vesicle, and otic vesicle. C1 Massachusetts Gen Hosp, Myogenesis Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Miller, JB (reprint author), Massachusetts Gen Hosp, Myogenesis Res Lab, 149 13th St, Charlestown, MA 02129 USA. NR 34 TC 6 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD FEB PY 2000 VL 11 IS 2 BP 104 EP 110 DI 10.1007/s003350010021 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 276BV UT WOS:000084856500004 PM 10656923 ER PT J AU Landefeld, CS AF Landefeld, CS TI Different strokes for different folks - Are differences in physician practices good for older persons with diabetes? SO MEDICAL CARE LA English DT Editorial Material C1 Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94118 USA. Univ Calif San Francisco, Ctr Excellence Acad Geriatr, San Francisco, CA 94118 USA. Univ Calif San Francisco, Ctr Aging, San Francisco, CA 94118 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Landefeld, CS (reprint author), Univ Calif San Francisco, Div Geriatr, Box 1265,3333 Calif St,Suite 380, San Francisco, CA 94118 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2000 VL 38 IS 2 BP 125 EP 127 DI 10.1097/00005650-200002000-00001 PG 3 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 280ZH UT WOS:000085133300001 PM 10659685 ER PT J AU Erickson, LA Jin, L Goellner, JR Lohse, C Pankratz, VS Zukerberg, LR Thompson, GB van Heerden, JA Grant, CS Lloyd, RV AF Erickson, LA Jin, L Goellner, JR Lohse, C Pankratz, VS Zukerberg, LR Thompson, GB van Heerden, JA Grant, CS Lloyd, RV TI Pathologic features, proliferative activity, and cyclin D1 expression in Hurthle cell neoplasms of the thyroid SO MODERN PATHOLOGY LA English DT Article DE cyclin D1; Hurthle cell; Ki67; thyroid ID RETINOBLASTOMA PROTEIN EXPRESSION; HUMAN BREAST-CANCER; CARCINOMA; TUMORS; OVEREXPRESSION; GENE; AMPLIFICATION; MALIGNANCY; ONCOGENE; GLAND AB Making a histologic distinction between Hurthle cell adenomas and carcinomas sometimes may be difficult. We analyzed a series of Hurthle cell lesions to determine whether specific histologic features and expression of Ki67 and cyclin D1 could be useful in distinguishing Hurthle cell adenomas from carcinomas. Formalin-fixed, paraffin-embedded tissues from 128 Hurthle cell neoplasms, including 59 adenomas; 55 carcinomas; and 14 tumors classified as neoplasms of uncertain malignant behavior (UMB), which had equivocal capsular invasion but no vascular invasion, were analyzed for expression of Ki67 and cyclin D1 by immunostaining. The distribution of immunoreactivity for Ki67 with antibody MIB-1 was analyzed by quantifying the percentage of positive nuclei that was expressed as the labeling index. None of the patients with adenomas or UMB tumors developed recurrent or metastatic disease after a mean follow-up of 7.8 and 7.9 years, respectively. Of the 55 patients with Hurthle cell. carcinoma, 19 were associated with metastatic disease, 13 of whom died with disease. No patient with a Hurthle cell carcinoma without vascular invasion developed metastatic disease. The mean tumor size for Hurthle cell carcinomas (4.8 cm) was significantly larger than that of Hurthle cell adenomas (3.1 cm) or UMB tumors (3.7 cm). No patient with a Hurthle cell tumor smaller than 3.5 cm developed metastatic disease, even when vascular invasion was present. The Ki67 labeling index in Hurthle cell carcinomas (10.0 +/- 1.2) was 3-fold higher than in Hurthle cell adenomas (3.2 +/- 0.3), The Ki67 labeling index in the UMB group was 5.0 +/- 0.7, Cyclin D1 showed diffuse nuclear staining in 1 of the 59 (1.7%) Hurthle cell adenomas, in 10 of the 55 (18%) Hurthle cell carcinomas, and in none of the UMB tumors. In summary, analyses of the cell cycle proteins Ki67 and cyclin D1 in Hurthle cell thyroid neoplasms indicate that these markers may assist in distinguishing some Hurthle cell carcinomas from adenomas. Among the Hurthle cell carcinomas, large tumor size and vascular invasion are associated with clinically aggressive tumors. Our study also suggests that Hurthle cell neoplasms with only equivocal capsular invasion and no vascular invasion should behave in a benign manner. C1 Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Stat, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Surg, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Lloyd, RV (reprint author), Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Rochester, MN 55905 USA. NR 37 TC 41 Z9 44 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2000 VL 13 IS 2 BP 186 EP 192 DI 10.1038/modpathol.3880034 PG 7 WC Pathology SC Pathology GA 286BF UT WOS:000085423200013 PM 10697277 ER PT J AU Harris, NL Jaffe, ES Diebold, J Flandrin, G Muller-Hermelink, HK Vardiman, J Lister, TA Bloomfield, CD AF Harris, NL Jaffe, ES Diebold, J Flandrin, G Muller-Hermelink, HK Vardiman, J Lister, TA Bloomfield, CD TI The World Health Organization classification of hematological malignancies report of the Clinical Advisory Committee Meeting, Airlie House, Virginia, November 1997 SO MODERN PATHOLOGY LA English DT Article DE classification; histiocytic; leukemia; lymphoma; mast cell; myeloid ID AMERICAN AB Since 1995, the European Association of Pathologists and the Society for Hematopathology have been developing a new World Health Organization (WHO) classification of hematologic malignancies. The classification includes lymphoid, myeloid, histiocytic, and mast cell neoplasms. The WHO project involves 10 committees of pathologists, who have developed Lists and definitions of disease entities. A Clinical Advisory Committee of international hematologists and oncologists was formed to ensure that the classification will be useful to clinicians. A meeting was held in November 1997 to discuss clinical issues related to the classification. The WHO has adopted the Revised European-American Classification of Lymphoid Neoplasms, published in 1994 by the International Lymphoma Study Group, as the classification of lymphoid neoplasms. This approach to classification is based on the principle that a classification is a list of "real" disease entities, which are defined by a combination of morphology, immunophenotype, genetic features, and clinical features. The relative importance of each of these features varies among diseases, and there is no one "gold standard." The WHO classification has applied the principles of the Revised European-American Classification of Lymphoid Neoplasms to myeloid and histiocytic neoplasms. The classification of myeloid neoplasms recognizes distinct entities defined by a combination of morphology and cytogenetic abnormalities. The Clinical Advisory Committee meeting, which was organized around a series of clinical questions, was able to reach a consensus on most of the questions posed. The questions and the consensus are discussed in detail in this article. Among other things, the Clinical Advisory Committee concluded that clinical grouping of lymphoid neoplasms was neither necessary nor desirable. Patient treatment is determined by the specific type of lymphoma, with the addition of grade within the tumor type, if applicable, and clinical prognostic factors such as the international prognostic index. The experience of developing the WHO classification has produced a new and exciting degree of cooperation and communication between oncologists and pathologists from around the world. This should facilitate progress in the understanding and treatment of hematologic malignancies. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Hotel Dieu, Paris, France. Hop Necker Enfants Malad, Paris, France. Univ Wurzburg, Wurzburg, Germany. Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. St Bartholomews Hosp, Dept Med Oncol, London, England. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP Harris, NL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,Fruit St, Boston, MA 02114 USA. NR 4 TC 288 Z9 306 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2000 VL 13 IS 2 BP 193 EP 207 DI 10.1038/modpathol.3880035 PG 15 WC Pathology SC Pathology GA 286BF UT WOS:000085423200014 PM 10697278 ER PT J AU Dobashi, K Ghosh, B Orak, JK Singh, I Singh, AK AF Dobashi, K Ghosh, B Orak, JK Singh, I Singh, AK TI Kidney ischemia-reperfusion: Modulation of antioxidant defenses SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE kidney; ischemia-reperfusion injury; free radicals; reactive oxygen species; gene expression; antioxidant enzymes ID ACUTE-RENAL-FAILURE; RAT-LIVER PEROXISOMES; SUPEROXIDE-DISMUTASE; PROXIMAL TUBULE; TISSUE-INJURY; FREE-RADICALS; OXYGEN; ENZYMES; ACTIVATION; CATALASE AB Reactive oxygen species (ROS; O-2-, H2O2, and OH.), normal by-products of cellular metabolic processes, are kept in control by antioxidant enzymes, such as catalase, glutathione peroxidase (GPX) and superoxide dismutases (SODs). To understand the role of antioxidant enzymatic defenses against ROS injury following ischemia-reperfusion, we examined the effect on kidney exposed to varying periods (30, 60 or 90 min) of ischemia followed by different periods of reperfusion. The enzymatic activities and protein levels of catalase, GPX, CuZnSOD and MnSOD were relatively unaffected at 30 min of ischemia followed by 0, 2 or 24 h reperfusion. However, 60 or 90 min of ischemia followed by 0, 2 or 24 h of reperfusion resulted in a decrease in activities and protein levels which paralleled the duration of ischemic injury. MnSOD activity tended to recover towards normal during reperfusion. Examination of the mRNA levels of these antioxidant enzymes demonstrated a severe decrease in mRNA levels of catalase and GPX at a time point of minimal ischemic injury (30 min of ischemia followed by reperfusion) suggesting that loss of mRNA of catalase and GPX may be the first markers of alterations in cellular redox in ischemia-reperfusion injury. Greater loss of mRNA for catalase, GPX and CuZnSOD were observed following longer periods (60 or 90 min) of ischemia. The mRNA for MnSOD was upregulated at all time points of ischemia-reperfusion injury. Actually, the greater decrease in mRNAs for catalase, GPX and CuZnSOD in the acute phase (within 24 h) subsequently showed a further decrease in these enzyme activities in the subacute phase (72 or 120 h after ischemia). These enzyme activities in the 30 min ischemia group, but not in the 90 min group, already showed tendencies for normalization at 120 h after ischemia. To understand the molecular basis of the loss of mRNA of these antioxidant enzymes during ischemia-reperfusion injury, we examined the rate of transcription by nuclear run-on assays. The similar rates of transcription in control and kidney exposed to ischemia-reperfusion indicates that the loss of mRNA for catalase, GPX and CuZnSOD are possibly due to the increased rate of turnover of their mRNAs. These studies suggest that expression of antioxidant genes during ischemia-reperfusion are not coordinately expressed and the differential loss of antioxidant enzymes may be the contributing factor(s) towards the heterogeneous renal tissue damage as a result of ischemia-reperfusion induced oxidative stress. C1 Ralph Johnson Vet Affairs Med Ctr, Dept Pathol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. RP Singh, AK (reprint author), Ralph Johnson Vet Affairs Med Ctr, Dept Pathol, Charleston, SC 29425 USA. FU NINDS NIH HHS [NS-22576, NS-34741, NS-37766] NR 38 TC 119 Z9 128 U1 0 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD FEB PY 2000 VL 205 IS 1-2 BP 1 EP 11 DI 10.1023/A:1007047505107 PG 11 WC Cell Biology SC Cell Biology GA 288QU UT WOS:000085575400001 PM 10821417 ER PT J AU Dickson, MA Hahn, WC Ino, Y Ronfard, V Wu, JY Weinberg, RA Louis, DN Li, FP Rheinwald, JG AF Dickson, MA Hahn, WC Ino, Y Ronfard, V Wu, JY Weinberg, RA Louis, DN Li, FP Rheinwald, JG TI Human keratinocytes that express hTERT and also bypass a p16(INK4a)-enforced mechanism that limits life span become immortal yet retain normal growth and differentiation characteristics SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN EPIDERMAL-KERATINOCYTES; MAMMARY EPITHELIAL-CELLS; CPG ISLAND METHYLATION; REPLICATIVE SENESCENCE; TELOMERASE ACTIVITY; HUMAN FIBROBLASTS; MESOTHELIAL CELLS; TUMOR SUPPRESSION; GENE; CANCER AB Normal human cells exhibit a limited replicative Life span in culture, eventually arresting growth by a process termed senescence. Progressive telomere shortening appears to trigger senescence in normal human fibroblasts and retinal pigment epithelial cells, as ectopic expression of the telomerase catalytic subunit, hTERT, immortalizes these cell types directly, Telomerase expression alone is insufficient to enable certain other cell types to evade senescence, hoc-ever. Such cells, including keratinocytes and mammary epithelial cells, appear to require loss of the pRB/p16(INK4a) cell cycle control mechanism in addition to hTERT expression to achieve immortality, To investigate the relationships among telomerase activity, cell cycle control, senescence, and differentiation, we expressed hTERT in two epithelial cell types, keratinocytes and mesothelial cells, and determined the effect on proliferation potential and on the function of cell-type-specific growth control and differentiation systems, Ectopic hTERT expression immortalized normal mesothelial cells and a premalignant, p16(INK4a)-negative keratinocyte line. In contrast when four keratinocyte strains cultured from normal tissue were transduced to express hTERT, they were incompletely rescued from senescence. After reaching the population doubling limit of their parent cell strains, hTERT(+) keratinocytes entered a slow growth phase of indefinite length, from which rare, rapidly dividing immortal cells emerged. These immortal cell lines frequently had sustained deletions of the CDK2NA/INK4A locus or otherwise were deficient in p16(INK4a) expression. They nevertheless typically retained other keratinocyte growth controls and differentiated normally in culture and in xenografts. Thus, keratinocyte replicative potential is limited by a p16(INK4n)-dependent mechanism, the activation of which can occur independent of telomere length, Abrogation of this mechanism together with telomerase expression immortalizes keratinocytes without affecting other major growth control or differentiation systems. C1 Harvard Univ, Sch Med, Dept Med, Div Dermatol, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Harvard Skin Dis Res Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA 02115 USA. MIT, Whitehead Inst Biomed Res, Cambridge, MA USA. MIT, Dept Biol, Cambridge, MA USA. Organogenesis Inc, Lab Cell & Tissue Dev, Canton, MA USA. RP Rheinwald, JG (reprint author), Harvard Univ, Inst Med, Room 664,77 Ave Louis Pasteur, Boston, MA 02115 USA. FU NIAMS NIH HHS [P30 AR042689, P30 AR42689]; NIDCR NIH HHS [P01 DE012467, P01 DE12467] NR 62 TC 512 Z9 527 U1 2 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 2000 VL 20 IS 4 BP 1436 EP 1447 DI 10.1128/MCB.20.4.1436-1447.2000 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 279EJ UT WOS:000085031200035 PM 10648628 ER PT J AU Kahn, CR Rafferty, JF AF Kahn, CR Rafferty, JF TI Series: Molecular medicine institutions - The Joslin Diabetes Center SO MOLECULAR MEDICINE LA English DT Editorial Material C1 Joslin Diabet Ctr, Commun Off, Boston, MA 02215 USA. RP Rafferty, JF (reprint author), Joslin Diabet Ctr, Commun Off, 1 Joslin Pl, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 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 FEB PY 2000 VL 6 IS 2 BP 65 EP 68 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 315JQ UT WOS:000087110900001 PM 10859023 ER PT J AU Dunah, AW Wang, YH Yasuda, RP Kameyama, K Huganir, RL Wolfe, BB Standaert, DG AF Dunah, AW Wang, YH Yasuda, RP Kameyama, K Huganir, RL Wolfe, BB Standaert, DG TI Alterations in subunit expression, composition, and phosphorylation of striatal N-methyl-D-aspartate glutamate receptors in a rat 6-hydroxydopamine model of Parkinson's disease SO MOLECULAR PHARMACOLOGY LA English DT Article ID ENHANCED TYROSINE PHOSPHORYLATION; CENTRAL-NERVOUS-SYSTEM; NMDA RECEPTOR; BASAL GANGLIA; L-DOPA; DOPAMINERGIC DENERVATION; PROTEIN-KINASE; BINDING-SITES; 2B SUBUNIT; ANTAGONISTS AB Recent evidence has linked striatal N-methyl-D-aspartate (NMDA) receptor function to the adverse effects of long-term dopaminergic treatment in Parkinson's disease. We have studied the abundance, composition, and phosphorylation of NMDA receptor subunits (NRs) in the rat 6-hydroxydopamine lesion model of parkinsonism. In lesioned striatum, the abundance of NR1 and NR2B in striatal membranes was decreased to 68 +/- 3.2 and 62 +/- 4.4%, respectively, relative to the unlesioned striata, whereas the abundance of NR2A was unchanged. Coimmunoprecipitation of NMDA receptors under nondenaturing conditions revealed that these changes reflected a selective depletion of receptors composed of NR1/NR2B, without alteration in receptors composed of NR1/NR2A. However, the abundance and composition of striatal NMDA receptors in extracts containing both cytoplasmic and membrane proteins were not altered in lesioned rats, suggesting that the changes in the membrane fraction resulted from intracellular redistribution of receptors. The phosphorylation of NR1 protein at serine 890 and serine 896, but not at serine 897, and the tyrosine phosphorylation of NR2B but not NR2A were decreased in the membrane fraction of the lesioned striatum. Chronic treatment of lesioned rats with L-dopa normalized the alterations in the abundance and subunit composition of the NMDA receptors in striatal membranes, and produced striking hyperphosphorylation, both of NR1 at serine residues, and NR2A and NR2B at tyrosine residues. These findings suggest that the adverse motor effects of chronic L-dopa therapy may result from alterations in regulatory phosphorylation sites on NMDA receptors. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Georgetown Univ, Sch Med, Dept Pharmacol, Washington, DC USA. Johns Hopkins Univ, Med Ctr, Dept Neurosci, Baltimore, MD 21218 USA. RP Standaert, DG (reprint author), Massachusetts Gen Hosp, Dept Neurol, Warren 408,32 Fruit St, Boston, MA 02114 USA. OI Standaert, David/0000-0003-2921-8348 FU NINDS NIH HHS [NS31579, NS2830, NS34361] NR 45 TC 184 Z9 189 U1 0 U2 2 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 FEB PY 2000 VL 57 IS 2 BP 342 EP 352 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 280BC UT WOS:000085081300015 PM 10648644 ER PT J AU Dranoff, C AF Dranoff, C TI Targeting gene therapy - A reality? SO MOLECULAR THERAPY LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Dranoff, C (reprint author), Dana Farber Canc Inst, Dana 510E,44 Binney St, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD FEB PY 2000 VL 1 IS 2 BP 117 EP 118 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 366RN UT WOS:000090018500003 ER PT J AU Eroglu, A Russo, MJ Bieganski, R Fowler, A Cheley, S Bayley, H Toner, M AF Eroglu, A Russo, MJ Bieganski, R Fowler, A Cheley, S Bayley, H Toner, M TI Intracellular trehalose improves the survival of cryopreserved mammalian cells SO NATURE BIOTECHNOLOGY LA English DT Article DE trehalose; alpha-toxin; cryopreservation; fibroblasts; keratinocytes ID PORE-FORMING PROTEIN; ALPHA-TOXIN; STABILIZATION; MEMBRANE; SWITCH AB We report that the introduction of low concentrations of intracellular trehalose can greatly improve the survival of mammalian cells during cryopreservation. Using a genetically engineered mutant of Staphylococcus aureus alpha-hemolysin to create pores in the cellular membrane, we were able to load trehalose into cells. Low concentrations (0.2 M) of trehalose permitted long-term post-thaw survival of more than 80% of 3T3 fibroblasts and 70% of human keratinocytes. These results indicate that simplified and widely applicable freezing protocols may be possible using sugars as intracellular cryoprotective additives. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Serv, Boston, MA 02114 USA. Shriners Hosp Crippled Children, Boston, MA 02114 USA. Texas A&M Univ, Dept Med Biochem & Genet, College Stn, TX 77843 USA. Univ Massachusetts, Dept Mech Engn, N Dartmouth, MA 02747 USA. RP Toner, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK46270]; NINDS NIH HHS [NS26760] NR 23 TC 270 Z9 283 U1 6 U2 34 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD FEB PY 2000 VL 18 IS 2 BP 163 EP 167 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 281FH UT WOS:000085146900022 PM 10657121 ER PT J AU O'Hagan, RC Schreiber-Agus, N Chen, K David, G Engelman, JA Schwab, R Alland, L Thomson, C Ronning, DR Sacchettini, JC Meltzer, P DePinho, RA AF O'Hagan, RC Schreiber-Agus, N Chen, K David, G Engelman, JA Schwab, R Alland, L Thomson, C Ronning, DR Sacchettini, JC Meltzer, P DePinho, RA TI Gene-target recognition among members of the Myc superfamily and implications for oncogenesis SO NATURE GENETICS LA English DT Article ID C-MYC; DNA-BINDING; REPRESSES TRANSCRIPTION; CELL-GROWTH; IN-VIVO; MAX; PROTEIN; DOMAIN; DIFFERENTIATION; NETWORK AB Myc and Mad family proteins regulate multiple biological processes through their capacity to influence gene expression directly. Here we show that the basic regions of Myc and Mad proteins are not functionally equivalent in oncogenesis, have separable E-box-binding activities and engage both common and distinct gene targets. Our data support the view that the opposing biological actions of Myc and Mxi1 extend beyond reciprocal regulation of common gene targets. Identification of differentially regulated gene targets provides a framework for understanding the mechanism through which the Myc superfamily governs the growth, proliferation and survival of normal and neoplastic cells. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. Texas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NEI NIH HHS [R01EY09300]; NICHD NIH HHS [R01HD28317] NR 37 TC 115 Z9 117 U1 0 U2 1 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 FEB PY 2000 VL 24 IS 2 BP 113 EP 119 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 280LQ UT WOS:000085104600009 PM 10655054 ER PT J AU Jain, RK Munn, LL AF Jain, RK Munn, LL TI Leaky vessels? Call Angl1! SO NATURE MEDICINE LA English DT Editorial Material ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY; ANGIOGENESIS; ADHESION; MICE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Steele Lab, Boston, MA 02114 USA. RP Jain, RK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Steele Lab, Boston, MA 02114 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 17 TC 65 Z9 69 U1 0 U2 5 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 FEB PY 2000 VL 6 IS 2 BP 131 EP 132 DI 10.1038/72212 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 278YQ UT WOS:000085016900021 PM 10655092 ER PT J AU Baba, TW Liska, V Hofmann-Lehmann, R Vlasak, J Xu, WD Ayehunie, S Cavacini, LA Posner, MR Katinger, H Stiegler, G Bernacky, BJ Rizvi, TA Schmidt, R Hill, LR Keeling, ME Lu, YC Wright, JE Chou, TC Ruprecht, RM AF Baba, TW Liska, V Hofmann-Lehmann, R Vlasak, J Xu, WD Ayehunie, S Cavacini, LA Posner, MR Katinger, H Stiegler, G Bernacky, BJ Rizvi, TA Schmidt, R Hill, LR Keeling, ME Lu, YC Wright, JE Chou, TC Ruprecht, RM TI Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection SO NATURE MEDICINE LA English DT Article ID COMPLEMENT-MEDIATED LYSIS; CELL-FREE SIV; SYNERGISTIC NEUTRALIZATION; TYPE-1; MACAQUES; HIV-1; MONKEYS; EPITOPE; BINDING; GP120 AB Although maternal human immunodeficiency virus type 1 (HIV-1) transmission occurs during gestation, intrapartum and postpartum (by breast-feeding), 50-70% of all infected children seem to acquire HIV-1 shortly before or during delivery(1). Epidemiological evidence indicates that mucosal exposure is an important aspect of intrapartum HIV transmission(2,3). A simian immunodeficiency virus (SIV) macaque model has been developed(4) that mimics the mucosal exposure that can occur during intrapartum HIV-1 transmission. To develop immunoprophylaxis against intrapartum HIV-1 transmission, we used SHIV-vpu(+) (refs. 5,6), a chimeric simian-human virus that encodes the env gene of HIV-IIIB. Several combinations of human monoclonal antibodies against HIV-1. have been identified that neutralize SHIV-vpu(+) completely in vitro through synergistic interaction(7). Here, we treated four pregnant macaques with a triple combination of the human IgG1 monoclonal antibodies F105, 2G12 and 2F5. All four macaques were protected against intravenous SHIV-vpu(+) challenge after delivery. The infants received monoclonal antibodies after birth and were challenged orally with SHIV-vpu(+) shortly thereafter. We found no evidence of infection in any infant during 6 months of follow-up. This demonstrates that IgG1 monoclonal antibodies protect against mucosal lentivirus challenge in neonates. We conclude that epitopes recognized by the three monoclonal antibodies are important determinants for achieving substantial protection, thus providing a rational basis for AIDS vaccine development. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Tufts Univ, Sch Med, Dept Pediat, Div Newborn Med, Boston, MA 02111 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Inst Appl Microbiol, A-1190 Vienna, Austria. Univ Texas, MD Anderson Canc Ctr, Dept Vet Sci, Bastrop, TX 78602 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Biochem Pharmacol Lab, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Preclin Pharmacol Core Facil, New York, NY 10021 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RI Hofmann-Lehmann, Regina/C-6528-2009; Chou, Ting-Chao/B-4111-2009 OI Chou, Ting-Chao/0000-0002-3340-1594 FU NIAID NIH HHS [R01 AI26926, R01 AI32330, R01 AI34266] NR 25 TC 664 Z9 674 U1 1 U2 15 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 FEB PY 2000 VL 6 IS 2 BP 200 EP 206 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 278YQ UT WOS:000085016900042 PM 10655110 ER PT J AU Lu, QR Yuk, DI Alberta, JA Zhu, ZM Pawlitzky, I Chan, J McMahon, AP Stiles, CD Rowitch, DH AF Lu, QR Yuk, DI Alberta, JA Zhu, ZM Pawlitzky, I Chan, J McMahon, AP Stiles, CD Rowitch, DH TI Sonic hedgehog-regulateld oligodendrocyte lineage genes encoding bHLH proteins in the mammalian central nervous system SO NEURON LA English DT Article ID VENTRAL NEURAL-TUBE; ZONE PROGENITOR CELLS; SPINAL-CORD; FLOOR PLATE; VENTRICULAR ZONE; STEM-CELLS; HOMEODOMAIN PROTEIN; NEURONAL FATE; MESSENGER-RNA; GROWTH-FACTOR AB During development, basic helix-loop-helix (bHLH) proteins regulate formation of neurons from multipotent progenitor cells. However, bHLH factors linked to gliogenesis have not been described. We have isolated a pair of oligodendrocyte lineage genes (Olg-1 and Olg-2) that encode bHLH proteins and are tightly associated with development of oligodendrocytes in the vertebrate central nervous system (CNS). Ectopic expression of Olg-1 in rat cortical progenitor cell cultures promotes formation of oligodendrocyte precursors. In developing mouse embryos, Olg gene expression overlaps but precedes the earliest known markers of the oligodendrocyte lineage. Olg genes are expressed at the tetencephalon-diencephalon border and adjacent to the floor plate, a source of the secreted signaling molecule Sonic hedgehog (Shh). Gain- and loss-of-function analyses in transgenic mice demonstrate that Shh is both necessary and sufficient for Olg gene expression in vivo. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Stiles, CD (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RI Messier, Claude/A-2322-2008 OI Messier, Claude/0000-0002-4791-1763 FU NICHD NIH HHS [HD01182, HD24296] NR 66 TC 557 Z9 577 U1 1 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD FEB PY 2000 VL 25 IS 2 BP 317 EP 329 DI 10.1016/S0896-6273(00)80897-1 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 288EL UT WOS:000085549100011 PM 10719888 ER PT J AU Field, MD Maywood, ES O'Brien, JA Weaver, DR Reppert, SM Hastings, MH AF Field, MD Maywood, ES O'Brien, JA Weaver, DR Reppert, SM Hastings, MH TI Analysis of clock proteins in mouse SCN demonstrates phylogenetic divergence of the circadian clockwork and resetting mechanisms SO NEURON LA English DT Article ID SUPRACHIASMATIC NUCLEUS; DROSOPHILA CLOCK; PERIOD HOMOLOGS; LIGHT; TIMELESS; MPER1; PHOSPHORYLATION; NEURONS; GENE AB The circadian clock in the suprachiasmatic nuclei (SCN) is comprised of a cell-autonomous, autoregulatory transcriptional/translational feedback loop. Its molecular components include three period and two cryptochrome genes. We describe circadian patterns of expression of mPER2 and mPER3 in the mouse SCN that are synchronous to those for mPER1, mCRY1, and mCRY2. Coimmunoprecipitation experiments demonstrate in vivo associations of the SCN mPER proteins with each other and with the mCRY proteins, and of mCRY proteins with mTIM, but no mPER/mTIM interactions. Examination of the effects of weak and strong resetting light pulses on SCN clock proteins highlights a central role for mPER1 in photic entrainment, with no acute light effects on either the mCRY or mTIM proteins. These crock protein interactions and photic responses in mice are divergent from those described in Drosophila. C1 Univ Cambridge, Dept Anat, Cambridge CB2 3DY, England. MRC, Mol Biol Lab, Div Neurobiol, Cambridge CB2 2QH, England. Massachusetts Gen Hosp, Serv Pediat, Lab Dev Chronobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Hastings, MH (reprint author), Univ Cambridge, Dept Anat, Downing St, Cambridge CB2 3DY, England. OI Weaver, David/0000-0001-7941-6719 FU NICHD NIH HHS [R37 HD14427] NR 40 TC 253 Z9 256 U1 1 U2 13 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD FEB PY 2000 VL 25 IS 2 BP 437 EP 447 DI 10.1016/S0896-6273(00)80906-X PG 11 WC Neurosciences SC Neurosciences & Neurology GA 288EL UT WOS:000085549100020 PM 10719897 ER PT J AU Santarius, T Kirsch, M Nikas, DC Imitola, J Black, PM AF Santarius, T Kirsch, M Nikas, DC Imitola, J Black, PM TI Molecular analysis of alterations of the p18(INK4c) gene in human meningiomas SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY LA English DT Article DE immunohistochemistry; loss of heterozygosity; meningioma; mutation; p18; tumour suppressor gene ID ALLELIC LOSS; BREAST-CANCER; P18 GENES; INHIBITOR; DELETIONS; IDENTIFICATION; CHROMOSOME; TUMORS; 1P32; 19Q AB Meningiomas are common primary brain tumours frequently presenting with deleted and/or mutated NF2 gene located on 22q.1p has been reported as the second most commonly deleted chromosomal region in these neoplasms. A new member of the INK4 family of CDK inhibitors, the p18(INK4c) gene, has recently been mapped to this chromosomal arm. By virtue of its structural and functional similarities with the p16 gene, p18 has been implicated as a tumour suppressor gene in a variety of cancers. In this paper 40 human meningiomas were analysed for loss of heterozygosity (LOH) at the p18 locus, mutations and inactivating methylation of the p18 gene. LOH at D1S193, D1S463 and D1S211 microsatellite marker loci mapped to 1p32 was detected in 13 of 35 (37%), four of 20 (20%), and six of 24 (25%) tumour samples, respectively. One sample presented with homozygous deletion at D1S193. Mutational analysis using single stranded conformational polymorphism (SSCP) and direct sequencing did not detect any missense mutation but revealed a novel silent mutation, G to T, at coding nucleotide 435. Analysis of HgaI, BsaHI, ScrFI and Eco0109I restriction sites of p18 exon 1 revealed absence of inactivating methylation. Immunohistochemistry with p18 monoclonal antibody detected presence of cytoplasmic p18 staining in 21 of 22 examined samples. One sample did not stain and was shown to carry homozygous deletion at D1S193. Despite the high frequency of LOH at 1p32 microsatellite markers, the lack of genetic and epigenetic aberrations in the p18 gene together with the presence of p18 protein in all but one meningioma samples argues against the role of p18 as a tumour suppressor gene important for meningioma development. C1 Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Brigham & Womens Hosp, Neurosurg Labs, Boston, MA 02115 USA. Brigham & Womens Hosp, Brain Tumor Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Dana Farber Canc Inst, Boston, MA 02115 USA. Birmingham Heartlands Hosp, Dept ENT, Birmingham B9 5ST, W Midlands, England. Univ Birmingham, Queen Elizabeth Hosp, Dept Neurosurg, Birmingham B15 2TH, W Midlands, England. Tech Univ Dresden, Carl Gustav Carus Univ Klinikum, Neurochirurg Klin, D-8027 Dresden, Germany. RP Black, PM (reprint author), Childrens Hosp, Dept Neurosurg, 300 Longwood Ave, Boston, MA 02115 USA. RI Kirsch, Matthias/F-2824-2014 FU NINDS NIH HHS [1F05NS10174-01] NR 28 TC 21 Z9 23 U1 1 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0305-1846 J9 NEUROPATH APPL NEURO JI Neuropathol. Appl. Neurobiol. PD FEB PY 2000 VL 26 IS 1 BP 67 EP 75 DI 10.1046/j.1365-2990.2000.00219.x PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 293HN UT WOS:000085846200008 PM 10736068 ER PT J AU Loda, M Xu, X Pession, A Vortmeyer, A Giangaspero, F AF Loda, M Xu, X Pession, A Vortmeyer, A Giangaspero, F TI Membranous expression of glucose transporter-1 protein (GLUT-1) in embryonal neoplasms of the central nervous system SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY LA English DT Article DE brain neoplasms; embryonal neoplasms; glucose transporter protein; medulloblastoma; PNET ID BLOOD-BRAIN-BARRIER; ATYPICAL TERATOID/RHABDOID TUMOR; PRIMITIVE NEUROECTODERMAL TUMORS; NEURAL TRANSPLANTS; CELL-LINE; IMMUNOPHENOTYPE; LOCALIZATION; ONTOGENY AB The human erythrocyte GLUT-1 is a transmembrane protein which facilitates transport of glucose in the cell in an energy-independent fashion. Neuroectodermal stem cells show strong membrane immunoreactivitry with this marker at early developmental stages in rodents. Membranous expression by undifferentiated neuroectodermal cells gradually decreases while GLUT-1 becomes confined to the endothelial cells, when these acquire blood-brain barrier function. We thus sought to determine whether GLUT-1 expression was limited to embryonal neoplasms of the central nervous system (CNS) which are presumably derived from developmentally arrested neuroectodermal stem cells. Archival material of 40 primary CNS neoplasms were examined for immunoreactivity with anti-GLUT-1. This included both non-embryonal neoplasms (18 astrocytic tumours, one ependymoma and three oligodendroglioma) and embryonal neoplasms (12 cerebellar medulloblastomas, four supratentorial PNETs and two atypical teratoid/rhabdoid tumours (AT/RhT)). In addition, cell lines and nude mice xenografts derived from both undifferentiated and differentiated tumours were assessed for GLUT-1 immunoreactivity by both immunohistochemistry and Western blotting. All embryonal tumours, MBs and PNET xenografts consistently showed GLUT-1 membrane staining. Non-embryonal neoplasms were negative except for vascular staining. Membrane protein fraction of embryonal tumours cell lines immunoreacted by immunoblot with GLUT-1, whereas the glioblastoma cell line was negative. Expression of GLUT-1 supports the stem cell nature of the cells of origin of MBs, supratentorial PNET and AT/RhTs. As a result, GLUT-1 is a useful marker to define the embryonal nature of CNS neoplasms. C1 Osped M Bufalini, Ist Anat Patol, Dept Anat Pathol, I-47023 Cesena, Italy. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. Univ Bologna, Dept Expt Pathol, I-40126 Bologna, Italy. NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Giangaspero, F (reprint author), Osped M Bufalini, Ist Anat Patol, Dept Anat Pathol, Viale G Ghirotti 286, I-47023 Cesena, Italy. RI Pession, Annalisa/B-9014-2012; OI Pession, Annalisa/0000-0001-9035-9698 NR 23 TC 15 Z9 15 U1 2 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0305-1846 J9 NEUROPATH APPL NEURO JI Neuropathol. Appl. Neurobiol. PD FEB PY 2000 VL 26 IS 1 BP 91 EP 97 DI 10.1046/j.1365-2990.2000.00225.x PG 7 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 293HN UT WOS:000085846200010 PM 10736070 ER PT J AU Kim, I Leinweber, BD Morgalla, M Butler, WE Seto, M Sasaki, Y Peterson, JW Morgan, KG AF Kim, I Leinweber, BD Morgalla, M Butler, WE Seto, M Sasaki, Y Peterson, JW Morgan, KG TI Thin and thick filament regulation of contractility in experimental cerebral vasospasm SO NEUROSURGERY LA English DT Article DE calponin; myosin light chain phosphorylation; proteolysis; spasm; vascular smooth muscle ID LIGHT-CHAIN PHOSPHORYLATION; SMOOTH-MUSCLE CONTRACTION; PROTEIN-KINASE INHIBITOR; SUBARACHNOID HEMORRHAGE; MYOSIN PHOSPHORYLATION; CALPONIN; HA1077; CALCIUM; CALPAIN; ARTERY AB OBJECTIVE: Cerebral vasospasm is a potentially fatal consequence of aneurysmal subarachnoid hemorrhage and influences the prognosis of the patient. The purpose of this study was to evaluate the status of thin (actin) and thick (myosin) filament regulation of smooth muscle contraction in the double-subarachnoid hemorrhage canine model of cerebral vasospasm and to determine the effects of a kinase inhibitor reported to be effective in vasospasm, HA1077, on thin and thick filament regulation. METHODS: Cerebral vasospasm was assessed by vertebral angiography. Myosin regulatory light chain phosphorylation was measured using glycerol-urea gels, whereas protein levels of the thin filament-associated protein calponin were measured by Western blot. RESULTS: The basilar arteries of dogs in which subarachnoid hemorrhage was induced narrowed to 36% +/- 2.0% of their size on the first day (n = 12). The phosphorylation of the regulatory light chain tended to increase, but the change did not reach statistical significance (35% +/- 5.9% [n = 12] versus 25% +/- 4.8% [n = 10] in control arteries). In contrast to this increase, significant degradation of calponin was observed in the samples from vasospastic dogs (85.4% +/- 5.45% [n = 5] versus 15.2% +/- 6.21% [n = 5]; P < 0.01). Prophylactic treatment with intravenous injections of HA1077 at 0.67 mg/kg b.i.d. significantly inhibited vasospasm (diameters, 65% +/- 10.2% of Day 1 diameters [n = 5]; P < 0.05), and calponin degradation (57.8% +/- 13.9% [n = 4]) was substantially reduced. CONCLUSION: These data suggest that degradation of the thin filament-associated protein calponin plays a role in cerebral vasospasm and that the antivasospastic action of HA1077 is, at least in part, due to prevention of calponin degradation. C1 Boston Biomed Res Inst, Signal Transduct Grp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Asahi Chem Ind Co Ltd, Frontier Project 21, Life Sci Res Ctr, Shizuoka, Japan. RP Morgan, KG (reprint author), Boston Biomed Res Inst, Signal Transduct Grp, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL31704, HL42293] NR 22 TC 29 Z9 31 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 FEB PY 2000 VL 46 IS 2 BP 440 EP 446 DI 10.1097/00006123-200002000-00033 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 281ZR UT WOS:000085191800096 PM 10690734 ER PT J AU Akpek, EK Hasiripi, H Christen, WG Kalayci, D AF Akpek, EK Hasiripi, H Christen, WG Kalayci, D TI A randomized trial of low-dose, topical mitomycin-C in the treatment of severe vernal keratoconjunctivitis SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Centennial Meeting of the American-Academy-of-Ophthalmology CY OCT 27-31, 1996 CL CHICAGO, ILLINOIS SP Amer Acad Ophthalmol ID PTERYGIUM EXCISION; NEOPLASIA; TRABECULECTOMY; CYCLOSPORINE; CONJUNCTIVAL; THERAPY; SURGERY AB Objective: To evaluate the efficacy and safety of low-dose, topical mitomycin-C in patients with severe vernal keratoconjunctivitis. Design: Placebo-controlled, double-masked, randomized clinical trial. Participants: Twenty-six patients with vernal keratoconjunctivitis refractory to combination of steroid and mast-cell stabilizer treatment. intervention: Patients were randomly assigned (2:1) to treatment with topical 0.01% mitomycin-C eye drops (n = 17) or placebo (n = 9) three times daily for 2 weeks. Main Outcome Measures: Symptoms (itching, tearing, photophobia, ropy mucous discharge, foreign body sensation) and signs (conjunctival hyperemia, epithelial punctate keratitis, Trantas' dots, limbal edema, and palpebral conjunctival giant papillae) of vernal keratoconjunctivitis recorded on the day of enrollment and at the end of the treatment period. Results: There was a statistically significant decrease in ropy mucous discharge, photophobia, conjunctival hyperemia, and limbal edema in the mitomycin-C treated group compared with the placebo group at the end of the 2-week treatment period. In addition, none of the 17 treated patients, but all 9 of the placebo patients, required medication during the dr-week posttreatment follow-up period. No adverse effects of treatment with mitomycin-C were observed. Conclusions: Short-term, low-dose, topical mitomycin-C may be considered in the acute exacerbation periods of patients with severe vernal keratoconjunctivitis refractory to conventional treatment. (C) 2000 by the American Academy of Ophthalmology. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Immunol Serv, Boston, MA 02115 USA. Ankara Numune Hosp, Dept Ophthalmol, Cornea & External Dis Serv, Ankara, Turkey. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Prevent Med, Boston, MA 02115 USA. RP Akpek, EK (reprint author), Johns Hopkins Hosp, Wilmer Eye Inst, Cornea & External Dis Serv, 600 N Wolfe St,Maumenee Bldg 327, Baltimore, MD 21287 USA. NR 39 TC 25 Z9 28 U1 0 U2 1 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 FEB PY 2000 VL 107 IS 2 BP 263 EP 269 DI 10.1016/S0161-6420(99)00096-2 PG 7 WC Ophthalmology SC Ophthalmology GA 279ZY UT WOS:000085078200021 PM 10690822 ER PT J AU Gasch, AT Wang, P Pasquale, LR AF Gasch, AT Wang, P Pasquale, LR TI Determinants of glaucoma awareness in a general eye clinic SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of ARVO CY MAY, 1999 CL FT LAUDERDALE, FLORIDA SP ARVO ID QUALITY-OF-LIFE; OPEN-ANGLE GLAUCOMA; PREVALENCE; AMERICANS; KNOWLEDGE; BLINDNESS; EDUCATION; BALTIMORE AB Purpose: Heightened public awareness about glaucoma may increase the chance of identifying undetected cases. To ascertain determinants of glaucoma awareness, we surveyed a population visiting a general eye clinic, Design: Cross-sectional study. Participants: 1197 general eye clinic patients and their companions. Methods: We designed and administered a questionnaire about glaucoma to general eye clinic patients and their companions. We created multivariate logistic regression models to ascertain the effect of demographic and clinical features on the likelihood of being unaware of glaucoma. Main Outcome Measures: Adjusted odds ratio (OR) with 95% confidence intervals of survery attributes associated with self-perceived unfamiliarity with glaucoma. Results: Glaucoma awareness overall (72%) approached that found in the subgroup self-reporting a diagnosis of glaucoma (80%), Survey attributes associated with an increased likelihood of being unaware of glaucoma were African American race (OR = 1.69 [1.28-2,20], Hispanic ethnicity (OR = 2.13 [1.46-3.02]), and less than a college education (OR = 1,67 [1,37-2,05]). Age was also a determinant of glaucoma awareness (for ages 50-64 years, OR = 0.60 [0.44-0.80] and for ages 65-79 years, OR = 0.56 [0.41-0.75] compared with ages less than 35 years). A self-report of glaucoma was not a determinant of glaucoma awareness (OR = 0.63 [0,33-1,17]), although there was a trend toward enhanced glaucoma awareness in this subgroup. Finally, respondents with a history of employment in the health field (OR = 0.63 [0.49-0.82]) myopia (OR = 0.68 [0,56-0.82]), glaucoma in a first-degree relative (OR = 0.68 [0.53-0.87]), and respondents who reported having a dilated eye examination (OR = 0.53 [0.42-0.66]) were less likely to be unaware of glaucoma than those who did not have these attributes. Conclusions: Although glaucoma awareness in this population was high, Hispanics, African Americans, and those with less than a college education were more likely to be unfamiliar with the disease, Interestingly, a self-report of having glaucoma was not a statistically significant determinant of glaucoma awareness. (C) 2000 by the American Academy of Ophthalmology. C1 Massachusetts Eye & Ear Infirm, Glaucoma Consultat Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Ophthalmol, Boston, MA 02115 USA. RP Pasquale, LR (reprint author), Massachusetts Eye & Ear Infirm, Glaucoma Consultat Serv, 243 Charles St, Boston, MA 02114 USA. NR 27 TC 42 Z9 47 U1 1 U2 5 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 FEB PY 2000 VL 107 IS 2 BP 303 EP 308 DI 10.1016/S0161-6420(99)00076-7 PG 6 WC Ophthalmology SC Ophthalmology GA 279ZY UT WOS:000085078200030 PM 10690830 ER PT J AU Levin, LA Gragoudas, ES Lessell, S AF Levin, LA Gragoudas, ES Lessell, S TI Endothelial cell loss in irradiated optic nerves SO OPHTHALMOLOGY LA English DT Article ID DELAYED RADIATION NECROSIS; HYPERBARIC-OXYGEN; RAT LUNG; NEUROPATHY; BRAIN; INJURY; DISEASE; CHIASM AB Objective: Radiation optic neuropathy usually occurs months to years after exposure of the anterior visual pathways to ionizing radiation. It is characterized by high signal on gadolinium-enhanced T1-weighted magnetic resonance imaging. Radiation-induced endothelial cell damage resulting in blood-nerve barrier breakdown is hypothesized to produce this pattern, but histologic evidence of this in the optic nerve is lacking. We attempted to evaluate the effect of radiation on endothelial cells in the optic nerve. Design: Case-controlled histologic study. Methods: We studied the optic nerves of 16 enucleated eyes from patients with uveal melanoma treated with proton beam irradiation, 6 from normal eyes and 5 from eyes with unirradiated uveal melanomas. Binding of Ulex europaeus agglutinin I (UEA-I) lectin was used to identify endothelial cells in single paraffin sections. Transverse and longitudinal sections of vessels were counted in masked fashion. Results: There were 49.4 +/- 6.9 transversely sectioned endothelial cells per millimeter of nerve in 6 optic nerves exposed to 0 to 1000 cGyE ("low-dose") compared with 17.3 +/- 5.3 in 10 nerves exposed to 5500 to 7000 cGyE ("high-dose") (P = 0.002). Longitudinally sectioned vessels stained with UEA-I were separately identified, with 11.5 +/- 2.1 in the low-dose group and 5.6 +/- 1.6 in the high-dose group (P = 0.044). The thickness and staining of the endothelial cell layer appeared greater in the high-dose group. Endothelial cell counts did not correlate with age, gender, acuity, or interval after irradiation. Conclusions: Increased radiation dosage to the optic nerve correlates with smaller numbers of endothelial cells. (C) 2000 by the American Academy of Ophthalmology. C1 Univ Wisconsin, Sch Med, Dept Ophthalmol & Visual Sci K6456, Madison, WI 53792 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Levin, LA (reprint author), Univ Wisconsin, Sch Med, Dept Ophthalmol & Visual Sci K6456, 600 Highland Ave, Madison, WI 53792 USA. NR 37 TC 26 Z9 29 U1 0 U2 1 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 FEB PY 2000 VL 107 IS 2 BP 370 EP 374 DI 10.1016/S0161-6420(99)00054-8 PG 5 WC Ophthalmology SC Ophthalmology GA 279ZY UT WOS:000085078200044 PM 10690841 ER PT J AU Kayhan, FT Zurakowski, D Rauch, SD AF Kayhan, FT Zurakowski, D Rauch, SD TI Toronto Facial Grading System: Interobserver reliability SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT World Congress of Otolaryngology CY MAR 02-07, 1997 CL SYDNEY, AUSTRALIA AB The Toronto Facial Grading System (TFGS) is an observer scale for rating facial nerve dysfunction. The TFGS scores aspects of resting symmetry, symmetry of voluntary movement, and synkinesis for each division of the face (subscores) and then provides calculated total scores and an overall composite score of facial function. The developers of the scale have validated its sensitivity for identifying small changes in facial dysfunction and the independence of the different components measured. Herein we report our results in a study of interobserver reliability using the TFGS. Twenty-five patients from the Massachusetts Eye and Ear Infirmary Facial Nerve Center with varying degrees of facial paresis, paralysis, and synkinesis were videotaped, and the video recordings were scored by 5 independent observers using the TFGS, Intraclass correlation coefficients (kappa) and 95% confidence intervals were calculated for subscores and for each total and composite score. Intraclass correlation coefficients ranged from 0.59 to 0.85, all considered substantial to near-perfect agreement between observers, We believe the TFGS is superior to other scales by virtue of its sensitivity, comprehensiveness, ease of use, and interobserver reliability The TFGS presently appears to be the best option in those situations in which accurate and precise documentation of facial function is required. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Res Comp & Biostat, Boston, MA 02115 USA. RP Rauch, SD (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. NR 14 TC 31 Z9 33 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD FEB PY 2000 VL 122 IS 2 BP 212 EP 215 DI 10.1016/S0194-5998(00)70241-5 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 281KG UT WOS:000085158200010 PM 10652392 ER PT J AU Siegel, NS Gliklich, RE Taghizadeh, F Chang, YC AF Siegel, NS Gliklich, RE Taghizadeh, F Chang, YC TI Outcomes of septoplasty SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 13-16, 1998 CL SAN ANTONIO, TEXAS SP Amer Acad Otolaryngol Head & Neck Surg ID NASAL AIRWAY-RESISTANCE; CHRONIC SINUSITIS; SURGERY; FLOW; RHINOMANOMETRY; OTOLARYNGOLOGY; QUALITY AB A prospective nonrandomized study of consecutive patients presenting to the Massachusetts Eye and Ear Infirmary for septoplasty was conducted to evaluate patient-based outcome. Patients received statistically validated measures of general health status (Short Form-12) and nasal specific health (Nasal Health Survey) before and 6 and 12 months after surgery. Multiple perioperative patient- and surgeon-dependent treatment variables were also evaluated to determine the impact on outcome. A total of 161 patients were entered into the study, and 93 were available for statistical analysis. At 9 months the mean follow-up (range 6-12 months), both symptom and medication subscores of the Nasal Health Survey, and the total score demonstrated significant improvement (P < 0.05); 71% of patients had clinically significant improvement as determined by at least a 50% decrease in duration of nasal symptoms. Measures of general health did not differ significantly from normative values at baseline and did not change after surgical intervention. Predictor analysis revealed that female gender and a history of previous nasal surgery predicted worse outcome. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Clin Outcomes Res Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Outcome Sci LLC, Boston, MA USA. RP Gliklich, RE (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 23 TC 66 Z9 67 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD FEB PY 2000 VL 122 IS 2 BP 228 EP 232 DI 10.1016/S0194-5998(00)70244-0 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 281KG UT WOS:000085158200013 PM 10652395 ER PT J AU Chang, L Mayer, EA Johnson, T FitzGerald, LZ Naliboff, B AF Chang, L Mayer, EA Johnson, T FitzGerald, LZ Naliboff, B TI Differences in somatic perception in female patients with irritable bowel syndrome with and without fibromyalgia SO PAIN LA English DT Article DE irritable bowel syndrome; fibromyalgia; female; somatic perception ID LONGITUDINAL DATA-ANALYSIS; CONVERGENT NEURONS; PAIN; HYPERSENSITIVITY; CLASSIFICATION; HYPERALGESIA; DYSFUNCTION; STIMULATION; DISTENSION; AFFERENTS AB Background: Irritable bowel syndrome (IBS) and fibromyalgia (FM) an considered chronic syndromes of altered visceral and somatic perception, respectively. Because there is a significant overlap of IBS and FM, shared pathophysiological mechanisms have been suggested. Although visceral perception has been well studied in IBS, somatic perception has npt. Aims: To compare hypervigilance and altered sensory perception in response to somatic stimuli in patients with IBS, IBS + FM, and healthy controls. Methods: Eleven IBS females (mean age 40), 11 IBS + FM females (mean age 46), and ten healthy female controls (mean age 39) rated pain perception in response to pressure stimuli administered to active somatic tender points, non-render control points and the T-12 dermatome, delivered in a predictable ascending series, and delivered in an unpredictable randomized fashion (fixed stimulus). Results. Although IBS patients had similar pain thresholds during the ascending series compared with controls, they were found to have somatic hypoalgesia with higher pain thresholds and lower pain frequency and severity during fixed stimulus series compared with IBS + FM patients and controls (P < 0.05), Patients with IBS + FM were more bothered by the somatic stimuli and had somatic hyperalgesia with lower pain thresholds and higher pain frequency and severity. Conclusions: Both hypervigilance and somatic hypoalgesia contribute to the altered somatic perception in IBS patients. Co-morbidity with FM results in somatic hyperalgesia in IBS patients. (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V. C1 Univ Calif Los Angeles, Sch Med, Dept Med, CURE Neuroenter Dis Program, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Biostat & Biomath, Los Angeles, CA 90024 USA. RP Chang, L (reprint author), Univ Calif Los Angeles, CURE Neuroenter Dis Program, VA Greater Los Angeles Healthcare Syst, W Los Angeles VA Healthcare Ctr, Bldg 115,Room 223, Los Angeles, CA 90073 USA. FU NCRR NIH HHS [M01RR00425-27S2] NR 43 TC 124 Z9 126 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD FEB PY 2000 VL 84 IS 2-3 BP 297 EP 307 DI 10.1016/S0304-3959(99)00215-8 PG 11 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 282ZP UT WOS:000085251900021 PM 10666535 ER PT J AU Shah, U Habib, Z Kleinman, RE AF Shah, U Habib, Z Kleinman, RE TI Liver failure attributable to hepatitis A virus infection in a developing country SO PEDIATRICS LA English DT Article DE hepatitis A; liver failure; hepatic encephalopathy ID ACUTE VIRAL-HEPATITIS; A-NON-B; FULMINANT-HEPATITIS; CHILDREN; ETIOLOGY AB In young children hepatitis A virus (HAV) infections are usually subclinical events. However, HAV is also associated with progressive hepatic failure and even death in some patients. This study was undertaken to characterize the course of hepatitis A-related acute liver failure in children from a developing country where hepatitis A is endemic and produces significant morbidity. Patients <15 years of age with confirmed hepatitis A, seen at the Aga Khan University Hospital between January 1991 and August 1998 were identified using the patient registry. Of the 2735 patients seen with hepatitis A, 232 were admitted to the hospital. Of these 30 patients developed progressive hepatic dysfunction and liver failure. During this period, 45 children were admitted with liver failure attributable to other causes. Of the patients admitted with hepatitis A-related liver failure, 25 (83.3%) were encephalopathic at presentation and 36.7% of the patients died. The prothrombin time was the most significant predictor of survival. There was a significant difference between those who survived and those who died on discriminant analysis with respect to age, grade of hepatic encephalopathy, duration of hospitalization, prothrombin time, and duration of jaundice when taken as a group. There is a striking prevalence of liver dysfunction progressing to hepatic failure among children seen at a hospital in Karachi, Pakistan. This study demonstrates the significant morbidity and mortality that can attend HAV infections in children in a developing country despite tertiary medical facilities. The risk of HAV and its sequelae could probably be effectively reduced in these settings with improved sanitation and universal immunization. C1 Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. Aga Khan Univ Hosp, Dept Pediat & Physiotherapy, Karachi, Pakistan. RP Kleinman, RE (reprint author), Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, 32 Fruit St,VBK 107, Boston, MA 02114 USA. NR 26 TC 28 Z9 36 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD FEB PY 2000 VL 105 IS 2 BP 436 EP 438 DI 10.1542/peds.105.2.436 PG 4 WC Pediatrics SC Pediatrics GA 280ML UT WOS:000085106500039 PM 10654972 ER PT J AU Lan, AJ Colford, JM AF Lan, AJ Colford, JM TI The impact of dosing frequency on the efficacy of 10-day penicillin or amoxicillin therapy for streptococcal tonsillopharyngitis: A meta-analysis SO PEDIATRICS LA English DT Article DE amoxicillin; group A streptococcal; penicillin; pharyngitis; streptococcal infections; Streptococcus pyogenes ID V THERAPY; ANTIBIOTIC-THERAPY; PHARYNGITIS; PHARYNGOTONSILLITIS; CHILDREN; TRIAL AB Objective. The recommended dosing frequency of oral penicillin for the treatment of acute streptococcal tonsillopharyngitis has long been 3 to 4 times daily. In 1994, treatment guidelines included twice-daily (BID) dosing for the first time, a recommendation that could significantly increase the ease of compliance. This meta-analysis was performed to determine whether overall cure rates differed between BID or once-daily (QD) versus more frequent dosing schedules in the treatment of streptococcal tonsillopharyngitis. Data Sources. Candidate studies for this meta-analysis included all clinical trials of therapy for streptococcal tonsillopharyngitis published through August 1998 and identified using Medline, Dissertation Abstracts, conference proceedings, and bibliographies of all retrieved articles. Study Selection. A study was eligible for inclusion if it was a randomized clinical trial that compared the efficacies of different dosing frequencies of 10-day penicillin or amoxicillin in the treatment of streptococcal tonsillopharyngitis. Of the 30 articles initially identified, 6 studies met eligibility criteria. Outcome Measure. The measure of interest was the difference in proportion cured between the BID or QD dosing group and the comparison group with more frequent dosing. Results. The results of this analysis suggest that BID dosing of 10-day penicillin is as efficacious as more frequent dosing regimens in the treatment of streptococcal tonsillopharyngitis. This result also holds true in a subgroup analysis confined to pediatric cases and does not vary with total daily dose of the regimen. QD dosing of penicillin is associated with a cure rate that is 12 percentage points lower than more frequent dosing (95% confidence interval: 3-21). In contrast, this decreased efficacy is not found with QD dosing of amoxicillin. Conclusions. This meta-analysis supports current recommendations for BID dosing of penicillin in treating streptococcal tonsillopharyngitis. QD penicillin is associated with decreased efficacy and should not be used. Simplified regimens of amoxicillin of shorter duration or of less frequent dosing should be further investigated. C1 Univ Calif Berkeley, Sch Publ Hlth, Dept Publ Hlth Biol & Epidemiol, Berkeley, CA 94720 USA. Univ Calif San Diego, San Diego, CA 92103 USA. San Francisco Vet Affairs Med Ctr, Infect Dis Sect, San Francisco, CA USA. RP Colford, JM (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Dept Publ Hlth Biol & Epidemiol, 113 Haviland Hall 7360, Berkeley, CA 94720 USA. NR 37 TC 22 Z9 22 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 FEB PY 2000 VL 105 IS 2 BP art. no. EP e19 DI 10.1542/peds.105.2.e19 PG 8 WC Pediatrics SC Pediatrics GA 280ML UT WOS:000085106500002 PM 10654979 ER PT J AU Zygmanski, P Gall, KP Rabin, MSZ Rosenthal, SJ AF Zygmanski, P Gall, KP Rabin, MSZ Rosenthal, SJ TI The measurement of proton stopping power using proton-cone-beam computed tomography SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID RECONSTRUCTION; ALGORITHM; PROJECTIONS AB xA cone-beam computed tomography (CT) system utilizing a proton beam has been developed and tested. The cone beam is produced by scattering a 160 MeV proton beam with a modifier that results in a signal in the detector system, which decreases monotonically with depth in the medium. The detector system consists of a Gd2O2S:Tb intensifying screen viewed by a cooled CCD camera. The Feldkamp-Davis-Kress cone-beam reconstruction algorithm is applied To the projection data to obtain the CT voxel data representing proton stopping power. The system described is capable of reconstructing data over a 16 x 16 x 16 cm(3) volume into 512 x 512 x 512 voxels. A spatial and contrast resolution phantom was scanned to determine the performance of the system. Spatial resolution is significantly degraded by multiple Coulomb scattering effects. Comparison of the reconstructed proton CT values with x-ray CT derived proton stopping powers shows that there may be some advantage to obtaining stopping powers directly with proton CT. The system described suggests a possible practical method of obtaining this measurement in vivo. C1 Univ Massachusetts, Dept Phys & Astron, Amherst, MA 01003 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. FU NCI NIH HHS [5-P01-CA21239-22] NR 40 TC 52 Z9 52 U1 0 U2 7 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD FEB PY 2000 VL 45 IS 2 BP 511 EP 528 DI 10.1088/0031-9155/45/2/317 PG 18 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 285WB UT WOS:000085410400019 PM 10701518 ER PT J AU Kearns, GJ Padwa, BL Mulliken , JB Kaban, LB AF Kearns, GJ Padwa, BL Mulliken , JB Kaban, LB TI Progression of facial asymmetry in hemifacial microsomia SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 55th Annual Meeting of the American-Cleft-Palate-and-Craniofacial-Association CY APR 22-25, 1998 CL BALTIMORE, MARYLAND SP Amer Cleft Palate & Craniofacial Assoc AB Hemifacial microsomia is a common craniofacial anomaly, variably affecting structures derived from the first and second pharyngeal arches. Correction of the skeletal deformity in children has been advocated to improve growth potential and reduce secondary deformity. However, contrary reports have suggested that facial asymmetry in hemifacial microsomia does not increase with growth; therefore, skeletal correction can be postponed, even until adolescence. The purpose of this study was to test the hypothesis that facial asymmetry in hemifacial microsomia is progressive. This is a retrospective evaluation of 67 patients with untreated hemifacial microsomia. The patients were categorized as: group I (mandible type I, IIa), n = 38, and group II (mandible type IIb, III), n = 29. Pretreatment posterior-anterior cephalometric radiographs were used to analyze asymmetry by measuring the angle between the true horizontal and the following planes: piriform rim, maxillary occlusal plane, and intergonial angle. Angular measurements were averaged for patients in the deciduous (<6 years), mixed (greater than or equal to 6<13 years), and permanent dentition (greater than or equal to 13 years). In group I, angle piriform rim, maxillary occlusal plane, and intergonial angle increased from 7.0, 4.3, and 4.4 to 8.4, 6.6, and 6.1 degrees, respectively [mean age, 4.1 (deciduous) to 8.6 (mixed) to 21.0 (permanent) years]. In group TI, angle piriform rim, maxillary occlusal plane, and intergonial angle increased from 9.5, 6.2, and 5.3 to 11.7, 7.6, and 8.0 degrees, respectively [mean age, 3.4 (deciduous) to 8.0 (mixed) years]. These data demonstrate that hemifacial microsomia is progressive and underscores the importance of early surgical correction of mandibular asymmetry in this disorder. C1 Childrens Hosp, Div Plast & Oral Surg, Craniofacial Ctr, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Oral & Maxillofacial Surg, Boston, MA USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Padwa, BL (reprint author), Childrens Hosp, Div Plast & Oral Surg, Craniofacial Ctr, 300 Longwood Ave, Boston, MA 02115 USA. NR 18 TC 43 Z9 45 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD FEB PY 2000 VL 105 IS 2 BP 492 EP 498 DI 10.1097/00006534-200002000-00002 PG 7 WC Surgery SC Surgery GA 284KZ UT WOS:000085332700002 PM 10697151 ER PT J AU Bakris, G Sowers, J Epstein, M Williams, M AF Bakris, G Sowers, J Epstein, M Williams, M TI Hypertension in patients with diabetes - Why is aggressive treatment essential? SO POSTGRADUATE MEDICINE LA English DT Article AB Hypertension and diabetes are interrelated diseases. Alone, each condition is a risk factor for cardiovascular disease and, together, they strongly predispose to endstage renal disease, coronary artery disease, and peripheral vascular and cerebrovascular disease. Pharmacologic treatment of hypertension can substantially reduce morbidity and mortality in diabetic patients with hypertension, but adequate control of blood pressure is seldom achieved in a clinical setting. More aggressive treatment is needed to improve the prognosis for this ever-expanding patient population. C1 Rush Presbyterian St Lukes Med Ctr, Dept Prevent Med, Chicago, IL 60612 USA. SUNY Hlth Sci Ctr, Coll Med, Brooklyn, NY 11203 USA. Univ Miami, Sch Med, Div Nephrol, Coral Gables, FL 33124 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dialysis Unit, Boston, MA USA. RP Bakris, G (reprint author), Rush Presbyterian St Lukes Med Ctr, Dept Prevent Med, 1700 W Van Buren,Suite 470, Chicago, IL 60612 USA. NR 9 TC 18 Z9 20 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD FEB PY 2000 VL 107 IS 2 BP 53 EP + PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 281WF UT WOS:000085183900009 PM 10689408 ER PT J AU ter Haar, E Harrison, SC Kirchhausen, T AF ter Haar, E Harrison, SC Kirchhausen, T TI Peptide-in-groove interactions link target proteins to the beta-propeller of clathrin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MEDIATED ENDOCYTOSIS; COATED VESICLES; NERVE-TERMINALS; BINDING-SITE; DOMAIN; RECEPTOR; AMPHIPHYSIN; ARRESTIN; IDENTIFICATION; ORGANIZATION AB The "WD40" domain is a widespread recognition module for linking partner proteins in intracellular networks of signaling and sorting. The clathrin amino-terminal domain, which directs incorporation of cargo into coated pits, is a beta-propeller closely related in structure to WD40 modules. The crystallographically determined structures of complexes of the clathrin-terminal domain with peptides derived from two different cargo adaptors, beta-arrestin 2 and the beta-subunit of the AP-3 complex, reveal strikingly similar peptide-in-groove interactions. The two peptides in our structures contain related, five-residue motifs, which form the core of their contact with clathrin. A number of other proteins involved in endocytosis have similar "clathrin-box" motifs, and it therefore is likely that they all bind the terminal domain in the same way. We propose that a peptide-in-groove interaction is an important general mode by which beta-propellers recognize specific target proteins. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Mol Med Lab, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. FU NIGMS NIH HHS [5 R01 GM36548-14, R01 GM036548] NR 52 TC 194 Z9 198 U1 0 U2 5 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 FEB 1 PY 2000 VL 97 IS 3 BP 1096 EP 1100 DI 10.1073/pnas.97.3.1096 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 281BM UT WOS:000085138300028 PM 10655490 ER PT J AU Giorgino, F de Robertis, O Laviola, L Montrone, C Perrini, S McCowen, KC Smith, RJ AF Giorgino, F de Robertis, O Laviola, L Montrone, C Perrini, S McCowen, KC Smith, RJ TI The sentrin-conjugating enzyme mUbc9 interacts with GLUT4 and GLUT1 glucose transporters and regulates transporter levels in skeletal muscle cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NUCLEAR-PORE COMPLEX; GTPASE-ACTIVATING PROTEIN; GROWTH-FACTOR-I; KAPPA-B-ALPHA; DEVELOPMENTAL REGULATION; SUMO-1 MODIFICATION; 3T3-L1 ADIPOCYTES; INSULIN; DEGRADATION; RAT AB Glucose transport in insulin-regulated tissues is mediated by the CLUT4 and GLUT1 transporters. Using the yeast two-hybrid system, we have cloned the sentrin-conjugating enzyme mUbc9 as a protein that interacts with the GLUT4 COOH-terminal intracellular domain. The mUbc9 enzyme was found to bind directly to GLUT4 and GLUT1 through an Il-aa sequence common to the two transporters and to modify both transporters covalently by conjugation with the mUbc9 substrate, sentrin, Overexpression of mUbc9 in L6 skeletal muscle cells decreased GLUT1 transporter abundance 65 %, resulting in decreased basal glucose transport, By contrast, mUbc9 overexpression increased GLUT4 abundance 8-fold, leading to enhanced transport stimulation by insulin. A dominant-negative mUbc9 mutant lacking catalytic activity had effects opposite to those of wild-type mUbc9, The regulation of GLUT4 and GLUT1 was specific, as evidenced by an absence of mUbc9 interaction with or regulation of the GLUT3 transporter isoform in L6 skeletal muscle cells. The mUbc9 sentrin-conjugating enzyme represents a novel regulator of GLUT1 and GLUT4 protein levels with potential importance as a determinant of basal and insulin-stimulated glucose uptake in normal and pathophysiological states. C1 Univ Bari, Sch Med, Ist Clin Med Endocrinol & Malattie Metab, I-70124 Bari, Italy. Harvard Univ, Sch Med, Joslin Diabet Ctr, Metab Sect, Boston, MA 02215 USA. RP Giorgino, F (reprint author), Univ Bari, Sch Med, Ist Clin Med Endocrinol & Malattie Metab, 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; Laviola, Luigi/0000-0001-8860-5845 FU NIDDK NIH HHS [DK36836, P30 DK036836] NR 38 TC 108 Z9 110 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 FEB 1 PY 2000 VL 97 IS 3 BP 1125 EP 1130 DI 10.1073/pnas.97.3.1125 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 281BM UT WOS:000085138300033 PM 10655495 ER PT J AU Pahlavani, MA Vargas, DM AF Pahlavani, MA Vargas, DM TI Influence of aging and caloric restriction on activation of Ras/MAPK, calcineurin, and CaMK-IV activities in rat T cells SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID DEPENDENT PROTEIN-KINASE; PHOSPHOLIPASE C-GAMMA-1; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; EXPRESSION; TRANSCRIPTION; STIMULATION; GROWTH; LYMPHOCYTES; LONGEVITY AB The signaling cascade mediated by Ras (p21(ras)) and MAPK (mitogen-activated protein kinase) and calcium/calmodulin regulating enzymes, calcineurin (CaN) and CaMK-IV, are considered to be essential for T-cell growth and function. In the present study, the effect of aging and caloric restriction (CR) on the induction of Has and MAPK activation by concanavalin A (ConA) was studied. Splenic T cells were isolated from young (4-6 months) and old (22-24 months) rats that had free access to food (control group), and from caloric restricted old (22-24 months) rats that beginning at 6 weeks of age were fed 60%(40% caloric restriction) of the diet consumed by the control rats. We found that the induction of Has activity in T cells isolated from control old rats was lower (P < 0.001) than that in control young rats. However, the levels of Has activity in T cells isolated from CR old rats were similar to the levels in the age-matched control rats. The induction of MAPK activity in T cells isolated from control old rats and CR old rats was significantly less than in T cells isolated from control young rats, and caloric restriction significantly (P < 0.05) reduced the age-related decline in MAPK activation. We also measured the induction of CaN and CaMK-IV activities by ConA in T cells from control young and old and CR old rats. The induction of both CaN and CaMK-IV activity decreased with age. Caloric restriction significantly (P < 0.05) reduced the age-related decline in CaN activity, but had no significant effect on CaMK-IV activity, The changes in Ras/MAPK activation and in CaN and CaMK-IV activity with age or with CR were not associated with alterations in their corresponding protein levels, Thus, caloric restriction has a differential effect on the activation of the upstream signaling molecules that are altered with age. C1 Audie L Murphy Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr GRECC182, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. RP Pahlavani, MA (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr GRECC182, S Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. EM Pahlavani@uthscsa.edu FU NIA NIH HHS [AG00677, AG14088] NR 43 TC 26 Z9 26 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD FEB PY 2000 VL 223 IS 2 BP 163 EP 169 DI 10.1046/j.1525-1373.2000.22322.x PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 278KP UT WOS:000084989200008 PM 10654619 ER PT J AU Goldstein, G Shemansky, WJ AF Goldstein, G Shemansky, WJ TI Length and number of hospitalizations in two cohorts of veterans with chronic schizophrenia SO PSYCHIATRIC SERVICES LA English DT Article AB Two cohorts of male veteran patients with schizophrenia were compared on several clinical and demographic measures. The first cohort, hospitalized in one of two Veterans Affairs hospitals between 1965 and 1975, consisted largely of Korean-era veterans. The second cohort, hospitalized between 1991 and 1994, were largely Vietnam-era veterans. Although treatment and management of patients with schizophrenia differed during the two eras and the second cohort had a significantly higher mean number of hospitalizations than the first, the two cohorts did not differ in total time hospitalized. The finding suggests the need to improve methods for relapse prevention. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. RP Goldstein, G (reprint author), VA Pittsburgh Healthcare Syst, 7180 Highland Dr 151R, Pittsburgh, PA 15206 USA. NR 10 TC 6 Z9 6 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD FEB PY 2000 VL 51 IS 2 BP 245 EP 247 DI 10.1176/appi.ps.51.2.245 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 280AL UT WOS:000085079500020 PM 10655012 ER PT J AU Michelson, D Amsterdam, J Apter, J Fava, M Londborg, P Tamura, R Pagh, L AF Michelson, D Amsterdam, J Apter, J Fava, M Londborg, P Tamura, R Pagh, L TI Hormonal markers of stress response following interruption of selective serotonin reuptake inhibitor treatment SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE fluoxetine; sertraline; paroxetine; SSRI; stress-response; treatment interruption ID BIOCHEMICAL MANIFESTATIONS; DISCONTINUATION SYNDROME; TYROSINE-HYDROXYLASE; CHRONIC IMIPRAMINE; GROWTH-HORMONE; DEPRESSION; NEUROBIOLOGY; FLUOXETINE AB Depressive illness is associated with loss of the usual regulation of stress-responsive hormonal and neurotransmitter systems, and antidepressants have intrinsic effects reducing the activity of these systems. Abrupt interruption of treatment with some antidepressants has been associated with a self-limited syndrome of physical and psychological symptoms distinct from relapse, of which drug half-life appears to be the major determinant. We hypothesized that reactivation of stress-response systems could play a role in this syndrome and studied the effects of treatment interruption in patients successfully treated with the antidepressant fluoxetine, paroxetine or sertraline. During placebo substitution, interruption of paroxetine was associated with statistically significant increases in plasma IGF-1 and heart rate. These data suggest that some activation of physiologic stress-responses may accompany symptom increases during treatment interruption of shorter half-life agents. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Univ Penn, Philadelphia, PA 19104 USA. Princeton Biomed Res, Princeton, NJ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Seattle Clin Res Ctr, Seattle, WA USA. RP Michelson, D (reprint author), Lilly Corp Ctr, Lilly Res Labs, Drop Code 2423, Indianapolis, IN 46285 USA. NR 16 TC 24 Z9 24 U1 0 U2 0 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 FEB PY 2000 VL 25 IS 2 BP 169 EP 177 DI 10.1016/S0306-4530(99)00046-3 PG 9 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 276RH UT WOS:000084890800005 PM 10674280 ER PT J AU Rigalleau, F Caplan, D AF Rigalleau, F Caplan, D TI Effects of gender marking in pronominal coindexation SO QUARTERLY JOURNAL OF EXPERIMENTAL PSYCHOLOGY SECTION A-HUMAN EXPERIMENTAL PSYCHOLOGY LA English DT Article ID IMPLICIT CAUSALITY; PRONOUN RESOLUTION; ONLINE RESOLUTION; COMPREHENSION; DISCOURSE; CONSTRAINTS AB The naming latency of a pronoun was measured when a single previously presented name in a discourse either agreed or did not agree with the pronoun in gender and person. An effect of agreement was found both under conditions in which subjects were likely to have engaged in strategic processing of the pronoun (Experiment 1) and under conditions in which this was unlikely (Experiment 3). The effect of gender agreement was also investigated when two noun phrases were present in the discourse. The results continued to show an immediate effect of gender agreement (naming latencies increased when a pronoun did not agree with one of two previously presented nouns) under experimental conditions likely to engender strategic processing (Experiment 2). This last effect was not significant under experimental conditions that were not likely to engender strategic processing (Experiment 3) Thp results are discussed in terms of models of the process of identifying the referent of a pronoun in a discourse. C1 Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, Vincent Burnham 827,Fruit St, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC00942] NR 33 TC 16 Z9 16 U1 1 U2 3 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0272-4987 J9 Q J EXP PSYCHOL-A JI Q. J. Exp. Psychol. Sect A-Hum. Exp. Psychol. PD FEB PY 2000 VL 53 IS 1 BP 23 EP 52 DI 10.1080/027249800390655 PG 30 WC Psychology; Psychology, Experimental SC Psychology GA 286QB UT WOS:000085455700002 PM 10718062 ER PT J AU Sitek, MA Yanch, JC Held, KD AF Sitek, MA Yanch, JC Held, KD TI Epithermal neutron RBE determination via proton bombardment of V79 cells SO RADIATION RESEARCH LA English DT Meeting Abstract C1 MIT, Dept Nucl Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD FEB PY 2000 VL 153 IS 2 BP 231 EP 232 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 280BK UT WOS:000085082000027 ER PT J AU Moore, A Marecos, E Bogdanov, A Weissleder, R AF Moore, A Marecos, E Bogdanov, A Weissleder, R TI Tumoral distribution of long-circulating dextran-coated iron oxide nanoparticles in a rodent model SO RADIOLOGY LA English DT Article DE animals; brain, iron; brain neoplasms; brain neoplasms, MR; contrast media, experimental studies; iron; neoplasms, experimental studies ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; CONTRAST AGENTS; EXPRESSION; GLIOMAS; CELLS; MACROPHAGES; METASTASES; PARTICLES; DELIVERY; BRAIN AB PURPOSE: To investigate the accumulation and cellular uptake of long-circulating dextran-coated iron oxide (LCDIO) particles in malignant neoplasms in vivo. MATERIALS AND METHODS: A gliosarcoma rodent model was established to determine the distribution of a model LCDIO preparation in tumors. LCDIO accumulation in tissue sections was evaluated with multichannel fluorescence microscopy with rhodaminated LCDIO, green fluorescent protein as a tumor marker, and Hoechst 33258 dye as an intravital endothelial stain. Uptake into tumor cells was corroborated with results of immunohistochemical and cell culture uptake experiments. The effect of intratumoral LCDIO uptake on magnetic resonance (MR) imaging signal intensity was evaluated with a 1.5-T superconducting magnet. RESULTS: Tumoral accumulation of LCDIO was 0.11% +/- 0.06 of the injected dose per gram of tissue in brain tumors and was sufficient for detection at MR imaging. In tumor sections, LCDIO was preferentially localized in tumor cells (49.0% +/- 4.6) but was also taken up by macrophages in tumors (21.0% +/- 3.1) and by endothelial cells in the areas of active angiogenesis (6.5% +/- 1.4). In cell culture, LCDIO uptake was strongly correlated with growth rate of tumor cell lines. CONCLUSION: Tumoral LCDIO accumulation was not negligible and helped explain MR imaging signal intensity changes observed in clinical trials. Microscopically, LCDIO accumulated predominantly in tumor cells and tumor-associated macrophages. Uptake into tumor cells appeared to be directly proportional to cellular proliferation rates. C1 Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Bldg 149,13th St 5403, Charlestown, MA 02129 USA. FU NCI NIH HHS [5-RO1-CA54886-06, R01-CA74424-01]; NINDS NIH HHS [5-RO1-NS335258-03] NR 30 TC 258 Z9 272 U1 3 U2 32 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 2000 VL 214 IS 2 BP 568 EP 574 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 279BL UT WOS:000085023400039 PM 10671613 ER PT J AU Campbell, EG Weissman, JS Causino, N Blumenthal, D AF Campbell, EG Weissman, JS Causino, N Blumenthal, D TI Data withholding in academic medicine: characteristics of faculty denied access to research results and biomaterials SO RESEARCH POLICY LA English DT Article DE faculty; research results; biomaterials; secrecy data sharing ID LIFE AB The sharing and withholding of research results is a topic of intense debate within the scientific community. However, few studies have addressed this issue. This study examines how frequently academic scientists are denied access to other investigators' research results and the characteristics of faculty who are most likely to have this experience. This paper is based on data from a mailed survey of a stratified, random sample of faculty in 117 US medical schools (n = 2366, response rate 62.2%) conducted in 1996-1997. The results show that 12.5% of researchers in medical schools have been denied access to other academic investigators' data within the last 3 years. Researchers who were most likely to be victims of data withholding were those who have withheld research results from others, published more than 20 articles in the last 3 years, to have applied for a patent, or spent more than 40 hours per week in research activities. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Div Gen Internal Med, Inst Hlth Policy, Boston, MA 02114 USA. Partners HealthCare Syst, Boston, MA 02114 USA. Harvard Med Sch, Dept Med, Cambridge, MA USA. Harvard Med Sch, Dept Hlth Care Policy, Cambridge, MA USA. RP Campbell, EG (reprint author), Inst Hlth Policy, 9th Floor,50 Staniford St, Boston, MA 02114 USA. NR 14 TC 62 Z9 62 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0048-7333 J9 RES POLICY JI Res. Policy PD FEB PY 2000 VL 29 IS 2 BP 303 EP 312 DI 10.1016/S0048-7333(99)00068-2 PG 10 WC Management; Planning & Development SC Business & Economics; Public Administration GA 280WA UT WOS:000085125700015 ER PT J AU Kuna, ST AF Kuna, ST TI Respiratory-related activation and mechanical effects of the pharyngeal constrictor muscles SO RESPIRATION PHYSIOLOGY LA English DT Article; Proceedings Paper CT 6th International Symposium on Sleep and Respiration CY MAR 27-31, 1999 CL ALBERTA, CANADA DE mammals, humans; mammals, cat; muscle, pharyngeal constrictor; sleep, apnea, obstructive; upper airways, patency, sleep ID OBSTRUCTIVE SLEEP-APNEA; NORMAL ADULT HUMANS; WAKEFULNESS; CAT AB We have examined the respiratory-related activation of pharyngeal constrictor (PC) muscles in decerebrate cats, normal adult humans and patients with obstructive sleep apnea. In decerebrate cats and awake normal adult humans, phasic expiratory PC activity is uniformly present under hypercapnic and hypoxic conditions. While the PC muscles are electrically silent during quiet breathing in normal adult humans in NREM sleep, an activation pattern very similar to that of other upper airway dilators, such as the genioglossus muscle, is present during spontaneous and induced apneas in patients with obstructive sleep apnea. Experiments using an isolated, sealed upper airway preparation in decerebrate cat show that selective activation of the PC muscles stiffens the pharyngeal airway. The results also show that activation of the PC muscles constricts the airway at relatively high airway volumes but dilates the airway at relatively low airway volumes. These results suggest that PC muscle activation at the end of an apneic episode, when airway volume is relatively low, may help restore airway patency in patients with obstructive sleep apnea. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Penn, Pulm Crit Care & Sleep Sect, Dept Internal Med, Philadelphia Vet Affairs Med Ctr 111P, Philadelphia, PA 19104 USA. RP Kuna, ST (reprint author), Univ Penn, Pulm Crit Care & Sleep Sect, Dept Internal Med, Philadelphia Vet Affairs Med Ctr 111P, Univ & Woodland Ave, Philadelphia, PA 19104 USA. FU NHLBI NIH HHS [HL 27520] NR 20 TC 30 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0034-5687 J9 RESP PHYSIOL JI Respir. Physiol. PD FEB PY 2000 VL 119 IS 2-3 BP 155 EP 161 DI 10.1016/S0034-5687(99)00110-3 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 299BQ UT WOS:000086176300007 PM 10722858 ER PT J AU Compton, CC AF Compton, CC TI Serous cystic tumors of the pancreas SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Review DE pancreas; serous cystadenoma; von Hippel-Lindau; pathology ID HIPPEL-LINDAU-DISEASE; FINE-NEEDLE ASPIRATION; MICROCYSTIC ADENOMA; DIFFERENTIAL-DIAGNOSIS; COMPUTED-TOMOGRAPHY; ENDOSCOPIC RETROGRADE; EVANS-SYNDROME; FLUID ANALYSIS; VHL GENE; CYSTADENOMA AB Serous cystic tumors of the pancreas are unique among pancreatic cystic neoplasms in that they are almost always cytologically monomorphous and biologically benign. The diagnostic challenge for the surgical pathologist is to recognize the spectrum of architectural variation that may read to misdiagnosis, either preoperatively or postoperatively, and the additional lesions and conditions with which serous tumors may be associated. Copyright (C) 2000 by W.B. Saunders Company. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Compton, CC (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 256,55 Fruit St, Boston, MA 02114 USA. NR 108 TC 76 Z9 87 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 0740-2570 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD FEB PY 2000 VL 17 IS 1 BP 43 EP 55 PG 13 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 293GD UT WOS:000085842700005 PM 10721806 ER PT J AU Roberts, JD Zapol, WM AF Roberts, JD Zapol, WM TI Inhaled nitric oxide SO SEMINARS IN PERINATOLOGY LA English DT Review ID RESPIRATORY-DISTRESS-SYNDROME; PERSISTENT PULMONARY-HYPERTENSION; NEWBORN; INHALATION; VASOCONSTRICTION; IMPROVEMENT; DISEASE; ARTERY; RAT C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Roberts, JD (reprint author), Massachusetts Gen Hosp E, Dept Anesthesia & Crit Care, 149 13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [K08 HL004237, K08 HL004237-01] NR 21 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0146-0005 J9 SEMIN PERINATOL JI Semin. Perinatol. PD FEB PY 2000 VL 24 IS 1 BP 55 EP 58 DI 10.1016/S0146-0005(00)80057-9 PG 4 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 288FR UT WOS:000085552400014 PM 10709861 ER PT J AU Huang, PL AF Huang, PL TI Lessons learned from nitric oxide synthase knockout animals SO SEMINARS IN PERINATOLOGY LA English DT Review ID MICE LACKING; CEREBRAL-ISCHEMIA; GENE; RESPONSES; MUTANT C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Huang, PL (reprint author), Massachusetts Gen Hosp E, Cardiovasc Res Ctr, 149 E 13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL57818]; NINDS NIH HHS [R01 NS33335] NR 18 TC 38 Z9 42 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0146-0005 J9 SEMIN PERINATOL JI Semin. Perinatol. PD FEB PY 2000 VL 24 IS 1 BP 87 EP 90 DI 10.1016/S0146-0005(00)80064-6 PG 4 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 288FR UT WOS:000085552400021 PM 10709868 ER PT J AU Ibrahim, JG Chen, MH AF Ibrahim, JG Chen, MH TI Power prior distributions for regression models SO STATISTICAL SCIENCE LA English DT Article DE cure rate model; generalized linear model; Gibbs sampling; historical data; prior elicitation; model selection; proportional hazards model; random effects model ID IMMUNODEFICIENCY-VIRUS INFECTION; VARIABLE SELECTION; CONTROLLED TRIAL; ZIDOVUDINE; SURVIVAL AB We propose a general class of prior distributions for arbitrary regression models. We discuss parametric and semiparametric models. The prior specification for the regression coefficients focuses on observable quantities in that the elicitation is based on the availability of historical data D-0 and a scalar quantity a(0) quantifying the uncertainty in D-0. Then D-0 and a(0) are used to specify a prior for the regression coefficients in a semiautomatic fashion. The most natural specification of D-0 arises when the raw data from a similar previous study are available. The availability of historical data is quite common in clinical trials, carcinogenicity studies, and environmental studies, where large data bases are available from similar previous studies. Although the methodology we present here is quite general, we will focus only on using historical data from similar previous studies to construct the prior distributions. The prior distributions are based on the idea of raising the likelihood function of the historical data to the power a(0), where 0 less than or equal to a(0) less than or equal to 1. We call such prior distributions power prior distributions. We examine the power prior for four commonly used classes of regression models. These include generalized Linear models, generalized linear mixed models, semiparametric proportional hazards models, and cure rate models for survival data. For these classes of models, me discuss the construction of the power prior, prior elicitation issues, propriety conditions, model selection, and several other properties. For each class of models, we present real data sets to demonstrate the proposed methodology. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Worcester Polytech Inst, Dept Math Sci, Worcester, MA 01609 USA. RP Ibrahim, JG (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. NR 24 TC 161 Z9 166 U1 2 U2 15 PU INST MATHEMATICAL STATISTICS PI HAYWARD PA IMS BUSINESS OFFICE-SUITE 7, 3401 INVESTMENT BLVD, HAYWARD, CA 94545 USA SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD FEB PY 2000 VL 15 IS 1 BP 46 EP 60 PG 15 WC Statistics & Probability SC Mathematics GA 318VB UT WOS:000087303600004 ER PT J AU Kim, SS Sundback, CA Kaihara, S Benvenuto, MS Kim, BS Mooney, DJ Vacanti, JP AF Kim, SS Sundback, CA Kaihara, S Benvenuto, MS Kim, BS Mooney, DJ Vacanti, JP TI Dynamic seeding and in vitro culture of hepatocytes in a flow perfusion system SO TISSUE ENGINEERING LA English DT Article ID HOLLOW-FIBER; BIODEGRADABLE SPONGES; POLYMER SCAFFOLDS; LIVER-TISSUE; IN-VITRO; TRANSPLANTATION; DIFFERENTIATION; CARTILAGE; MATRICES; GROWTH AB Our laboratory has investigated hepatocyte transplantation using biodegradable polymer matrices as an alternative treatment to end-stage liver disease. One of the major limitations has been the insufficient survival of an adequate mass of transplanted cells. This study investigates a novel method of dynamic seeding and culture of hepatocytes in a flow perfusion system. In experiment I, hepatocytes were flow-seeded onto PGA scaffolds and cultured in a flow perfusion system for 24 h. Overall metabolic activity and distribution of cells were assessed by their ability to reduce MTT. DNA quantification was used to determine the number of cells attached. Culture medium was analyzed for albumin content. In Experiment II, hepatocyte/polymer constructs were cultured in a perfusion system for 2 and 7 days. The constructs were examined by SEM and histology. Culture medium was analyzed for albumin. In experiment I, an average of 4.4 x 10(6) cells attached to the scaffolds by DNA quantification. Cells maintained a high metabolic activity and secreted albumin at a rate of 13 pg/cell/day. In experiment II, SEM demonstrated successful attachment of hepatocytes on the scaffolds after 2 and 7 days. Cells appeared healthy on histology and maintained a high rate of albumin secretion through day 7. Hepatocytes can be dynamically seeded onto biodegradable polymers and survive with a high rate of albumin synthesis in the flow perfusion culture system. C1 Childrens Hosp, Lab Transplantat & Tissue Engn, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Chicago Hosp, Dept Surg, Chicago, IL 60637 USA. Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Surg, 100 Fruit St, Boston, MA 02114 USA. RI Kim, Byung-Soo/O-2352-2013 NR 30 TC 97 Z9 104 U1 0 U2 8 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 FEB PY 2000 VL 6 IS 1 BP 39 EP 44 DI 10.1089/107632700320874 PG 6 WC Cell & Tissue Engineering SC Cell Biology GA 311AK UT WOS:000086861900005 PM 10941199 ER PT J AU Hoerstrup, SP Sodian, R Sperling, JS Vacanti, JP Mayer, JE AF Hoerstrup, SP Sodian, R Sperling, JS Vacanti, JP Mayer, JE TI New pulsatile bioreactor for in vitro formation of tissue engineered heart valves SO TISSUE ENGINEERING LA English DT Article ID FLUID SHEAR-STRESS; ENDOTHELIAL-CELLS; WALL AB Two potential obstacles to the creation of implantable tissue engineered heart valves are inadequate mechanical properties (ability to withstand hemodynamic stresses) and adverse host-tissue reactions due to the presence of residual nondegraded polymer scaffold. In an attempt to address these problems, we developed an in vitro cell culture system that provides physiological pressure and flow of nutrient medium to the developing valve constructs. It is anticipated that in vitro physical stress will stimulate the tissue engineered heart valve construct to develop adequate strength prior to a possible implantation. Long-term in vitro development will be realized by an isolated and thereby contamination-resistant system. Longer in vitro development will potentially enable more complete biodegradation of the polymeric scaffold during in vitro cultivation. This new dynamic bioreactor allows for adjustable pulsatile flow and varying levels of pressure. The system is compact and easily fits into a standard cell incubator, representing a highly isolated dynamic cell culture setting with maximum sterility, optimal gas supply and stable temperature conditions especially suited for long-term experiments. C1 Harvard Univ, Childrens Hosp, Dept Cardiovasc Surg, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA USA. RP Hoerstrup, SP (reprint author), Harvard Univ, Childrens Hosp, Dept Cardiovasc Surg, Sch Med, 300 Longwood Ave, Boston, MA 02115 USA. NR 9 TC 123 Z9 132 U1 4 U2 24 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 FEB PY 2000 VL 6 IS 1 BP 75 EP 79 DI 10.1089/107632700320919 PG 5 WC Cell & Tissue Engineering SC Cell Biology GA 311AK UT WOS:000086861900009 PM 10941203 ER PT J AU Grocela, JA McDougal, WS AF Grocela, JA McDougal, WS TI Utility of nuclear matrix protein (NMP22) in the detection of recurrent bladder cancer SO UROLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID TRANSITIONAL-CELL-CARCINOMA; MARKER AB This article examines the Nuclear Matrix Protein (NMP22) urine test for recurrent bladder cancer detection. Studies with NMP22 are compared to cytology for sensitivity and specificity False positives and false negatives do occur, and consequences of these are discussed. Speculations are made regarding possible future uses of this test. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. RP Grocela, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Bigelow 1102, Boston, MA 02114 USA. NR 14 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0094-0143 J9 UROL CLIN N AM JI Urol. Clin. N. Am. PD FEB PY 2000 VL 27 IS 1 BP 47 EP + DI 10.1016/S0094-0143(05)70233-0 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 281TR UT WOS:000085177300006 PM 10696244 ER PT J AU Krieger, JN Jacobs, R Ross, SO AF Krieger, JN Jacobs, R Ross, SO TI Detecting urethral and prostatic inflammation in patients with chronic prostatitis SO UROLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; CHRONIC IDIOPATHIC PROSTATITIS; FIRST-VOID URINE; CHLAMYDIA-TRACHOMATIS; GENITAL MYCOPLASMAS; REACTION ASSAY; MEN; DIAGNOSIS; HERPES; MALES AB Objectives. Diagnosis of urethral and prostatic inflammation can represent a challenge, We compare the accuracy of diagnostic methods for detecting inflammation in lower urinary specimens/samples. Methods. A standardized protocol was used to evaluate urethral smear, first-void urine (VB1), midstream urine (VB2), expressed prostatic secretions (EPS), and postmassage urine (VB3) in urologic patients with no symptoms or signs of urethritis who were attending our prostatitis clinic. Results. Of 235 subjects, 60 (26%) had leukocytes detected by the Gram-stained urethral smear, 44 (18%) by the VB1, and only 14 (6%) by the VB2. Compared with the urethral swab, VB1 had 0% to 22% sensitivity and 81% to 98% specificity, and VB2 had 8% to 11% sensitivity. Of 83 subjects with prostatic inflammation, the EPS detected 65 (76%) and the VB3 detected 68 (82%). Conclusions. VB1 or VB2 examinations had low sensitivity for detecting urethral inflammation. Examining; both the EPS and VB3 proved best for detecting prostatic fluid inflammation. Combining the urethral smear with lower urinary tract localization ("four-glass test") represents an optimal approach for detecting urethral and prostatic inflammation. (C) 2000, Elsevier Science Inc. C1 Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA. RP Krieger, JN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Urol Sect, 112UR,1660 S Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [R01-DK38955] NR 34 TC 18 Z9 18 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD FEB PY 2000 VL 55 IS 2 BP 186 EP 191 DI 10.1016/S0090-4295(99)00437-9 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 281TT UT WOS:000085177400007 PM 10688076 ER PT J AU Rose, AG Cooper, DKC AF Rose, AG Cooper, DKC TI Venular thrombosis is the key event in the pathogenesis of antibody-mediated cardiac rejection SO XENOTRANSPLANTATION LA English DT Article DE allograft; antibody-mediated rejection; cardiac xenograft; hyperacute rejection; venous thrombosis; venular endothelial mediators of inflammation ID ALLOGRAFT-REJECTION; HEART-TRANSPLANTATION; HYPERACUTE REJECTION; VERVET MONKEY; BABOON; XENOGRAFT; PIG; THERAPY; BLOOD; SERUM AB A review of the histopathologic features of serial biopsies and excised grafts of 117 experimental and clinical cardiac allografts and xenografts revealed a common sequence in the development of histopathologic changes in grafts showing antibody-mediated (hyperacute and acute vascular) rejection. Based on these observations, we propose the new concept that thrombosis of cardiac veins and venules is the initial key event in antibody-mediated rejection. This is followed by the development of congestion in the subtended venules and capillaries accompanied by interfascicular and, later, intermyocyte edema. Subsequently, focal or diffuse interstitial hemorrhage affecting the subendocardium, extending sometimes to involve the inner half of the ventricular myocardium, is observed. Antibody-mediated rejection therefore appears to be analogous to incomplete venous infarction of the heart. The observed histopathology (in which venular thrombosis plays a key role) favors a thrombogenic basis for the classical features of antibody-mediated rejection, namely edema, vascular thrombi and interstitial hemorrhage. A key role for venular thrombosis would explain the non-uniform distribution of the changes and may suggest new ways of preventing antibody-mediated xenograft rejection. C1 Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Fairview Univ, Med Ctr, Minneapolis, MN USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. RP Rose, AG (reprint author), Univ Minnesota, Dept Lab Med & Pathol, Box 76,Mayo,420 Delaware St SE, Minneapolis, MN 55455 USA. NR 36 TC 51 Z9 51 U1 0 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD FEB PY 2000 VL 7 IS 1 BP 31 EP 41 DI 10.1034/j.1399-3089.2000.00042.x PG 11 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 311YA UT WOS:000086912800005 PM 10809055 ER PT J AU Yang, YG Chen, AM Garrett, LJ Sergio, JJ Theodore, P Awwad, M VerHalen, J Bodine, DM Sachs, DH Sykes, M AF Yang, YG Chen, AM Garrett, LJ Sergio, JJ Theodore, P Awwad, M VerHalen, J Bodine, DM Sachs, DH Sykes, M TI Development and analysis of transgenic mice expressing porcine hematopoietic cytokines: a model for achieving durable porcine hematopoietic chimerism across an extensive xenogeneic barrier SO XENOTRANSPLANTATION LA English DT Article DE bone marrow transplantation; cytokine; hematopoietic chimerism; transgenics; xenotransplantation ID BONE-MARROW TRANSPLANTATION; IMMUNE-DEFICIENT MICE; NONLETHAL PREPARATIVE REGIMEN; SCID MICE; IMMUNODEFICIENT MICE; ALLOGRAFT TOLERANCE; MIXED CHIMERISM; CELLS; ENGRAFTMENT; SWINE AB The capacity of mixed hematopoietic chimerism to induce tolerance has not been demonstrated in discordant xenogeneic species combinations because of the difficulty in achieving lasting hematopoietic engraftment. In an effort to create a model of long-lasting disparate xenogeneic hematopoietic chimerism, we have developed transgenic (Tg) mice carrying porcine cytokines. Three lines of Tg mice were generated: one carrying porcine IL-3 and GM-CSF genes only (termed IL/GM) and the remaining two lines carrying in addition, the soluble SCF gene (termed IL/GM/sS) or membrane-bound SCF gene (termed IL/GM/mS). Sera from mice with IL/GM and IL/GM/sS transgenes markedly stimulated the proliferation of swine marrow cells in vitro. However, proliferation of swine marrow cells was not induced in cultures containing IL/GM/mS sera. Consistent with these observations, ELISA assays revealed detectable levels of porcine cytokines in the sera of IL/GM and IL/GM/sS, but not in sera of IL/GM/mS Tg mice. Marrow stromal cells prepared from all three kinds of Tg mice, but not those from non-Tg littermates, were capable of supporting the growth of porcine hematopoietic cells in vitro. Immunodeficient Tg mice were generated by crossing Tg founders with C.B-17 SCID mice for five generations. All Tg immunodeficient mice showed improved porcine hematopoietic engraftment compared with non-Tg controls. These Tg mice provide a useful model system for studying porcine hematopoietic stem cells, and for evaluating the feasibility of donor-specific tolerance induction by mixed chimerism across highly disparate xenogeneic barriers. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. NIH, Natl Ctr Human Genome Res, Lab Gene Transfer, Hematopoiesis Sect, Bethesda, MD 20892 USA. BioTransplant Inc, Charlestown, MA 02129 USA. RP Yang, YG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [R01 HL 54038, R01 HL49915]; NIAID NIH HHS [P01 AI39755] NR 31 TC 13 Z9 14 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD FEB PY 2000 VL 7 IS 1 BP 58 EP 64 DI 10.1034/j.1399-3089.2000.00044.x PG 7 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 311YA UT WOS:000086912800008 PM 10809058 ER PT J AU Kawakubo, K Yang, H Tache, Y AF Kawakubo, K Yang, H Tache, Y TI Intracisternal PYY inhibits gastric lesions induced by ethanol in rats: role of PYY-preferring receptors? SO BRAIN RESEARCH LA English DT Article DE PYY; [Pro(34)]PYY; gastric protection; RX 77368; ethanol; gastric lesion ID DORSAL VAGAL COMPLEX; THYROTROPIN-RELEASING-HORMONE; NEUROPEPTIDE-Y; PEPTIDE-YY; PANCREATIC-POLYPEPTIDE; CLONED RAT; BINDING; PROJECTIONS; STIMULATION; SUBTYPES AB We previously reported that intracisternal (i.c.) injection of peptide YY (PYY) and low doses of thyrotropin-releasing hormone (TRH) or TRH analog, RX 77368, increased the resistance of the gastric mucosa to ethanol injury through vagal pathways in rats. The gastroprotective effect of i.c. injection of PYY/neuropeptide NPY (NPY) agonists with differential in vitro affinity to the Y receptor subtypes was examined in urethane-anesthetized rats. Intragastric administration of ethanol (45%, 5 ml/kg) results in mucosal lesions covering 23 +/- 2% of the gastric corpus in 1 h. PW (500 ng, i.c.) significantly reduced ethanol-induced gastric lesions by 52%. [Pro(34)]PYY (PYY-preferring/Y-1/Y-5/Y-4 subtypes) injected i.c. at 50, 100, 200 or 500 ng, reduced dose dependently gastric lesions to 15.4 +/- 2.2%, 11.4 +/- 3.1%, 8.6 +/- 2.9% and 5.4 +/- 2.2%, respectively. PYY3-36, (Y-2/Y-4 subtypes), [Leu(31), Pro(34)]NPY (Y-1/Y-5), NPY (Y-3/Y-1/Y-5/Y-2) and pancreatic polypeptide (PP, Y-4) injected i.c. at 500 ng did not influence significantly ethanol-induced gastric lesions. Combined i.c. injection of RX 77368 (1 ng) and Pro(34)PYY (25 ng), at sub-threshold doses given singly, reduced ethanol-induced gastric injury to 12.9 +/- 2.3% while RX 77368 (1 ng) plus PYY3-36 (500 ng) or [Leu(31), Pro(34)]NPY (25 ng) had no effect. These findings indicate that i.c. PYY-induced gastric protection against 45% ethanol is mediated by a Y receptor subtype which bears similarity with the putative PYY-preferring receptor and distinct from the currently defined Y-1/Y-5; in addition, there is a synergistic interaction between activation of this PYY-preferring receptor and i.c. TRH to increase the resistance of the gastric mucosa to injury caused by 45% ethanol. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Vet Adm Greater Los Angeles Healthcare Syst, Digest Dis Res Ctr, CURE, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Div Digest Dis, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Inst Brain Res, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Digest Dis Res Ctr, CURE, Bldg 115,Rm 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-30110, DK 41301] NR 31 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 31 PY 2000 VL 854 IS 1-2 BP 30 EP 34 DI 10.1016/S0006-8993(99)02293-3 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 280UN UT WOS:000085122300005 PM 10784103 ER PT J AU Kano, T Katayama, Y Tejima, E Lo, EH AF Kano, T Katayama, Y Tejima, E Lo, EH TI Hemorrhagic transformation after fibrinolytic therapy with tissue plasminogen activator in a rat thromboembolic model of stroke SO BRAIN RESEARCH LA English DT Article DE rat; thromboembolic stroke; tPA; reperfusion; hemorrhagic infarction; polymorphonuclear leukocyte ID CEREBRAL-ARTERY OCCLUSION; POLYMORPHONUCLEAR LEUKOCYTES; URGENT THERAPY; REPERFUSION; ISCHEMIA; BLOOD; ACCUMULATION; MINUTES; INJURY AB In this study, the effects of early vs. delayed tPA treatment on the development of hemorrhagic transformation was compared in a rat thromboembolic model of stroke. Fibrinolysis was performed by administering tPA intravenously at 2 or 6 h after ischemic onset. Twenty-four hours later, confluent hemorrhagic infarction was observed only in rats treated with tPA at 6 h at the rate of 50%. In this delayed treatment group, significantly increased numbers of polymorphonuclear leukocytes (PMNL) were observed to accumulate inside microvessels within the ischemic core. PMNL accumulation may be related to the induction of hemorrhagic infarction after delayed tPA treatment. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Nihon Univ, Sch Med, Dept Neurosurg, Itabashi Ku, Tokyo 173, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA 02129 USA. RP Kano, T (reprint author), Nihon Univ, Sch Med, Dept Neurosurg, Itabashi Ku, 30-1 Oyaguchi Kamimachi, Tokyo 173, Japan. FU NINDS NIH HHS [R01-NS37074, R29-NS32806] NR 18 TC 40 Z9 42 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 31 PY 2000 VL 854 IS 1-2 BP 245 EP 248 DI 10.1016/S0006-8993(99)02276-3 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 280UN UT WOS:000085122300032 PM 10784130 ER PT J AU Stack, AM Malley, R Saladino, RA Montana, JB MacDonald, KL Molrine, DC AF Stack, AM Malley, R Saladino, RA Montana, JB MacDonald, KL Molrine, DC TI Primary respiratory syncytial virus infection: pathology, immune response, and evaluation of vaccine challenge strains in a new mouse model SO VACCINE LA English DT Article DE respiratory syncytial virus; animal model; vaccine ID RSV CHALLENGE; COTTON RATS; MICE; CHILDREN; DISEASE; BRONCHIOLITIS; IMMUNIZATION; INFANTS; CELLS AB Respiratory syncytial virus (RSV) is the primary cause of lower respiratory tract illness in young children. Vaccine development has been hampered by the experience of the formalin-inactivated vaccine tested in the 1960's. Currently, several vaccine candidates are under development and immune response to these candidate vaccines must be evaluated closely. We introduce a novel low-dose murine model of RSV infection and a new pathologic scoring system for the resultant pulmonary disease. We have also developed new sensitive methods for measuring cytokine expression. We then used this new model to test vaccine challenge strains of RSV in order to determine their pathogenicity. (C) 2000 Elsevier Science Led. All rights reserved. C1 Harvard Univ, Sch Med, Dept Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. RP Stack, AM (reprint author), Harvard Univ, Sch Med, Dept Med, Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. NR 24 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JAN 31 PY 2000 VL 18 IS 14 BP 1412 EP 1418 DI 10.1016/S0264-410X(99)00399-0 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 277FY UT WOS:000084923100017 PM 10618539 ER PT J AU Bonetti, M AF Bonetti, M TI A new geometric approach to data analysis using the Minkowski polytope SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article DE exploratory data analysis; clustering of disease; flatness; leukemia ID CLUSTERS; DISEASE AB We introduce a new approach to the analysis of random samples in R-d, based on a geometric transformation called the "Minkowski polytope" (MP). We describe how a theorem by Minkowski guarantees the existence and uniqueness of such a transformation, discuss its construction, and state a result about the almost sure convergence of a scaled version of the MP in R-2. We show how the shape of the MP is sensitive to the presence of outliers and correlation in the sample. Finally, we use the MP to develop a new Monte Carlo test for spatial randomness over non-uniform populations, and illustrate its application on a well-known dataset of leukemia cases in the state of New York. (C) 2000 Published by Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. OI Bonetti, Marco/0000-0003-2304-4180 NR 17 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD JAN 28 PY 2000 VL 32 IS 3-4 BP 259 EP 271 DI 10.1016/S0167-9473(99)00080-8 PG 13 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 285QJ UT WOS:000085399500004 ER PT J AU Faccio, L Fusco, C Chen, A Martinotti, S Bonventre, JV Zervos, AS AF Faccio, L Fusco, C Chen, A Martinotti, S Bonventre, JV Zervos, AS TI Characterization of a novel human serine protease that has extensive homology to bacterial heat shock endoprotease HtrA and is regulated by kidney ischemia SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; PROTEINS; GENE; DOMAINS; KINASE; IDENTIFICATION; TEMPERATURES; PRODUCT; GROWTH; DEGP AB We report the isolation and characterization of a cDNA encoding the novel mammalian serine protease Omi. Omi protein consists of 458 amino acids and has homology to bacterial HtrA endoprotease, which acts as a chaperone at low temperatures and as a proteolytic enzyme that removes denatured or damaged substrates at elevated temperatures. The carboxyl terminus of Omi has extensive homology to a mammalian protein called L56 (human HtrA), but unlike L56, which is secreted, Omi is localized in the endoplasmic reticulum, Omi has several novel putative protein-protein interaction motifs, as well as a PDZ domain and a Src homology 3-binding domain, Omi mRNA is expressed ubiquitously, and the gene is localized on human chromosome 2p12, Omi interacts with Mxi2, an alternatively spliced form of the p38 stress-activated kinase, Omi protein, when made in a heterologous system, shows proteolytic activity against a nonspecific substrate beta-casein, The proteolytic activity of Omi is markedly up-regulated in the mouse kidney following ischemia/reperfusion. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Renal Unit, Med Serv, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02129 USA. Univ Aquila, Dept Expt Med, I-67100 Laquila, Italy. RP Zervos, AS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, 149 13th St, Boston, MA 02129 USA. FU NIDDK NIH HHS [R01 DK55734-01] NR 33 TC 155 Z9 171 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 28 PY 2000 VL 275 IS 4 BP 2581 EP 2588 DI 10.1074/jbc.275.4.2581 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 280XA UT WOS:000085128000049 PM 10644717 ER PT J AU Yang, BX Fukuda, N van Hoek, A Matthay, MA Ma, TH Verkman, AS AF Yang, BX Fukuda, N van Hoek, A Matthay, MA Ma, TH Verkman, AS TI Carbon dioxide permeability of aquaporin-1 measured in erythrocytes and lung of aquaporin-1 null mice and in reconstituted proteoliposomes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHIP28 WATER CHANNELS; KIDNEY COLLECTING DUCT; ION CONDUCTANCE; XENOPUS OOCYTES; EXPRESSION; GLYCEROL; CLONING; MEMBRANES; CELLS; TRANSPORTER AB Measurements of CO2 permeability in oocytes and liposomes containing water channel aquaporin-1 (AQP1) have suggested that AQP1 is able to transport both water and CO2. We studied the physiological consequences of CO2 transport by AQP1 by comparing CO2 permeabilities in erythrocytes and intact lung of wild-type and AQP1 null mice. Erythrocytes from wild-type mice strongly expressed AQP1 protein and had 7-fold greater osmotic water permeability than did erythrocytes from null mice. CO2 permeability was measured from the rate of intracellular acidification in response to addition of CO2/HCO3- in a stopped-flow fluorometer using 2',7'-bis-(2-carboxyethyl)-5-(and -6)-carboxyfluorescein (BCECF) as a cytoplasmic pH indicator, In erythrocytes from wild-type mice, acidification was rapid (t(1/2), 7.3 +/- 0.4 ms, S.E., n = 11 mice) and blocked by acetazolamide and increasing external pH (to decrease CO2/HCO3- ratio). Apparent CO2 permeability (P-CO2) was not different in erythrocytes from wild-type (0.012 +/- 0.0008 cm/s) versus null (0.011 +/- 0.001 cm/s) mice. Lung CO2 transport was measured in anesthetized, ventilated mice subjected to a decrease in inspired CO2 content from 5% to 0%, producing an average decrease in arterial blood pCO(2) from 77 +/- 4 to 39 +/- 3 mm Hg (14 mice) with a t(1/2) of 1.4 min. The pCO(2) values and kinetics of decreasing pCO(2) were not different in wild-type versus null mice. Because AQP1 deletion did not affect CO2 transport in erythrocytes and lung we re-examined CO2 permeability in AQP1-reconstituted liposomes containing carbonic anhydrase (CA) and a fluorescent pH indicator. Whereas osmotic water permeability in AQP1-reconstituted liposomes was >100-fold greater than that in control liposomes, apparent P-CO2 (similar to 10(-3) cm/s) did not differ. Measurements using different CA concentrations and HgCl2 indicated that liposome P-CO2 is unstirred layer-limited and that HgCl2 slows acidification because of inhibition of CA rather than AQP1, These results provide direct evidence against physiologically significant AQP1-mediated CO2 transport and establish an upper limit to the CO2 permeability through single AQP1 water channels. C1 Univ Calif San Francisco, Inst Cardiovasc Res, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Inst Cardiovasc Res, Dept Physiol, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02114 USA. RP Verkman, AS (reprint author), Univ Calif San Francisco, Inst Cardiovasc Res, Dept Med, 1246 Hlth sci E Tower, San Francisco, CA 94143 USA. FU NHLBI NIH HHS [HL59198, HL60288]; NIDDK NIH HHS [DK35124] NR 34 TC 125 Z9 128 U1 1 U2 16 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 JAN 28 PY 2000 VL 275 IS 4 BP 2686 EP 2692 DI 10.1074/jbc.275.4.2686 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 280XA UT WOS:000085128000062 PM 10644730 ER PT J AU Lian, JP Marks, PG Wang, JY Falls, DL Badwey, JA AF Lian, JP Marks, PG Wang, JY Falls, DL Badwey, JA TI A protein kinase from neutrophils that specifically recognizes Ser-3 in cofilin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIN-DEPOLYMERIZING FACTOR; NADPH OXIDASE COMPLEX; STIMULATED HUMAN-NEUTROPHILS; RESPIRATORY BURST OXIDASE; P21-ACTIVATED KINASES; RAPID ACTIVATION; PHOSPHORYLATION; DEPHOSPHORYLATION; COMPONENTS; IDENTIFICATION AB Cofilin promotes the depolymerization of actin filaments, which is required for a variety of cellular responses such as the formation of lamellipodia and chemotaxis. Phosphorylation of cofilin on serine residue 3 is known to block these activities. We now report that neutrophils contain a protein kinase that selectively catalyzes the phosphorylation of cofilin on serine 3 (greater than or equal to 70%) and a nonspecific kinase that recognizes multiple sites in this protein. The selective serine 3 cofilin kinase binds to a deoxyribonuclease I affinity column, whereas the nonspecific cofilin kinase does not. Deoxyribonuclease I forms a very tight complex with actin, and deoxyribonuclease affinity columns have been utilized to identify a variety of proteins that interact with the cytoskeleton. The serine 3 cofilin kinase did not react with antibodies to LIM kinase 1 or 2, which can catalyze the phosphorylation of cofilin in other cell types. The activity of the serine 3 cofilin kinase was insensitive to a variety of selective antagonists of protein kinases but was blocked by staurosporine. This pattern of inhibition is similar to that observed for the kinase that is active with cofilin in intact neutrophils. Thus, neutrophils contain a protein kinase distinct from LIM kinase-1/2 that selectively recognizes serine 3 in cofilin. C1 Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Emory Univ, Dept Biol, Atlanta, GA 30322 USA. Boston Biomed Res Inst, Boston, MA 02114 USA. RP Badwey, JA (reprint author), Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Thorn Bldg,Rm 703,75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [K08 HL-03235]; NIAID NIH HHS [AI 23323]; NIDDK NIH HHS [DK 50015] NR 51 TC 16 Z9 16 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 JAN 28 PY 2000 VL 275 IS 4 BP 2869 EP 2876 DI 10.1074/jbc.275.4.2869 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 280XA UT WOS:000085128000086 PM 10644754 ER PT J AU Chritton, SL Sheng, M AF Chritton, SL Sheng, M TI CYRL, a novel cytokine receptor-like protein expressed in testis, lung, and spleen SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE interleukin-3 receptor; cDNA; brain; rat ID COLONY-STIMULATING FACTOR; GROWTH SIGNAL-TRANSDUCTION; ALPHA-CHAIN; CYTOPLASMIC DOMAIN; MESSENGER-RNA; BETA-SUBUNIT; GM-CSF; INTERLEUKIN-3; CLONING; IL-3 AB The interleukin-3 receptor is composed of a ligand-specific Lu subunit (IL-3R alpha) and a beta subunit (beta(c) or beta(IL3)). Here we report the cloning of a rat brain cDNA transcript with significant homology to IL-3R alpha, which we have termed CYRL, for CYtokine Receptor-Like protein. A number of conserved motifs identify CYRL as a member of the alpha family of cytokine receptor subunits, but the extracellular domain was too divergent from the mouse IL-3R alpha sequence to suggest that CYRL is the rat ortholog of IL-3R alpha. CYRL mRNA expression by Northern blotting was highest in the testis, intermediate in the lung, and modest in spleen, brain, and heart. Antibodies generated against the extracellular domain of CYRL specifically labeled a broad immunoreactive band of M-r similar to 50,000 in membrane fractions of testis, lung, and spleen. CYRL appears to be a novel cytokine receptor alpha-subunit of unknown function and with no defined ligands. (C) 2000 Academic Press. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Harvard Med Sch, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. RP Sheng, M (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Harvard Med Sch, 50 Blossom St, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM07592] NR 25 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 27 PY 2000 VL 267 IS 3 BP 697 EP 702 DI 10.1006/bbrc.1999.2025 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 280YR UT WOS:000085131800004 PM 10673354 ER PT J AU Menaa, C Kurihara, N Roodman, GD AF Menaa, C Kurihara, N Roodman, GD TI CFU-GM-derived cells form osteoclasts at a very high efficiency SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE osteoclasts; CFU-GM; precursors; bone resorption ID BONE-MARROW CULTURES; MULTINUCLEATED CELLS; PRECURSORS; ANTIGEN AB The granulocyte-macrophage progenitor (CFU-GM) is a multipotent cell that can differentiate to osteoclasts (OCLs), macrophages, or granulocytes, However, the relative potential of CFU-GM to efficiently form OCLs is unknown. In this report we demonstrate that granulocyte-macrophage colony-forming unit (CFU-GM)-derived cells represent an easily obtainable highly purified source of human OCL precursors that form OCLs at very high efficiency (greater than 90%) when cultured with RANK ligand (RANKL), macrophage colony-stimulating factor (M-CSF), and dexamethasone, The OCLs that formed have high bone-resorbing activity and form multiple resorption lacunae per OCL on dentin slices. Similarly, murine marrow-derived CFU-GM also formed OCLs at a high efficiency (>80%) when treated with RANKL, M-CSF, and dexamethasone. In contrast, more committed macrophage colony-forming unit (CFU-M)-derived cells form few OCLs under these conditions, (C) 2000 Academic Press. C1 Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med Hematol, San Antonio, TX 78229 USA. RP Roodman, GD (reprint author), Audie L Murphy Mem Vet Hosp, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NIA NIH HHS [AG13625]; NIAMS NIH HHS [AR41336, AR44603] NR 18 TC 42 Z9 46 U1 0 U2 3 PU ACADEMIC PRESS INC 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 JAN 27 PY 2000 VL 267 IS 3 BP 943 EP 946 DI 10.1006/bbrc.1999.2042 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 280YR UT WOS:000085131800046 PM 10673396 ER PT J AU Choi, SW Elmaleh, DR Hanson, RN Fischman, AJ AF Choi, SW Elmaleh, DR Hanson, RN Fischman, AJ TI Novel 3-aminomethyl- and 4-aminopiperidine analogues of 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazines: Synthesis and evaluation as dopamine transporter ligands SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HIGH-AFFINITY; 1-<2-ETHYL>-4-(3-PHENYLPROPYL)PIPERAZINES GBR-12935; REUPTAKE INHIBITORS; COCAINE; BINDING; RAT; IDENTIFICATION; SELECTIVITY; POTENT; BRAIN AB We have undertaken a program to develop cocaine antagonists based on the premise that such compounds should block cocaine binding but permit reuptake of dopamine at the dopamine transporter (DAT). To evaluate the structural features of potential cocaine antagonists, 3-aminomethylpiperidine and 4-aminopiperidine moieties were incorporated at the central bridge region (piperazine ring) of GBR 12935. The compounds were assayed as inhibitors of [I-125]RTI-55 binding at the DAT and monoamine transport. The results indicated that most of the new compounds preferentially inhibited norepinephrine reuptake by its transporter (NET) but in some cases retained binding selectivity for the DAT. In general, the binding selectivity and potency of [H-3]NE reuptake inhibition were very sensitive to modifications of the central bridge diamine moiety (position of two basic nitrogen atoms). Compound 6 exhibited the highest ratio (14-fold) of DA reuptake inhibition to RTI-55 binding inhibition at the DAT; however, in an in vitro assay of cocaine antagonism, this compound failed to reduce inhibition of [H-3]DA uptake by cocaine. These results demonstrated that separation of biological activities into the binding and reuptake inhibition can be achieved by alterations in the internal diamine component of GBR 12935, but additional modifications are necessary before these agents constitute lead compounds for development as cocaine antagonists. C1 Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Northeastern Univ, Bouve Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, Boston, MA 02115 USA. RP Fischman, AJ (reprint author), Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. NR 34 TC 15 Z9 15 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 27 PY 2000 VL 43 IS 2 BP 205 EP 213 DI 10.1021/jm9902178 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 279FP UT WOS:000085034000009 PM 10649976 ER PT J AU O'Donnell, HC Rosand, J Knudsen, KA Furie, KL Segal, AZ Chiu, RI Ikeda, D Greenberg, SM AF O'Donnell, HC Rosand, J Knudsen, KA Furie, KL Segal, AZ Chiu, RI Ikeda, D Greenberg, SM TI Apolipoprotein E genotype and the risk of recurrent lobar intracerebral hemorrhage. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CEREBRAL AMYLOID ANGIOPATHY; E EPSILON-4 ALLELE; ALZHEIMERS-DISEASE; HIGH-FREQUENCY; STROKE; HEMATOMAS; ONSET AB Background: Recurrent lobar intracerebral hemorrhage is the hallmark of cerebral amyloid angiopathy. The factors that predispose patients to early recurrence of lobar hemorrhage are unknown. One candidate is the apolipoprotein E gene, since both the epsilon 2 and the epsilon 4 alleles of apolipoprotein E appear to be associated with the severity of amyloid angiopathy. Methods: We performed a prospective, longitudinal study of consecutive elderly patients who survived a lobar intracerebral hemorrhage. The patients were followed for recurrent hemorrhagic stroke by interviews at six-month intervals and reviews of medical records and computed tomographic scans. Results: Nineteen of 71 enrolled patients had recurrent hemorrhages during a mean (+/-SD) follow-up period of 23.9+/-14.8 months, yielding a 2-year cumulative rate of recurrence of 21 percent. The apolipoprotein E genotype was significantly associated with the risk of recurrence. Carriers of the epsilon 2 or epsilon 4 allele had a two-year rate of recurrence of 28 percent, as compared with only 10 percent for patients with the common apolipoprotein E epsilon 3/epsilon 3 genotype (risk ratio, 3.8; 95 percent confidence interval, 1.2 to 11.6; P=0.01). Early recurrence occurred in eight patients, four of whom had the uncommon epsilon 2/epsilon 4 genotype. Also at increased risk for recurrence were patients with a history of hemorrhagic stroke before entry into the study (two-year recurrence, 61 percent; risk ratio, 6.4; 95 percent confidence interval, 2.2 to 18.5; P<0.001). Conclusions: The apolipoprotein E genotype can identify patients with lobar intracerebral hemorrhage who are at highest risk for early recurrence. This finding makes possible both the provision of prognostic information to patients with lobar hemorrhage and a method of targeting and assessing potential strategies for prevention. (N Engl J Med 2000;342:240-5.) (C)2000, Massachusetts Medical Society. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Wang ACC 836, Boston, MA 02114 USA. FU NIA NIH HHS [AG00725] NR 33 TC 279 Z9 286 U1 0 U2 11 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 27 PY 2000 VL 342 IS 4 BP 240 EP 245 DI 10.1056/NEJM200001273420403 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 277PB UT WOS:000084941000003 PM 10648765 ER PT J AU DiSalvo, TG King, ME Smith, RN Ko, JP Mark, EJ Baker, GP Demirjian, Z Bloch, KJ AF DiSalvo, TG King, ME Smith, RN Ko, JP Mark, EJ Baker, GP Demirjian, Z Bloch, KJ TI A 66-year-old woman with diabetes, coronary disease, orthostatic hypotension, and the nephrotic syndrome - Systemic amyloidosis, AL type, with restrictive cardiomyopathy and involvement of the kidneys, spleen, larynx, blood vessels, and peripheral nerves. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID VENTRICULAR DIASTOLIC FUNCTION; CARDIAC AMYLOIDOSIS; ENDOMYOCARDIAL BIOPSY; ECHOCARDIOGRAPHIC FINDINGS; DOPPLER ECHOCARDIOGRAPHY; CONDUCTION SYSTEM; NECROPSY PATIENTS; MEDICAL PROGRESS; HEART-DISEASE; SARCOIDOSIS C1 Massachusetts Gen Hosp, Cardiac Transplant Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP DiSalvo, TG (reprint author), Massachusetts Gen Hosp, Cardiac Transplant Unit, Boston, MA 02114 USA. NR 49 TC 6 Z9 6 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 27 PY 2000 VL 342 IS 4 BP 264 EP 273 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 277PB UT WOS:000084941000008 ER PT J AU Minassian, BA Ianzano, L Delgado-Escueta, AV Scherer, SW AF Minassian, BA Ianzano, L Delgado-Escueta, AV Scherer, SW TI Identification of new and common mutations in the EPM2A gene in Lafora disease SO NEUROLOGY LA English DT Article DE Lafora disease; EPM2A; Laforin; epilepsy; mutation; EPM2B ID PROGRESSIVE MYOCLONUS EPILEPSY; BIOPSY AB Lafora disease is a teenage onset progressive myoclonus epilepsy caused by mutations in the EPM2A gene. in this report, we describe new mutations within EPM2A, review the known mutations to date to identify the most common, and describe three simple tests for prenatal and carrier screening. C1 Hosp Sick Children, Dept Genet, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Dept Paediat, Div Neurol, Toronto, ON M5G 1X8, Canada. Univ Toronto, Toronto, ON M5G 1X8, Canada. Univ Calif Los Angeles, Sch Med, Dept Neurol, Comprehens Epilepsy Program, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA 90024 USA. W Los Angeles DVA Med Ctr, Los Angeles, CA USA. RP Scherer, SW (reprint author), Hosp Sick Children, Dept Genet, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. RI Howe, Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013 OI Scherer, Stephen /0000-0002-8326-1999 FU NINDS NIH HHS [5P01-NS21908] NR 10 TC 34 Z9 34 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 JAN 25 PY 2000 VL 54 IS 2 BP 488 EP 490 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 279KW UT WOS:000085043800041 PM 10668720 ER PT J AU Henson, JW Thornton, AF Louis, DN AF Henson, JW Thornton, AF Louis, DN TI Spinal cord astrocytoma: Response to PCV chemotherapy SO NEUROLOGY LA English DT Article DE spinal neoplasm; astrocytoma; chemotherapy ID RADIOTHERAPY; TUMORS; MANAGEMENT AB Information regarding the value of chemotherapy for spinal cord astrocytomas that progress after irradiation is limited. Wt describe a patient whose conus medullaris astrocytoma responded to PCV (procarbazine, lomustine, and vincristine) chemotherapy after failing radiation and cisplatin-based chemotherapy, PCV should be considered in patients with progressive spinal cord astrocytomas. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Spine Tumor Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Henson, JW (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, Cox 315,100 Blossom St, Boston, MA 02114 USA. NR 9 TC 11 Z9 11 U1 1 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 JAN 25 PY 2000 VL 54 IS 2 BP 518 EP 520 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 279KW UT WOS:000085043800052 PM 10668731 ER PT J AU Krings, T Topper, R Reinges, MHT Foltys, H Spetzger, U Chiappa, KH Gilsbach, JM Thron, A AF Krings, T Topper, R Reinges, MHT Foltys, H Spetzger, U Chiappa, KH Gilsbach, JM Thron, A TI Hemodynamic changes in simple partial epilepsy: A functional MRI study SO NEUROLOGY LA English DT Article DE MRI; functional MRI; MR signal time course; epilepsy; cerebral hemodynamics ID LOCALIZATION; EEG AB We performed functional MRI (fMRI) on a patient with a mass lesion while she happened to experience a simple partial seizure. We used regional T2* signal changes to localize seizure-related hemodynamic changes. Seizure activity was associated with changes in MR signal in different regions that showed sequential activation and deactivation. Our study has shown that epileptic activity leads to changes in cerebral hemodynamics. In selected patients, therefore, it might be possible to use fMRI as a noninvasive tool to detect and investigate cortical patterns of activation associated with seizure activity. C1 Aachen Tech Univ, Univ Hosp, Dept Neuroradiol, D-52057 Aachen, Germany. Aachen Tech Univ, Univ Hosp, Dept Neurol, D-52057 Aachen, Germany. Aachen Tech Univ, Univ Hosp, Interdisciplinary Ctr Clin Res Cent Nervous Syst, D-52057 Aachen, Germany. Aachen Tech Univ, Univ Hosp, Dept Neurosurg, D-52057 Aachen, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Clin Neurophysiol Lab, Boston, MA USA. RP Krings, T (reprint author), Aachen Tech Univ, Univ Hosp, Dept Neuroradiol, Pauwelsstr 30, D-52057 Aachen, Germany. NR 10 TC 37 Z9 38 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 JAN 25 PY 2000 VL 54 IS 2 BP 524 EP 527 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 279KW UT WOS:000085043800055 PM 10668734 ER PT J AU Lotufo, PA Chae, CU Ajani, UA Hennekens, CH Manson, JE AF Lotufo, PA Chae, CU Ajani, UA Hennekens, CH Manson, JE TI Male pattern baldness and coronary heart disease - The physicians' health study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID POLYCYSTIC-OVARY-SYNDROME; UNITED-STATES PHYSICIANS; MYOCARDIAL-INFARCTION; ANDROGEN RECEPTORS; RANDOMIZED TRIAL; NATIONAL SAMPLE; BETA-CAROTENE; RISK-FACTORS; MEN; TESTOSTERONE AB Objective: To examine the association between male pattern baldness and the risk of coronary heart disease (CHD) events. Design, Setting, and Participants: Retrospective cohort study among 22 071 US male physicians aged 40 to 84 years enrolled in the Physicians' Health Study. Of these, 19 112 were free of CHD at baseline and completed a questionnaire at the Ii-year follow-up concerning their pattern of hair loss at age 45 years. Response options included no hair loss, frontal baldness only, or frontal baldness with mild, moderate, or severe vertex baldness. Main Outcome Measures: Coronary heart disease events defined as nonfatal myocardial infarction (MI), angina pectoris, and/or coronary revascularization. Results: During 11 years of follow-up, we documented 1446 CHD events in this cohort. Compared with men with no hair loss, those with frontal baldness had an adjusted relative risk (RR) of CHD of 1.09 (95% confidence interval [Cl], 0.94-1.25), while those with mild, moderate, or severe vertex baldness had RRs of 1.23 (95% CI, 1.05-1.43), 1.32 (95% CI, 1.10-1.59),and 1.36 (95% CI, 1.11-1.67), respectively (P for trend, <.001). Multivariate adjustment for age, parental history of MI, height, body mass index (weight in kilograms divided by the square of the height in meters as a continuous variable), smoking, history of hypertension, diabetes, high cholesterol level, physical activity, and alcohol intake did not materially alter these associations. Results were similar when nonfatal MI, angina, and coronary revascularization were examined separately, and when events were analyzed among men older and younger than 55 years at baseline. Vertex baldness was more strongly associated with CHD risk among men with hypertension (multivariate RR, 1.79; 95% CI, 1.31-2.44) or high cholesterol levels (multivariate RR, 2.78; 95% CI, 1.09-7.12). Conclusion: Vertex pattern baldness appears to be a marker for increased risk of CHD events, especially among men with hypertension or high cholesterol levels. C1 Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Div Prevent Med, Dept Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. RP Manson, JE (reprint author), Brigham & Womens Hosp, Div Prevent Med, Dept Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. RI Lotufo, Paulo/A-9843-2008 OI Lotufo, Paulo/0000-0002-4856-8450 FU NCI NIH HHS [CA34944]; NHLBI NIH HHS [HL26490, HL34595] NR 38 TC 72 Z9 73 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JAN 24 PY 2000 VL 160 IS 2 BP 165 EP 171 DI 10.1001/archinte.160.2.165 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 276KV UT WOS:000084877700006 PM 10647754 ER PT J AU Roy, P Roth, CM Margolies, MN Yarmush, ML AF Roy, P Roth, CM Margolies, MN Yarmush, ML TI Aromatic residues mediate the pressure-induced association of digoxigenin and antibody 26-10 SO BIOPHYSICAL CHEMISTRY LA English DT Article DE hydrostatic pressure; association volume; antigen-antibody complex; mutant fab fragments; aromatic amino acid residues ID AFFINITY; DISSOCIATION; SPECIFICITY; RECOGNITION; COMPLEX; ACID AB We have previously found that the complex between fluorescently labeled digoxigenin and the monoclonal antibody 26-10 forms with a decrease in volume of approximately 30 ml/mol, leading to increased association of these species under applied hydrostatic pressure. In the present study, we have utilized a panel of mutant antibodies and Fab fragments, previously characterized for their importance in the binding affinity of digoxin:26-10, to probe the molecular basis of pressure sensitivity in this complex, as measured by fluorescence polarization spectroscopy. Several mutations that result in marked decreases in affinity exerted little or no significant effect on the association volume. Mutation at any of several key aromatic residues of the 26-10 Fab heavy chain led to a decrease in the pressure-induced association, and two mutants with Trp --> Arg mutations at heavy chain residue 100 exhibited pressure-induced dissociation. The effect of charged groups was found to depend on their proximity to contacting aromatic groups, The ability to understand and control the pressure sensitivity of antigen-antibody complexes has numerous potential applications in immunoseparations and immunosensors. (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, 55 Fruit St,GRB 1401, Boston, MA 02114 USA. OI Roth, Charles/0000-0002-4924-0721 FU NHLBI NIH HHS [R01 HL47415] NR 21 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD JAN 24 PY 2000 VL 83 IS 3 BP 171 EP 177 DI 10.1016/S0301-4622(99)00139-8 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 273JR UT WOS:000084704600001 PM 10647847 ER PT J AU Lau, KS Grange, RW Isotani, E Sarelius, IH Kamm, KE Huang, PL Stull, JT AF Lau, KS Grange, RW Isotani, E Sarelius, IH Kamm, KE Huang, PL Stull, JT TI nNOS and eNOS modulate cGMP formation and vascular response in contracting fast-twitch skeletal muscle SO PHYSIOLOGICAL GENOMICS LA English DT Article DE endothelial nitric oxide synthase; neuronal nitric oxide synthase; arteriolar relaxation ID NITRIC-OXIDE SYNTHASE; SMOOTH-MUSCLE; BLOOD-FLOW; MUSCULAR-DYSTROPHY; ENDOTHELIAL-CELLS; VASOCONSTRICTION; VASODILATION; HYPEREMIA; ADENOSINE; EXERCISE AB Nitric oxide (NO) from Ca2+-dependent neuronal nitric oxide synthase (nNOS) in skeletal muscle fibers may modulate vascular tone by a cGMP-dependent pathway similar to NO derived from NOS in endothelial cells (eNOS). In isolated fast-twitch extensor digitorum longus (EDL) muscles from control mice, cGMP formation increased similar to 166% with electrical stimulation (30 Hz, 15 s). cGMP levels were not altered in slow-twitch soleus muscles. The NOS inhibitor N-omega-nitro-L-arginine abolished the contraction-induced increase in cGMP content in EDL muscles, and the NO donor sodium nitroprusside (SNP) increased cGMP content similar to 167% in noncontracting EDL muscles. SNP treatment but not electrical stimulation increased cGMP formation in muscles from nNOS(-/-) mice. cGMP formation in control and stimulated EDL muscles from eNOS(-/-) mice was less than that obtained with similarly treated muscles from control mice. Arteriolar relaxation in contracting fast-twitch mouse cremaster muscle was attenuated in muscles from mice lacking either nNOS or eNOS. These findings suggest that increases in cGMP and NO-dependent vascular relaxation in contracting fast-twitch skeletal muscle may require both nNOS and eNOS. C1 Univ Texas, SW Med Ctr, Dept Physiol, Dallas, TX 75235 USA. Univ Rochester, Med Ctr, Sch Med & Dent, Dept Physiol & Pharmacol, Rochester, NY 14642 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA. RP Lau, KS (reprint author), Univ Texas, SW Med Ctr, Dept Physiol, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. FU NHLBI NIH HHS [HL-06296, HL-56574] NR 32 TC 113 Z9 113 U1 2 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD JAN 24 PY 2000 VL 2 IS 1 BP 21 EP 27 PG 7 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 317PE UT WOS:000087234400004 PM 11015578 ER PT J AU Wright, HM Clish, CB Mikami, T Hauser, S Yanagi, K Hiramatsu, R Serhan, CN Spiegelman, BM AF Wright, HM Clish, CB Mikami, T Hauser, S Yanagi, K Hiramatsu, R Serhan, CN Spiegelman, BM TI A synthetic antagonist for the peroxisome proliferator-activated receptor gamma inhibits adipocyte differentiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DIGLYCIDYL ETHER BADGE; BISPHENOL-A; GENE-EXPRESSION; LIGAND; J(2) AB While searching for natural ligands for the peroxisome proliferator-activated receptor (PPAR) gamma, we identified a synthetic compound that binds to this receptor. Bisphenol A diglycidyl ether (BADGE) is a ligand for PPAR gamma with a K-d(app) of 100 mu M. This compound has no apparent ability to activate the transcriptional activity of PPAR gamma; however, BADGE can antagonize the ability of agonist ligands such as rosiglitazone to activate the transcriptional and adipogenic action of this receptor. BADGE also specifically blocks the ability of natural adipogenic cell lines such as 3T3-L1 and 3T3-F442A cells to undergo hormone-mediated cell differentiation. These results provide the first pharmacological evidence that PPAR gamma activity is required for the hormonally induced differentiation of adipogenic cells. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Anesthesia, Ctr Expt Therapeut & Reperfus Injury, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Sumitomo Chem Co Ltd, Biotechnol Lab, Takarazuka, Hyogo 6658555, Japan. RP Spiegelman, BM (reprint author), Dana Farber Canc Inst, 1 Jimmy Fund Way,Smith 958, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM38765] NR 16 TC 269 Z9 272 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 21 PY 2000 VL 275 IS 3 BP 1873 EP 1877 DI 10.1074/jbc.275.3.1873 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 277NQ UT WOS:000084940000050 PM 10636887 ER PT J AU Brooks, CC Scherer, PE Cleveland, K Whittemore, JL Lodish, HF Cheatham, B AF Brooks, CC Scherer, PE Cleveland, K Whittemore, JL Lodish, HF Cheatham, B TI Pantophysin is a phosphoprotein component of adipocyte transport vesicles and associates with GLUT4-containing vesicles SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INSULIN-STIMULATED TRANSLOCATION; SYNAPTOPHYSIN GENE FAMILY; SYNAPTIC VESICLE; 3T3-L1 ADIPOCYTES; MEMBRANE-PROTEIN; SUBCELLULAR-LOCALIZATION; POTENTIAL MECHANISM; GLUCOSE-TRANSPORT; PLASMA-MEMBRANE; RAT ADIPOCYTES AB Pantophysin, a protein related to the neuroendocrine-specific synaptophysin, recently has been identified in non-neuronal tissues. In the present study, Northern blots showed that pantophysin mRNA was abundant in adipose tissue and increased during adipogenesis of 3T3-L1 cells. Immunoblot analysis of subcellular fractions showed pantophysin present exclusively in membrane fractions and relatively evenly distributed in the plasma membrane and internal membrane fractions. Sucrose gradient ultracentrifugation demonstrated that pantophysin and GLUT4 exhibited overlapping distribution profiles. Furthermore, immunopurified GLUT4 vesicles contained pantophysin, and both GLUT4 and pantophysin were depleted from this vesicle population following treatment with insulin. Additionally, a subpopulation of immunopurified pantophysin vesicles contained insulin-responsive GLUT4, Consistent with the interaction of synaptophysin with vesicle-associated membrane protein 2 in neuroendocrine tissues, pantophysin associated with vesicle-associated membrane protein 2 in adipocytes, Furthermore, in [P-32]orthophosphate-labeled cells, pantophysin was phosphorylated in the basal state. This phosphorylation was unchanged in response to insulin; however, insulin stimulated the phosphorylation of a 77-kDa protein associated with alpha-pantophysin immunoprecipitates. Although the functional role of pantophysin in vesicle trafficking is unclear, its presence on GLUT4 vesicles is consistent with the emerging role of soluble N-ethylmaleimide-sensitive protein receptor (SNARE) factor complex and related proteins in regulated vesicle transport in adipocytes. In addition, pantophysin may provide a marker for the analysis of other vesicles in adipocytes. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Cheatham, B (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NICHD NIH HHS [HD07938]; NIDDK NIH HHS [DK47618, DK51668] NR 56 TC 35 Z9 35 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 JAN 21 PY 2000 VL 275 IS 3 BP 2029 EP 2036 DI 10.1074/jbc.275.3.2029 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 277NQ UT WOS:000084940000069 PM 10636906 ER PT J AU de Caestecker, MP Yahata, T Wang, D Parks, WT Huang, SX Hill, CS Shioda, T Roberts, AB Lechleider, RJ AF de Caestecker, MP Yahata, T Wang, D Parks, WT Huang, SX Hill, CS Shioda, T Roberts, AB Lechleider, RJ TI The Smad4 activation domain (SAD) is a proline-rich, p300-dependent transcriptional activation domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TGF-BETA; TUMOR-SUPPRESSOR; HETERO-OLIGOMERIZATION; BINDING-PROTEIN; DNA-BINDING; COACTIVATOR; CELLS; PHOSPHORYLATION; DOWNSTREAM; RESPONSES AB Transforming growth factor-p (TGF-P) family members signal through a unique set of intracellular proteins called Smads, Smad4, previously identified as the tumor suppressor DPC4, is functionally distinct among the Smad family, and is required for the assembly and transcriptional activation of diverse, Smad-DNA complexes. We previously identified a 48-amino acid proline-rich regulatory element within the middle linker domain of this molecule, the Smad4 activation domain (SAD), which is essential for mediating these signaling activities. We now characterize the functional activity of the SAD. Mutants lacking the SAD are still able to form complexes with other Smad family members and associated transcription factors, but cannot activate transcription in these complexes. Furthermore, the SAD itself is able to activate transcription in heterologous reporter assays, identifying it as a proline-rich transcriptional activation domain, and indicating that the SAD is both necessary and sufficient to activate Smad-dependent transcriptional responses. We show that transcriptional activation by the SAD is p300-dependent, and demonstrate that this activity is associated with a physical interaction of the SAD with the amino terminus of p300, These data identify a novel function of the middle linker region of Smad4, and define the role of the SAD as an important locus determining the transcriptional activation of the Smad complex. C1 NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Ctr Canc, Lab Tumor Biol, Charlestown, MA 02129 USA. Imperial Canc Res Fund, Dev Signaling Lab, London WC2A 3PX, England. RP Lechleider, RJ (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. OI Parks, W. Tony/0000-0001-7341-3277 NR 38 TC 123 Z9 128 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 JAN 21 PY 2000 VL 275 IS 3 BP 2115 EP 2122 DI 10.1074/jbc.275.3.2115 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 277NQ UT WOS:000084940000079 PM 10636916 ER PT J AU Andreassen, OA Finsen, B Ostergaard, K West, MJ Jorgensen, HA AF Andreassen, OA Finsen, B Ostergaard, K West, MJ Jorgensen, HA TI Reduced number of striatal neurons expressing preprosomatostatin mRNA in rats with oral dyskinesias after long-term haloperidol administration SO NEUROSCIENCE LETTERS LA English DT Article DE neuroleptics; neuropeptides; stereology; densitometry; vacuous chewing movements; tardive dyskinesia ID IN-SITU HYBRIDIZATION; TARDIVE-DYSKINESIA; MESSENGER-RNA; NEUROLEPTIC DRUGS; NEUROPEPTIDE-Y; SOMATOSTATIN; SCHIZOPHRENIA; DIAPHORASE; BRAIN AB Neuroleptic-induced oral dyskinesia in rats, a putative analogue to human tardive dyskinesia, may be due to degeneration within the striatum. Using unbiased stereological methods, a decreased number of striatal neurons expressing preprosomatostatin mRNA was observed only in rats that developed pronounced oral dyskinesias after 30 weeks of haloperidol administration. The amount of preprosomatostatin mRNA in each striatal neuron, measured in terms of optical densities of individual neurons, was not affected by haloperidol. A tendency toward a reduction in the number of NADPH-diaphorase positive neurons was observed in rats receiving haloperidol. These results indicate that the mechanism by which neuroleptics induce oral dyskinesias in rats, and perhaps tardive dyskinesia in humans, involves a functional disruption and possibly damage of a subpopulation of interneurons in the striatum. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Bergen, Dept Physiol, N-5009 Bergen, Norway. Odense Univ, Dept Anat & Cell Biol, Odense, Denmark. Univ Aarhus, Dept Neurobiol, DK-8200 Aarhus, Denmark. Univ Bergen, Dept Psychiat, Sandviken Hosp, Bergen, Norway. RP Andreassen, OA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Warren 411,Fruit St, Boston, MA 02114 USA. NR 23 TC 11 Z9 11 U1 3 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JAN 21 PY 2000 VL 279 IS 1 BP 21 EP 24 DI 10.1016/S0304-3940(99)00939-8 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 277WK UT WOS:000084956400006 PM 10670778 ER PT J AU Weeks, DL Eskandari, S Scott, DR Sachs, G AF Weeks, DL Eskandari, S Scott, DR Sachs, G TI A H+-gated urea channel: The link between Helicobacter pylori urease and gastric colonization SO SCIENCE LA English DT Article ID PROTEIN; PH; TRANSPORTER; METABOLISM; MEMBRANES; ACID AB Acidic media trigger cytoplasmic urease activity of the unique human gastric pathogen Helicobacter pylori. Deletion of urel prevents this activation of cytoplasmic urease that is essential for bacterial acid resistance. Urel is an inner membrane protein with six transmembrane segments as shown by in vitro transcription/translation and membrane separation. Expression of Urel in Xenopus oocytes results in acid-stimulated urea uptake, with a pH profile similar to activation of cytoplasmic urease, Mutation of periplasmic histidine 123 abolishes stimulation. Urel-mediated transport is urea specific, passive, nonsaturable, nonelectrogenic, and temperature independent. Urel functions as a H+-gated urea channel regulating cytoplasmic urease that is essential for gastric survival and colonization. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. RP Sachs, G (reprint author), VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK46917, DK43462, DK41301] NR 22 TC 256 Z9 277 U1 4 U2 15 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 JAN 21 PY 2000 VL 287 IS 5452 BP 482 EP 485 DI 10.1126/science.287.5452.482 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 277JF UT WOS:000084929900047 PM 10642549 ER PT J AU Hendel, RC Henry, TD Rocha-Singh, K Isner, JM Kereiakes, DJ Giordano, FJ Simons, M Bonow, RO AF Hendel, RC Henry, TD Rocha-Singh, K Isner, JM Kereiakes, DJ Giordano, FJ Simons, M Bonow, RO TI Effect of intracoronary recombinant human vascular endothelial growth factor on myocardial perfusion - Evidence for a dose-dependent effect SO CIRCULATION LA English DT Article DE growth substances; tomography; angiogenesis ID GENE-TRANSFER; ISCHEMIC MYOCARDIUM; HEART-DISEASE; ANGIOGENESIS; MODULATION; LIMB AB Background-Animal models of therapeutic angiogenesis have stimulated development of clinical application in patients with limited options for coronary revascularization. The impact of recombinant human vascular endothelial growth factor (rhVEGF) on myocardial perfusion in humans has not been reported. Methods and Results-Fourteen patients underwent exercise (n=11), dobutamine (n=2), or dipyridamole (n=1) myocardial perfusion single photon emission CT (SPECT) before as well as 30 and 60 days after rhVEGF administration. After uniform processing and display, 2 observers blinded to the timing of the study and dose of rhVEGF reviewed the SPECT images. By a visual, semiquantitative 20-segment scoring method, summed stress scores (SSS) and summed rest scores (SRS) were generated. Although the SSS did not change from baseline to 30 days (21.6 versus 21.5; P=NS), the SRS improved after rhVEGF (13.2 versus 10.4; P<0.05). Stress and rest perfusion improved in >2 segments infrequently in patients treated with low-dose rhVEGF, However, 5 of 6 patients had improvement in >2 segments at rest and stress with the higher rhVEGF doses. Furthermore, although neither the SSS nor the SRS changed in patients treated with the low doses, the SRS decreased in the high-dose rhVEGF patients at 60 days (14.7 versus 10.7; P<0.05). Quantitative analysis was consistent with the visual findings but failed to demonstrate statistical significance. Conclusions-Although not designed to demonstrate rhVEGF efficacy, these phase 1 data support the concept that rhVEGF improves myocardial perfusion at rest and provide evidence of a dose-dependent effect. C1 Northwestern Univ, Sch Med, Chicago, IL 60611 USA. Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. Prairie Cardiovasc Consultants, Springfield, IL USA. St Elizabeths Med Ctr, Boston, MA USA. Lindner Ctr Clin Cardiovasc Res, Cincinnati, OH USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. Beth Israel Beth Deaconess Med Ctr, Boston, MA USA. RP Hendel, RC (reprint author), 1725 W Harrison St, Chicago, IL 60612 USA. RI Simons, Michael/G-8553-2014 OI Simons, Michael/0000-0003-0348-7734 NR 12 TC 202 Z9 222 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 18 PY 2000 VL 101 IS 2 BP 118 EP 121 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 275LM UT WOS:000084821700009 PM 10637195 ER PT J AU Miyamoto, MI del Monte, F Schmidt, U DiSalvo, TS Kang, ZB Matsui, T Guerrero, JL Gwathmey, JK Rosenzweig, A Hajjar, RJ AF Miyamoto, MI del Monte, F Schmidt, U DiSalvo, TS Kang, ZB Matsui, T Guerrero, JL Gwathmey, JK Rosenzweig, A Hajjar, RJ TI Adenoviral gene transfer of SERCA2a improves left-ventricular function in aortic-banded rats in transition to heart failure SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SARCOPLASMIC-RETICULUM CA2+-ATPASE; PRESSURE-OVERLOAD HYPERTROPHY; CONVERTING ENZYME-INHIBITION; FORCE-FREQUENCY-RELATIONSHIP; NONFAILING HUMAN MYOCARDIUM; DILATED CARDIOMYOPATHY; CONTRACTION; EXPRESSION; MYOCYTES; OVEREXPRESSION AB In human and experimental models of heart failure, sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) activity is decreased, resulting in abnormal calcium handling. The disturbances in calcium metabolism have been shown to contribute significantly to the contractile dysfunction observed in heart failure. We investigated whether increasing SERCA2a expression can improve ventricular function in an animal model of heart failure obtained by creating ascending aortic constriction in rats. After 19-23 wk of banding during the transition from compensated hypertrophy to heart failure (documented by >25% decrease in fractional shortening), rats were randomized to receive either an adenovirus carrying the SERCA2a gene (Ad.SERCA2a, n = 13) or beta-galactosidase (Ad.beta gal, n = 14) by using a catheter-based technique. The failing hearts infected with Ad.beta gal were characterized by a significant decrease in SERCA2a expression and a decrease in SERCA2a activity compared with nonfailing sham-operated rats (n = 11). In addition, these failing hearts had reduced left-ventricular systolic: pressure, maximal rate of left-ventricular pressure rise and decline (+dP/dt, -dP/dt), and rate of isovolumic: relaxation (tau). Overexpression of SERCA2a restored both SERCA2a expression and ATPase activity to nonfailing levels. Furthermore, rats infected with Ad.SERCA2a had significant improvement in left-ventricular systolic pressure, +dP/dt, -dP/dt, and rate of isovolumic relaxation (tau) normalizing them back to levels comparable to sham-operated rats. In this study, we show that in an animal model of heart failure where SERCA2a protein levels and activity are decreased and severe contractile dysfunction is present, overexpression of SERCA2a in vivo restores both systolic and diastolic function to normal levels. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Heart Failure & Cardiac Transplantat Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02129 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Hajjar, RJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St,CNY-4, Boston, MA 02129 USA. FU NHLBI NIH HHS [R01 HL061557, HL 54202, HL 50361, R01 HL059521, HL 57623] NR 37 TC 314 Z9 333 U1 0 U2 15 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 JAN 18 PY 2000 VL 97 IS 2 BP 793 EP 798 DI 10.1073/pnas.97.2.793 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 276HX UT WOS:000084873100051 PM 10639159 ER PT J AU Taupin, DR Kinoshita, K Podolsky, DK AF Taupin, DR Kinoshita, K Podolsky, DK TI Intestinal trefoil factor confers colonic epithelial resistance to apoptosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cell survival; signal transduction; cell adhesion; colonic neoplasm; cultured tumor cells ID GROWTH-FACTOR RECEPTOR; BETA-CATENIN; CARCINOMA CELLS; GENE-EXPRESSION; FAS LIGAND; PHOSPHORYLATION; KINASE; PATHWAY; RESTITUTION; INHIBITION AB Intestinal trefoil factor (ITF) is an essential regulator of colonic epithelial restitution, the rapid migration of colonocytes over mucosal wounds, High levels of ITF are frequently present in colorectal cancers and derived cell lines. Mucosal restitution requires the detachment of epithelium from substrate, which would be expected to induce apoptosis, However, mice deficient in ITF showed an increase in colonocyte apoptosis unaccompanied by changes in expression of receptor-related (TNFR/Fas) or stress-related (Bcl-family) cell death regulators. An ITF-expressing colonic (HT-ITF1) cell line was resistant to apoptosis induced by serum starvation and ceramide, Exogenous ITF also protected another human colonic carcinoma-derived cell line (HCT116) and a nontransformed rat intestinal epithelial cell line (IEC-6) from apoptosis, This effect was abrogated by wortmannin and tyrphostin A25, indicating the potential involvement of phosphatidylinositol 3-kinase and epidermal growth factor (ECF) receptor activation, Expression of phosphorylated Akt, which lies downstream of phosphatidylinositol 3-kinase activation, was elevated in this HT-29-ITF line. p53-dependent cell death in the AGS human gastric cancer cell line after etoposide was similarly inhibited by transient expression of ITF but not a C-terminal truncation mutant of ITF, and it required functional phosphatidylinositol 3-kinase and EGF receptor. These findings support a central role for ITF in the maintenance of intestinal mucosal continuity, and conversely demonstrate the potential for ITF expression to confer resistance of colorectal tumors to therapy. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ-719, Boston, MA 02114 USA. FU NIDDK NIH HHS [P30 DK043351, DK 43351, DK 46906, R01 DK046906] NR 36 TC 193 Z9 204 U1 4 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 JAN 18 PY 2000 VL 97 IS 2 BP 799 EP 804 DI 10.1073/pnas.97.2.799 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 276HX UT WOS:000084873100052 PM 10639160 ER PT J AU Barlow, C Ribaut-Barassin, C Zwingman, TA Pope, AJ Brown, KD Owens, JW Larson, D Harrington, EA Haeberle, AM Mariani, J Eckhaus, M Herrup, K Bailly, Y Wynshaw-Boris, A AF Barlow, C Ribaut-Barassin, C Zwingman, TA Pope, AJ Brown, KD Owens, JW Larson, D Harrington, EA Haeberle, AM Mariani, J Eckhaus, M Herrup, K Bailly, Y Wynshaw-Boris, A TI ATM is a cytoplasmic protein in mouse brain required to prevent lysosomal accumulation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ATAXIA-TELANGIECTASIA; DEFICIENT MICE; NERVOUS-SYSTEM; GENE-PRODUCT; NEURONS; EXPRESSION; LOCALIZATION; UBIQUITIN; DEFECTS AB We previously generated a mouse model with a mutation in the murine Atm gene that recapitulates many aspects of the childhood neurodegenerative disease ataxia-telangiectasia. Atm-deficient (Atm-/-) mice show neurological defects detected by motor function tests including the rota-rod, open-field tests and hindpaw footprint analysis. However, no gross histological abnormalities have been observed consistently in the cerebellum of any line of Atm-/- mice analyzed in most laboratories, Therefore, it may be that the neurologic dysfunction found in these animals is associated with predegenerative lesions. We performed a detailed analysis of the cerebellar morphology in two independently generated lines of Atm-/- mice to determine whether there was evidence of neuronal abnormality, We found a significant increase in the number of lysosomes in Atm-/- mice in the absence of any detectable signs of neuronal degeneration or other ultrastructural anomalies. In addition, we found that the ATM protein is predominantly cytoplasmic in Purkinje cells and other neurons, in contrast to the nuclear localization of ATM protein observed in cultured cells, The cytoplasmic localization of ATM in Purkinje cells is similar to that found in human cerebellum, These findings suggest that ATM may be important as a cytoplasmic protein in neurons and that its absence leads to abnormalities of cytoplasmic organelles reflected as an increase in lysosomal numbers. C1 Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA. NIH, Natl Ctr Human Genome Res, Genet Dis Res Branch, Bethesda, MD 20892 USA. CNRS, Ctr Neurochim, Lab Neurobiol Cellulaire, Unite Propre Rech 9009,Ctr Neurochim, F-67084 Strasbourg, France. Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Alzheimers Res Lab, Cleveland, OH 44106 USA. Louisiana State Univ, Med Ctr, Dept Biochem & Mol Biol, New Orleans, LA 70112 USA. Louisiana State Univ, Med Ctr, Stanley S Scott Canc Ctr, New Orleans, LA 70112 USA. Off Res Serv, Vet Resources Program, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Ctr Canc, Mol Oncol Lab, Charlestown, MA USA. Univ Paris 06, Lab Dev & Vieillissement Syst Nerveux, Unite Mixte Rech 7624, CNRS, F-75005 Paris, France. RP Barlow, C (reprint author), Salk Inst Biol Studies, Genet Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. FU NCRR NIH HHS [R25 RR010836, 5R25 RR10836-02]; NINDS NIH HHS [NS18381, NS20591, R01 NS018381, R01 NS020591] NR 26 TC 111 Z9 113 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 JAN 18 PY 2000 VL 97 IS 2 BP 871 EP 876 DI 10.1073/pnas.97.2.871 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 276HX UT WOS:000084873100064 PM 10639172 ER PT J AU Chong, MJ Murray, MR Gosink, EC Russell, HRC Srinivasan, A Kapsetaki, M Korsmeyer, SJ McKinnon, PJ AF Chong, MJ Murray, MR Gosink, EC Russell, HRC Srinivasan, A Kapsetaki, M Korsmeyer, SJ McKinnon, PJ TI Atm and Bax cooperate in ionizing radiation-induced apoptosis in the central nervous system SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INDUCED CELL-DEATH; DEFICIENT MICE; IN-VIVO; ATAXIA-TELANGIECTASIA; NEURONAL DEATH; P53; ACTIVATION; FAMILY; PHOSPHORYLATION; TUMORIGENESIS AB Ataxia-telangiectasia is a hereditary multisystemic disease resulting from mutations of ataxia telangiectasia, mutated (ATM) and is characterized by neurodegeneration, cancer, immune defects, and hypersensitivity to ionizing radiation. The molecular details of ATM function in the nervous system are unclear, although the neurological lesion in ataxia-telangiectasia becomes apparent early in life, suggesting a developmental origin. The central nervous system (CNS) of Atm-null mice shows a pronounced defect in apoptosis induced by genetoxic stress, suggesting ATM functions to eliminate neurons with excessive genomic damage. Here, we report that the death effector Bax is required for a large proportion of Atm-dependent apoptosis in the developing CNS after ionizing radiation (IR). Although many of the same regions of the CNS in both Bax-/- and Atm-/- mice were radioresistant, mice nullizygous for both Bax and Atm showed additional reduction in IR-induced apoptosis in the CNS. Therefore, although the major IR-induced apoptotic pathway in the CNS requires Atm and Bax, a p53-dependent collateral pathway exists that has both Atm- and Bax-independent branches. Further, Atm- and Bax-dependent apoptosis in the CNS also required caspase-3 activation. These data implicate Bax and caspase-3 as death effecters in neurodegenerative pathways. C1 St Jude Childrens Res Hosp, Dept Genet, Memphis, TN 38101 USA. IDUN Pharmaceut Inc, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol & Med, Boston, MA 02115 USA. RP McKinnon, PJ (reprint author), St Jude Childrens Res Hosp, Dept Genet, 332 N Lauderdale, Memphis, TN 38101 USA. EM peter.mckinnon@stjude.org FU NINDS NIH HHS [NS-37956, R01 NS037956, R56 NS037956] NR 46 TC 114 Z9 124 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 JAN 18 PY 2000 VL 97 IS 2 BP 889 EP 894 DI 10.1073/pnas.97.2.889 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 276HX UT WOS:000084873100067 PM 10639175 ER PT J AU Furukawa, K D'Souza, I Crudder, CH Onodera, H Itoyama, Y Poorkaj, P Bird, TD Schellenberg, GD AF Furukawa, K D'Souza, I Crudder, CH Onodera, H Itoyama, Y Poorkaj, P Bird, TD Schellenberg, GD TI Pro-apoptotic effects of tau mutations in chromosome 17 frontotemporal dementia and parkinsonism SO NEUROREPORT LA English DT Article DE apoptosis; calcium; frontotemporal dementia and parkinsonism; mutation; tau ID PROTECTS HIPPOCAMPAL-NEURONS; EXCITOTOXICITY; FTDP-17; GENE AB It was recently discovered that mutations of tau cause hereditary frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Here we repels that cultured SH-SY5Y human neuroblastoma cells transfected with mutated tau genes are more vulnerable to apoptotic stimulus. Two kinds of mutations of tau causing FTDP-17 were examined in the present study: one was in exon 10 (N279K) and the other was in exon 12 (V337M). SH-SY5Y cells transfected with either mutated tau were more vulnerable to serum withdrawal, whereas cells transfected with the wild-type tau or vector alone showed no significant change in apoptotic vulnerability. The increase in the intracellular calcium concentration by the serum withdrawal was significantly greater in the SH-SY5Y cells transfected with mutated tau genes than in cells transfected with the wild-type tau or vector alone. These results suggest that mutations of tau might cause FTDP-17 by these proapoptotic functions by disrupting the intracellular calcium homeostasis. NeuroReport 11:57-60 (C) 2000 Lippincott Williams & Wilkins. C1 Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle Div, Seattle, WA 98108 USA. Univ Washington, Dept Neurol & Pharmacol, Seattle, WA 98195 USA. Univ Washington, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. Tohoku Univ, Sch Med, Dept Neurol, Aoba Ku, Sendai, Miyagi 9808574, Japan. RP Furukawa, K (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle Div, Seattle, WA 98108 USA. NR 8 TC 22 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JAN 17 PY 2000 VL 11 IS 1 BP 57 EP 60 DI 10.1097/00001756-200001170-00011 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 274YA UT WOS:000084791600012 PM 10683829 ER PT J AU Kowall, NW Hantraye, P Brouillet, E Beal, MF McKee, AC Ferrante, RJ AF Kowall, NW Hantraye, P Brouillet, E Beal, MF McKee, AC Ferrante, RJ TI MPTP induces alpha-synuclein aggregation in the substantia nigra of baboons SO NEUROREPORT LA English DT Article DE baboon; MPTP; synuclein; substantia nigra ID PARKINSONS-DISEASE; LEWY BODIES; TRANSGLUTAMINASE; MUTATION; MUTANT; FILAMENTS; PROTEINS; PEPTIDE; MICE AB 1-Methyl-4-phenyl-1,2,3,6-retrahydropyridine (MPTP) neurotoxicity reproduces many of the features of Parkinson's disease (PD). alpha-Synuclein has been identified as a prominent component of the Lewy body (LB), the pathological hallmark of PD. MPTP-treated primates have been reported to develop intraneuronal inclusions but not true Lewy bodies. We administered MPTP to baboons and used a monoclonal alpha-synuclein antibody to define the relationship between neuronal degeneration and alpha-synuclein immunoreactivity in the substantia nigra. MPTP-induced neuronal degeneration was associated with the redistribution of alpha-synuclein from its normal synaptic location to aggregates in degenerating neuronal cell bodies. alpha-Synuclein aggregation induced by MPTP models the early stages of Lewy body formation and may be a fundamental step in the evolution of neuronal degeneration in PD. NeuroReport 11:211-213 (C) 2000 Lippincott Williams & Wilkins. C1 Vet Affairs Med Ctr, Geriatr Res Educ Clin Ctr, Bedford, MA 01730 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. CEA, Serv Hosp Frederic Joliot, CNRS, URA 2210, F-91406 Orsay, France. Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kowall, NW (reprint author), Vet Affairs Med Ctr, Geriatr Res Educ Clin Ctr, Bedford, MA 01730 USA. RI Kowall, Neil/G-6364-2012; Brouillet, Emmanuel/B-4784-2014 OI Kowall, Neil/0000-0002-6624-0213; Brouillet, Emmanuel/0000-0001-6322-7403 FU NIA NIH HHS [AG13846]; NINDS NIH HHS [NS16367, NS37102] NR 24 TC 149 Z9 153 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JAN 17 PY 2000 VL 11 IS 1 BP 211 EP 213 DI 10.1097/00001756-200001170-00041 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 274YA UT WOS:000084791600043 PM 10683860 ER PT J AU Weitzel, JN Ding, SF Larson, GP Nelson, RA Goodman, A Grendys, EC Ball, HG Krontiris, TG AF Weitzel, JN Ding, SF Larson, GP Nelson, RA Goodman, A Grendys, EC Ball, HG Krontiris, TG TI The HRAS1 minisatellite locus and risk of ovarian cancer SO CANCER RESEARCH LA English DT Article ID GENETIC-HETEROGENEITY; BREAST; CARRIERS; FAMILIES; ALLELES; BRCA1 AB Approximately 10% of ovarian cancers are due to mutations in highly penetrant inherited cancer susceptibility genes. The highly polymorphic HRAS1 minisatellite locus, located just downstream from the proto-oncogene H-ras-1 on chromosome 11p, consists of four common progenitor alleles and several dozen rare alleles, which apparently derive from mutations of the progenitors. Mutant alleles of this locus represent a major risk factor for cancers of the breast, colorectum, and bladder, and it was found that BRCA1 mutation carriers with at least one rare HRAS1 allele have a greater risk of ovarian cancer than BRCA1 carriers with only common HRAS1 alleles, There are no conclusive studies of HRAS1 alleles in sporadic epithelial ovarian cancer. A case-control study of HRAS1 alleles was performed on DNA from 136 Caucasian patients with ovarian cancer and 108 cancer-free controls using conventional (Southern blot) and PCR-based methods to determine the frequency of rare HRAS1 alleles, Odds ratios (ORs) were estimated using unconditional logistic regression methods, A single degree of freedom test was used to assess the significance of linear trend across categories of increasing exposure. A statistically significant association between rare HRAS1 alleles and risk of ovarian cancer was observed [OR, 1.70; 95% confidence interval (CI), 1.03-2.80; P = 0.04]. Having only one rare allele was associated with a relative risk of 1.66 (95% CI, 0.91-3.01), whereas having two rare alleles increased the relative risk to 2.86 (95% CI, 0.75-10.94; trend P = 0.03). Analysis of HRAS1 allele types hy the age of the case at diagnosis revealed that younger cases (<45 years) had a borderline statistically significant increased association with rare HRAS1 alleles compared to older cases (greater than or equal to 60 years; OR, 1.89; 95% CI, 0.90-3.98; P = 0.09). Rare HRAS1 alleles contribute to ovarian cancer predisposition in the general population. Thus, the HRAS1-variable number of tandem repeats locus may function as a modifier of ovarian cancer risk in both sporadic and hereditary ovarian cancer. C1 City Hope Natl Med Ctr, Dept Clin Canc Genet, Duarte, CA 91010 USA. City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. New England Med Ctr, Boston, MA 02111 USA. RP Weitzel, JN (reprint author), City Hope Natl Med Ctr, Dept Clin Canc Genet, 1500 E Duarte Rd, Duarte, CA 91010 USA. RI Nelson, Rebecca/C-4438-2014 FU NCI NIH HHS [1RO3-CA74766-01] NR 19 TC 33 Z9 34 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 JAN 15 PY 2000 VL 60 IS 2 BP 259 EP 261 PG 3 WC Oncology SC Oncology GA 279JZ UT WOS:000085041800013 PM 10667571 ER PT J AU Anderson, IC Mari, SE Broderick, RJ Mari, BP Shipp, MA AF Anderson, IC Mari, SE Broderick, RJ Mari, BP Shipp, MA TI The angiogenic factor interleukin 8 is induced in non-small cell lung cancer/pulmonary fibroblast cocultures SO CANCER RESEARCH LA English DT Article ID HUMAN-MELANOMA CELLS; GENE-EXPRESSION; GROWTH-FACTOR; NONSMALL CELL; CHEMOKINES; TUMORIGENESIS; INHIBITION; INDUCTION; CARCINOMA; CANCER AB The interactions between tumor cells and surrounding stromal elements may promote the release of angiogenic factors. Although interleukin 8 (IL-8) is a major angiogenic factor in non-small cell lung cancer (NSCLC), the stromal contribution to IL-8 expression in primary NSCLC remains to be defined. To elucidate the role of stromal elements in NSCLC IL-8 production, normal pulmonary fibroblasts were cocultured with six representative NSCLC lines in direct and transwell assays. IL-8 transcripts and protein were consistently induced in fibroblasts and a subset of NSCLCs as a consequence of tumor/stromal coculture, In these cocultures, IL-8 was induced by IL-1 alpha and an additional, as yet unidentified, soluble factor. These data underscore the importance of tumor/stromal interaction in the production of angiogenic peptides such as IL-8 in NSCLC. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Shipp, MA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Mari, Bernard/F-8960-2013; Mari, Bernard/D-7445-2015 OI Mari, Bernard/0000-0002-0422-9182 FU NCI NIH HHS [1KO8CA69133-01, 1RO1CA76286-01] NR 21 TC 50 Z9 56 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2000 VL 60 IS 2 BP 269 EP 272 PG 4 WC Oncology SC Oncology GA 279JZ UT WOS:000085041800016 PM 10667574 ER PT J AU Yu, Q Stamenkovic, I AF Yu, Q Stamenkovic, I TI Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis SO GENES & DEVELOPMENT LA English DT Article DE MMP-9; CD44; TGF-beta; tumor angiogenesis; tumor invasion ID GROWTH-FACTOR-BETA; ENDOTHELIAL-CELLS; CARCINOMA-CELLS; IN-VITRO; CD44; CANCER; METASTASIS; INDUCTION; RECEPTOR; INVASIVENESS AB We have uncovered a novel functional relationship between the hyaluronan receptor CD44, the matrix metalloproteinase-9 (MMP-9) and the multifunctional cytokine TGF-beta in the control of tumor-associated tissue remodeling. CD44 provides a cell surface docking receptor for proteolytically active MMP-9 and we show here that localization of MMP-9 to cell surface is required for its ability to promote tumor invasion and angiogenesis. Our observations also indicate that MMP-9, as well as MMP-2, proteolytically cleaves latent TGF-beta, providing a novel and potentially important mechanism for TGF-beta activation. In addition, we show that MMP-9, localization to the surface of normal keratinocytes is CD44 dependent and can activate latent TGF-beta. These observations suggest that coordinated CD44, MMP-9, and TGF-beta function may provide a physiological mechanism of tissue remodeling that can be adopted by malignant cells to promote tumor growth and invasion. C1 Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02129 USA. RP Stamenkovic, I (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02129 USA. FU NCI NIH HHS [CA09216, CA55375, T32 CA009216]; NIGMS NIH HHS [GM48614] NR 40 TC 1190 Z9 1240 U1 7 U2 66 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 JAN 15 PY 2000 VL 14 IS 2 BP 163 EP 176 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 279QG UT WOS:000085056200006 PM 10652271 ER PT J AU Pohl, U Smith, JS Tachibana, I Ueki, K Lee, HK Ramaswamy, S Wu, Q Mohrenweiser, HW Jenkins, RB Louis, DN AF Pohl, U Smith, JS Tachibana, I Ueki, K Lee, HK Ramaswamy, S Wu, Q Mohrenweiser, HW Jenkins, RB Louis, DN TI EHD2, EHD3, and EHD4 encode novel members of a highly conserved family of EH domain-containing proteins SO GENOMICS LA English DT Article ID TUMOR-SUPPRESSOR GENE; MEDIATED ENDOCYTOSIS; EXON AMPLIFICATION; CHROMOSOME 19Q13.3; EPS15; OLIGODENDROGLIOMAS; ASTROCYTOMAS; SPECIFICITY; DELETION; REGION AB Exon trapping from a bacterial artificial chromosome (BAC 78138) mapping to the 19q13.3 glioma tumor suppressor candidate region yielded two exons that recognized a 3.6-kb transcript on Northern blot, Screening of a human fetal brain cDNA library with these exons identified three novel genes, designated EHD2, EHD3, and EHD4, which are homologous to the recently characterized human EHD1 (testilin/HPAST) and its mouse homolog Ehd1, as well as to homologs in Drosophila (Past1) and Caenorhabditis elegans. Alignment of the predicted peptide sequences revealed striking similarities, with multiple conserved regions that include a nucleotide-binding consensus site at the N-terminus, a bipartite nuclear localization signal, and an eps15 homology (EH) protein-binding domain with an EF-hand motif at the C-terminus. The genes are specifically expressed, with EHD2 highly expressed in heart, EHD3 in brain and heart, and EHD4 in heart and pancreas. EHD2 was confirmed to originate from BAC 78138 at 19q13.3; radiation hybrid mapping localized EHD3 and EHD4 to 2p21 and 15q11.1, respectively; EHD1 has been previously mapped to 11q13. The three EHD1 paralogs therefore represent novel members of a family of human EH domain-containing proteins that may play a role in endocytosis and signaling. Mutation analysis of the five coding exons of EHD2 in gliomas failed to detect any tumor-specific alterations, thus indicating that EHD2 is an unlikely candidate for the 19q tumor suppressor gene. (C) 2000 Academic Press. C1 Massachusetts Gen Hosp, Dept Pathol, Mol Neurooncol Lab, Boston, MA 02129 USA. Massachusetts Gen Hosp, Neurosurg Serv, Mol Neurooncol Lab, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Mayo Clin & Mayo Fdn, Div Lab Genet, Rochester, MN 55905 USA. Harvard Univ, Dept Cellular & Mol Biol, Cambridge, MA 02138 USA. Univ Calif Lawrence Livermore Natl Lab, Livermore, CA 94550 USA. RP Louis, DN (reprint author), Massachusetts Gen Hosp, Mol Neurooncol Lab, Dept Pathol, CNY6,149 13th St, Charlestown, MA 02129 USA. RI imoto, Issei/D-8065-2012; Wu, Qiang/A-6751-2009 OI Wu, Qiang/0000-0003-3841-3591 FU NCI NIH HHS [CA 69285, CA 50905] NR 30 TC 68 Z9 72 U1 0 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JAN 15 PY 2000 VL 63 IS 2 BP 255 EP 262 DI 10.1006/geno.1999.6087 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 286PB UT WOS:000085453400009 PM 10673336 ER PT J AU Tarbell, NJ Smith, AR Adams, J Loeffler, JS AF Tarbell, NJ Smith, AR Adams, J Loeffler, JS TI The challenge of conformal radiotherapy in the curative treatment of medulloblastoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Tarbell, NJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Bulfinch 360,55 Fruit St, Boston, MA 02114 USA. NR 2 TC 17 Z9 17 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 JAN 15 PY 2000 VL 46 IS 2 BP 265 EP 266 DI 10.1016/S0360-3016(99)00366-1 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 277TY UT WOS:000084950700002 PM 10661330 ER PT J AU Hill, GR Teshima, T Rebel, VI Krijanovski, OI Cooke, KR Brinson, YS Ferrara, JLM AF Hill, GR Teshima, T Rebel, VI Krijanovski, OI Cooke, KR Brinson, YS Ferrara, JLM TI The p55 TNF-alpha receptor plays a critical role in T cell alloreactivity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; VERSUS-HOST DISEASE; BONE-MARROW TRANSPLANTATION; DEFICIENT MICE; IN-VIVO; PROLIFERATION; ACTIVATION; P75; STIMULATION; CYTOKINES AB TNF-alpha is known to be an important mediator of tissue damage during allograft rejection and graft-vs-host disease (GVHD), but its role in supporting T cell responses to allogeneic Ags is unclear. We have studied this question by comparing normal mice with those lacking the P55 (p55 TNFR-/-) or p75 (p75 TNFR-/-) TNF-alpha receptors as donors in well-defined bone marrow transplant (BMT) models. Recipients of p55 TNFR-/- cells had significantly reduced mortality and morbidity from GVHD compared with the other two sources of T cells, In vitro, T cells lacking the p55 (but not the p75) TNF-alpha receptor exhibited decreased proliferation and production of Th1 cytokines in MLC, This defect was only partially restored by exogenous IL-2 and affected both CD4(+) and CD8(+) populations. CD8(+) p55 TNFR-/- proliferation was impaired independently of IL-2 whereas CTL effector function was impaired in an IL-2-dependent fashion. Inhibition of TNF-alpha with TNFR:Fc in primary MLC also impaired the proliferation and Th1 differentiation of wild-type T cells. BMT mixing experiments demonstrated that the reduced ability of p55 TNFR-/- donor cells to induce GVHD was due to the absence of the p55 TNFR on T cells rather than bone marrow cells. These data highlight the importance of TNF-alpha in alloreactive T cell responses and suggest that inhibition of the T cell p55 TNF-alpha receptor may provide an additional useful therapeutic maneuver to inhibit alloreactive T cell responses following bone marrow and solid organ transplantation. C1 Univ Michigan, Ctr Canc, Dept Internal Med, Bone Marrow Transplant Program, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Mater Med Res Inst, S Brisbane, Australia. Univ Michigan, Ctr Canc, Dept Pediat, Bone Marrow Transplant Program, Ann Arbor, MI 48109 USA. RP Ferrara, JLM (reprint author), Univ Michigan, Ctr Canc, Dept Internal Med, Bone Marrow Transplant Program, Ann Arbor, MI 48109 USA. RI teshima, takanori/G-1671-2012; Hill, Geoffrey/O-2630-2016 OI Hill, Geoffrey/0000-0003-2994-0429 FU NCI NIH HHS [CA-39542]; NHLBI NIH HHS [HL-55162] NR 46 TC 97 Z9 97 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2000 VL 164 IS 2 BP 656 EP 663 PG 8 WC Immunology SC Immunology GA 273LF UT WOS:000084708600016 PM 10623807 ER PT J AU Kalka-Moll, WM Tzianabos, AO Wang, Y Carey, VJ Finberg, RW Onderdonk, AB Kasper, DL AF Kalka-Moll, WM Tzianabos, AO Wang, Y Carey, VJ Finberg, RW Onderdonk, AB Kasper, DL TI Effect of molecular size on the ability of zwitterionic polysaccharides to stimulate cellular immunity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL INTRAABDOMINAL ABSCESSES; INTRA-ABDOMINAL ABSCESS; RECEPTOR-BETA-CHAIN; BACTEROIDES-FRAGILIS; CLASS-II; CAPSULAR POLYSACCHARIDE; GROUP-B; 3-DIMENSIONAL STRUCTURE; IMMUNOCHEMICAL CHARACTERIZATION; CRYSTAL-STRUCTURE AB The large-molecular-sized zwitterionic capsular polysaccharide of the anaerobe Bacteroides fragilis NCTC 9343, designated polysaccharide (PS) A, stimulates T cell proliferation in vitro and induces T cell-dependent protection against abscess formation in vivo. In the present study, we utilized a modification of a recently developed ozonolytic method for depolymerizing polysaccharides to examine the influence of the molecular size of PS A on cell-mediated immunity. Ozonolysis successfully depolymerized PS A into structurally intact fragments. PS A with average molecular sizes of 129.0 (native), 77.8, 46.9, and 17.1 kDa stimulated CD4(+)-cell proliferation in vitro to the same degree, whereas the 5.0-kDa fragment was much less stimulatory than the control 129.0-kDa PS A. Rats treated with 129.0-kDa, 46.9-kDa, and 17.1-kDa PS A molecules, but not those treated with the 5.0-kDa molecule, were protected against intraabdominal abscesses induced by challenge with viable B, fragilis, These results demonstrate that a zwitterionic polysaccharide as small as 22 repeating units (88 monosaccharides) elicits a T cell-dependent immune response. These findings clearly distinguish zwitterionic T cell-dependent polysaccharides from T-cell-independent polysaccharides and give evidence of the existence of a novel mechanism for a polysaccharide-induced immune response. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Infect Dis, Boston, MA 02115 USA. RP Kasper, DL (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. RI Finberg, Robert/E-3323-2010 FU NIAID NIH HHS [AI 39576, AI 34073] NR 55 TC 37 Z9 39 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2000 VL 164 IS 2 BP 719 EP 724 PG 6 WC Immunology SC Immunology GA 273LF UT WOS:000084708600024 PM 10623815 ER PT J AU Watanabe, H Garnier, G Circolo, A Wetsel, RA Ruiz, P Holers, VM Boackle, SA Colten, HR Gilkeson, GS AF Watanabe, H Garnier, G Circolo, A Wetsel, RA Ruiz, P Holers, VM Boackle, SA Colten, HR Gilkeson, GS TI Modulation of renal disease in MRL/lpr mice genetically deficient in the alternative complement pathway factor B SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; WIRE-LOOP LESIONS; RHEUMATOID-FACTOR; IMMUNE-COMPLEXES; BLOOD MONOCYTES; GLOMERULONEPHRITIS; INDUCTION; PROTEINS; CELLS; SOLUBILIZATION AB In systemic lupus erythematosus, the renal deposition of complement-containing immune complexes initiates an inflammatory cascade resulting in glomerulonephritis. Activation of the classical complement pathway with deposition of C3 is pathogenic in lupus nephritis, Although the alternative complement pathway is activated in lupus nephritis, its role in disease pathogenesis is unknown. To determine the role of the alternative pathway in lupus nephritis, complement factor B-deficient mice were backcrossed to MRL/lpr mice. MRL/lpr mice develop a spontaneous lupus-like disease characterized by immune complex glomerulonephritis, We derived complement factor B wild-type (B+/+), homozygous knockout (B-/-), and heterozygous (B+/-) MRL/lpr mice, Compared with B+/- or B+/+ mice, MRL/lpr B-/- mice developed significantly less proteinuria, less glomerular IgG deposition, and decreased renal scores as well as lower IgG3 cryoglobulin production and vasculitis. Serum C3 levels were normal in the B-/- mice compared with significantly decreased levels in the other two groups. These results suggest that: 1) factor B plays an important role in the pathogenesis of glomerulonephritis and vasculitis in MRL/lpr mice; and 2) activation of the alternative pathway, either by the amplification loop or by IgA immune complexes, has a prominent effect on serum C3 levels in this lupus model. C1 Med Univ S Carolina, Div Rheumatol Immunol, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Med Res Serv, Charleston, SC 29425 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. Univ Miami, Sch Med, Dept Pathol, Miami, FL 33125 USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. RP Gilkeson, GS (reprint author), Med Univ S Carolina, Div Rheumatol Immunol, Dept Med, Charleston, SC 29425 USA. FU NIAID NIH HHS [R01 AI24739, R01 AI25011, R01 AI31105] NR 48 TC 120 Z9 121 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 JAN 15 PY 2000 VL 164 IS 2 BP 786 EP 794 PG 9 WC Immunology SC Immunology GA 273LF UT WOS:000084708600033 PM 10623824 ER PT J AU Kaur, A Yang, J Hempel, D Gritz, L Mazzara, GP McClure, H Johnson, RP AF Kaur, A Yang, J Hempel, D Gritz, L Mazzara, GP McClure, H Johnson, RP TI Identification of multiple simian immunodeficiency virus (SIV)-specific CTL epitopes in sooty mangabeys with natural and experimentally acquired SIV infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; T-LYMPHOCYTE RESPONSES; RHESUS MACAQUES; SEQUENCE VARIATION; NONHUMAN-PRIMATES; CELLS; ANTIGEN; SELECTION; MONKEYS; VARIANTS AB Host immune responses to SIV infection in sooty mangabeys are likely to be an important determinant of how such nonhuman primate species maintain asymptomatic lentivirus infection. We have previously described two patterns of asymptomatic SIV infection in sooty mangabeys: low viral loads with vigorous SIV-specific CTL activity in SIVmac239-infected sooty mangabeys, and high viral loads with generally weak or absent SIV-specific CTL activity in naturally infected sooty mangabeys, To define the specificity of the CTL response in SIV-infected mangabeys, we characterized CTL epitopes in two naturally infected and three SIVmac239-infected sooty mangabeys, Compared with that in SIVmac239-infected mangabeys, the yield of SIV-specific CTL clones was significantly lower in naturally infected sooty mangabeys. All CTL clones were phenotypically CD3(+) CD8(+), and lysis was MHC restricted. Seven SIV CTL epitopes were identified in five sooty mangabeys: one in Gag and three each in Nef and Envelope (Env). The CTL epitopes mapped to conserved regions in the SIV genome and were immunodominant. Several similar or identical CTL epitopes were recognized by both naturally infected and SIVmac239-infected mangabeys that shared class I MHC alleles, To our knowledge, this is the first report of SIV-specific CTL epitopes in sooty mangabeys, Longitudinal studies of viral load and sequence variation in CTL epitopes may provide useful information on the role of CTL in control or persistence of sn infection in sooty mangabeys. C1 Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Therion Biol Corp, Cambridge, MA 02142 USA. Emory Univ, Yerkes Reg Primate Res Ctr, Div Res Resources, Atlanta, GA 30322 USA. Emory Univ, Yerkes Reg Primate Res Ctr, Div Microbiol & Immunol, Atlanta, GA 30322 USA. RP Kaur, A (reprint author), Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Immunol, 1 Pinehill Dr, Southborough, MA 01772 USA. FU NCRR NIH HHS [RR00168]; NIAID NIH HHS [AI38559, AI43890] NR 40 TC 27 Z9 28 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 JAN 15 PY 2000 VL 164 IS 2 BP 934 EP 943 PG 10 WC Immunology SC Immunology GA 273LF UT WOS:000084708600051 PM 10623842 ER PT J AU Cario, E Rosenberg, IM Brandwein, SL Beck, PL Reinecker, HC Podolsky, DK AF Cario, E Rosenberg, IM Brandwein, SL Beck, PL Reinecker, HC Podolsky, DK TI Lipopolysaccharide activates distinct signaling pathways in intestinal epithelial cell lines expressing toll-like receptors SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FACTOR KAPPA-B; LPS BINDING-PROTEIN; SOLUBLE CD14; BACTERIAL LIPOPOLYSACCHARIDE; REGULATED EXPRESSION; DROSOPHILA TOLL; KINASE; P38; MACROPHAGES; CYTOKINES AB LPS elicits several immediate proinflammatory responses in peripheral blood leukocytes via a recently described pathway including CD14, Toll-like receptors (TLR), serine-threonine kinases, and NF-kappa B transcription factor. However, the functional responses of intestinal epithelial cells (IEC) to stimulation with LPS are unknown, Expression of mRNA and protein for CD14 and TLRs were assessed by RT-PCR, immunoblotting, and immunohistochemistry in mouse and human IEC lines, LPS-induced activation of signaling pathways (p42/p44 mitogen-activated protein kinase (MAPK), c-Jun NH2-terminal kinase (JNK), p38, p65, NF-kappa B) were assessed by immunoblotting and gel shifts. CD14 mRNA and protein expression were not detectable in IEC. However, human TLR2, TLR3, and TLR4 mRNA were present in IEC, TLR4 protein was expressed in all cell lines; however, TLR2 protein was absent in HT29 cells. Immunofluorescent staining of T84 cells demonstrated the cell-surface presence of the TLRs, LPS-stimulation of IEC resulted in activation (>1.5-fold) of the three members of the MAPK family. In contrast, LPS did not significantly induce activation of JNK and p38 in CMT93 cells, p38 in T84 cells and MAPK and JNK in HT29 cells, Downstream, LPS activated NF-kappa B in IEC in a time-, dose-, and serum-dependent manner. IEC express TLRs that appear to mediate LPS stimulation of specific intracellular signal transduction pathways in IEC, Thus, IEC may play a frontline role in monitoring lumenal bacteria. C1 Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit GRJ719, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit GRJ719, 32 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK41557, DK43351, DK51003] NR 53 TC 512 Z9 532 U1 2 U2 36 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2000 VL 164 IS 2 BP 966 EP 972 PG 7 WC Immunology SC Immunology GA 273LF UT WOS:000084708600055 PM 10623846 ER PT J AU Delmonico, FL AF Delmonico, FL TI Analyzing risk factors of renal transplant outcome SO TRANSPLANTATION LA English DT Editorial Material ID MYCOPHENOLATE-MOFETIL; ALLOGRAFT; NEPHROPATHY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Delmonico, FL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 11 TC 1 Z9 1 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 JAN 15 PY 2000 VL 69 IS 1 BP 1 EP 2 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 276DJ UT WOS:000084860100001 PM 10653370 ER PT J AU Richter, S Yamauchi, JI Minor, T Vollmar, B Menger, MD AF Richter, S Yamauchi, JI Minor, T Vollmar, B Menger, MD TI Effect of warm ischemia time and organ perfusion technique on liver microvascular preservation in a non-heart-beating rat model SO TRANSPLANTATION LA English DT Article ID DONORS; TRANSPLANTATION; VIABILITY; REPERFUSION; PROCUREMENT; ALLOGRAFTS; PRESSURE AB Background Current organ shortage has led to a reconsideration of non-heart-beating cadaveric donation. Methods. We assessed the effectivity of dual, i.e., arterial and portal-venous versus exclusive, arterial gravity perfusion for procurement of rat livers after 30 min and 60 min of cardiac arrest, analyzing the rate and homogeneity of microvascular perfusion by in situ fluorescence microscopy, Results. After 30 min of cardiac arrest, a nearly 100% recovery of acinar perfusion with a sinusoidal density not significantly different from that, of normal, nonischemic livers was achieved by dual gravity perfusion. Prolongation of cardiac arrest: to 60 ruin caused an almost 50% deficit of acinar and sinusoidal perfusion (P<0.05) with a concomitant 2-3-fold increase of heterogeneity of hepatic microperfusion, Regardless of the warm ischemic time period, dually perfused livers exhibited significantly (P<0.05) higher rates of both acinar and sinusoidal perfusion with increased homogeneity of microcirculation when compared with exclusive arterial perfusion, Conclusion, These data underline the need and benefit of dual perfusion as well as the limitation of warm ischemic tolerance to 30 min for safe liver procurement of non-heart beating donors. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Bonn, Surg Clin, Div Surg Res, D-53127 Bonn, Germany. Univ Saarlandes, Inst Clin & Expt Surg, D-66421 Homburg, Germany. RP Vollmar, B (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. NR 22 TC 13 Z9 14 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 JAN 15 PY 2000 VL 69 IS 1 BP 20 EP 24 DI 10.1097/00007890-200001150-00005 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 276DJ UT WOS:000084860100005 PM 10653374 ER PT J AU Colby, C Chang, Q Fuchimoto, Y Ferrara, V Murphy, M Sackstein, R Spitzer, TR White-Scharf, ME Sachs, DH AF Colby, C Chang, Q Fuchimoto, Y Ferrara, V Murphy, M Sackstein, R Spitzer, TR White-Scharf, ME Sachs, DH TI Cytokine-mobilized peripheral blood progenitor cells for allogeneic reconstitution of miniature swine SO TRANSPLANTATION LA English DT Article ID COLONY-STIMULATING FACTOR; BONE-MARROW TRANSPLANTATION; DIFFERENTIATION CD ANTIGENS; INTERNATIONAL WORKSHOP; GROWTH-FACTORS; STEM-CELLS; ENGRAFTMENT; LYMPHOMA; CLUSTER AB Background. Because of the relative ease of acquisition, increased yield, and improved engraftment characteristics, mobilized peripheral blood progenitor (stem) cells (PBSCs) have recently become the preferred source for hematopoietic stem cell transplantation. In our laboratory, procurement of a megadose of PBSCs is necessary for on-going studies evaluating non-myelosuppressive transplant regimens for the induction of mixed chimerism and allograft tolerance. To exploit hematopoietic growth factor synergy, we have sought to combine growth factors with proven utility to improve PBSC mobilization and maximize our PBSC procurement through an automated collection procedure. Methods. Mobilization characteristics of PBSCs were determined in 2-5-month-old miniature swine. Animals received either swine recombinant stem cell factor (pSCF, 100 mu g/kg) and swine recombinant interleukin 3 (pIL-3, 100 mu g/kg), administered intramuscularly for 8 days, or pSCF, pIL-3, and human recombinant granulocyte-colony stimulating factor (hG-CSF), at 10 mu g/kg. Leukapheresis was performed beginning on day 5 of cytokine treatment and continued daily for 3 days. Results. Collection of PBSCs from cytokine-mobilized animals via an automated leukapheresis procedure demonstrated a 10-fold increase in the number of total nucleated cells (TNC) (20-30x10(10) TNC) compared to bone marrow harvesting (2-3x10(10) total TNC), A more rapid rise in white blood cells (WBCs) was seen after administration of all three cytokines compared to pSCF and pIL-3 alone. An increase in colony-forming unit granulocyte-macrophage frequency measured daily from peripheral blood during cytokine treatment, was seen with the addition of hG-CSF to pSCF/pIL-3 correlating well with the rise in WBCs. Similarly, the addition of IG-CSF demonstrated a notable increase in the median progenitor cell yield from the 3-day leukapheresis procedure. Cytokine-mobilized PBSCs were capable of hematopoietic reconstitution. PBSCs mobilized with pSCF/pIL-3 were infused into an SLA-matched recipient conditioned with cyclophosphamide (50 mg/kg) and total body irradiation 1150 cGy, Neutrophil and platelet engraftment occurred on days 5 and 7, respectively, with minimal evidence of graft-versus-host disease. Complete donor chimerism has been demonstrated 331 days after transplant. Conclusions. Our preliminary results show that in this well-defined miniature swine model, recombinant swine cytokine combinations (pSCF, pIL-3 with or without hG-CSF) successfully mobilize a high yield of progenitor cells for allogeneic transplantation. Furthermore these cytokine-mobilized PBSCs demonstrate the potential to reconstitute hematopoiesis and provide long-term engraftment in miniature swine. C1 Harvard Univ, Transplantat Biol Res Ctr, Dept Surg, Massachusetts Gen Hosp,Sch Med, Boston, MA 02129 USA. Harvard Univ, Bone Marrow Transplantat Program, Dept Med, Massachusetts Gen Hosp,Sch Med, Boston, MA 02129 USA. BioTransplant Inc, Boston, MA 02129 USA. RP Colby, C (reprint author), Harvard Univ, Transplantat Biol Res Ctr, Dept Surg, Massachusetts Gen Hosp,Sch Med, MGH-E,Bldg 149-9019, Boston, MA 02129 USA. FU NCI NIH HHS [5RO1 CA61537]; NIAID NIH HHS [5PO1 AI39755] NR 19 TC 15 Z9 17 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 JAN 15 PY 2000 VL 69 IS 1 BP 135 EP 140 DI 10.1097/00007890-200001150-00023 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 276DJ UT WOS:000084860100023 PM 10653392 ER PT J AU Yang, YG Chen, AM Sergio, JJ Zhou, Y Sykes, M AF Yang, YG Chen, AM Sergio, JJ Zhou, Y Sykes, M TI Role of antibody-independent complement activation in rejection of porcine bone marrow cells in mice SO TRANSPLANTATION LA English DT Article ID NONLETHAL PREPARATIVE REGIMEN; MIXED CHIMERISM; TOLERANCE; INDUCTION; LECTIN AB Background Although complement activation has been shown to be important in the rejection of solid organs in some xenogeneic species combinations, its role in the rejection of xenogeneic marrow engraftl ment is unknown. Methods. The effect of complement depletion with cobra venom factor on porcine bone marrow cell (BMC) engraftment was examined in 3 Gy-irradiated C.B-17 severe combined immunodeficiency mice receiving 10(8) pig BMC. Results. At 26 days after transplantation, the percentages of swine class 1(+), myeloid, and CD2(+) cells in marrow, spleen, and peripheral blood, and the numbers of porcine myeloid progenitor cells in marrow, were increased in cobra venom factor-treated recipients compared with simultaneous control recipients. Consistent with the in vivo results, preheating serum (56 degrees C for 30 min) reduced the inhibitory effect of severe combined immunodeficiency mouse serum on the proliferation of pig BMC in vitro. Conclusion. Murine complement is capable of resisting xenogeneic hematopoietic engraftment through an antibody-independent mechanism. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr,Surg Serv, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr,Surg Serv, Bldg 149-5102,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [P01 HL18646, R01 HL49915] NR 15 TC 12 Z9 12 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 JAN 15 PY 2000 VL 69 IS 1 BP 163 EP 165 DI 10.1097/00007890-200001150-00027 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 276DJ UT WOS:000084860100027 PM 10653396 ER PT J AU Shen, Y Lyons, P Cooley, M Davidson, D Veillette, A Salgia, R Griffin, JD Schaller, MD AF Shen, Y Lyons, P Cooley, M Davidson, D Veillette, A Salgia, R Griffin, JD Schaller, MD TI The noncatalytic domain of protein-tyrosine phosphatase-PEST targets paxillin for dephosphorylation in vivo SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FOCAL ADHESION KINASE; CELL-MIGRATION; PTP-PEST; LIM DOMAIN; SH3 DOMAIN; IDENTIFICATION; INHIBITION; P130(CAS); BINDING; SRC AB The noncatalytic domain of protein-tyrosine phosphatase (PTP)-PEST contains a binding site for the focal adhesion-associated protein paxillin. This binding site has been narrowed to a 52-residue sequence that is composed of two nonoverlapping, weak paxillin binding sites. The PTP-PEST binding site on paxillin has been mapped to the two carboxyl-terminal LIM (lin11, isl-1, and mec-3) domains, Transient expression of PTP-PEST reduced tyrosine phosphorylation of p130(cas), as anticipated. A PTP-PEST mutant defective for binding p130(cas) does not cause a reduction in its tyrosine phosphorylation in vivo, Expression of PTP-PEST also caused a reduction of phosphotyrosine on paxillin. Expression of mutants of PTP-PEST with deletions in the paxillin-binding site did not associate with paxillin in vivo and failed to cause a reduction in the phosphotyrosine content of paxillin, These results demonstrate that paxillin can serve as a PTP-PEST substrate in vivo and support the model that a noncatalytic domain interaction recruits paxillin to PTP-PEST to facilitate its dephosphorylation. C1 Univ N Carolina, Dept Cell Biol & Anat, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. McGill Univ, Ctr Canc, Montreal, PQ H3G 1Y6, Canada. Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Schaller, MD (reprint author), Univ N Carolina, Dept Cell Biol & Anat, Taylor Hall CB 7090, Chapel Hill, NC 27599 USA. FU NIGMS NIH HHS [GM53666, GM57943] NR 40 TC 56 Z9 58 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 14 PY 2000 VL 275 IS 2 BP 1405 EP 1413 DI 10.1074/jbc.275.2.1405 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 275TQ UT WOS:000084836600096 PM 10625692 ER PT J AU Yokogami, K Wakisaka, S Avruch, J Reeves, SA AF Yokogami, K Wakisaka, S Avruch, J Reeves, SA TI Serine phosphorylation and maximal activation of STAT3 during CNTF signaling is mediated by the rapamycin target mTOR SO CURRENT BIOLOGY LA English DT Article ID P70 S6 KINASE; MAMMALIAN TARGET; PROTEIN; TRANSCRIPTION; TYROSINE; PATHWAY; YEAST AB Neuropoietic cytokines such as ciliary neurotrophic factor (CNTF) can activate multiple signaling pathways in parallel, including those involving Janus kinase (JAK)-signal transducers and activators of transcription (STATs) [1], mitogen activated protein kinase (MAPK) [2], phosphatidylinositol 3 kinase (PI 3 kinase) and mammalian target of rapamycin (mTOR)-p70 S6 kinase [3], Crosstalk occurs between these pathways, because studies have shown that STATE requires phosphorylation on tyrosine and serine residues by independent protein kinase activities for maximal activation of target gene transcription [4]. Members of the JAk/Tyk family of tyrosine kinases mediate phosphorylation of STATE at Tyr705 during CNTF signaling; however, the kinase responsible for phosphorylation at STATE Tyr727 appears to depend on both the extracellular stimulus and the cellular context [5-8], Here we investigate the kinase activity responsible for phosphorylation of STATE on Ser727 in CNTF stimulated neuroblastoma cells. We found that CNTF induced phosphorylation of Ser727 was inhibited by the mTOR inhibitor rapamycin, but not by inhibitors of MAPK and protein kinase C (PKC) activation, A STATE peptide was efficiently phosphorylated on Ser727 in a CNTF dependent manner by mTOR, but not by a kinase-inactive mTOR mutant or by p70 S6 kinase, In agreement with these biochemical studies, rapamycin treatment of cells transfected with a STAT-responsive promoter reporter decreased activation of the reporter to the same degree as a STATE Ser727Ala mutant. The ability of mTOR to contribute to activation of STATE extends the function of mTOR [9] in mammalian cells to include transcriptional regulation. C1 Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Miyazaki Med Coll, Dept Neurosurg, Miyazaki 8891601, Japan. Massachusetts Gen Hosp, Diabet Unit & Med Serv, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Reeves, SA (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02129 USA. FU NINDS NIH HHS [R01 NS35996] NR 20 TC 272 Z9 288 U1 1 U2 13 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JAN 13 PY 2000 VL 10 IS 1 BP 47 EP 50 DI 10.1016/S0960-9822(99)00268-7 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 274YF UT WOS:000084792100024 PM 10660304 ER PT J AU Kantoff, PW Pena, CS Briggs, SM Oliva, E Scully, RE Smith, M Kaufman, DS AF Kantoff, PW Pena, CS Briggs, SM Oliva, E Scully, RE Smith, M Kaufman, DS TI A 27-year-old man with a painful retroperitoneal mass - Seminoma, retroperitoneal, consistent with retrogressed testicular seminoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID GERM-CELL TUMORS; UNKNOWN PRIMARY SITE; POORLY DIFFERENTIATED CARCINOMA; KETTERING CANCER-CENTER; INGUINAL-HERNIA; TESTIS; CHEMOTHERAPY; ADENOCARCINOMA; CRYPTORCHIDISM; EXPERIENCE C1 Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kantoff, PW (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. NR 51 TC 4 Z9 5 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 13 PY 2000 VL 342 IS 2 BP 115 EP 122 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 273TQ UT WOS:000084723900008 ER PT J AU Wells, KB Sherbourne, C Schoenbaum, M Duan, N Meredith, L Unutzer, J Miranda, J Carney, MF Rubenstein, LV AF Wells, KB Sherbourne, C Schoenbaum, M Duan, N Meredith, L Unutzer, J Miranda, J Carney, MF Rubenstein, LV TI Impact of disseminating quality improvement programs for depression in managed primary care - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MAJOR DEPRESSION; MAPROTILINE; OUTPATIENTS; PAROXETINE; OUTCOMES AB Context Care of patients with depression in managed primary care settings often fails to meet guideline standards, but the long-term impact of quality improvement (QI) programs for depression care in such settings is unknown. Objective To determine if QI programs in managed care practices for depressed primary care patients improve quality of care, health outcomes, and employment. Design Randomized controlled trial initiated from June 1996 to March 1997. Setting Forty-six primary care clinics in 6 US managed care organizations. Participants Of 27 332 consecutively screened patients, 1356 with current depressive symptoms and either 12-month, lifetime, or no depressive disorder were enrolled. Interventions Matched clinics were randomized to usual care (mailing of practice guidelines) or to 1 of 2 QI programs that involved institutional commitment to QI, training local experts and nurse specialists to provide clinician and patient education, identification of a pool of potentially depressed patients, and either nurses for medication follow-up or access to trained psychotherapists. Main Outcome Measures Process of care (use of antidepressant medication, mental health specialty counseling visits, medical visits for mental health problems, any medical visits), health outcomes (probable depression and health-related quality of life [HRQOL]), and employment at baseline and at 6- and 12-month follow-up. Results Patients in QI (n = 913) and control (n = 443) clinics did not differ significantly at baseline in service use, HRQOL, or employment after nonresponse weighting. At 6 months, 50.9% of QI patients and 39.7% of controls had counseling or used antidepressant medication at an appropriate dosage (P<.001), with a similar pattern at 12 months (59.2% vs 50.1%; P = .006). There were no differences in probability of having any medical visit at any point teach P greater than or equal to.21). At 6 months, 47.5% of QI patients and 36.6% of controls had a medical visit for mental health problems (P = .001), and QI patients were more likely to see a mental health specialist at 6 months (39.8% vs 27.2%; P<.001) and at 12 months (29.1% vs 22.7%; P = .03). At 6 months, 39.9% of QI patients and 49.9% of controls still met criteria for probable depressive disorder (P = .001), with a similar pattern at 12 months (41.6% vs 51.2%; P = .005). Initially employed QI patients were more likely to be working at 12 months relative to controls (P = .05). Conclusions When these managed primary care practices implemented QI programs that improve opportunities for depression treatment without mandating it, quality of care, mental health outcomes, and retention of employment of depressed patients improved over a year, while medical visits did not increase overall. C1 RAND Corp, Hlth Program, Santa Monica, CA 90407 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Georgetown Univ, Med Ctr, Dept Psychiat, Washington, DC 20007 USA. VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. RP Wells, KB (reprint author), RAND Corp, Hlth Program, 1700 Main St, Santa Monica, CA 90407 USA. FU AHRQ HHS [R01-HS08349]; NIMH NIH HHS [MH01170-05, P50 MH54623] NR 45 TC 745 Z9 747 U1 7 U2 34 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 JAN 12 PY 2000 VL 283 IS 2 BP 212 EP 220 DI 10.1001/jama.283.2.212 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 272QA UT WOS:000084661400027 PM 10634337 ER PT J AU Meigs, JB Mittleman, MA Nathan, DM Tofler, GH Singer, DE Murphy-Sheehy, PM Lipinsky, I D'Angostino, R Wilson, PWF AF Meigs, JB Mittleman, MA Nathan, DM Tofler, GH Singer, DE Murphy-Sheehy, PM Lipinsky, I D'Angostino, R Wilson, PWF TI Hyperinsulinemia, hyperglucemia, and impaired hemostasis - The Framingham offspring study SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; INSULIN-RESISTANCE SYNDROME; CORONARY-HEART-DISEASE; LINKED IMMUNOSORBENT-ASSAY; VON-WILLEBRAND-FACTOR; RISK FACTOR; VASCULAR COMPLICATIONS; CARDIOVASCULAR-DISEASE; OBESE SUBJECTS; MYOCARDIAL-INFARCTION AB Context Increased risk for cardiovascular disease in persons with glucose intolerance (impaired glucose tolerance and type 2 diabetes mellitus) is not fully explained by concomitant elevations in traditional atherosclerosis risk factors. Hyperinsulinemia associated with glucose intolerance may increase risk directly, or its effect could be mediated through impaired hemostatic function. Objective To evaluate associations between fasting insulin levels and hemostatic factors in subjects with normal and impaired glucose homeostasis. Design Cross-sectional analysis conducted between January 1991 and June 1995. Setting The population-based Framingham Offspring Study. Subjects A total of 1331 men and 1631 women aged 26 to 82 years, without diagnosed diabetes or cardiovascular disease and classified as having normal glucose tolerance (80.2%) or glucose intolerance (impaired glucose tolerance and impaired fasting glucose combined, 15.2%; previously undiagnosed diabetes, 4.7%) using an oral glucose tolerance test. Main Outcome Measures Trends across quintiles of fasting insulin in levels of plasminogen activator inhibitor 1 (PAI-1) antigen, tissue-type plasminogen activator (tPA) antigen, von Willebrand factor (VWF) antigen, factor VII antigen, fibrinogen, and plasma viscosity. We stratified analyses by sex and glucose tolerance status and adjusted hemostatic factor levels for obesity, lipid levels, and traditional cardiovascular disease risk factors. Results Mean levels of all hemostatic factors (except for fibrinogen in men) increased across fasting insulin quintiles among subjects with normal glucose tolerance (P<.001 for trend). Levels of PAI-1 and tPA antigens, but not other hemostatic factors, were higher comparing subjects with glucose intolerance with those with normal glucose tolerance (P<.001). Among subjects with glucose intolerance, levels of PAI-1 and tPA antigen in men and women (P<.01 for trend) and VWF antigen in men (P<.05 for trend) increased significantly across insulin quintiles, but levels of factor VII antigen, fibrinogen, and plasma viscosity did not increase. Conclusions Elevated levels of fasting insulin are associated with impaired fibrinolysis and hypercoagulability in subjects with normal glucose tolerance. Hyperinsulinemia is associated primarily with impaired fibrinolysis in subjects with glucose intolerance. Excess risk for cardiovascular disease associated with hyperinsulinemia and glucose intolerance may be mediated in part by enhanced potential for acute thrombosis. C1 Massachusetts Gen Hosp, Gen Internal Med Unit S50 9, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Inst Prevent & Cardiovasc Dis, Cardiovasc Div,Beth Israel Deaconess Med Ctr, Boston, MA USA. Boston Univ, Dept Math, Stat & Consulting Unit, Boston, MA 02215 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Framingham Heart Study, Framingham, MA USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Gen Internal Med Unit S50 9, Div Gen Med, Boston, MA 02114 USA. FU NHLBI NIH HHS [N01-HC-38083, R01 HL48157] NR 77 TC 359 Z9 383 U1 1 U2 4 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 JAN 12 PY 2000 VL 283 IS 2 BP 221 EP 228 DI 10.1001/jama.283.2.221 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 272QA UT WOS:000084661400028 PM 10634338 ER PT J AU Price, BK Adams, RD Coyle, JT AF Price, BK Adams, RD Coyle, JT TI Neurology and psychiatry - Closing the great divide SO NEUROLOGY LA English DT Editorial Material ID OBSESSIVE-COMPULSIVE DISORDER; GLUCOSE METABOLIC-RATE; BEHAVIOR-THERAPY; DISEASE; BRAIN C1 McLean Hosp, Dept Neurol, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. RP Price, BK (reprint author), McLean Hosp, Dept Neurol, 115 Mill St, Belmont, MA 02478 USA. NR 45 TC 55 Z9 56 U1 0 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN 11 PY 2000 VL 54 IS 1 BP 8 EP 14 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 273VE UT WOS:000084727900004 PM 10636118 ER PT J AU Willems, DL Daniels, ER van der Wal, G van der Maas, PJ Emanuel, EJ AF Willems, DL Daniels, ER van der Wal, G van der Maas, PJ Emanuel, EJ TI Attitudes and practices concerning the end of life - A comparison between physicians from the United States and from the Netherlands SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ASSISTED SUICIDE; EUTHANASIA; REQUESTS; DOCTORS; DEATH AB Background: This study compares attitudes and practices concerning the end-of-life decisions between physicians in the United States and in the Netherlands, using the same set of questions. Methods: A total of 152 physicians from Oregon and 67 from the Netherlands were interviewed using the same questions about (1) their attitudes toward increasing morphine with premature death as a likely consequence, physician-assisted suicide (PAS), and euthanasia; and (2) their involvement in cases of euthanasia, PAS, or the ending of life without an explicit request from the patient. Odds ratios, with 95% confidence intervals, were calculated to investigate relation between attitudes and various characteristics of the respondents. Results: American physicians found euthanasia less often acceptable than the Dutch, but there was similarity in attitudes concerning increasing morphine and PAS. American physicians found increasing morphine and PAS more often acceptable in cases where patients were concerned about becoming a burden to their family. There was a discrepancy between the attitudes and practices of Dutch physicians concerning PAS. The proportions of physicians having practiced euthanasia, PAS, or ending of life without an explicit request from the patient differ more between the countries than do their attitudes, with American physicians having been involved in these practices less often than the Dutch. Conclusions: In this study of American and Dutch physicians, 2 important differences emerge: different attitudes toward the patient who is concerned over being a burden, and different frequency of euthanasia and PAS in the two countries. C1 Free Univ Amsterdam, Inst Extramural Med, NL-1081 BT Amsterdam, Netherlands. Free Univ Amsterdam, Dept Social Med, NL-1081 BT Amsterdam, Netherlands. Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Erasmus Univ, Inst Publ Hlth, Rotterdam, Netherlands. RP Willems, DL (reprint author), Free Univ Amsterdam, Inst Extramural Med, Van Boechorstr 7, NL-1081 BT Amsterdam, Netherlands. NR 21 TC 63 Z9 63 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JAN 10 PY 2000 VL 160 IS 1 BP 63 EP 68 DI 10.1001/archinte.160.1.63 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 271RU UT WOS:000084607900007 PM 10632306 ER PT J AU Halm, EA Atlas, SJ Borowsky, LH Benzer, TI Metlay, JP Chang, YC Singer, DE AF Halm, EA Atlas, SJ Borowsky, LH Benzer, TI Metlay, JP Chang, YC Singer, DE TI Understanding physician adherence with a pneumonia practice guideline - Effects of patient, system, and physician factors SO ARCHIVES OF INTERNAL MEDICINE 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 ID CLINICAL-PRACTICE GUIDELINES; COMMUNITY-ACQUIRED PNEUMONIA; INTERVENTIONAL TRIAL; RISK ATTITUDES; OUTCOMES; UNCERTAINTY; DECISIONS; EMERGENCY; SUBJECT; CARE AB Background: Adherence with clinical practice guidelines is highly variable. Reasons for their inconsistent performance have not been well studied. Objective: To determine the patient, system, and physician factors that may explain why physicians may not follow guidelines. Methods: We used chart review and physician surveys to measure adherence with an actively implemented guideline to reduce hospitalizations for patients coming to the emergency department with community-acquired pneumonia. Logistic regression analyses were used to identify factors associated with guideline nonadherence. Results: Overall nonadherence with the guideline was 43.6%, with 71 of 163 low-risk patients with pneumonia being hospitalized despite the recommendation for outpatient therapy. In univariate analyses, nonadherence to the guideline was more likely for patients who were aged 65 years or older, were male, were employed, and had multilobar disease or other comorbid conditions (P<.05). Active involvement of a primary care physician in the admission decision also increased nonadherence (odds ratio, 4.9; 95% confidence interval, 2.2-11.0). Physicians with more pneumonia experience were more likely not to follow the guideline (P<.001). In multivariate models, the odds of nonadherence were 2 to 3 times greater when patients were 65 years or older, were male, or had multilobar disease, or the primary care physician was involved in the triage decision (P<.05). Physicians' reasons for admission were the presence of active comorbidities (55%), the primary care physician's wish for hospitalization (41%), the presence of worse pneumonia than the guideline indicated (36%), patient preference (17%), and inadequate home support (16%). Conclusions: Nonadherence to a pneumonia guideline was associated with a variety of patient, system, and physician factors. Guideline implementation strategies should take into account the heterogeneous forces that can influence physician decision making. C1 Mt Sinai Med Ctr, Dept Hlth Policy, New York, NY 10029 USA. Mt Sinai Med Ctr, Dept Med, New York, NY 10029 USA. Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Halm, EA (reprint author), Mt Sinai Med Ctr, Dept Hlth Policy, Box 1077,1 Gustave L Levy Pl, New York, NY 10029 USA. FU BHP HRSA HHS [PE11001-08] NR 29 TC 104 Z9 105 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JAN 10 PY 2000 VL 160 IS 1 BP 98 EP 104 DI 10.1001/archinte.160.1.98 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 271RU UT WOS:000084607900011 PM 10632310 ER PT J AU Lorson, MA Horvitz, HR van den Heuvel, S AF Lorson, MA Horvitz, HR van den Heuvel, S TI LIN-5 is a novel component of the spindle apparatus required for chromosome segregation and cleavage plane specification in Caenorhabditis elegans SO JOURNAL OF CELL BIOLOGY LA English DT Article DE lin-5; mitosis; cytokinesis; microtubules; mitotic checkpoint ID C-ELEGANS; CELL-CYCLE; MITOTIC SPINDLE; GENE-EXPRESSION; COILED COILS; NEMATODE; MUTANTS; DIVISION; LINEAGES; EMBRYOS AB Successful divisions of eukaryotic cells require accurate and coordinated cycles of DNA replication, spindle formation, chromosome segregation, and cytoplasmic cleavage. The Caenorhabditis elegans gene lin-5 is essential for multiple aspects of cell division. Cells in lin-5 null mutants enter mitosis at the normal time and form bipolar spindles, but fail chromosome alignment at the metaphase plate, sister chromatid separation, and cytokinesis. Despite these defects, cells exit from mitosis without delay and progress through subsequent rounds of DNA replication, centrosome duplication, and abortive mitoses, In addition, early embryos that lack lin-5 function show defects in spindle positioning and cleavage plane specification. The lin-5 gene en-codes a novel protein with a central coiled-coil domain. This protein localizes to the spindle apparatus in a cell cycle- and microtubule-dependent manner. The LIN-5 protein is located at the centrosomes throughout mitosis, at the kinetochore microtubules in metaphase cells, and at the spindle during meiosis. Our results show that LIN-5 is a novel component of the spindle apparatus required for chromosome and spindle movements, cytoplasmic cleavage, and correct alternation of the S and RI phases of the cell cycle. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02139 USA. RP Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM heuvel@helix.mgh.harvard.edu RI van den Heuvel, Sander/B-8892-2011 NR 53 TC 57 Z9 60 U1 1 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD JAN 10 PY 2000 VL 148 IS 1 BP 73 EP 86 DI 10.1083/jcb.148.1.73 PG 14 WC Cell Biology SC Cell Biology GA 274ZQ UT WOS:000084795300013 PM 10629219 ER PT J AU Tiffany, AM Manganas, LN Kim, EJ Hsueh, YP Sheng, M Trimmer, JS AF Tiffany, AM Manganas, LN Kim, EJ Hsueh, YP Sheng, M Trimmer, JS TI PSD-95 and SAP97 exhibit distinct mechanisms for regulating K+ channel surface expression and clustering SO JOURNAL OF CELL BIOLOGY LA English DT Article DE ion channel localization; protein binding; COS cells; membrane proteins; nerve tissue proteins ID TRANSFECTED MAMMALIAN-CELLS; BETA-SUBUNIT POLYPEPTIDES; CHAIN BINDING-PROTEIN; POTASSIUM CHANNEL; GUANYLATE KINASES; ALPHA-SUBUNITS; PDZ DOMAIN; RAT-BRAIN; MEMBRANE; ASSOCIATION AB Mechanisms of ion channel clustering by cytoplasmic membrane-associated guanylate kinases such as postsynaptic density 95 (PSD-95) and synapse-associated protein 97 (SAP97) are poorly understood. Here, we investigated the interaction of PSD-95 and SAP97 with voltage-gated or Kv K+ channels. Using Kv channels with different surface expression properties, we found that clustering by PSD-95 depended on channel cell surface : expression. Moreover, PSD-95-induced clusters of Kv1 K+ channels were present on the cell surface. This was most dramatically demonstrated for Kv1.2 K+ channels, where surface expression and clustering by PSD-95 were coincidentally promoted by coexpression with cytoplasmic Kv beta subunits, Consistent with a mechanism of plasma membrane channel-PSD-95 binding, coexpression with PSD-95 did not affect the intrinsic surface expression characteristics of the differ ent Ky channels. In contrast, the interaction of Kv1 channels with SAP97 was independent of Kv1 surface expression, occurred intracellularly, and prevented further biosynthetic trafficking of Kv1 channels. As such, SAP97 binding caused an intracellular accumulation of each Kv1 channel tested, through the accretion of SAP97 channel clusters in large (3-5 mu m) ER-derived intracellular membrane vesicles. Together, these data show that ion channel clustering by PSD-95 and SAP97 occurs by distinct mechanisms, and suggests that these channel-clustering proteins may play diverse roles in regulating the abundance and distribution of channels at synapses and other neuronal membrane specializations. C1 SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA. SUNY Stony Brook, Inst Cell & Dev Biol, Stony Brook, NY 11794 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurobiol,Howard Hughes Med Inst, Boston, MA 02214 USA. RP Trimmer, JS (reprint author), SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA. RI Kim, Eunjoon/C-1566-2011; OI Hsueh, Yi-Ping/0000-0002-0866-6275 FU NIGMS NIH HHS [T32 GM008444]; NINDS NIH HHS [NS34383, R01 NS034383, R37 NS034383] NR 44 TC 131 Z9 134 U1 1 U2 1 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 JAN 10 PY 2000 VL 148 IS 1 BP 147 EP 157 DI 10.1083/jcb.148.1.147 PG 11 WC Cell Biology SC Cell Biology GA 274ZQ UT WOS:000084795300019 PM 10629225 ER PT J AU Precious, HM Gunthard, HF Wong, JK D'Aquila, RT Johnson, VA Kuritzkes, DR Richman, DD Brown, AJL AF Precious, HM Gunthard, HF Wong, JK D'Aquila, RT Johnson, VA Kuritzkes, DR Richman, DD Brown, AJL TI Multiple sites in HIV-1 reverse transcriptase associated with virological response to combination therapy SO AIDS LA English DT Article DE antiretroviral therapy; HIV drug resistance; HIV sequence variability; viral load; reverse transcriptase inhibitors ID HUMAN-IMMUNODEFICIENCY-VIRUS; ZIDOVUDINE RESISTANCE; DRUG-RESISTANCE; DISEASE PROGRESSION; TYPE-1 VARIANTS; RNA LEVELS; MUTATIONS; INHIBITORS; NEVIRAPINE; DIDANOSINE AB Objective: To determine whether analysis of sequence variation in reverse transcriptase at baseline can explain differences in response to combination antiretroviral therapy. Methods: Amino acid sequences of reverse transcriptase obtained from baseline isolates from 55 patients included in a trial of zidovudine and didanosine versus zidovudine/didanosine/nevirapine (ACTG241) were analysed. Simple and multiple linear regression were used to determine the relationship between numbers and identity of mutations at baseline and virological response after 8 and 48 weeks. Results: Numbers of baseline zidovudine resistance mutations were predictive of short-term response (week 8). Amino acid identity-at position 215 explained > 20% of the variation in response at week 8, but less at week 48. Multiple regression identified the combinations: 215 + 44 and 41 + 202, each of which explained about 30% of the variation in week 8 response. A model incorporating amino acids 214 + 215 + 60 + 202 + baseline viral load explained > 40% of the variation in response at week 48. Unexpectedly, the mutant combination 601 + 215Y/F responded threefold better than 60V + 215Y/F over 48 weeks. Conclusions: Use of clinical data to analyse virological response to combination therapy has revealed effects of baseline amino acidmutations at sites not previously identified as being important in antiretroviral resistance. Predictors of long-term responses were different from those involved in the short term and may require more complex analysis. (C) 2000 Lippincott Williams & Wilkins. C1 Univ Edinburgh, Ctr HIV Res, Inst Cell Anim & Populat Biol, Edinburgh EH9 3JN, Midlothian, Scotland. Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. San Diego Vet Affairs Med Ctr, La Jolla, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Alabama, Dept Infect Dis, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Colorado, Hlth Sci Ctr, Div Infect Dis, Denver, CO USA. Vet Affairs Med Ctr, Denver, CO USA. RP Brown, AJL (reprint author), Univ Edinburgh, Ctr HIV Res, Inst Cell Anim & Populat Biol, Waddington Bldg,W Mains Rd, Edinburgh EH9 3JN, Midlothian, Scotland. RI Leigh Brown, Andrew/F-3802-2010; gunthard, huldrych/F-1724-2011 OI gunthard, huldrych/0000-0002-1142-6723 FU FIC NIH HHS [TW00767]; NIAID NIH HHS [AI 27670, K 11 AI01361] NR 32 TC 25 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 7 PY 2000 VL 14 IS 1 BP 31 EP 36 DI 10.1097/00002030-200001070-00004 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 276WQ UT WOS:000084901700004 PM 10714565 ER PT J AU Appel, H Gauthier, L Pyrdol, J Wucherpfennig, KW AF Appel, H Gauthier, L Pyrdol, J Wucherpfennig, KW TI Kinetics of T-cell receptor binding by bivalent HLA-DR center dot peptide complexes that activate antigen-specific human T-cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MYELIN BASIC-PROTEIN; ALPHA-BETA; DROSOPHILA-MELANOGASTER; TRANSMEMBRANE REGION; DENDRITIC CELLS; CD3 COMPLEX; DIMERIZATION; CHAIN; TCR; ASSOCIATION AB Monovalent major histocompatibility complex-peptide complexes dissociate within seconds from the T-cell receptor (TCR), indicating that dimerization/multimerization may be important during early stages of T-cell activation. Soluble bivalent HLA-DR2.myelin basic protein (MBP) peptide complexes were expressed by replacing the F(ab) arms of an IgG2a antibody with HLA-DR2.MBP peptide complexes. The binding of bivalent HLA-DR2.peptide complexes to recombinant TCR was examined by surface plasmon resonance, The bivalent nature greatly enhanced TCR binding and slowed dissociation from the TCR, with a t(1/2) of 2.1 to 4.6 min. Soluble bivalent HLA-DR2.MBP peptide complexes activated antigen-specific T-cells in the absence of antigen presenting cells. In contrast, soluble antibodies to the TCR.CD3 complex were ineffective, indicating that they failed to induce an active TCR dimer. TCR/CD3 antibodies induced T-cell proliferation when bound by antigen presenting cells that expressed Fc receptors, In the presence of dendritic cells, bivalent HLA-DR2.MBP peptide complexes induced T-cell activation at >100-fold lower concentrations than TCR/CD3 antibodies and were also superior to peptide or antigen. These results demonstrate that bivalent HLA-DR.peptide complexes represent effective ligands for activation of the TCR, The data support a role for TCR dimerization in early TCR signaling and kinetic proofreading. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 53 TC 53 Z9 55 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 7 PY 2000 VL 275 IS 1 BP 312 EP 321 DI 10.1074/jbc.275.1.312 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 295DN UT WOS:000085951600044 PM 10617620 ER PT J AU Kharbanda, S Saxena, S Yoshida, K Pandey, P Kaneki, M Wang, QZ Cheng, K Chen, YN Campbell, A Sudha, T Yuan, ZM Narula, J Weichselbaum, R Nalin, C Kufe, D AF Kharbanda, S Saxena, S Yoshida, K Pandey, P Kaneki, M Wang, QZ Cheng, K Chen, YN Campbell, A Sudha, T Yuan, ZM Narula, J Weichselbaum, R Nalin, C Kufe, D TI Translocation of SAPK/JNK to mitochondria and interaction with Bcl-x(L) in response to DNA damage SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED-PROTEIN-KINASE; RADIATION-INDUCED APOPTOSIS; PROGRAMMED CELL-DEATH; TUMOR-NECROSIS-FACTOR; ABL TYROSINE KINASE; CYTOCHROME-C; SIGNAL-TRANSDUCTION; IONIZING-RADIATION; GAMMA-RADIATION; BCL-2 AB Activation of the stress-activated protein kinase (SAPK/JNK) by genotoxic agents is necessary for induction of apoptosis, We report here that ionizing radiation ionizing radiation exposure induces translocation of SAPK to mitochondria and association of SAPK with the anti-apoptotic Bcl-x(L) protein. SAPK phosphorylates Bcl-x(L) on threonine 47 (Thr-47) and threonine 115 (Thr-115) in vitro and in vivo. In contrast to wild-type Bcl-x(L), a mutant Bcl-x(L) with the two threonines substituted by alanines (Ala-47, Ala-115) is a more potent inhibitor of ionizing radiation-induced apoptosis, These findings indicate that translocation of SAPK to mitochondria is functionally important for interactions with Bcl-x(L) in the apoptotic response to genotoxic stress. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Div Canc Pharmacol, Boston, MA 02115 USA. Univ Manitoba, Manitoba Inst Cell Biol, Winnipeg, MB R3E 0V9, Canada. Novartis Pharmaceut Corp, Preclin Res, Oncol Res Program, E Hanover, NJ 07936 USA. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. RP Kharbanda, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Div Canc Pharmacol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 55421, CA 75216] NR 55 TC 330 Z9 341 U1 0 U2 7 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 JAN 7 PY 2000 VL 275 IS 1 BP 322 EP 327 DI 10.1074/jbc.275.1.322 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 295DN UT WOS:000085951600045 PM 10617621 ER PT J AU Xu, YY Circolo, A Jing, H Wang, Y Narayana, SVL Volanakis, JE AF Xu, YY Circolo, A Jing, H Wang, Y Narayana, SVL Volanakis, JE TI Mutational analysis of the primary substrate specificity pocket of complement factor B - Asp(226) is a major structural determinant for P-1-Arg binding SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN CATHEPSIN-G; CRYSTAL-STRUCTURE; COLLAGENOLYTIC SERINE-PROTEASE-1; DIRECTED MUTAGENESIS; SERINE PROTEASES; PROTEIN-B; TRYPSIN; SITE; CHYMOTRYPSIN; RESOLUTION AB Factor B is a serine protease, which despite its trypsin-like specificity has Asn instead of the typical Asp at the bottom of the S-1 pocket (position 189, chymotrypsinogen numbering). Asp residues are present at positions 187 and 226 and either one could conceivably provide the negative charge for binding the P-1-Arg of the substrate. Determination of the crystal structure of the factor B serine protease domain has revealed that the side chain of Asp(226) is within the S-1 pocket, whereas Asp(187) is located outside the pocket. To investigate the possible role of these atypical structural features in substrate binding and catalysis, we constructed a panel of mutants of these residues. Replacement of Asp(187) caused moderate (50-60%) decrease in hemolytic activity, compared with wild type factor B, whereas replacement of Asn(189) resulted in more profound reductions (71-95%). Substitutions at these two positions did not significantly affect assembly of the alternative pathway C3 convertase. In contrast, elimination of the negative charge from Asp(296) completely abrogated hemolytic activity and also affected formation of the C3 convertase. Kinetic analyses of the hydrolysis of a P-1-Arg containing thioester by selected mutants confirmed that residue Asp(226) is a primary structural determinant for P-1-Arg binding and catalysis. C1 Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. Univ Alabama, Ctr Macromol Crystallog, Birmingham, AL 35294 USA. Harvard Univ, Sch Med, Ctr Blood Res, Cambridge, MA 02138 USA. Biomed Sci Res Ctr A Fleming, Vari 16672, Greece. RP Xu, YY (reprint author), Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, THT,Rm 437,1900 Univ Blvd, Birmingham, AL 35294 USA. FU NIAID NIH HHS [AI21067, AI39818]; NIAMS NIH HHS [P60AR20614] NR 40 TC 13 Z9 13 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 7 PY 2000 VL 275 IS 1 BP 378 EP 385 DI 10.1074/jbc.275.1.378 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 295DN UT WOS:000085951600052 PM 10617628 ER PT J AU Yu, CL Jin, YJ Burakoff, SJ AF Yu, CL Jin, YJ Burakoff, SJ TI Cytosolic tyrosine dephosphorylation of STAT5 - Potential role of SHP-2 in STAT5 regulation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL TRANSDUCER; NUCLEAR TRANSLOCATION; TRANSCRIPTION FACTORS; PHOSPHATASE SHP-1; GENE-EXPRESSION; DNA-BINDING; ACTIVATION; PROTEIN; INDUCTION; RECEPTOR AB STAT5, a member of the signal transducers and activators of transcription (STATs), is important in modulating T cell functions through interleukin-2 (IL-2) receptors, Like other STAT proteins, STAT5 undergoes a rapid activation and inactivation cycle upon cytokine stimulation. Tyrosine phosphorylation and dephosphorylation are critical in regulating STAT5 activity. A number of protein tyrosine kinases have been shown to phosphorylate STAT5; however, the phosphatases responsible for STAT5 dephosphorylation remain unidentified, Using CTLL-20 as a model system, we provide evidence that tyrosine dephosphorylation of STAT5 subsequent to IL-2-induced phosphorylation occurs in the absence of STAT5 nuclear translocation and new protein synthesis. Nevertheless, down-regulation of the upstream Janus kinase activity during the deactivation cycle of IL-2-induced signaling does involve new protein synthesis. These findings point to the constitutive presence of STAT5 tyrosine phosphatase activity in the cytosolic compartment. We further demonstrate that SHP-2, but not SHP-1, directly dephosphorylates STAT5 in an in vitro tyrosine phosphatase assay with purified proteins. Furthermore, tyrosine-phosphorylated STAT5 associates with the substrate-trapping mutant (Cys --> Ser) of SHP-2 but not SHP-1, These results suggest a potential role for cytoplasmic protein-tyrosine phosphatases in directly dephosphorylating STAT proteins and in maintaining a basal steady state level of STAT activity. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Burakoff, SJ (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. RI Yu, Chao-Lan/D-1834-2011 OI Yu, Chao-Lan/0000-0002-9381-6011 FU NCI NIH HHS [1-F32-CA-79154-01, CA-70758] NR 47 TC 114 Z9 120 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 7 PY 2000 VL 275 IS 1 BP 599 EP 604 DI 10.1074/jbc.275.1.599 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 295DN UT WOS:000085951600080 PM 10617656 ER PT J AU Walhout, AJM Sordella, R Lu, XW Hartley, JL Temple, GF Brasch, MA Thierry-Mieg, N Vidal, M AF Walhout, AJM Sordella, R Lu, XW Hartley, JL Temple, GF Brasch, MA Thierry-Mieg, N Vidal, M TI Protein interaction mapping in C-elegans using proteins involved in vulval development SO SCIENCE LA English DT Article ID PAPILLOMAVIRUS TYPE-16 E1; CELL-CYCLE REGULATORS; MAP KINASE CASCADE; CAENORHABDITIS-ELEGANS; GENOME; EXPRESSION; PATHWAY; MEMBERS; LIN-15; FAMILY AB Protein interaction mapping using large-scale two-hybrid analysis has been proposed as a way to functionally annotate large numbers of uncharacterized proteins predicted by complete genome sequences. This approach was examined in Caenorhabditis elegans, starting with 27 proteins involved in vulval development. The resulting map reveals both known and new potential interactions and provides a functional annotation for approximately 100 uncharacterized gene products. A protein interaction mapping project is now feasible for C. elegans on a genome-wide scale and should contribute to the understanding of molecular mechanisms in this organism and in human diseases. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. Life Technol Inc, Rockville, MD 20850 USA. Lab LSR IMAG, F-38402 St Martin Dheres, France. RP Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, 44 Binney St, Boston, MA 02115 USA. EM Marc_Vidal@DFCI.Harvard.edu RI Thierry-Mieg, Nicolas/M-6007-2014 FU NCI NIH HHS [1 R21 CA81658 A 01]; NHGRI NIH HHS [1 RO1 HG01715-01] NR 58 TC 518 Z9 586 U1 2 U2 26 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD JAN 7 PY 2000 VL 287 IS 5450 BP 116 EP 122 DI 10.1126/science.287.5450.116 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 271DG UT WOS:000084578400048 PM 10615043 ER PT J AU Nakagawa, T Zhu, H Morishima, N Li, E Xu, J Yankner, BA Yuan, JY AF Nakagawa, T Zhu, H Morishima, N Li, E Xu, J Yankner, BA Yuan, JY TI Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta SO NATURE LA English DT Article ID CELL-DEATH; ALZHEIMERS-DISEASE; PROTEASE; RECEPTOR; PROTEINS; COMPLEX; ICE AB Apoptosis, or cellular suicide, is important for normal development and tissue homeostasis, but too much or too Little apoptosis can also cause disease(1,2). The family of cysteine proteases, the so-called caspases, are critical mediators of programmed cell death(3), and thus far 14 family members have been identified. Some of these, such as caspase-(8) (refs 4, 5), mediate signal transduction downstream of death receptors located on the plasma membrane. Others, such as caspase-9 (ref. 6), mediate apoptotic signals after mitochondrial damage. Stress in the endoplasmic reticulum (ER) can also result in apoptosis(7). Here we show that caspase-12 is localized to the ER and activated by ER stress, including disruption of ER calcium homeostasis and accumulation of excess proteins in ER, but not by membrane- or mitochondrial-targeted apoptotic signals. Mice that are deficient in caspase-12 are resistant to ER stress-induced apoptosis, but their cells undergo apoptosis in response to other death stimuli. Furthermore, we show that caspase-12-deficient cortical neurons are defective in apoptosis induced by amyloid-beta protein but not by staurosporine or trophic factor deprivation. Thus, caspase-12 mediates an ER-specific apoptosis pathway and may contribute to amyloid-beta neurotoxicity. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RIKEN, Inst Phys & Chem Res, Biodesign Res Grp, Wako, Saitama 3510198, Japan. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02119 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Yuan, JY (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. EM jyuan@hms.harvard.edu RI Morishima, Nobuhiro/D-3946-2017 NR 17 TC 2215 Z9 2390 U1 42 U2 255 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 6 PY 2000 VL 403 IS 6765 BP 98 EP 103 DI 10.1038/47513 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 273BM UT WOS:000084687400051 PM 10638761 ER PT J AU Sheridan, RL Hinson, MI Liang, MH Nackel, AF Schoenfeld, DA Ryan, CM Mulligan, JL Tompkins, RG AF Sheridan, RL Hinson, MI Liang, MH Nackel, AF Schoenfeld, DA Ryan, CM Mulligan, JL Tompkins, RG TI Long-term outcome of children surviving massive burns SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SF-36 HEALTH SURVEY; THERMAL-INJURY; FULL-THICKNESS; BODY-SURFACE; VALIDITY; QUALITY; LIFE; MORTALITY; EXCISION; DETERMINANTS AB Context Major advances in treatment of burn injuries in the last 20 years have made it possible to save the lives of children with massive burns, but whether their survival comes at the cost of impaired quality of life is unknown. Objective To investigate the long-term quality of life in children who have survived massive burns. Design and Setting Retrospective, cross-sectional study conducted in a regional pediatric burn center. Patients Eighty subjects who were younger than 18 years at the time of injury, who survived massive burns involving greater than or equal to 70% of the body surface, and who were admitted to the burn center between 1969 and 1992 were evaluated an average (SD) of 14.7 (6.0) years after injury. Main Outcome Measures Short Form 36 (SF-36) scores of the 60 patients aged at least 14 years were compared with national norms and the impact of clinical variables on individual domain scores was assessed. Results The SF-36 domain scores of the study patients, who had survived massive burns at a mean (SD) age of 8.8 (5.5) years, were generally similar to the normal population). However, 15% and 20% of the burn patients had scores in the physical functioning and physical role domains, respectively, that were more than 2 SDs below the relevant norm, indicating that a few patients had continuing serious physical disability. Better functional status of the family predicted a higher score in physical role (P = .04). The child's early reintegration with preburn activities predicted higher scores in general health (P = .03), physical functioning (P = .003), and physical role (P = .01). Children followed up consistently in the multidisciplinary burn clinic for 2 years had higher physical functioning (P = .04). Conclusions In this study, while some children surviving severe burns had lingering physical disability, most had a satisfying quality of life. Comprehensive burn care that included experienced multidisciplinary aftercare played an important role in recovery. C1 Massachusetts Gen Hosp, Burn Serv, Boston, MA 02114 USA. Shriners Burns Hosp Children, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Tompkins, RG (reprint author), Massachusetts Gen Hosp, Burn Serv, GRB1302,55 Fruit St, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM T32-07035, GM P50-21700] NR 32 TC 144 Z9 148 U1 2 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 5 PY 2000 VL 283 IS 1 BP 69 EP 73 DI 10.1001/jama.283.1.69 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 270AZ UT WOS:000084514400027 PM 10632282 ER PT J AU Lee, TH Cleeman, JI Grundy, SM Gillett, C Pasternak, RC Seidman, J Sennett, C AF Lee, TH Cleeman, JI Grundy, SM Gillett, C Pasternak, RC Seidman, J Sennett, C TI Clinical coals and performance measures for cholesterol management in secondary prevention of coronary heart disease SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SERUM-CHOLESTEROL; LOWERING THERAPY; EVENTS; RISK; PRAVASTATIN; REDUCTION; PROGRAM; TRIAL; DEATH AB Guidelines from the National Cholesterol Education Program (NCEP) recommend reduction of low-density lipoprotein cholesterol (LDL-C) to 100 mg/dL (2.59 mmol/l)or less in patients with established coronary heart disease (CHD), However, the National Committee for Quality Assurance (NCQA) is implementing a new performance measure as part of the Health Plan Employer and Data Information Set (HEDIS) that appears to endorse a different target. The new HEDIS measure will require managed care organizations seeking NCQA accreditation to measure and report the percentage of patients who have had major CHD events who achieve LDL-C levels less than 130 mg/dL (3.36 mmol/L) between 60 and 365 days after discharge. These different LDL-C thresholds emphasize the difference between a clinical goal for the management of individual patients (less than or equal to 100 mg/dL) and a performance measure used to evaluate the care of a population of patients (<130 mg/dL), This article discusses the rationale for each threshold and explains the use of 2 different thresholds for these 2 purposes. Both the NCQA and NCEP expect that the new HEDIS measure will encourage managed care organizations to develop systems that improve secondary prevention of CHD. C1 Partners Community HealthCare Inc, Boston, MA 02199 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NHLBI, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Grp Hlth Cooperat Puget Sound, Clin Planning & Improvement, Seattle, WA 98121 USA. Natl Comm Qual Assurance, Washington, DC USA. RP Lee, TH (reprint author), Partners Community HealthCare Inc, Prudential Tower,Suite 1150,800 Boylston St, Boston, MA 02199 USA. NR 16 TC 35 Z9 36 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 JAN 5 PY 2000 VL 283 IS 1 BP 94 EP 98 DI 10.1001/jama.283.1.94 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 270AZ UT WOS:000084514400031 PM 10632286 ER PT J AU Kim, SH Titlow, CC Margolies, MN AF Kim, SH Titlow, CC Margolies, MN TI An approach for preventing recombination-deletion of the 40-50 anti-digoxin antibody V-H gene from the phage display vector pComb3 SO GENE LA English DT Article DE anti-digoxin antibodies; bacterial fab expression; phage display ID HUMAN-IMMUNODEFICIENCY-VIRUS; SINGLE-CHAIN FV; FILAMENTOUS PHAGE; AFFINITY; BINDING; REACTIVITY; EXPRESSION; EVOLUTION; SYSTEM AB Phage display has been used extensively in antibody (Ab) engineering. Sometimes, however, phage display vectors exhibit deletion of immunoglobulin (Ig) genes. As an approach to circumvent the recombination-deletion of the murine anti-digoxin Fab 40-50 cloned into the pComb3 vector, the vector was modified with short synthetic oligonucleotides by replacing a pelB leader sequence with a gene 3 (g3) leader sequence and by using a single lacZ promoter sequence. By this means, the N-terminal amino acids of the L chain and Fd remained unchanged, and a random HCDR3 library built on this newly designed vector did not exhibit the recombination-deletion. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Margolies, MN (reprint author), MGH E, Antibody Engn Lab, 149 13th St,Box 31, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL47415] NR 19 TC 5 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JAN 4 PY 2000 VL 241 IS 1 BP 19 EP 25 DI 10.1016/S0378-1119(99)00462-X PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 278CX UT WOS:000084971300003 PM 10607894 ER PT J AU Harth, G Zamecnik, PC Tang, JY Tabatadze, D Horwitz, MA AF Harth, G Zamecnik, PC Tang, JY Tabatadze, D Horwitz, MA TI Treatment of Mycobacterium tuberculosis with antisense oligonucleotides to glutamine synthetase mRNA inhibits glutamine synthetase activity, formation of the poly-L-glutamate/glutamine cell wall structure, and bacterial replication SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATES; EXPRESSION; RESISTANCE; RNA AB New antibiotics to combat the emerging pandemic of drug-resistant strains of Mycobacterium tuberculosis are urgently needed. We have investigated the effects on M. tuberculosis of phosphorothioate-modified antisense oligodeoxyribonucleotides (PS-ODNs) against the mRNA of glutamine synthetase, an enzyme whose export is associated with pathogenicity and with the formation of a poly-L-glutamate/glutamine cell wall structure. Treatment of virulent M. tuberculosis with 10 mu M antisense PS-ODNs reduced glutamine synthetase activity and expression by 25-50% depending on whether one. two, or three different PS-ODNs were used and the PS-ODNs' specific target sites on the mRNA. Treatment with PS-ODNs of a recombinant strain of Mycobacterium smegmatis expressing M. tuberculosis glutamine synthetase selectively inhibited the recombinant enzyme but not the endogenous enzyme for which the mRNA transcript was mismatched by 2-4 nt, Treatment of M. tuberculosis with the antisense PS-ODNs also reduced the amount of poly-L-glutamate/glutamine in the cell wall by 24%. Finally, treatment with antisense PS-ODNs reduced M. tuberculosis growth by 0.7 logs (1 PS-ODN) to 1.25 logs (3 PS-ODNs) but had no effect on the growth of M, smegmatis, which does not export glutamine synthetase nor possess the poly-L-glutamate/glutamine (P-L-glx) cell wall structure. The experiments indicate that the antisense PS-ODNs enter the cytoplasm of M. tuberculosis and bind to their cognate targets. Although more potent ODN technology is needed, this study demonstrates the feasibility of using antisense ODNs in the antibiotic armamentarium against M. tuberculosis. C1 Univ Calif Los Angeles, Div Infect Dis, Dept Med, Sch Med, Los Angeles, CA 90095 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Hybridon Inc, Milford, MA 01757 USA. RP Horwitz, MA (reprint author), Univ Calif Los Angeles, Div Infect Dis, Dept Med, Sch Med, 37-121 CHS,10833 Conte Ave, Los Angeles, CA 90095 USA. FU NCRR NIH HHS [1S10RR05554]; NIAID NIH HHS [AI 42925, R01 AI031338, AI 31338] NR 25 TC 96 Z9 104 U1 2 U2 10 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 JAN 4 PY 2000 VL 97 IS 1 BP 418 EP 423 DI 10.1073/pnas.97.1.418 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 271ZA UT WOS:000084624500076 PM 10618433 ER PT J AU Wang, L Grossman, SR Kieff, E AF Wang, L Grossman, SR Kieff, E TI Epstein-Barr virus nuclear protein 2 interacts with p300, CBP, and PCAF histone acetyltransferases in activation of the LMP1 promoter SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LYMPHOCYTE GROWTH TRANSFORMATION; CREB-BINDING-PROTEIN; TRANSCRIPTIONAL ACTIVATION; HIV-1 TAT; IN-VIVO; J-KAPPA; DOMAIN; NUCLEAR-PROTEIN-2; TRANSACTIVATION; COACTIVATORS AB The Epstein-Barr virus (EBV) nuclear protein 2 (EBNA2) and herpes simplex virion protein 16 (VP16) acidic domains that mediate transcriptional activation now are found to have affinity for p300, CBP, and PCAF histone acetyltransferases (HATs). Transcriptionally inactive point mutations in these domains lack affinity for p300, CBP. or PCAF, P300 and CBP copurify with the principal HAT activities that bind to EBNA2 or VP16 acidic domains through velocity sedimentation and anion-exchange chromatography. EBNA2 binds to both the N- and C-terminal domains of p300 and coimmune-precipitates from transfected 293T cells with p300, In EBV-infected Akata Burkitt's tumor cells that do not express the EBV encoded oncoproteins EBNA2 or LMP1, p300 expression enhances the ability of EBNA2 to up-regulate LMP? expression. Through its intrinsic: HAT activity, PCAF can further potentiate the p300 effect. In 293 T cells, P300 and CBP (but not PCAF) can also coactivate transcription mediated by the EBNA2 or VP16 acidic domains and HAT-negative mutants of p300 have partial activity. Thus, the EBNA2 and VP16 acidic domains can utilize the intrinsic HAT or scaffolding properties of p300 to activate transcription. C1 Brigham & Womens Hosp, Dept Microbiol, Project Virol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Mol Genet, Project Virol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Project Virol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Kieff, E (reprint author), Brigham & Womens Hosp, Dept Med, Project Virol, 181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA47006, R01 CA047006, R35 CA047006] NR 52 TC 143 Z9 148 U1 3 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 JAN 4 PY 2000 VL 97 IS 1 BP 430 EP 435 DI 10.1073/pnas.97.1.430 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 271ZA UT WOS:000084624500078 PM 10618435 ER PT J AU Tissenbaum, HA Hawdon, J Perregaux, M Hotez, P Guarente, L Ruvkun, G AF Tissenbaum, HA Hawdon, J Perregaux, M Hotez, P Guarente, L Ruvkun, G TI A common muscarinic pathway for diapause recovery in the distantly related nematode species Caenorhabditis elegans and Ancylostoma caninum SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LIM HOMEOBOX GENE; INFECTIVE LARVAE; RECEPTOR; INSULIN; LONGEVITY; SIGNALS; DAF-16 AB Converging TGF-beta and insulin-like neuroendocrine signaling pathways regulate whether Caenorhabditis elegans develops reproductively or arrests at the dauer larval stage. We examined whether neurotransmitters act in the dauer entry or recovery pathways. Muscarinic: agonists promote recovery from dauer arrest induced by pheromone as well as by mutations in the TGF-beta pathway. Dauer recovery in these animals is inhibited by the muscarinic antagonist atropine. Muscarinic agonists do not induce dauer recovery of either daf-a or age-1 mutant animals, which have defects in the insulin-like signaling pathway. These data suggest that a metabotropic acetylcholine signaling pathway activates an insulin-like signal during C. elegans dauer recovery. Analogous and perhaps homologous cholinergic regulation of mammalian insulin release by the autonomic nervous system has been noted. In the parasitic nematode Ancylostoma caninum, the dauer larval stage is the infective stage, and recovery to the reproductive stage normally is induced by host factors. Muscarinic agonists also induce and atropine potently inhibits in vitro recovery of A. caninum dauer arrest. We suggest that host or parasite insulin-like signals may regulate recovery of A. caninum and could be potential targets for antihelminthic drugs. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02144 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02144 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Yale Univ, Med Helminthol Lab, New Haven, CT 06520 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 50 Blossom St, Boston, MA 02144 USA. FU NIA NIH HHS [R01 AG014161, R01AG14161] NR 36 TC 73 Z9 83 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 4 PY 2000 VL 97 IS 1 BP 460 EP 465 DI 10.1073/pnas.97.1.460 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 271ZA UT WOS:000084624500083 PM 10618440 ER PT J AU Stein, JV Rot, A Luo, Y Narasimhaswamy, M Nakano, H Gunn, MD Matsuzawa, A Quackenbush, EJ Dorf, ME von Andrian, UH AF Stein, JV Rot, A Luo, Y Narasimhaswamy, M Nakano, H Gunn, MD Matsuzawa, A Quackenbush, EJ Dorf, ME von Andrian, UH TI The CC chemokine thymus-derived chemotactic agent 4 (TCA-4, secondary lymphoid tissue chemokine, 6Ckine, exodus-2) triggers lymphocyte function-associated antigen 1-mediated arrest of rolling T lymphocytes in peripheral lymph node high endothelial venules SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE homing; intravital microscopy; adhesion; T cell ID SELECTIN-DEFICIENT MICE; EBI1-LIGAND CHEMOKINE; VASCULAR ADDRESSIN; MOLECULAR MECHANISMS; BETA-CHEMOKINE; RECEPTOR CCR7; IN-SITU; B-CELLS; MIGRATION; LIGAND AB T cell homing to peripheral lymph nodes (PLNs) is defined by a multistep sequence of interactions between lymphocytes and endothelial cells in high endothelial venules (HEVs). After initial tethering and rolling via L-selectin, firm adhesion of T cells requires rapid upregulation of lymphocyte function-associated antigen 1 (LFA-1) adhesiveness by a previously unknown pathway that activates a G alpha(i)-linked receptor. Here, we used intravital microscopy of murine PLNs to study the role of thymus-derived chemotactic agent (TCA)-4 (secondary lymphoid tissue chemokine, 6Ckine, Exodus-2) in homing of adoptively transferred T cells from T-GFP mice, a transgenic strain that expresses green fluorescent protein (GFP) selectively in naive T lymphocytes (T-GFP cells). TCA-4 was constitutively presented on the luminal surface of HEVs, where it was required for LFA-1 activation on rolling TGFP cells. Desensitization of the TCA-4 receptor, CC chemokine receptor 7 (CCR7), blocked T-GFP cell adherence in wild-type HEVs, whereas desensitization to stromal cell-derived factor (SDF)-1 alpha (the ligand for CXC chemokine receptor 4 [CXCR4]) did not affect T-GFP cell behavior. TCA-4 protein was not detected on the luminal surface of PLN HEVs in plt/plt mice, which have a congenital defect in T cell homing to PLNs. Accordingly, T-GFP cells rolled but did not arrest in plt/plt HEVs. When TCA-4 was injected intracutaneously into plt/plt mice, the chemokine entered afferent lymph vessels and accumulated in draining PLNs. 2 h after intracutaneous inject ion, luminal presentation of TCA-4 was detectable in a subset of HEVs, and LFA-1-mediated T-GFP cell adhesion was restored in these vessels. We conclude that TCA-4 is both required and sufficient for LFA-1 activation on rolling T cells in PLN HEVs. This study also highlights a hitherto undocumented role for chemokines contained in afferent lymph, which may modulate leukocyte recruitment in draining PLNs. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Novartis Forschungsinst, A-1235 Vienna, Austria. Toho Univ, Sch Med, Dept Immunol, Tokyo 1438540, Japan. Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA. Univ Tokyo, Inst Med Sci, Tokyo 1088639, Japan. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [HL54936, HL56949, P01 HL056949, R01 HL054936] NR 64 TC 300 Z9 306 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 JAN 3 PY 2000 VL 191 IS 1 BP 61 EP 75 DI 10.1084/jem.191.1.61 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 273MT UT WOS:000084712000007 PM 10620605 ER PT J AU Frazier, JA Biederman, J Jacobs, TG Tohen, MF Toma, V Feldman, PD Rater, MA Tarazi, RA Kim, GA Garfield, SB Gonzalez-Heydrich, J Nowlin, ZM AF Frazier, JA Biederman, J Jacobs, TG Tohen, MF Toma, V Feldman, PD Rater, MA Tarazi, RA Kim, GA Garfield, SB Gonzalez-Heydrich, J Nowlin, ZM TI Olanzapine in the treatment of bipolar-disorder in juveniles SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Psychopharmacol Clin, Boston, MA 02114 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Childrens Hosp, Dept Psychiat, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 3 PY 2000 VL 41 IS 1 SI SI MA B49 BP 194 EP 194 DI 10.1016/S0920-9964(00)90775-8 PG 1 WC Psychiatry SC Psychiatry GA 279PP UT WOS:000085054600461 ER PT J AU Elman, I Goldstein, DS Adler, CM Breier, A AF Elman, I Goldstein, DS Adler, CM Breier, A TI Effects of risperidone on catecholaminergic function in patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN 3 PY 2000 VL 41 IS 1 SI SI MA B71 BP 201 EP 201 DI 10.1016/S0920-9964(00)90797-7 PG 1 WC Psychiatry SC Psychiatry GA 279PP UT WOS:000085054600483 ER PT J AU Tapp, A Wood, AE Chandran, M Secrest, L AF Tapp, A Wood, AE Chandran, M Secrest, L TI Combination antipsychotic therapy in clinical practice SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Amer Lake Div, Mental Illness Res Educ & Clin Ctr, Tacoma, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN 3 PY 2000 VL 41 IS 1 SI SI MA B114 BP 216 EP 217 DI 10.1016/S0920-9964(00)90840-5 PG 2 WC Psychiatry SC Psychiatry GA 279PP UT WOS:000085054600526 ER PT J AU Scheiner, JD Novelline, RA AF Scheiner, JD Novelline, RA TI Radiology clerkships are necessary for teaching medical students appropriate imaging work-ups SO ACADEMIC RADIOLOGY LA English DT Article C1 Brown Univ, Sch Med, Rhode Isl Hosp, Dept Diagnost Imaging, Providence, RI 02903 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Scheiner, JD (reprint author), Brown Univ, Sch Med, Rhode Isl Hosp, Dept Diagnost Imaging, 593 Eddy St, Providence, RI 02903 USA. NR 5 TC 23 Z9 23 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JAN PY 2000 VL 7 IS 1 BP 40 EP 45 DI 10.1016/S1076-6332(00)80442-0 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 284EW UT WOS:000085318600010 PM 10645457 ER PT J AU Evliyaoglu, C Carroll, R Folkerth, R Bello, L Bruns, DE Black, PM AF Evliyaoglu, C Carroll, R Folkerth, R Bello, L Bruns, DE Black, PM TI Parathyroid hormone-related protein and its receptor in human glial tumors SO ACTA NEUROCHIRURGICA LA English DT Article DE calcification; gliomas; immunohistochemistry; oligodendroglioma; PTH/PTHrP receptor; PTHrP; Western Blot ID HUMAN BREAST-CANCER; HUMAN PROSTATE-CANCER; SMOOTH-MUSCLE CELLS; PEPTIDE GENE; IMMUNOHISTOCHEMICAL LOCALIZATION; PTH/PTHRP RECEPTOR; ENDOTHELIAL-CELLS; GROWTH-FACTOR; IN-VITRO; EXPRESSION AB Objective. Parathyroid hormone-related protein (PTHrP) and its mRNA have been found to be expressed in a variety of human tumors including breast, prostate, colon, lung, renal and ovarian cancers. The purpose of this study is to evaluate the expression of PTH/PTHrP receptor and ligand in human glial tumors. Methods. We examined the coexpression of PTH/PTHrP receptor and ligand in 73 glial tumors of different histological grades and 4 nonneoplastic human brain specimens and three glioblastoma cell lines, by using Western Blot analysis and immunohistochemical analysis. Results. PTHrP and PTH/PTHrP receptors were shown in the neurons, reactive astrocytes and the endothelial cells of normal brain tissue as well as tumor cells, reactive astrocytes and vasculature of nonneoplastic tissue. They were expressed at higher levels in pure astrocytic tumors as compared to tumors with oligodendroglial components. Conclusion. PTH/PTHrP receptor and PTHrP ligand are coexpressed in human glial tumors. There increased expression suggests an autocrine and/or paracrine loop may exist. C1 Kocaeli Univ, Tip Fak, Norosirurji ABD, TR-41900 Derince, Kocaeli, Turkey. Harvard Univ, Childrens Hosp, Brigham & Womens Hosp, Div Neurosurg,Sch Med, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Brigham & Womens Hosp, Brain Tumor Lab,Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pathol, Boston, MA 02115 USA. Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA. RP Evliyaoglu, C (reprint author), Kocaeli Univ, Tip Fak, Norosirurji ABD, TR-41900 Derince, Kocaeli, Turkey. NR 46 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0001-6268 J9 ACTA NEUROCHIR JI Acta Neurochir. PY 2000 VL 142 IS 8 BP 871 EP 878 DI 10.1007/s007010070072 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 358BD UT WOS:000089536600011 PM 11086825 ER PT J AU Brisman, JL Borges, LF Ogilvy, CS AF Brisman, JL Borges, LF Ogilvy, CS TI Extramedullary hemangioblastoma of the conus medullaris SO ACTA NEUROCHIRURGICA LA English DT Article DE hemangioblastoma; conus medullaris; spinal AVF ID SPINAL-CORD; ARTERIOVENOUS-MALFORMATIONS; GADOLINIUM-DTPA AB Background. We report the case of an extramedullary pathologically proven hemangioblastoma of the conus medullaris. As spinal dural arteriovenous fistulas most commonly present with a conus medullaris syndrome, our presentation of the MRI, myelographic, and angiographic findings of this unique lesion may be useful in differentiating these two entities. Clinical Material. We report the case of a 57 year old woman with a two year history of progressive low back and right lower extremity pain and weakness. Spinal MRI and myelography demonstrated serpiginous vasculature on the dorsum of the spinal cord consistent with either a vascular tumor or malformation. Selective spinal angiography was thus undertaken by the neuroendovascular team which revealed a tumor nodule consistent with vascular tumor. T12-L1 laminectomy was performed and a 6 mm vascularized tumor was found in the intradural extramedullary compartment adjacent to the conus medullaris. The tumor was completely removed and pathological analysis was consistent with hemangioblastoma. Conclusion. This report documents a unique location for extramedullary spinal hemangioblastomas. Although both MRI and myelography are helpful in studying these lesions, angiography remains the gold standard in differentiating between vascular tumor and malformation. We suggest that the angiography be performed by a neurointerventional team to facilitate embolization, should this be warranted. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Ogilvy, CS (reprint author), Harvard Univ, Sch Med, 55 Fruit St,Vincent Burnham 710, Boston, MA 02114 USA. NR 17 TC 19 Z9 21 U1 0 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0001-6268 J9 ACTA NEUROCHIR JI Acta Neurochir. PY 2000 VL 142 IS 9 BP 1059 EP 1062 DI 10.1007/s007010070063 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 362DA UT WOS:000089762300029 PM 11086817 ER PT J AU Maass, N Hojo, T Zhang, M Sager, R Jonat, W Nagasaki, K AF Maass, N Hojo, T Zhang, M Sager, R Jonat, W Nagasaki, K TI Maspin - A novel protease inhibitor with tumor-suppressing activity in breast cancer SO ACTA ONCOLOGICA LA English DT Review ID PLASMINOGEN-ACTIVATOR; EXPRESSION GENETICS; CELL; SERPIN; MAMMARY; CARCINOMA; INVASION; MOTILITY; RNA AB Maspin (mammary serpin) is a novel serine protease inhibitor related to the serpin Family with a tumor-suppressing function in breast cancer. Maspin was originally identified from normal mammary epithelium by subtractive hybridization and might function as a class II tumor-suppressor gene. Maspin's decreased expression with increased level of malignancy and its loss in metastatic cells is regulated at the transcriptional level. Cytosin methylation and heterochromatinization in the promoter region might account for this down-regulation of maspin. Transfection of tumor cells with maspin cDNA inhibits invasion and motility and decreases tumor growth and metastatic ability in nude mice. Maspin interacts with the p53 tumor-suppressor pathway and function as an inhibitor of angiogenesis in vitro and in vivo. The progressive loss of expression of maspin during tumor progression makes this new protein an interesting diagnostic and prognostic marker. The re-expression of maspin by pharmacological intervention potentially offers a promising approach as a therapeutic option in breast cancer therapy. C1 Univ Kiel, Dept Obstet & Gynecol, Div Gynecol Oncol, DE-24105 Kiel, Germany. Natl Canc Ctr, Res Inst, Div Growth Factor, Tokyo 104, Japan. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Maass, N (reprint author), Univ Kiel, Dept Obstet & Gynecol, Div Gynecol Oncol, Michaelisstr 16, DE-24105 Kiel, Germany. RI Jonat, Walter/E-3024-2010; Maass, Nicolai/F-2639-2014 NR 40 TC 47 Z9 55 U1 0 U2 2 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0284-186X J9 ACTA ONCOL JI Acta Oncol. PY 2000 VL 39 IS 8 BP 931 EP 934 PG 4 WC Oncology SC Oncology GA 393QG UT WOS:000166480700007 PM 11206999 ER PT J AU Pyykko, I Poe, D Ishizaki, H AF Pyykko, I Poe, D Ishizaki, H TI Laser-assisted myringoplasty - technical aspects SO ACTA OTO-LARYNGOLOGICA LA English DT Article; Proceedings Paper CT XXVIIth Congress of the Nordic-Oto-Laryngological-Society CY AUG 12-15, 1999 CL ODENSE, DENMARK SP Nordic Oto Laryngol Soc DE KTP laser; mini-invasive surgery; tissue damage; welding ID ALBUMIN SOLDER; ARGON-LASER; IN-VITRO; TISSUE; SURGERY AB At lower power, lasers fuse collagen fibres and weld tissues. Welded collagen fibres make a solid bond and allow tissue growth along the bonded edges. Our aim was to study applicability of lasers in myringoplasty. We used a KTP-531 laser in outpatient myringoplasty. The laser beam was delivered through a micromanipulator connected to a microscope or through a 200 400-mu m silica fibre. The perichondrium was used for transplantant and hal vested from the tragus. The margins of the perforation in the eardrum were evaporated, with the laser operating in a continuous mode at 2-4 W. The middle ear was filled with gelfilm to provide support for the transplant. The perichondrium was placed under the margins of the tympanic membrane and lazed at low power (0.2-1.5 W) in continuous mode. In pale tissues, venous blood, methylene blue or fluorescein was used to enhance the tissue admittance of laser energy. Surgical failures were linked to thermal tissue damage due to excessive energy during lazing. In two cases, visibility via microscope into the anterior edge was not complete and the transplantant did not adhere in the relatively limited area. One patient had epidermal growth under the tympanic membrane and developed local cholesteatoma. Laser-assisted myringoplasty provides several advantages over traditional myringoplasty: it is minimally invasive, no manipulation of the ossicles is needed and it is convenient in anterior perforations, where it can be done endoscopically. We prefer a fiber delivery system to a micromanipulator, as lazing with endoscopes is possible and thermal damage is easier to prevent. C1 Karolinska Hosp, Dept Otolaryngol, SE-17176 Stockholm, Sweden. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Pyykko, I (reprint author), Karolinska Hosp, Dept Otolaryngol, SE-17176 Stockholm, Sweden. EM iipo@ent.ks.se NR 10 TC 3 Z9 3 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0001-6489 J9 ACTA OTO-LARYNGOL JI Acta Oto-Laryngol. PY 2000 SU 543 BP 135 EP 138 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 328RA UT WOS:000087862800043 ER PT J AU Kleinman, R AF Kleinman, R TI Towards a "new beginning": dietary fat restrictions in infancy? SO ACTA PAEDIATRICA LA English DT Editorial Material ID CORONARY HEART-DISEASE; SERUM-CHOLESTEROL; CHILDREN; GROWTH; TRIAL; RISK C1 Massachusetts Gen Hosp, Pediat Gastrointestinal & Nutr Unit, Boston, MA 02114 USA. RP Kleinman, R (reprint author), Massachusetts Gen Hosp, Pediat Unit, 55 Fruit St,VBK-107, Boston, MA 02114 USA. NR 26 TC 3 Z9 3 U1 0 U2 1 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD JAN PY 2000 VL 89 IS 1 BP 2 EP 4 DI 10.1080/080352500750028942 PG 3 WC Pediatrics SC Pediatrics GA 278CK UT WOS:000084970200002 PM 10677046 ER PT J AU Marder, SR AF Marder, SR TI Integrating pharmacological and psychosocial treatments for schizophrenia SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article; Proceedings Paper CT 1st International Zurich Conference on Clinical and Social Psychiatry CY SEP 09-12, 1999 CL ZURICH, SWITZERLAND SP Eli Lilly Suisse DE antipsychotic drugs; schizophrenia; psychosocial treatment ID EXPRESSED EMOTION; RELAPSE; FLUPHENAZINE; AFTERCARE AB Objective: The objective of this study was to develop principles of combining pharmacological and psychosocial treatment that can be useful for clinicians who are treating patients with schizophrenia. Method: Research studies in schizophrenia that controlled both pharmacological and psychosocial treatments were reviewed. These included studies using conventional and newer antipsychotics as well as a number of psychosocial methods. Results: The interactions between the forms of treatment appear to be more than merely additive, since each can enhance the effects of the other. Drug and psychosocial treatments may affect different outcome domains. with the former affecting symptoms and the later affecting social outcomes. Recent studies using newer antipsychotics suggest that these agents improve the participation of patients in psychosocial treatments. Conclusion: Understanding the interactions between psychosocial and pharmacological treatments can be useful for clinicians who are developing treatment strategies for patients with schizophrenia. Newer agents with different side-effect profiles and broader effectiveness appear to have improved the outcomes of psychosocial treatments. C1 W Los Angeles Vet Affairs Med Ctr, Psychiat Serv 116A, VISN 22 Mental Illness Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Marder, SR (reprint author), W Los Angeles Vet Affairs Med Ctr, Psychiat Serv 116A, VISN 22 Mental Illness Res Educ & Clin Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 12 TC 6 Z9 6 U1 1 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PY 2000 VL 102 SU 407 BP 87 EP 90 PG 4 WC Psychiatry SC Psychiatry GA 399BH UT WOS:000166790600018 ER PT J AU Bardone, AM Krahn, DD Goodman, BM Searles, JS AF Bardone, AM Krahn, DD Goodman, BM Searles, JS TI Using interactive voice response technology and timeline follow-back methodology in studying binge eating and drinking behavior: Different answers to different forms of the same question? SO ADDICTIVE BEHAVIORS LA English DT Article DE binge eating; alcohol; methodology; interactive voice response; timeline follow-back ID RELIABILITY; VALIDATION AB As part of a study of the relationship of binge eating, alcohol use, mood, and stressors, we compared the results of two forms of reporting on binge eating and drinking behavior. Forty-three first-year college women participated in an interactive voice response (IVR) study for 12 weeks. Participants answered computer-administered questions daily via IVR technology on number of eating binges and number of alcoholic drinks consumed. After 12 weeks, participants completed a Timeline Follow-back (TLFB) interview retrospectively for number of binges and drinks in the past 12 weeks. Results of this distally retrospective methodology (commonly used in drinking research and applied here also to binge eating) were compared to the results of daily IVR reporting, There was convergence across measures for drinking behavior, but divergence between IVR and TLFB for binge eating reports, TLFB reports underrepresented actual binge eating frequency, which calls into question the validity of applying this methodology to the assessment of binge eating. (C) 2000 Elsevier Science Ltd. C1 Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA. William S Middleton Mem Vet Hosp, Geriatr Res Educ Clin Ctr, Madison, WI USA. Univ Vermont, Vermont Alcohol Res Ctr, Burlington, VT 05405 USA. RP Bardone, AM (reprint author), Univ Wisconsin, Dept Psychol, 1202 W Johnson St, Madison, WI 53706 USA. NR 11 TC 46 Z9 46 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD JAN-FEB PY 2000 VL 25 IS 1 BP 1 EP 11 DI 10.1016/S0306-4603(99)00031-3 PG 11 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 278NF UT WOS:000084995300001 PM 10708315 ER PT J AU Bardeesy, N Wong, KK DePinho, RA Chin, L AF Bardeesy, N Wong, KK DePinho, RA Chin, L TI Animal models of melanoma: Recent advances and future prospects SO ADVANCES IN CANCER RESEARCH, VOL 79 SE ADVANCES IN CANCER RESEARCH LA English DT Review ID FIBROBLAST-GROWTH-FACTOR; TUMOR-SUPPRESSOR GENE; RECEPTOR-TYROSINE KINASES; HUMAN-MALIGNANT MELANOMA; PEUTZ-JEGHERS-SYNDROME; HUMAN MELANOCYTES; CUTANEOUS MELANOMA; TRANSGENIC MICE; CELL-LINES; ULTRAVIOLET-RADIATION C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Bardeesy, N (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [5T32CA091-25]; NEI NIH HHS [R01EY09300]; NICHD NIH HHS [R01HD28317] NR 186 TC 27 Z9 28 U1 2 U2 10 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-230X J9 ADV CANCER RES JI Adv.Cancer Res. PY 2000 VL 79 BP 123 EP 156 DI 10.1016/S0065-230X(00)79004-X PG 34 WC Oncology SC Oncology GA BQ13E UT WOS:000087256400004 PM 10818679 ER PT J AU Bauch, A Alt, FW Crabtree, GR Snapper, SB AF Bauch, A Alt, FW Crabtree, GR Snapper, SB TI The cytoskeleton in lymphocyte signaling SO ADVANCES IN IMMUNOLOGY, VOL 75 SE ADVANCES IN IMMUNOLOGY LA English DT Review ID WISKOTT-ALDRICH-SYNDROME; T-CELL RECEPTOR; ACTIN-DEPOLYMERIZING PROTEIN; WASP-RELATED PROTEIN; HUMAN ARP2/3 COMPLEX; EXCHANGE FACTOR VAV; ADAPTER PROTEIN; TYROSINE PHOSPHORYLATION; RHO-FAMILY; N-WASP C1 Stanford Univ, Sch Med, Beckman Ctr Mol & Genet Med, Dept Pathol & Dev Biol,Howard Hughes Med Inst, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Gastrointestinal Univ,Med Serv, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis,Dept Med, Boston, MA 02115 USA. RP Bauch, A (reprint author), Stanford Univ, Sch Med, Beckman Ctr Mol & Genet Med, Dept Pathol & Dev Biol,Howard Hughes Med Inst, Stanford, CA 94305 USA. NR 125 TC 15 Z9 16 U1 2 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 J9 ADV IMMUNOL JI Adv.Immunol. PY 2000 VL 75 BP 89 EP 114 DI 10.1016/S0065-2776(00)75002-4 PG 26 WC Immunology SC Immunology GA BQ69A UT WOS:000089205100002 PM 10879282 ER PT J AU Cantor, H AF Cantor, H TI T-cell receptor crossreactivity and autoimmune disease SO ADVANCES IN IMMUNOLOGY, VOL 75 SE ADVANCES IN IMMUNOLOGY LA English DT Review ID HERPES-SIMPLEX VIRUS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MHC CLASS-II; MYASTHENIA-GRAVIS PATIENTS; SINGLE MHC/PEPTIDE LIGAND; B-LYMPHOMA CELLS; POSITIVE SELECTION; STROMAL KERATITIS; INTERFERON-GAMMA; GM ALLOTYPES C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Cantor, H (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NR 127 TC 22 Z9 24 U1 2 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 J9 ADV IMMUNOL JI Adv.Immunol. PY 2000 VL 75 BP 209 EP 233 DI 10.1016/S0065-2776(00)75005-X PG 25 WC Immunology SC Immunology GA BQ69A UT WOS:000089205100005 PM 10879285 ER PT J AU Abrass, CK AF Abrass, CK TI The nature of chronic progressive nephropathy in aging rats SO ADVANCES IN RENAL REPLACEMENT THERAPY LA English DT Article DE kidney; aging; structure; extracellular matrix; glomerulosclerosis ID RENAL GLOMERULUS; S-LAMININ; KIDNEY; PROTEINURIA; MECHANISMS; EXPRESSION; NEPHROSIS; LESIONS; DISEASE; MATRIX AB Increases in glomerular size and thickening of the glomerular basement membrane are constant features that accompany growth and maturation in animals. Yet, some animals have chronic progressive nephropathy characterized by glomerulosclerosis and tubulointerstitial fibrosis. In these animals, clinically significant reductions in glomerular filtration rate may compromise hearth, particularly when other renal diseases occur concomitantly. Progressive thickening of the glomerular basement membrane is accompanied by changes in its composition, which may be responsible for changes in podocyte morphology and proteinuria. Within the tubulointerstitium, generalized accumulation of fibronectin and thrombospondin are accompanied by brood vessel proliferation. Fragility of these blood vessels with intermittent bleeding may initiate an inflammatory process that leads to focal areas of tubular atrophy and scarring. The pathogenesis of these lesions is unknown. Genetic background, sex, and environmental factors influence the tempo of progressive sclerosis, although these factors are not primary determinants of this lesion. This review highlights the structural changes that occur in the kidney with aging. Because the lesions are structurally similar, information gleaned from studies of aging animals should be relevant to understanding the loss of renal function that occurs in aging humans. (C) 2000 by the National Kidney Foundation, Inc. C1 Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Nephrol, Seattle, WA 98108 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. RP Abrass, CK (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Nephrol, MD 111A,1660 S Columbian Way, Seattle, WA 98108 USA. NR 35 TC 26 Z9 27 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1073-4449 J9 ADV RENAL REPLACE TH JI Adv. Renal Replace. Ther. PD JAN PY 2000 VL 7 IS 1 BP 4 EP 10 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 286CT UT WOS:000085426600002 PM 10672913 ER PT J AU Fraefel, C Jacoby, DR Breakefield, XO AF Fraefel, C Jacoby, DR Breakefield, XO TI Herpes simplex virus type 1-based amplicon vector systems SO ADVANCES IN VIRUS RESEARCH, VOL 55 SE ADVANCES IN VIRUS RESEARCH LA English DT Review ID EPSTEIN-BARR-VIRUS; HOST SHUTOFF FUNCTION; TEMPERATURE-SENSITIVE MUTANT; INDUCIBLE GENE-EXPRESSION; PROTECT CULTURED NEURONS; IN-VIVO; ADENOASSOCIATED VIRUS; MAMMALIAN-CELLS; DNA-REPLICATION; GLYCOPROTEIN-C C1 Univ Zurich, Inst Virol, CH-8057 Zurich, Switzerland. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Mol Neurogenet Unit, Charlestown, MA 02129 USA. RP Fraefel, C (reprint author), Univ Zurich, Inst Virol, CH-8057 Zurich, Switzerland. FU NCI NIH HHS [CA35258]; NINDS NIH HHS [NS24279]; PHS HHS [K01887] NR 122 TC 22 Z9 24 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3527 J9 ADV VIRUS RES JI Adv.Virus Res. PY 2000 VL 55 BP 425 EP 451 DI 10.1016/S0065-3527(00)55011-8 PG 27 WC Virology SC Virology GA BR12A UT WOS:000165695700011 PM 11050950 ER PT J AU Johnson, RP AF Johnson, RP TI The dynamics of T-lymphocyte turnover in AIDS SO AIDS LA English DT Article DE cellular immunity; CD4; CD8; immune reconstitution; pathogenesis; T-cell dynamics ID HIV-1 INFECTION; ANTIRETROVIRAL THERAPY; CELL-PROLIFERATION; RAPID TURNOVER; IN-VIVO; CD4(+); KINETICS; MACAQUES; DISEASE; ANTIGEN C1 Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. RP Johnson, RP (reprint author), Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Immunol, POB 9102,1 Pine Hill Dr, Southborough, MA 01772 USA. FU NCRR NIH HHS [RR00168]; NIAID NIH HHS [AI45314] NR 44 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PY 2000 VL 14 SU 3 BP S3 EP S9 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 371RN UT WOS:000165192100002 PM 11086844 ER PT J AU Ohagen, A Li, L Rosenweig, A Gabuzda, D AF Ohagen, A Li, L Rosenweig, A Gabuzda, D TI Cell-dependent mechanisms restrict the HIV type 1 coreceptor activity of US28, a chemokine receptor homolog encoded by human cytomegalovirus SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROTEIN-COUPLED RECEPTOR; FUNCTIONAL CORECEPTOR; INFECTION; ENTRY; MACROPHAGES; FUSION; 7-TRANSMEMBRANE; IDENTIFICATION; EXPRESSION AB Several members of the chemokine receptor family are used together with CD4 for HIV-1 entry into target cells, The human cytomegalovirus US28 gene encodes a chemokine receptor homolog that has been reported to function as an HIV-1 coreceptor, However, studies of US28 have given conflicting results regarding its ability to mediate HIV-1 entry. We examined the ability of US28 to function as an HIV-1 coreceptor in various cell lines and found that its coreceptor activity is highly cell dependent. US28 could function as a coreceptor for HIV-1 entry in HeLa and U87 cells but not in COS-1 and Cf2Th cells. In COS-1 cells, US28 was expressed on the cell surface and could mediate cell-cell fusion with HIV-1 Env-expressing cells, suggesting that the block to infection may result from a defect in virus internalization or postentry steps. In Cf2Th cells, US28 was expressed at high levels intracellularly but was not transported to the cell surface. The block in US28 coreceptor function in COS-1 and Cf2Th cells was coreceptor dependent, since CCR5, CXCR4, and other coreceptors can mediate HIV-1 entry in these cell lines. HIV-1 viruses pseudotyped with the MuLV or VSV Env entered and replicated at similar efficiency in COS-1 and U87 cells in single-cycle infections, suggesting that postentry and other early events in the HIV-1 life cycle are not intrinsically inefficient in COS-1 cells, These results identify two distinct mechanisms that can restrict the HIV-1 coreceptor activity of US28 in a cell- and coreceptor-dependent manner, and help to explain the existing controversy regarding the ability of US28 to mediate HIV-1 entry. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. FU NINDS NIH HHS [NS37277] NR 45 TC 15 Z9 15 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN 1 PY 2000 VL 16 IS 1 BP 27 EP 35 DI 10.1089/088922200309575 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 309QQ UT WOS:000086781100005 PM 10628814 ER PT B AU Isaacson, KB AF Isaacson, KB BE Olive, DL Levy, BS Phillips, JM TI Update on flexible hysteroscopes SO ALTERNATIVES TO HYSTERECTOMY LA English DT Proceedings Paper CT World Congress on Alternatives to Hysterectomy CY FEB 26-28, 1999 CL MIAMI BEACH, FL ID UTERINE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. RP Isaacson, KB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC GYNECOLOGIC LAPAROSCOPISTS PI SANTA FE SPRINGS PA 13021 EAST FLORENCE AVE, SANTA FE SPRINGS, CA 90670 USA BN 0-9628286-8-8 PY 2000 BP 141 EP 149 PG 9 WC Obstetrics & Gynecology; Surgery SC Obstetrics & Gynecology; Surgery GA BQ56B UT WOS:000088763000025 ER PT B AU Isaacson, KB AF Isaacson, KB BE Olive, DL Levy, BS Phillips, JM TI Complications of hysteroscopy SO ALTERNATIVES TO HYSTERECTOMY LA English DT Proceedings Paper CT World Congress on Alternatives to Hysterectomy CY FEB 26-28, 1999 CL MIAMI BEACH, FL ID AIR-EMBOLISM; OPERATIVE HYSTEROSCOPY; FLUID OVERLOAD; SURGERY; PREVENTION; ABSORPTION; RESECTION; GLYCINE C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Isaacson, KB (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 30 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC GYNECOLOGIC LAPAROSCOPISTS PI SANTA FE SPRINGS PA 13021 EAST FLORENCE AVE, SANTA FE SPRINGS, CA 90670 USA BN 0-9628286-8-8 PY 2000 BP 197 EP 206 PG 10 WC Obstetrics & Gynecology; Surgery SC Obstetrics & Gynecology; Surgery GA BQ56B UT WOS:000088763000034 ER PT J AU Bremner, WF Sothern, RB Kanabrocki, EL Ryan, M McCormick, JB Dawson, S Connors, ES Rothschild, R Third, JLHC Vahed, S Nemchausky, BM Shirazi, P Olwin, JH AF Bremner, WF Sothern, RB Kanabrocki, EL Ryan, M McCormick, JB Dawson, S Connors, ES Rothschild, R Third, JLHC Vahed, S Nemchausky, BM Shirazi, P Olwin, JH TI Relation between circadian patterns in levels of circulating lipoprotein(a), fibrinogen, platelets, and related lipid variables in men SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT International Congress on Chronobiology CY SEP 07-11, 1997 CL PARIS, FRANCE SP Univ Pierre & Marie Curie, Paris, Hopitaux Paris, Assistance Publique, INRA, INSERM ID CORONARY HEART-DISEASE; SUDDEN CARDIAC DEATH; ACUTE MYOCARDIAL-INFARCTION; RISK FACTOR; ARTERY DISEASE; CARDIOVASCULAR-DISEASE; PLASMA-LIPOPROTEINS; LP(A) LIPOPROTEIN; HEALTHY-SUBJECTS; APOLIPOPROTEINS AB Background A correlation has been reported between lipoprotein(a) [Lp(a)] concentration and risk for coronary artery disease. High concentrations of Lp(a) might be markers for vascular or tissue injury or might be associated with other genetic or environmental factors that can cause acute myocardial infarction. Methods We measured the circadian characteristics of circulating Lp(a), fibrinogen, platelets, cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol for a group of adult male volunteers who had no clinical symptoms. We obtained samples every 3 hours around the clock to assess the normal degree of variation within a 24 hour period and to test for similarities in circadian patterns and correlations with level of Lp(a). Results Each variable displayed a highly significant circadian rhythm. Lp(a), fibrinogen, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol peaked in the morning. Cholesterol and platelets peaked in the late afternoon, and triglycerides peaked in the evening. Conclusions Although peak levels of Lp(a) and fibrinogen coincide with reported morning peak frequencies of myocardial infarction and stroke, the platelet peak appears to coincide with late afternoon peak frequencies of sudden cardiac death and fatal stroke. The data suggest that proper timing of single samples may improve the usefulness and accuracy of diagnosis, risk assessment, and therapy. C1 MacNeal Cardiol Grp, Berwyn, IL 60402 USA. Univ Minnesota, Coll Biol Sci, St Paul, MN 55108 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Nucl Med, Hines, IL 60141 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Spinal Cord Injury, Hines, IL 60141 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Nursing Res, Hines, IL 60141 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Dietet Serv, Hines, IL 60141 USA. Swedish Covenant Hosp, Chicago, IL USA. Rush Presbyterian St Lukes Med Ctr, Dept Surg, Chicago, IL 60612 USA. RP Bremner, WF (reprint author), MacNeal Cardiol Grp, 3231 S Euclid Ave,Suite 201, Berwyn, IL 60402 USA. NR 75 TC 48 Z9 51 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JAN PY 2000 VL 139 IS 1 BP 164 EP 173 DI 10.1016/S0002-8703(00)90324-7 PN 1 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 272BU UT WOS:000084631300024 PM 10618578 ER PT J AU Kang, JX Leaf, A AF Kang, JX Leaf, A TI Prevention of fatal cardiac arrhythmias by polyunsaturated fatty acids SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT International Conference on Highly Unsaturated Fatty Acids in Nutrition and Disease Prevention CY NOV 04-06, 1996 CL BARCELONA, SPAIN SP F Hoffmann LaRoche Ltd, Int Soc Study Fatty Acids & Lipids, Inst Natl Rech, Japanese Soc Nutrit & Food Sci DE n-3 fatty acids; n-6 fatty acids; ventricular fibrillation; sudden cardiac death; cardiac arrhythmias ID RAT VENTRICULAR MYOCYTES; LONG-CHAIN; ISCHEMIA; MEMBRANE; CURRENTS; LYSOPHOSPHATIDYLCHOLINE; CHANNELS AB In animal feeding studies, and probably in humans, n-3 polyunsaturated fatty acids (PUFAs) prevent fatal ischemia-induced cardiac arrhythmias. We showed that n-3 PUFAs also prevented such arrhythmias in surgically prepared, conscious, exercising dogs. The mechanism of the antiarrhythmic action of n-3 PUFAs has been studied in spontaneously contracting cultured cardiac myocytes of neonatal rats. Adding arrhythmogenic toxins (eg, ouabain, high Ca2+, lysophosphatidylcholine, beta-adrenergic agonist, acylcarnitine, and the Ca2+ ionophore) to the myocyte perfusate caused tachycardia, contracture, and fibrillation of the cultured myocytes. Adding eicosapentaenoic acid (EPA: 5-15 mu mol/L) to the superfusate before adding the toxins prevented the expected tachyarrhythmias. If the arrhythmias were first induced, adding the EPA to the superfusate terminated the arrhythmias. This antiarrhythmic action occurred with dietary n-3 and n-6 PUFAs; saturated fatty acids and the monounsaturated oleic acid induced no such action. Arachidonic acid (AA; 20:4n-6) is anomalous because in one-third of the tests it provoked severe arrhythmias, which were found to result from cyclooxygenase metabolites of AA. When cyclooxygenase inhibitors were added with the AA, the antiarrhythmic effect was like those of EPA and DHA. The action of the n-3 and n-6 PUFAs is to stabilize electrically every myocyte in the heart by increasing the electrical stimulus required to elicit an action potential by approximate to 50% and prolonging the relative refractory time by approximate to 150%. These electrophysiologic effects result from an action of the free PUFAs to modulate sodium and calcium currents in the myocytes. The PUFAs also modulate sodium and calcium channels and have anticonvulsant activity in brain cells. C1 Brockton W Roxbury Vet Affairs Med Ctr, W Roxbury, MA USA. Harvard Med Sch, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Boston, MA USA. RP Leaf, A (reprint author), Massachusetts Gen Hosp, Dept Med, 4th Floor,149 13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [R01 DK 38165] NR 33 TC 60 Z9 65 U1 0 U2 1 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 2000 VL 71 IS 1 SU S BP 202S EP 207S PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 271VM UT WOS:000084614800007 PM 10617972 ER PT J AU Sloan, KL Kivlahan, D Saxon, AJ AF Sloan, KL Kivlahan, D Saxon, AJ TI Detecting bipolar disorder among treatment-seeking substance abusers SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article ID ADDICTION SEVERITY INDEX; PSYCHIATRIC-DISORDERS; COMORBIDITY; RELIABILITY; DEPENDENCE; ILLNESS; ALCOHOL AB Bipolar disorder is increasingly recognized to have frequent comorbidity with substance use disorders, but may be difficult to diagnose among patients with active substance use. The purpose of this paper is to describe a brief, self-report form for the efficient detection of bipolar disorder. The 19-item form was piloted in 373 consecutive applicants for substance abuse treatment at an urban Veterans Affairs (VA) medical center. Results show reasonable internal consistency (alpha = .850) and high rates of manic symptomatology (36%), previous bipolar diagnosis (30%, 51% of whom report prior psychiatric hospitalization), and exposure to mood stabilizers (20%, 66% of whom reported therapeutic benefit). Comparison of nine different scoring algorithms with chart diagnosis as the validating criterion found that self-report of bipolar diagnosis was optimally sensitive. Either self-report of bipolar diagnosis with hospitalization or self-report of exposure to mood stabilizers with therapeutic response was optimally specific. Symptom self-report items had significantly poorer sensitivity and specificity (F = 7.60, p < .01). We conclude that questions pertaining to diagnostic and treatment history (especially hospitalization or therapeutic medication response) are considerably superior to symptom-based screening for clinically diagnosed bipolar disorder. Further work using structured interview as the diagnostic criterion is under way to validate this instrument. C1 VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Sloan, KL (reprint author), Seattle VA Med Ctr 116 DDTP, 1600 S Columbian Way, Seattle, WA 98108 USA. NR 15 TC 9 Z9 9 U1 3 U2 3 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PY 2000 VL 26 IS 1 BP 13 EP 23 DI 10.1081/ADA-100100587 PG 11 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 284LB UT WOS:000085332900002 PM 10718160 ER PT J AU Faigel, DO Magaret, N Corless, C Lieberman, DA Fennerty, MB AF Faigel, DO Magaret, N Corless, C Lieberman, DA Fennerty, MB TI Evaluation of rapid antibody tests for the diagnosis of Helicobacter pylori infection SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID UREA BREATH TEST; WHOLE-BLOOD TEST; ENZYME-IMMUNOASSAY; NONINVASIVE TESTS; GOLD STANDARD; FLEXSURE HP; SEROLOGY; ACCURACY; GASTRITIS; SERUM AB OBJECTIVE: The aim of this study was to compare the performance characteristics of one serum and four whole blood rapid antibody tests for Helicobacter pylori infection. METHODS: A total of 97 outpatients referred for endoscopic evaluation of dyspepsia were included. Antral biopsies were obtained for histology and rapid urease test. Serum was tested with an enzyme-linked immunoassay (HM-CAP) and a rapid serology test (FlexSure HP). A commercially available C-13-urea breath test was performed. Capillary blood obtained by fingerstick was tested with FlexSure HP, QuickVue, Accustat, and StatSimple pylori tests. Sensitivity, specificity. and accuracy of each rapid test was calculated relative to a criterion standard of histological gastritis and at least two of the four following tests positive: identifiable organisms on specially stained slides, rapid urease test, urea breath test, or serum immunoassay. RESULTS: A total of 30 patients (31%) were infected. The FlexSure HP Serum, and FlexSure HP, QuickVue, Accustat, and StatSimple pylori whole blood tests had sensitivities of 90%, 87%, 83%, 76%, and 90%; specificities of 94%, 90%, 96%, 96%, and 98%, and accuracies of 93%, 88%, 92%, 87%, and 96%. respectively. Sensitivities were not statistically different. StatSimple pylori was more specific than FlexSure HP whole blood (p < 0.03), and more accurate than FlexSure whole blood (p < 0.024) and Accustat (p < 0.01). Serum immunoassay was significantly more sensitive (97%) than FlexSure whole blood, QuickVue, and Accustat (p < 0.01), but its specificity (95%) was not statistically different from the rapid tests. CONCLUSION: Rapid antibody testing provides an accurate diagnosis of H. pylori infection. In general, these tests are less sensitive than, but as specific as, standard serology. C1 Portland VA Med Ctr, Dept Med, Portland, OR 97201 USA. Portland VA Med Ctr, Dept Pathol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. RP Faigel, DO (reprint author), Portland VA Med Ctr, Dept Med, P3GI,3710 US Vet Hosp Rd, Portland, OR 97201 USA. NR 41 TC 25 Z9 26 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 2000 VL 95 IS 1 BP 72 EP 77 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 273CY UT WOS:000084690800014 PM 10638562 ER PT J AU Arora, S Baraona, E Lieber, CS AF Arora, S Baraona, E Lieber, CS TI Alcohol levels are increased in social drinkers receiving ranitidine SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID BLOOD-ALCOHOL; H2-RECEPTOR ANTAGONISTS; H-2-RECEPTOR ANTAGONISTS; DEHYDROGENASE ACTIVITY; ETHANOL INGESTION; METABOLISM; BIOAVAILABILITY; CIMETIDINE; ELIMINATION; INHIBITION AB OBJECTIVE: Ranitidine increases blood alcohol concentrations by decreasing the first pass metabolism of ethanol. The effect of ranitidine on alcohol levels has been found to be variable when using large doses of alcohol or conditions in which its first pass metabolism is known to be minimal. Despite a consensus that the drug increases alcohol levels after small doses of ethanol, this effect has been considered inconsequential, because of the low alcohol levels. However, social drinking comprises repetitive consumption of small doses of alcohol and the ranitidine effect could thereby be potentiated. METHODS: To study this factor, alcohol levels were determined by breath analysis in nine men (social drinkers), after four drinks of 0.15 g/kg ethanol given postprandially every 45 min, before and after ranitidine (150 mg b.i.d. for 7 days). RESULTS: Their blood alcohol increased with repeated doses, reaching peak values of 24 +/- 3 mg/dl before ranitidine and 33 +/- 2 after ranitidine (p = 0.04). In seven of the nine subjects blood alcohol exceeded 25 mg/dl, a level at which impairment of judgment and of finely tuned skills occurs and which exceeds legal limits of driving in some European countries. Moreover, the high levels persisted for a longer time with than without the drug. These effects were associated with a 62% decrease in first pass metabolism. CONCLUSION: Under conditions mimicking social drinking, ranitidine increases blood alcohol to levels known to impair psychomotor skills needed for driving. (Am J Gastroenterol 2000;95:208-213. (C) 2000 by Am. Cell. of Gastroenterology) C1 Bronx Vet Affairs Med Ctr, Ctr Alcohol Res & Treatment, New York, NY USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. RP Lieber, CS (reprint author), Alcohol Res Ctr, Vet Affairs Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. FU NIAAA NIH HHS [AA 05934, AA07275] NR 24 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 2000 VL 95 IS 1 BP 208 EP 213 DI 10.1016/S0002-9270(99)00745-5 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 273CY UT WOS:000084690800037 PM 10638585 ER PT J AU Hunt, MK Lederman, R Stoddard, A Potter, S Phillips, J Sorensen, G AF Hunt, MK Lederman, R Stoddard, A Potter, S Phillips, J Sorensen, G TI Process tracking results from the Treatwell 5-a-day worksite study SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE process tracking; worksite; 5-a-day; health promotion ID DISEASE PREVENTION PROGRAMS; HEALTH PROMOTION PROGRAMS; VEGETABLE INTAKE; UNITED-STATES; COMMUNITY; INTERVENTION; HEART; FRUIT; IMPLEMENTATION; PROJECT AB Purpose. To report findings from Treatwell 5-a-Day process tracking Design. Worksites were randomly assigned do a minimal intervention control, worksite-only condition, or worksite-plus-family condition. Setting. Twenty-two small community health centers in Massachusetts. Subjects. Employees of the community health centers. Intervention. Both intervention conditions included the formation of employee advisory boards; activities such as nutrition discussions and taste tests targeting individual behavior change; and point-of-purchase labeling as an environmental strategy. Worksite-plus-family sites incorporated activities such as family contests, campaigns, and picnics. Measures, Documentation of the number and type of activities for extent of implementation; number of participants in activities for reach; program awareness and participation from the follow-up employee survey (n = 1306, representing 76% [range, 56%-100%] of the sample); change in fruit and vegetable consumption from a comparison between the follow-up and baseline surveys (n = 1359, representing 87% [range, 75%-100%] of the sample). Results. A higher number of activities per employee was significantly correlated with greater program awareness (.68; p =. 006) and greater change in fruit and vegetable consumption (.55; p =.04). Greater participation in activities was significantly correlated with yr enter awareness (.67; p =.007), higher participation (.61; p =.02), and increase in fruit and vegetable consumption. (.55; p =.04). Conclusions. These results provide quantitative indicators of a dose-response relationship between the number of intervention activities per employee and higher percentage of employee participation and observed increases in fruit and vegetable consumption. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. RP Hunt, MK (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [5RO1 CA59728] NR 39 TC 16 Z9 16 U1 2 U2 5 PU AMER J HEALTH PROMOTION INC PI KEEGO HARBOR PA 1660 CASS LAKE RD, STE 104, KEEGO HARBOR, MI 48320 USA SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD JAN-FEB PY 2000 VL 14 IS 3 BP 179 EP 187 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 285PU UT WOS:000085398100007 PM 10787771 ER PT J AU Daw, EW Payami, H Nemens, EJ Nochlin, D Bird, TD Schellenberg, GD Wijsman, EM AF Daw, EW Payami, H Nemens, EJ Nochlin, D Bird, TD Schellenberg, GD Wijsman, EM TI The number of trait loci in late-onset Alzheimer disease SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID APOLIPOPROTEIN-E GENOTYPE; GENE; DEMENTIA; LINKAGE; AGE; SEX; METAANALYSIS; CHROMOSOME-1; SEGREGATION; ALLELE AB Although it is clear that apoE plays an important role in the genetics of late-onset Alzheimer disease (AD), evidence exists that additional genes may play a role in AD, and estimates of the total contribution of apoE to the variance in onset of AD vary widely. Unfortunately, little information is available on the number and contribution of additional genes. We estimated the number of additional quantitative-trait loci and their contribution to the variance in age at onset of AD, as well as the contribution of apoE and sex, in an oligogenic segregation analysis of 75 families (742 individuals) ascertained for members with late-onset AD. We found evidence that four additional loci make a contribution to the variance in age at onset of late-onset AD that is similar to or greater in magnitude than that made by apoE, with one locus making a contribution several times greater than that of apoE. Additionally, we confirmed previous findings of a dose effect for the apoE epsilon 4 allele, a protective effect for the epsilon 2 allele, evidence for allelic interactions at the apoE locus, and a small protective effect for males. Furthermore, although we estimate that the apoE genotype can make a difference of less than or equal to 17 years in age at onset of AD, our estimate of the contribution of apoE (7%-9%) to total variation in onset of AD is somewhat smaller than that which has previously been reported. Our results suggest that several genes that have not yet been localized may play a larger role than does apoE in late-onset AD. C1 Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. Univ Washington, Dept Stat, Seattle, WA 98195 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Neurol, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. RP Daw, EW (reprint author), Univ Washington, Dept Med, Div Med Genet, Box 357720, Seattle, WA 98195 USA. FU NIA NIH HHS [AG 05136, P30 AG008017, U24 AG021886, P50 AG005136, AG 08017]; NIGMS NIH HHS [GM 46255, R01 GM046255, R37 GM046255] NR 28 TC 166 Z9 171 U1 2 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN PY 2000 VL 66 IS 1 BP 196 EP 204 DI 10.1086/302710 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 279FK UT WOS:000085033600022 PM 10631151 ER PT J AU Mulrow, CD Williams, JW Chiquette, E Aguilar, C Hitchcock-Noel, P Lee, S Cornell, J Stamm, K AF Mulrow, CD Williams, JW Chiquette, E Aguilar, C Hitchcock-Noel, P Lee, S Cornell, J Stamm, K TI Efficacy of newer medications for treating depression in primary care patients SO AMERICAN JOURNAL OF MEDICINE LA English DT Review ID SEROTONIN REUPTAKE INHIBITORS; GENERAL-PRACTICE; DOUBLE-BLIND; MAJOR DEPRESSION; TRICYCLIC ANTIDEPRESSANTS; DISCONTINUATION RATES; CONTROLLED TRIAL; METAANALYSIS; MULTICENTER; ANXIETY AB PURPOSE: Several medications have recently been introduced for the treatment of depression. We reviewed the literature to summarize their efficacy in the treatment of depression in adult patients in primary care settings. METHODS: We searched the literature published from 1980 to January 1998 using the Cochrane Collaboration Depression Anxiety and Neurosis Group's specialized registry of 8,451 clinical trials, references from trials and 46 pertinent meta-analyses, and consultation with experts. We included randomized controlled trials of at least 6 weeks' duration that measured clinical outcomes and compared one of 32 newer medications with another newer antidepressant, an older antidepressant, a placebo, or a psychosocial intervention for the treatment of depressed patients in primary care settings. The primary outcome was response rate, defined as the proportion of patients experiencing a 50% or greater improvement in depressive symptoms. RESULTS: There were 28 randomized controlled trials involving 5,940 adult primary care patients with major depression, depression requiring treatment, dysthymia, or mixed anxiety depression. Newer agents, including selective serotonin re-uptake inhibitors, serotonin norepinephrine inhibitors, reversible inhibitors of monoamine oxidase, and dopamine antagonists, were usually compared with tricyclic agents. Average response rates were 63% for newer agents, 35% for placebo, and 60% for tricyclic agents. Newer agents were significantly more effective than placebo [risk ratio = 1.6; 95% confidence interval (CI), 1.2 to 2.1), but similar to tricyclic agents (risk ratio = 1.0; 95% CI 0.9 to 1.1). Response rates were similar in the different types of depressive disorders, except that two small trials in frail older patients showed no significant effects of newer agents compared with placebo. Dropout rates as a result of adverse effects were 8% with newer agents and 13% with tricyclic agents (P <0.05). CONCLUSIONS: In primary care settings, newer antidepressants are more effective than placebo and have similar efficacy compared with tricyclic agents in the acute treatment of depression. Dropout rates as a result of adverse effects are lower with newer compared with tricyclic agents. Future studies should compare the effectiveness of different therapies among primary care patients with less severe depression and greater medical and psychiatric comorbidity. Am J Med. 2000;108:54-64. (C)2000 by Excerpca Medica, Inc. C1 Audie L Murphy Mem Vet Affairs Hosp, Vet Affairs Cochrane Ctr, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Evidence Based Practice Ctr, San Antonio, TX 78284 USA. RP Mulrow, CD (reprint author), Audie L Murphy Mem Vet Affairs Hosp, Vet Affairs Cochrane Ctr, 7400 Merton Minter Blvd 11C6, San Antonio, TX 78284 USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 51 TC 76 Z9 76 U1 1 U2 4 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JAN PY 2000 VL 108 IS 1 BP 54 EP 64 DI 10.1016/S0002-9343(99)00316-2 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 273ME UT WOS:000084710800009 PM 11059441 ER PT J AU Staecker, H Merchant, SN AF Staecker, H Merchant, SN TI Temporal bone pathology case of the month - Congenital fixation of the incus SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Staecker, H (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. OI Staecker, Hinrich/0000-0002-0348-3015 NR 6 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD JAN PY 2000 VL 21 IS 1 BP 137 EP 138 DI 10.1016/S0196-0709(00)80089-7 PG 2 WC Otorhinolaryngology SC Otorhinolaryngology GA 273MA UT WOS:000084710400025 PM 10651449 ER PT J AU Detmar, M Velasco, P Richard, L Claffey, KP Streit, M Riccardi, L Skobe, M Brown, LF AF Detmar, M Velasco, P Richard, L Claffey, KP Streit, M Riccardi, L Skobe, M Brown, LF TI Expression of vascular endothelial growth factor induces an invasive phenotype in human squamous cell carcinomas SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID RECEPTOR TYROSINE KINASE; PERMEABILITY FACTOR; TUMOR-GROWTH; NORMAL EPIDERMIS; IN-VIVO; ANGIOGENESIS; INHIBITION; SUPPRESSES; SKIN; IDENTIFICATION AB Inhibition of the vascular endothelial growth factor (VEGF) receptor Flk-1 has been shown to prevent invasion of experimental squamous cell carcinomas (SCC), To directly investigate the role of VEGF in tumor invasion, we stably transfected human SCC-13 cells, which are characterized by a noninvasive phenotype in vivo, with expression vectors containing murine VEGF(164) in sense (SCC/VEGF+) or antisense (SCC/VEGF-) orientation or with vector alone (SCC/vec). SCC/vec cells formed slowly growing, well-differentiated tumors with well-defined borders between tumor and stroma, after intradermal or subcutaneous injection. In contrast, SCC/VEGF+ tumors were characterized by rapid tumor growth, with small cell groups and single cells invading into the surrounding tissue, and by admixture of blood vessels and tumor cells in areas of tumor invasion. We detected an increase in tumor vessel density and size in VEGF-overexpressing tumors, resulting in a more than fourfold increase in total vascular areas. In contrast, SCC/VEGF- clones formed noninvasive, sharply circumscribed tumors with reduced vascular density. These findings demonstrate that selective VEGF overexpression was sufficient to induce tumor invasiveness, and they provide further evidence for an active role of the tumor stroma in cancer progression. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, CBRC,Dept Dermatol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. RP Detmar, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, CBRC,Dept Dermatol, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA69184, R01 CA069184] NR 39 TC 70 Z9 71 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 2000 VL 156 IS 1 BP 159 EP 167 DI 10.1016/S0002-9440(10)64715-3 PG 9 WC Pathology SC Pathology GA 274PB UT WOS:000084773300019 PM 10623663 ER PT J AU Hanson, DB AF Hanson, DB TI Taphonomic considerations in bioarchaeological research in the Mariana Islands of western Micronesia. SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2000 SU 30 BP 172 EP 172 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 286RJ UT WOS:000085458900228 ER PT J AU Kieffer, TJ Habener, JF AF Kieffer, TJ Habener, JF TI The adipoinsular axis: effects of leptin on pancreatic beta-cells SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Review DE insulin secretion; diabetes ID DEPENDENT DIABETES-MELLITUS; SENSITIVE K+ CHANNELS; INDUCED INSULIN-SECRETION; WHITE ADIPOSE-TISSUE; MESSENGER-RNA LEVELS; OBESE GENE-PRODUCT; PERFUSED RAT PANCREAS; BODY-WEIGHT GAIN; CHAIN ACYL-COA; RECEPTOR OB-R AB The prevalence of obesity and related diabetes mellitus is increasing worldwide. Here we review evidence for the existence of an adipoinsular axis, a dual hormonal feedback loop involving the hormones insulin and leptin produced by pancreatic beta-cells and adipose tissue, respectively. Insulin is adipogenic, increases body fat mass, and stimulates the production and secretion of leptin, the satiety hormone that acts centrally to reduce food intake and increase energy expenditure. Leptin in turn suppresses insulin secretion by both central actions and direct actions on beta-cells. Because plasma levels of leptin are directly proportional to body fat mass, an increase of adiposity increases plasma leptin, thereby curtailing insulin production and further increasing fat mass. We propose that the adipoinsular axis is designed to maintain nutrient balance and that dysregulation of this axis may contribute to obesity and the development of hyperinsulinemia associated with diabetes. C1 Univ Alberta, Div Endocrinol & Metab, Heritage Med Res Ctr 370, Dept Med, Edmonton, AB T6G 2S2, Canada. Univ Alberta, Dept Physiol, Edmonton, AB T6G 2S2, Canada. Massachusetts Gen Hosp, Mol Endocrinol Lab, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kieffer, TJ (reprint author), Univ Alberta, Div Endocrinol & Metab, Heritage Med Res Ctr 370, Dept Med, Edmonton, AB T6G 2S2, Canada. NR 189 TC 262 Z9 281 U1 3 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JAN PY 2000 VL 278 IS 1 BP E1 EP E14 PG 14 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 273ZD UT WOS:000084738500001 PM 10644531 ER PT J AU Nagatomo, Y Carabello, BA Coker, ML McDermott, PJ Nemoto, S Hamawaki, M Spinale, FG AF Nagatomo, Y Carabello, BA Coker, ML McDermott, PJ Nemoto, S Hamawaki, M Spinale, FG TI Differential effects of pressure or volume overload on myocardial MMP levels and inhibitory control SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE myocardial remodeling; tissue inhibitor of metalloproteinases; hypertrophy; matrix metalloproteinase; left ventricular overload ID MATRIX METALLOPROTEINASE ACTIVITY; SANDWICH ENZYME-IMMUNOASSAY; NECROSIS FACTOR-ALPHA; TISSUE INHIBITOR; IV COLLAGENASE; INTERSTITIAL COLLAGENASE; DILATED CARDIOMYOPATHY; MONOCLONAL-ANTIBODIES; SYNOVIAL FIBROBLASTS; EXTRACELLULAR-MATRIX AB Left, ventricular (LV) pressure (PO) or volume (VO) overload is accompanied by myocardial remodeling, but mechanisms that contribute to this progressive remodeling process remain unclear. The matrix metalloproteinases (MMPs) contribute to tissue remodeling in a:number of disease states. This study tested the hypothesis that increased MMP expression and activity occur after the induction of an LV overload, which is accompanied by a loss;of endogenous MMP inhibitory control. LV MMP zymographic-activity and species abundance were measured in dogs cinder the following conditions: acute PO induced by ascending aortic balloon inflation (6 h, n = 9), prolonged PO by aortic banding (10 days, n = 5), acute VO through mitral regurgitation secondary to chordal rupture (6 h, n = 6), prolonged VO due to mitral regurgitation (14 days, n = 7), and sham-controls (n = 11). MMP zymographic activity in the 92-kDa region, indicative of MMP-9 activity, increased over threefold in acute PO and VO and fell to control levels in prolonged PO and VO. The MMP-9 activity-to-abundance ratio increased by over fourfold with acute VO and twofold in acute PO, suggesting a loss of inhibitory control. Endogenous MMP inhibitor content was unchanged with either PO or VO. Interstitial collagenase (MMP-1) content decreased by 50% with acute VO but not with acute PO. Stromelysin (MMP-3) levels increased by 40% with acute VO and increased by 80% with prolonged PO. Although changes in LV myocardial MMP activity and inhibitory control occurred in both acute and prolonged PO and VO states, these changes were not identical. These results suggest that the type of overload stimulus may selectively influence myocardial MMP activity and expression, which in turn would affect the overall LV myocardial remodeling process in LV overload. C1 Med Univ S Carolina, Div Cardiothorac Surg & Cardiol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Spinale, FG (reprint author), Med Univ S Carolina, Div Cardiothorac Surg & Cardiol, Rm 625,Strom Thurmond Res Bldg,770 MUSC Complex,1, Charleston, SC 29425 USA. FU NHLBI NIH HHS [HL-97012, P01-HL-48788, HL-45024] NR 49 TC 80 Z9 81 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JAN PY 2000 VL 278 IS 1 BP H151 EP H161 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 274UT UT WOS:000084784000018 PM 10644594 ER PT J AU Zhang, Z Yang, XY Soltoff, SP Cohen, DM AF Zhang, Z Yang, XY Soltoff, SP Cohen, DM TI PI3K signaling in the murine kidney inner medullary cell response to urea SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE sodium chloride; hypertonicity; mIMCD3 cells; apoptosis; stress ID P70 S6 KINASE; RENAL EPITHELIAL-CELLS; DUCT MIMCD3 CELLS; GROWTH-FACTOR; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE KINASE; POSITIVE REGULATION; RAT HEPATOCYTES; GENE-EXPRESSION; ACTIVATOR CREM AB Growth factors and other stimuli increase the activity of phosphatidylinositol-3 kinase (PI3K), an SH2 domain-containing lipid kinase. In the murine kidney inner medullary mIMCD3 cell line, urea (200 mM) increased PI3K activity in a time-dependent fashion as measured by immune complex kinase assay. The PI3K effector, Akt, was also activated by urea as measured by anti-phospho-Akt immunoblotting. In addition, the Akt (and PI3K) effector, p70 S6 kinase, was activated by urea treatment in a PI3K-dependent fashion. PI3K inhibition potentiated the proapoptotic effect of hypertonic and urea stress. Urea treatment also induced the tyrosine phosphorylation of Shc and the recruitment to Shc of Grb2. Coexistence of activated Shc and PI3K in a macromolecular complex was suggested by the increase in PI3K activity evident in anti-She immunoprecipitates prepared from urea-treated cells. Taken together, these data suggest that PI3K may regulate physiological events in the renal medullary cell response to urea stress and that an upstream tyrosine kinase conferring activation of both PI3K and Shc may govern urea signaling in these cells. C1 Oregon Hlth Sci Univ, Div Nephrol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Div Mol Med, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. RP Cohen, DM (reprint author), Oregon Hlth Sci Univ, Div Nephrol, PP262,3314 SW US Vet Hosp Rd, Portland, OR 97201 USA. EM cohend@ohsu.edu RI Zhang, Zheng/J-2388-2014 OI Zhang, Zheng/0000-0003-2497-0362 FU NIDCR NIH HHS [DE-10877]; NIDDK NIH HHS [DK-52494] NR 61 TC 35 Z9 36 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 2000 VL 278 IS 1 BP F155 EP F164 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 275KV UT WOS:000084820100017 PM 10644667 ER PT J AU McLoud, TC AF McLoud, TC TI Education in radiology: Challenges for the new millennium SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP McLoud, TC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, POB 9657,55 Fruit St, Boston, MA 02114 USA. NR 11 TC 16 Z9 17 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2000 VL 174 IS 1 BP 3 EP 8 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 269PT UT WOS:000084487300002 PM 10628444 ER PT J AU Rasool, A Palevsky, PM AF Rasool, A Palevsky, PM TI Treatment of edematous disorders with diuretics SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Review DE edema; diuretics; congestive heart failure; nephrotic syndrome; sodium hemostasis ID CONGESTIVE-HEART-FAILURE; CHRONIC RENAL-INSUFFICIENCY; EXPERIMENTAL NEPHROTIC SYNDROME; ATRIAL-NATRIURETIC-PEPTIDE; GLOMERULAR-FILTRATION RATE; DRUG-PROTEIN-BINDING; HIGH-DOSE FUROSEMIDE; SODIUM RETENTION; CONTINUOUS-INFUSION; VOLUME EXPANSION AB Generalized edema results from alterations in renal sodium homeostasis that ultimately result in an expansion of extracellular fluid volume and accumulation of interstitial fluid. The common edematous disorders include congestive heart failure, cirrhosis, nephrotic syndrome, and renal insufficiency. The abnormalities of sodium homeostasis contributing edema formation in each condition are discussed. Management of volume homeostasis, with an emphasis on the role of diuretic therapy, is reviewed. C1 VA Pittsburgh Healthcare Syst, Renal Sect 111FU, Univ Dr Div, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect 111FU, Univ Dr Div, Pittsburgh, PA 15240 USA. OI Palevsky, Paul/0000-0002-7334-5400 NR 148 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD JAN PY 2000 VL 319 IS 1 BP 25 EP 37 DI 10.1097/00000441-200001000-00003 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 276ZU UT WOS:000084908900003 PM 10653442 ER PT J AU Martyn, JAJ Goudsouzian, NG Chang, YC Szyfelbein, SK Schwartz, AE Patel, SS AF Martyn, JAJ Goudsouzian, NG Chang, YC Szyfelbein, SK Schwartz, AE Patel, SS TI Neuromuscular effects of mivacurium in 2-to 12-yr-old children with burn injury SO ANESTHESIOLOGY LA English DT Article DE pediatrics; plasma cholinesterase; relaxant resistance; succinylcholine; alternative to ID PEDIATRIC-PATIENTS; THERMAL-INJURY; INFUSION; PHARMACODYNAMICS; REQUIREMENTS; ATRACURIUM; BLOCKADE AB Background: Burned patients are usually resistant to the neuromuscular effects of nondepolarizing relaxants, mostly because of receptor changes. The magnitude of the resistance is related to burn size and time after burn. Mivacurium is a muscle relaxant, degraded by plasma cholinesterase, whose enzyme activity is decreased in burns. The present study tested the hypothesis that burn-induced depressed plasma cholinesterase activity counteracts the receptor-mediated resistance, resulting in a lack of resistance to mivacurium. Methods: Burned patients (n = 23), aged 2-12 yr, subclassified into burns of 10-30% or > 30% of body surface, were studied at less than or equal to 6 days and again at 1-12 weeks after burn if possible. Thirteen additional patients served as controls. Neuromuscular variables monitored included onset and recovery following bolus dose, continuous infusion rates required to maintain 95 +/- 4% paralysis, and recovery rates following infusion. Results: The onset times of maximal twitch suppression were not different between burns and controls, but recovery to 25% of baseline twitch height was prolonged in patients with > 30% burn irrespective of time after injury. The continuous infusion rates to maintain twitch suppression at 95 +/- 4% were not different between groups. The recovery indices, including train-of-four to > 75%, 25-75%, or 5-95% in burned patients, were similar or prolonged compared with controls. The prolonged recovery in burned patients was inversely related to plasma cholinesterase activity (R-2 = 0.86, r = -0.93, P < 0.001), and the decreased plasma cholinesterase activity was related to burn size and time after burn. Conclusions: A normal mivacurium dosage (0.2 mg/kg) effects good relaxation conditions in burned patients, with an onset time similar to that in controls. This finding contrasts with the response seen with other nondepolarizing drugs, higher doses of which are required to effect paralysis. The decreased metabolism of mivacurium, resulting from depressed plasma cholinesterase activity, probably counteracts the receptor-mediated potential for resistance. Because succinylcholine is contraindicated in burned patients, larger doses of nondepolarizing agents are advocated to effect rapid onset of paralysis. This generalization does not hold for mivacurium. C1 Harvard Univ, Dept Anesthesiol & Crit Care, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Shriners Burns Inst, Boston, MA USA. RP Martyn, JAJ (reprint author), Harvard Univ, Dept Anesthesiol & Crit Care, Massachusetts Gen Hosp, Sch Med, 32 Fruit St, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM55081-4, GM-31569-18] NR 20 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 2000 VL 92 IS 1 BP 31 EP 37 DI 10.1097/00000542-200001000-00011 PG 7 WC Anesthesiology SC Anesthesiology GA 273XZ UT WOS:000084735800007 PM 10638896 ER PT J AU Lehtinen, JT AF Lehtinen, JT TI Rheumatoid shoulder - A 15-year radiographic follow-up study of 148 shoulders SO ANNALES CHIRURGIAE ET GYNAECOLOGIAE LA English DT Article C1 Univ Tampere, Dept Surg, FIN-33101 Tampere, Finland. RP Lehtinen, JT (reprint author), Massachusetts Gen Hosp, Harvard Shoulder Serv, 275 Lambridge St, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU FINNISH SURGICAL SOC PI HELSINKI PA MAKELANKATU 2, SF-00550 HELSINKI, FINLAND SN 0355-9521 J9 ANN CHIR GYNAECOL FE JI Ann. Chir. Gynaecol. PY 2000 VL 89 IS 4 BP 321 EP 322 PG 2 WC Obstetrics & Gynecology; Surgery SC Obstetrics & Gynecology; Surgery GA 393BC UT WOS:000166448400016 ER PT J AU Tawil, R McDermott, MP Brown, R Shapiro, BC Ptacek, LJ McManis, PG Dalakas, MC Spector, SA Mendell, JR Hahn, AF Griggs, RC AF Tawil, R McDermott, MP Brown, R Shapiro, BC Ptacek, LJ McManis, PG Dalakas, MC Spector, SA Mendell, JR Hahn, AF Griggs, RC CA Working Grp Period Paralysis TI Randomized trials of dichlorphenamide in the periodic paralyses SO ANNALS OF NEUROLOGY LA English DT Article ID WEAKNESS AB Although the carbonic anhydrase inhibitors have been used in the treatment of the primary periodic paralyses (PPs), their efficacy has not been demonstrated in double-blind, placebo-controlled trials. Therefore, we tested the efficacy of dichlorphenamide (DCP; Daranide), a potent carbonic anhydrase inhibitor, in the treatment of episodic weakness in the primary PPs. We performed two multicenter, randomized, double-blind, placebo-controlled crossover trials, one involving 42 subjects with hypokalemic periodic paralysis (HypoPP) and the other involving 31 subjects with potassium-sensitive periodic paralysis (PSPP). In each trial, two 8-week treatment periods were separated by an active washout period of at least 9 weeks. The primary outcome variable in the HypoPP trial was the occurrence of an intolerable increase in attack severity or frequency (end point). The primary outcome variable in the PSPP trial was the number of attacks per week. In the HypoPP trial, there were 13 subjects who exhibited a preference (in terms of the end point) for either DCP or placebo, and Il of these preferred DCP. In the PSPP trial, DCP significantly reduced attack rates relative to placebo. DCP also significantly reduced attack rates relative to placebo in the HypoPP subjects, We conclude that DCP is effective in the prevention of episodic weakness in both HypoPP and PSPP. C1 Univ Rochester, Rochester, NY 14642 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Utah, Howard Hughes Med Inst, Salt Lake City, UT USA. Mayo Clin, Rochester, MN USA. NINDS, Bethesda, MD 20892 USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Western Ontario, London, ON, Canada. RP Tawil, R (reprint author), Univ Rochester, POB 673,601 Elmwood Ave, Rochester, NY 14642 USA. FU NCRR NIH HHS [M01-RR00044, M01-RR00585, M01-RR00034] NR 16 TC 77 Z9 80 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2000 VL 47 IS 1 BP 46 EP 53 DI 10.1002/1531-8249(200001)47:1<46::AID-ANA9>3.0.CO;2-H PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 272ED UT WOS:000084636800008 PM 10632100 ER PT J AU Harris, NL Jaffe, ES Diebold, J Flandrin, G Muller-Hermelink, HK Vardiman, J AF Harris, NL Jaffe, ES Diebold, J Flandrin, G Muller-Hermelink, HK Vardiman, J TI Lymphoma classification - from controversy to consensus: The REAL and WHO Classification of lymphoid neoplasms SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT International Conference on Malignant Lymphoma CY JUN 02-05, 1999 CL LUGANO, SWITZERLAND DE classification; lymphoma; pathology AB Background: Controversy in lymphoma classification dates back to the first attempts to formulate such classifications. Over the years, much of this controversy arose from the assumption that there had to be a single guiding principle - a 'gold standard - for classification, and from the existence of multiple different classifications. Design: The International Lymphoma Study Group (I.L.S.G.) developed a consensus list of lymphoid neoplasms, which was published in 1994 as the 'Revised European-American Classification of Lymphoid Neoplasms' (R.E.A.L.). The classification is based on the principle that a classification is a list of 'real' disease entities, which are defined by a combination of morphology, immunophenotype. genetic features, and clinical features. The relative importance of each of these features varies among diseases, and there is no one gold standard. In some tumors morphology is paramount, in others it is immunophenotype, a specific genetic abnormality, or clinical features. An international study of 1300 patients, supported by the San Salvatore Foundation, was conducted to determine whether the R.E.A.L. Classification could be used by expert pathologists and had clinical relevance. Since 1995, the European Association of Pathologists (EAHP) and the Society for Hematopathology (SH) have been developing a new World Health Organization (WHO) Classification of hematologic malignancies, using an updated R.E.A.L. Classification for lymphomas and applying the principles of the R.E.A.L. Classification to myeloid and histiocytic neoplasms. A Clinical Advisory Committee (CAC) was formed to ensure that the WHO Classification will be useful to clinicians. Results: The International Lymphoma Study showed that the R.E.A.L. Classification could be used by pathologists, with inter-observer reproducibility better than for other classifications (> 85%), Immunophenotyping was helpful in some diagnoses, but not required for many others. New entities not specifically recognized in the Working Formulation accounted for 27% of the cases. Diseases that would have been lumped together as 'low grade' or 'intermediate/high grade' in the Working Formulation showed marked differences in survival, confirming that they need to be treated as distinct entities, Clinical features such as the international Prognostic Index were also important in determining patient outcome. The WHO Clinical Advisory Committee concluded that clinical groupings of lymphoid neoplasms was neither necessary nor desirable. Patient treatment is determined by the specific type of lymphoma. with the addition of grade within the turner type, if applicable, and clinical prognostic factors such as the international Prognostic Index (IPI). Conclusions: The experience of developing the WHO Classification has produced a neu; and exciting degree of cooperation and communication between oncologists and pathologists from around the world, which should facilitate progress in the understanding and treatment of hematologic malignancies. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pathol Labs, Boston, MA 02114 USA. Natl Canc Inst, Dept Pathol, Bethesda, MD USA. Hotel Dieu, Dept Pathol, Paris, France. Hop Necker Enfants Malad, Dept Pathol, Paris, France. Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany. Univ Chicago, Pritzker Sch Med, Dept Pathol, Chicago, IL 60637 USA. RP Harris, NL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pathol Labs, Warren 2,Fruit St, Boston, MA 02114 USA. NR 18 TC 187 Z9 205 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2000 VL 11 SU 1 BP 3 EP 10 DI 10.1023/A:1008383406103 PG 8 WC Oncology SC Oncology GA 293YL UT WOS:000085882800002 PM 10707771 ER PT J AU Batist, G Winer, E Chan, S Jain, D Lee, L Azarnia, N AF Batist, G Winer, E Chan, S Jain, D Lee, L Azarnia, N TI Randomized phase III trials of Myocet (liposome-encapsulated doxorubicin) vs. doxorubicin or epirubicin in first-line treatment of metastatic breast cancer. SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Yale Univ, New Haven, CT USA. Liposome Co, Princeton, NJ USA. City Hosp Nottingham, Nottingham, England. Dana Farber Canc Inst, Boston, MA 02115 USA. McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. NR 0 TC 0 Z9 0 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2000 VL 11 SU 4 MA 103O BP 26 EP 26 PG 1 WC Oncology SC Oncology GA 357LV UT WOS:000089503900105 ER PT J AU Miller, KD Picus, J Blanke, C John, W Clark, J Shulman, LN Thornton, D Rowinsky, E Loehrer, PJ AF Miller, KD Picus, J Blanke, C John, W Clark, J Shulman, LN Thornton, D Rowinsky, E Loehrer, PJ TI Phase II study of the multitargeted antifolate LY231514 (ALIMTA (TM), MTA, pemetrexed disodium) in patients with advanced pancreatic cancer SO ANNALS OF ONCOLOGY LA English DT Article DE antifolate; chemotherapy; pancreatic cancer; thymidylate synthase inhibitor AB Purpose: To determine the safety and activity of LY231514 (ALIMTA(TM), MTA, pemetrexed disodium, Eli Lilly and Co., Indianapolis, IN) in chemotherapy-naive patients with advanced pancreatic cancer. Patients and methods: Patients with unresectable or metastatic pancreatic cancer received LY231514 600 mg/m(2) as a 10-minute infusion every three weeks. Results: Forty-two patients were enrolled in this phase II trial. The median age was 60.3 (range 37-77) years; 79% had metastatic disease. Neutropenia was common (40% of patients greater than or equal to grade 3) but infectious complications were rare. Significant anemia or thrombocytopenia occurred in < 20% of patients. Non-hematologic toxicities included grade 2 or 3 skin reaction which was ameliorated by dexamethasone. Elevations of bilirubin or transaminases were infrequent (< 25% of patients) and did not require dose reductions or treatment delays. Thirty-five patients received two cycles of therapy and were evaluable for response. One complete (duration 16.2 months) and one partial (duration 6.9 months) were observed resulting in an objective response rate of 5.7% for evaluable patients. In addition, 17 patients (40%) had stable disease that lasted greater than or equal to 6 months in 5 patients. The median survival was 6.5 months, with 28% of patients alive at one year. Conclusions: LY231514 is a well-tolerated agent with minimal objective antitumor activity in pancreatic cancer. The median and one year survival times, which may be important indicators in phase II trials of new agents, are of interest. Combination trials of LY231514 in pancreatic cancer are planned. C1 Indiana Univ, Indianapolis, IN 46204 USA. Washington Univ, St Louis, MO USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ Kentucky, Lexington, KY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. RP Miller, KD (reprint author), Indiana Canc Pavil, 535 Barnhill Dr RT-473, Indianapolis, IN 46202 USA. NR 7 TC 64 Z9 69 U1 2 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 2000 VL 11 IS 1 BP 101 EP 103 DI 10.1023/A:1008305205159 PG 3 WC Oncology SC Oncology GA 281ZK UT WOS:000085191200022 PM 10690396 ER PT J AU Treon, SP Shima, Y Grossbard, ML Preffer, FI Belch, AR Pilarski, LM Anderson, KC AF Treon, SP Shima, Y Grossbard, ML Preffer, FI Belch, AR Pilarski, LM Anderson, KC TI Treatment of multiple myeloma by antibody mediated immunotherapy and induction of myeloma selective antigens SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT International Conference on Malignant Lymphoma CY JUN 02-05, 1999 CL LUGANO, SWITZERLAND DE B cells; CD20; core protein; dexamethasone; immunotherapy; interferon-gamma; Muc-1; multiple myeloma; plasma cells; Rituximab ID PHASE-II TRIAL; ANTI-CD20 MONOCLONAL-ANTIBODY; HUMAN INTERFERON-GAMMA; MARROW PLASMA-CELLS; B-CELLS; UP-REGULATION; IN-VIVO; EXPRESSION; MUCIN; LYMPHOMA AB Background: In view of the successful use of serotherapy in many B-cell malignancies, we and others have sought to identify tumor selective antigens for the serotherapy of plasma cell dyscrasias (PCD) including multiple myeloma (MM), and Waldenstrom's macroglobulinemia (WM). We recently identified Muc-1 core protein as a MM selective antigen. Though Muc-1 core protein is abundantly expressed on most MM plasma cells, expression of this antigen can be absent, or weak on some plasma cells which could potentially result in the selection of Muc-1 core protein negative clones following serotherapy of PCD. In addition to Muc-1 core protein, we have also been examining the use of CD20 directed serotherapy for PCD. Design: As part of these efforts, we recently initiated a phase II clinical trial examining the use of Rituximab (Rituxan, MabThera) as a single agent in MM patients; as well several WM patients have been treated with Rituximab at our Institutions. Results: In previous studies, we have shown that CD20 is abundantly expressed on the plasma cells of most WM patients; in contrast, CD20 is expressed on plasma cells from a minority of MM patients, and in these patients expression of CD20 can be weak or heterogeneous with both CD20+ and CD20- plasma cells present. As such, we have sought out clinically useful inducers of Muc-1 core protein, and of CD20 on malignant plasma cells. Conclusions: These efforts resulted in the identification of dexamethasone (Dex) as a potent inducer of Muc-1 core protein on MM plasma cells, and interferon-gamma (IFN-gamma) as a potent inducer of CD20 on MM plasma cells and B-cells. Importantly, these agents induced their respective antigens at pharmacologically achievable doses. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Alberta, Cross Canc Inst, Edmonton, AB, Canada. RP Treon, SP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 52 TC 32 Z9 36 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2000 VL 11 SU 1 BP 107 EP 111 DI 10.1023/A:1008377727061 PG 5 WC Oncology SC Oncology GA 293YL UT WOS:000085882800021 PM 10707790 ER PT J AU Demetri, G Garcia-Carbonero, R Harmon, D Seiden, M Jimeno, J Merriam, P Waxman, A Supko, J Quigley, MT Ryan, D AF Demetri, G Garcia-Carbonero, R Harmon, D Seiden, M Jimeno, J Merriam, P Waxman, A Supko, J Quigley, MT Ryan, D TI Ecteinascidin-743 (ET-743) induces objective responses and disease control in patients with advanced non-osseous sarcomas: Results from phase II trials. SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 PharmaMar Inc, Madrid, Spain. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI IBIS, NUEVAS TERAPIA/P-3415-2015 NR 0 TC 1 Z9 1 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2000 VL 11 SU 4 MA 573O BP 126 EP 126 PG 1 WC Oncology SC Oncology GA 357LV UT WOS:000089503900574 ER PT J AU Crawford, J Glaspy, JA Demetri, GD AF Crawford, J Glaspy, JA Demetri, GD TI Epoetin alfa improves hematologic parameters and quality of life (QOL) in lung cancer patients. SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract ID COMMUNITY ONCOLOGY; CHEMOTHERAPY C1 Duke Univ, Med Ctr, Durham, NC USA. Univ Calif Los Angeles, Los Angeles, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2000 VL 11 SU 4 MA 685P BP 149 EP 150 PG 2 WC Oncology SC Oncology GA 357LV UT WOS:000089503900687 ER PT J AU Alpay, M Cassem, EH AF Alpay, M Cassem, EH TI Diagnosis and treatment of mood disorders in patients with rheumatic disease SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; DEPRESSIVE SYMPTOMS; ARTHRITIS PATIENTS; PREVALENCE C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Alpay, M (reprint author), Massachusetts Gen Hosp, Warren 604,Fruit St, Boston, MA 02114 USA. NR 16 TC 2 Z9 6 U1 1 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JAN PY 2000 VL 59 IS 1 BP 2 EP 4 DI 10.1136/ard.59.1.2 PG 3 WC Rheumatology SC Rheumatology GA 275KL UT WOS:000084819300003 PM 10627418 ER PT J AU Kirchhausen, T AF Kirchhausen, T TI Clathrin SO ANNUAL REVIEW OF BIOCHEMISTRY LA English DT Review DE membrane traffic; coated vesicles; protein sorting; endocytosis; secretion; adaptors; arrestin ID COATED-VESICLE FORMATION; RECEPTOR-MEDIATED ENDOCYTOSIS; PLECKSTRIN HOMOLOGY DOMAIN; HEAVY-CHAIN GENE; ANGSTROM CRYSTAL-STRUCTURE; ASSEMBLY PROTEIN AP-3; LIGHT-CHAINS; BINDING-SITE; SYNAPTIC VESICLES; PLASMA-MEMBRANE AB Clathrin was discovered nearly 25 years ago, Since then, a large number of other proteins that participate in the process by which clathrin-coated vesicles retrieve synaptic membranes or take up endocytic receptors have been identified. The functional relationships among these disparate components remain, in many cases, obscure. High-resolution structures of parts of clathrin, determined by X-ray crystallography, and lower-resolution images of assembled coats, determined by electron cryomicroscopy, now provide the information necessary to integrate various lines of evidence and to design experiments that test specific mechanistic notions. This review summarizes and illustrates the recent structural results and outlines what is known about coated-vesicle assembly in the context of this information. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. NR 146 TC 402 Z9 407 U1 3 U2 23 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4154 J9 ANNU REV BIOCHEM JI Annu. Rev. Biochem. PY 2000 VL 69 BP 699 EP 727 DI 10.1146/annurev.biochem.69.1.699 PG 29 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 361QZ UT WOS:000089735700023 PM 10966473 ER PT J AU Folch, A Toner, M AF Folch, A Toner, M TI Microengineering of cellular interactions SO ANNUAL REVIEW OF BIOMEDICAL ENGINEERING LA English DT Review DE cellular patterns; micropatterning; cell-cell interactions; cellular microdevices; lithography ID SELF-ASSEMBLED MONOLAYERS; COVALENTLY IMMOBILIZED INSULIN; TRANSMEMBRANE VOLTAGE MSORTV; PATTERNED SURFACE-CHEMISTRY; CAPILLARY ENDOTHELIAL-CELLS; BOVINE SERUM-ALBUMIN; GROWTH CONE GUIDANCE; DRY LIFT-OFF; MICROPATTERNED SURFACES; HIPPOCAMPAL-NEURONS AB Tissue function is modulated by an intricate architecture of cells and biomolecules on a micrometer scale. Until now, in vitro cellular interactions were mainly studied by random seeding over homogeneous substrates. Although this strategy has led to important discoveries, it is clearly a nonoptimal analog of the in vivo scenario. With the incorporation-and adaptation-of microfabrication technology into biology, it is now possible to design surfaces that reproduce some of the aspects of that architecture. This article reviews past research on the engineering of cell-substrate, cell-cell, and cell-medium interactions on the micrometer scale. C1 Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Serv, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA 02114 USA. RP Folch, A (reprint author), Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. NR 212 TC 438 Z9 450 U1 7 U2 80 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1523-9829 J9 ANNU REV BIOMED ENG JI Annu. Rev. Biomed. Eng. PY 2000 VL 2 BP 227 EP + DI 10.1146/annurev.bioeng.2.1.227 PG 37 WC Engineering, Biomedical SC Engineering GA 364HR UT WOS:000089887400009 PM 11701512 ER PT J AU Rosen, ED Spiegelman, BM AF Rosen, ED Spiegelman, BM TI Molecular regulation of adipogenesis SO ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY LA English DT Review DE white adipose tissue; brown adipose tissue; differentiation; adipogenesis ID ACTIVATED RECEPTOR-GAMMA; ENHANCER-BINDING-PROTEIN; TUMOR-NECROSIS-FACTOR; BROWN ADIPOSE-TISSUE; 3T3-L1 ADIPOCYTE DIFFERENTIATION; EPIDERMAL GROWTH-FACTOR; NUCLEAR HORMONE RECEPTORS; RETINOID-X-RECEPTOR; PPAR-GAMMA; GENE-EXPRESSION AB Adipogenesis, or the development of fat cells from preadipocytes, has been one of the most intensely studied models of cellular differentiation. In part this has been because of the availability of in vitro models that faithfully recapitulate most of the critical aspects of fat cell formation in vivo. More recently, studies of adipogenesis have proceeded with the hope that manipulation of this process in humans might one day lead to a reduction in the burden of obesity and diabetes. This review explores some of the highlights of a large and burgeoning literature devoted to understanding adipogenesis at the molecular level. The hormonal and transcriptional control of adipogenesis is reviewed, as well as studies on a less well known type of fat cell, the brown adipocyte. Emphasis is placed, where possible, on in vivo studies with the hope that the results discussed may one day shed light on basic questions of cellular growth and differentiation in addition to possible benefits in human health. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. RP Rosen, ED (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK54477, K08 DK02535, R37DK31405] NR 167 TC 795 Z9 828 U1 10 U2 87 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1081-0706 J9 ANNU REV CELL DEV BI JI Annu. Rev. Cell Dev. Biol. PY 2000 VL 16 BP 145 EP 171 DI 10.1146/annurev.cellbio.16.1.145 PG 31 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 385NH UT WOS:000166010200007 PM 11031233 ER PT J AU Olsen, BR Reginato, AM Wang, WF AF Olsen, BR Reginato, AM Wang, WF TI Bone development SO ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY LA English DT Review DE patterning; chondrogenesis; ossification; growth plate; joints ID MULTIPLE EPIPHYSEAL DYSPLASIA; GROWTH-FACTOR RECEPTOR-3; AUTOSOMAL SEX REVERSAL; SRY-RELATED GENE; T-BOX GENES; SCHMID METAPHYSEAL CHONDRODYSPLASIA; DOMINANT-NEGATIVE MUTATION; TRANSCRIPTION FACTOR AP-2; SAETHRE-CHOTZEN SYNDROME; APICAL ECTODERMAL RIDGE AB Early development of the vertebrate skeleton depends on genes that pattern the distribution and proliferation of cells from cranial neural crest, sclerotomes, and lateral plate mesoderm into mesenchymal condensations at sites of future skeletal elements. Within these condensations, cells differentiate to chondrocytes or osteoblasts and form cartilages and bones under the control of various transcription factors. In most of the skeleton, organogenesis results in cartilage models of future bones; in these models cartilage is replaced by bone by the process of endochondral ossification. Lastly, through a controlled process of bone growth and remodeling the final skeleton is shaped and molded. Significant and exciting insights into all aspects of vertebrate skeletal development have been obtained through molecular and genetic studies of animal models and humans with inherited disorders of skeletal morphogenesis, organogenesis, and growth. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Arthrit Unit, Boston, MA 02114 USA. RP Olsen, BR (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. EM bjorn_olsen@hms.harvard.edu; reginato_anthony@mgh.harvard.edu; wenfang_wang@hms.harvard.edu NR 208 TC 510 Z9 527 U1 11 U2 68 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1081-0706 J9 ANNU REV CELL DEV BI JI Annu. Rev. Cell Dev. Biol. PY 2000 VL 16 BP 191 EP 220 DI 10.1146/annurev.cellbio.16.1.191 PG 30 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 385NH UT WOS:000166010200009 PM 11031235 ER PT J AU Fearon, DT Carroll, MC AF Fearon, DT Carroll, MC TI Regulation of B lymphocyte responses to foreign and self-antigens by the CD19/CD21 complex SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE signal transduction; tolerance; costimulation; innate immunity; complement ID EPSTEIN-BARR-VIRUS; RECEPTOR-MEDIATED ACTIVATION; SIGNAL-TRANSDUCTION MOLECULE; FOLLICULAR DENDRITIC CELLS; BRUTONS TYROSINE KINASE; HUMORAL IMMUNE-RESPONSE; T-DEPENDENT ANTIGEN; MONOCLONAL-ANTIBODY; GERMINAL-CENTERS; PHOSPHATIDYLINOSITOL 3-KINASE AB The membrane protein complex CD19/CD21 couples the innate immune recognition of microbial antigens by the complement system to the activation of B cells. CD21 binds the C3d fragment of activated C3 that becomes covalently attached to targets of complement activation, and CD19 co-stimulates signaling through the antigen receptor, membrane immunoglobulin. CD21 is also expressed by follicular dendritic cells and mediates the long-term retention of antigen that is required for the maintenance of memory B cells. Understanding of the biology of this receptor complex has been enriched by analyses of genetically modified mice; these analyses have uncovered roles not only in positive responses to foreign antigens, but also in the development of tolerance to self-antigens. Studies of signal transduction have begun to determine the basis for the coreceptor activities of CD 19. The integration of innate and adaptive immune recognition at this molecular site on the B cell guides the appropriate selection of antigen by adaptive immunity and emphasizes the importance of this coreceptor complex. C1 Univ Cambridge, Sch Clin Med, Dept Med, Wellcome Trust Immunol Unit, Cambridge, England. Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02115 USA. RP Fearon, DT (reprint author), Univ Cambridge, Sch Clin Med, Dept Med, Wellcome Trust Immunol Unit, Cambridge, England. NR 131 TC 338 Z9 345 U1 2 U2 11 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2000 VL 18 BP 393 EP 422 DI 10.1146/annurev.immunol.18.1.393 PG 30 WC Immunology SC Immunology GA 317PX UT WOS:000087236500015 PM 10837064 ER PT J AU Schulz, JT Tompkins, RG Burke, JF AF Schulz, JT Tompkins, RG Burke, JF TI Artificial skin SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE skin structure; skin grafting; burn surgery; dermal replacement; tissue regeneration ID DIABETIC FOOT ULCERS; FULL-THICKNESS; BURN INJURIES; KERATINOCYTES; EQUIVALENT; MANAGEMENT; MORTALITY; EXCISION; CHILDREN; DESIGN AB The skin is a complex organ that is difficult to replace when it is irreversibly damaged by burns, trauma, or disease. Although autologous skin transplantation remains the most common form of treatment in patients with significant skin loss, there are now a number of commercially available products that can be used to replace the skin temporarily or permanently. Here we describe several such products under the rubric "artificial skin," focusing on two types of technology that have been applied to the problem of permanent skin replacement. C1 Massachusetts Gen Hosp, Div Burns & Trauma, Surg Serv, Boston, MA 02114 USA. RP Schulz, JT (reprint author), Massachusetts Gen Hosp, Div Burns & Trauma, Surg Serv, Boston, MA 02114 USA. NR 35 TC 48 Z9 54 U1 7 U2 21 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2000 VL 51 BP 231 EP 244 DI 10.1146/annurev.med.51.1.231 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 301ZE UT WOS:000086339800014 PM 10774462 ER PT J AU Masland, RH Raviola, E AF Masland, RH Raviola, E TI Confronting complexity: Strategies for understanding the microcircuitry of the retina SO ANNUAL REVIEW OF NEUROSCIENCE LA English DT Review DE anatomy; electrophysiology; molecular neurobiology; transgenes ID TIGER SALAMANDER RETINA; GREEN FLUORESCENT PROTEIN; ROD BIPOLAR CELLS; MEDIATED GENE-TRANSFER; MIDGET GANGLION-CELLS; MACAQUE MONKEY RETINA; RECOMBINANT ADENOASSOCIATED VIRUS; C-LIKE IMMUNOREACTIVITY; BEARING AMACRINE CELLS; AMINO-ACID SIGNATURES AB The mammalian retina contains upward of 50 distinct functional elements, each carrying out a specific task. Such diversity is not rare in the central nervous system, but the retina is privileged because its physical location, the distinctive morphology of its neurons, the regularity of its architecture, and the accessibility of its inputs and outputs permit a unique variety of experiments. Recent strategies for confronting the retina's complexity attempt to marry genetic approaches to new kinds of anatomical and electrophysiological techniques. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Masland, RH (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. NR 184 TC 64 Z9 65 U1 1 U2 1 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0147-006X J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 2000 VL 23 BP 249 EP 284 DI 10.1146/annurev.neuro.23.1.249 PG 36 WC Neurosciences SC Neurosciences & Neurology GA 308UD UT WOS:000086730500009 PM 10845065 ER PT J AU Sheng, M Pak, DTS AF Sheng, M Pak, DTS TI Ligand-gated ion channel interactions with cytoskeletal and signaling proteins SO ANNUAL REVIEW OF PHYSIOLOGY LA English DT Review DE NMDA receptors; AMPA receptors; GABA receptors; PDZ domains; scaffold protein ID D-ASPARTATE RECEPTOR; POSTSYNAPTIC DENSITY PROTEIN; LONG-TERM POTENTIATION; TUMOR-SUPPRESSOR PROTEIN; KINASE-ASSOCIATED PROTEIN; DOMAIN-CONTAINING PROTEIN; NITRIC-OXIDE SYNTHASE; NMDA RECEPTOR; PDZ-DOMAIN; AMPA RECEPTORS AB In recent years, it has become apparent that ligand-gated ion channels (ionotropic receptors) in the neuronal plasma membrane interact via their cytoplasmic domains with a multitude of intracellular proteins. Different classes of ligand-gated channels associate with distinct sets of intracellular proteins, often through specialized scaffold proteins containing PDZ domains. These specific interactions link the receptor channel to the cortical cytoskeleton and to appropriate signal transduction pathways in the cell. Thus ionotropic receptors are components of extensive protein complexes that are likely involved in the subcellular targeting, cytoskeletal anchoring, and localized clustering of the receptors at specific sites on the neuronal surface. In addition to structural functions, receptor-associated proteins can play important roles as activity modulators or downstream effecters of ligand-gated channels. C1 Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sheng, M (reprint author), Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. NR 123 TC 262 Z9 267 U1 1 U2 5 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4278 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 2000 VL 62 BP 755 EP 778 DI 10.1146/annurev.physiol.62.1.755 PG 24 WC Physiology SC Physiology GA 341KF UT WOS:000088589000030 PM 10845110 ER PT J AU McNicholl, JM Downer, MV Udhayakumar, V Alper, CA Swerdlow, DL AF McNicholl, JM Downer, MV Udhayakumar, V Alper, CA Swerdlow, DL TI Host-pathogen interactions in emerging and re-emerging infectious diseases: A genomic perspective of tuberculosis, malaria, human immunodeficiency virus infection, hepatitis B, and cholera SO ANNUAL REVIEW OF PUBLIC HEALTH LA English DT Review DE gene; polymorphism; susceptibility; resistance; vaccines ID TUMOR-NECROSIS-FACTOR; CHEMOKINE RECEPTOR GENE; MANNOSE-BINDING LECTIN; PULMONARY TUBERCULOSIS; CEREBRAL MALARIA; HIV-1 INFECTION; BLOOD-GROUP; PROMOTER REGION; OLIGONUCLEOTIDE HYBRIDIZATION; MYCOBACTERIUM-TUBERCULOSIS AB On exposure to a pathogen, a host may resist infection, become subclinically infected, or progress through several stages from mild to severe infection. Chronic sequelae may or may not occur. Host factors, particularly host genes, influence many of these stages. We have used a model of the continuum of pathogenesis of infectious diseases to consider the effect of host genes on five pathogens of significant public health burden: Mycobacterium tuberculosis, Plasmodium species, human immunodeficiency virus, hepatitis B virus, and Vibrio cholerae. The relationships between these infections and polymorphisms in human leukocyte antigen, cytokines, other immune response, or pathogen receptor genes are reviewed. We discuss gene-gene interactions and their effects in complex settings, such as coinfections with several pathogens. Priorities for prevention and control of these pathogens include vaccines and antimicrobial drugs. Research on how host genes can influence vaccine responses and the efficacy of drugs or other interventions, as well as further research into the relationship of host genes to infectious disease outcomes, may lead to new strategies for prevention and control. C1 Ctr Dis Control, Natl Ctr Infect Dis, Div AIDS STD & TB Lab Res, Atlanta, GA 30333 USA. Ctr Dis Control, Natl Ctr Infect Dis, Div Parasit Dis, Atlanta, GA 30333 USA. Ctr Dis Control, Natl Ctr Infect Dis, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. Ctr Blood Res Inc, Boston, MA 02115 USA. RP McNicholl, JM (reprint author), Ctr Dis Control, Natl Ctr Infect Dis, Div AIDS STD & TB Lab Res, Atlanta, GA 30333 USA. NR 149 TC 35 Z9 38 U1 2 U2 3 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0163-7525 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 2000 VL 21 BP 15 EP 46 DI 10.1146/annurev.publhealth.21.1.15 PG 32 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 329RJ UT WOS:000087921400003 PM 10884944 ER PT J AU Dagan, R Leibovitz, E Fliss, DM Leiberman, A Jacobs, MR Craig, W Yagupsky, P AF Dagan, R Leibovitz, E Fliss, DM Leiberman, A Jacobs, MR Craig, W Yagupsky, P TI Bacteriologic efficacies of oral azithromycin and oral cefaclor in treatment of acute otitis media in infants and young children SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MIDDLE-EAR FLUID; STREPTOCOCCUS-PNEUMONIAE; ANTIMICROBIAL RESISTANCE; PEDIATRIC-PATIENTS; CLINICAL EFFICACY; SENSITIVITY TEST; ANTIBIOTICS; ERYTHROMYCIN; MULTICENTER; CEFIXIME AB A prospective, open-label, randomized study was conducted in order to determine the bacteriologic efficacies of cefaclor and azithromycin in acute otitis media (AOM). Tympanocentesis was performed on entry into the study and 3 to 4 days after initiation of treatment. Bacteriologic failure after 3 to 4 days of treatment with both drugs occurred in a high proportion of culture-positive patients, especially in those in whom AOM was caused by Haemophilus influenzae (16 of 33 [53%] of those treated with azithromycin and 13 of 34 [52%] of those treated with cefaclor). Although a clear correlation of the persistence of the pathogen with increased MICs of the respective drugs could be demonstrated for Streptococcus pneumoniae, no such correlation was found for E-I. influenzae. It is proposed that susceptibility breakpoints for H. influenzae should be considerably lower than the current ones for both cefaclor and azithromycin for AOM caused by H. influenzae. C1 Soroka Univ, Med Ctr, Pediat Infect Dis Unit, IL-84101 Beer Sheva, Israel. Soroka Univ, Med Ctr, Dept Otolaryngol, IL-84101 Beer Sheva, Israel. Soroka Univ, Med Ctr, Clin Microbiol Lab, IL-84101 Beer Sheva, Israel. Ben Gurion Univ Negev, Fac Hlth Sci, IL-84101 Beer Sheva, Israel. Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. Univ Wisconsin, Dept Med, Madison, WI USA. William S Middleton Mem Vet Hosp, Madison, WI USA. RP Dagan, R (reprint author), Soroka Univ, Med Ctr, Pediat Infect Dis Unit, POB 151, IL-84101 Beer Sheva, Israel. NR 47 TC 105 Z9 106 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 2000 VL 44 IS 1 BP 43 EP 50 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 266EN UT WOS:000084287800008 PM 10602721 ER PT J AU Barchiesi, F Arzeni, D Fothergill, AW Di Francesco, LF Caselli, F Rinaldi, MG Scalise, G AF Barchiesi, F Arzeni, D Fothergill, AW Di Francesco, LF Caselli, F Rinaldi, MG Scalise, G TI In vitro activities of the new antifungal triazole SCH 56592 against common and emerging yeast pathogens SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IN-VITRO; CRYPTOCOCCUS-NEOFORMANS; CANDIDA-ALBICANS; SCH-56592; ITRACONAZOLE; ASPERGILLOSIS; SCH56592; THERAPY AB A broth microdilution method performed in accordance with the National Committee for Clinical Laboratory Standards guidelines was used to compare the in vitro activity of the new antifungal triazole SCH 56592 (SCH) to that of fluconazole (FLC), itraconazole (ITC), and ketoconazole (KETO) against 257 clinical yeast isolates. They included 220 isolates belonging to 12 different species of Candida, 15 isolates each of Cryptococcus neoformans and Saccharomyces cerevisiae, and seven isolates of Rhodotorula rubra. The MICs of SCH at which 50% (MIC50) and 90% (MIC90) of the isolates were inhibited were 0.06 and 2.0 mu g/ml, respectively. In general, SCH was considerably more active than FLC (MIC50 and MIC90 of 1.0 and 64 mu g/ml, respectively) and slightly more active than either ITC (MIC50 and MIC90 of 0.25 and 2.0 mu g/ml, respectively) and KETO (MIC50 and MIC90 of 0.125 and 4.0 mu g/ml, respectively). Our in vitro data suggest that SCH has significant potential for clinical development. C1 Univ Ancona, Ist Malattie Infett & Med Pubbl, Ancona, Italy. Univ Texas, Hlth Sci Ctr, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Barchiesi, F (reprint author), Univ Ancona, Ist Malattie Infect & Med Pubbl, Osped Umberto 1, Largo Cappelli 1, I-60121 Ancona, Italy. NR 14 TC 56 Z9 58 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 2000 VL 44 IS 1 BP 226 EP 229 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 266EN UT WOS:000084287800044 PM 10602757 ER PT S AU Sachdev, D Chirgwin, JM AF Sachdev, D Chirgwin, JM BE Thorner, J Emr, SD Abelson, JN TI Fusions to maltose-binding protein: Control of folding and solubility in protein purification SO APPLICATIONS OF CHIMERIC GENES AND HYBRID PROTEINS, PT A: GENE EXPRESSION AND PROTEIN PURIFICATION SE Methods in Enzymology LA English DT Review ID GLUTATHIONE-S-TRANSFERASE; SINGLE-STEP PURIFICATION; ESCHERICHIA-COLI; INCLUSION-BODIES; IN-VITRO; ASPARTIC PROTEINASES; PROCATHEPSIN-D; EXPRESSION; POLYPEPTIDES; THIOREDOXIN C1 Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. Univ Texas, Hlth Sci Ctr, Res Serv, Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78229 USA. RP Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. NR 38 TC 47 Z9 49 U1 0 U2 12 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182227-3 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2000 VL 326 BP 312 EP 321 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BR04M UT WOS:000165500400020 PM 11036650 ER PT J AU Krebber, H Silver, PA AF Krebber, H Silver, PA TI Directing proteins to nucleus by fusion to nuclear localization signal tags SO APPLICATIONS OF CHIMERIC GENES AND HYBRID PROTEINS PT B SE METHODS IN ENZYMOLOGY LA English DT Review ID RNA-BINDING-PROTEIN; NUCLEOCYTOPLASMIC TRANSPORT; IMPORT PATHWAY; HNRNP A1; SACCHAROMYCES-CEREVISIAE; RIBOSOMAL-PROTEINS; MAMMALIAN-CELLS; BASIC REGION; T-ANTIGEN; EXPORT C1 Univ Marburg, Inst Mol Biol & Tumorforsch, D-35033 Marburg, Germany. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Krebber, H (reprint author), Univ Marburg, Inst Mol Biol & Tumorforsch, Emil Mannkopff Str 2, D-35033 Marburg, Germany. NR 53 TC 4 Z9 4 U1 2 U2 6 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 2000 VL 327 BP 283 EP 296 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BR04N UT WOS:000165500500022 PM 11044991 ER PT J AU Endoh, H Walhout, AJM Vidal, M AF Endoh, H Walhout, AJM Vidal, M TI A green fluorescent protein-based reverse two-hybrid system: Application to the characterization of large numbers of potential protein-protein interactions SO APPLICATIONS OF CHIMERIC GENES AND HYBRID PROTEINS, PT C SE METHODS IN ENZYMOLOGY LA English DT Review ID SACCHAROMYCES-CEREVISIAE; EXPRESSION PATTERNS; 2-HYBRID SYSTEM; YEAST; GENOME; RECEPTOR; DOMAIN; MAP C1 MGH, Oncol Mol Lab, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Endoh, H (reprint author), MGH, Oncol Mol Lab, Ctr Canc, Charlestown, MA 02129 USA. OI Walhout, Marian/0000-0001-5587-3608 FU NCI NIH HHS [1 R21 CA81658A01]; NHGRI NIH HHS [1 RO1 HG01715-01] NR 21 TC 12 Z9 12 U1 0 U2 3 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 2000 VL 328 BP 74 EP 88 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BR47D UT WOS:000166565300006 PM 11075339 ER PT S AU Walhout, AJM Temple, GF Brasch, MA Hartley, JL Lorson, MA van den Heuvel, S Vidal, M AF Walhout, AJM Temple, GF Brasch, MA Hartley, JL Lorson, MA van den Heuvel, S Vidal, M BE Thorner, J Emr, SD Abelson, JN TI GATEWAY recombinational cloning: Application to the cloning of large numbers of open reading frames or ORFeomes SO APPLICATIONS OF CHIMERIC GENES AND HYBRID PROTEINS, PT C: PROTEIN-PROTEIN INTERACTIONS AND GENOMICS SE Methods in Enzymology LA English DT Review ID ELEGANS VULVAR INDUCTION; COMPLETE GENOME SEQUENCE; CAENORHABDITIS-ELEGANS; TRANSCRIPTIONAL PROGRAM; GENE-EXPRESSION; DNA; YEAST; SCALE; ARRAYS; SYSTEM C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Life Technol Inc, Rockville, MD 20850 USA. Massachusetts Gen Hosp, Ctr Canc, Mol Oncol Lab, Charlestown, MA 02129 USA. RP Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI van den Heuvel, Sander/B-8892-2011; OI Walhout, Marian/0000-0001-5587-3608 FU NCI NIH HHS [1 R21 CA81658A01]; NHGRI NIH HHS [1 RO1 HG01715-01] NR 30 TC 406 Z9 429 U1 4 U2 72 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182229-X J9 METHOD ENZYMOL JI Methods Enzymol. PY 2000 VL 328 BP 575 EP 592 PG 20 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BR47D UT WOS:000166565300034 PM 11075367 ER PT J AU Kodama, T Tomita, Y AF Kodama, T Tomita, Y TI Cavitation bubble behavior and bubble-shock wave interaction near a gelatin surface as a study of in vivo bubble dynamics SO APPLIED PHYSICS B-LASERS AND OPTICS LA English DT Article ID OPTICAL-BREAKDOWN; IMPULSIVE PRESSURE; AIR BUBBLES; JET IMPACT; COLLAPSE; LITHOTRIPSY; GENERATION; BOUNDARY; GROWTH; VAPOR AB The collapse of a single cavitation bubble near a gelatin surface, and the interaction of an air bubble attached to a gelatin surface with a shock wave, were investigated. These events permitted the study of the behavior of in vivo cavitation bubbles and the subsequent tissue damage mechanism during intraocular surgery, intracorporeal and extracorporeal shock wave lithotripsy. Results were obtained with high-speed framing photography. The cavitation bubbles near the gelatin surface did not produce significant liquid jets directed at the surface, and tended to migrate away from it. The period of the motion of a cavitation bubble near the gelatin surface was longer than that of twice the Rayleigh's collapse time for a wide range of relative distance, L/R-max, excepting for very small L/R-max values (L was the standoff distance between the gelatin surface and the laser focus position, and R-max was the maximum bubble radius). The interaction of an air bubble with a shock wave yielded a liquid jet inside the bubble, penetrating into the gelatin surface. The liquid jet had the potential to damage the gelatin. The results predicted that cavitation-bubble-induced tissue damage was closely related to the oscillatory bubble motion, the subsequent mechanical tissue displacement, and the liquid jet penetration generated by the interaction of the remaining gas bubbles with subsequent shock waves. The characteristic bubble motion and liquid jet formation depended on the tissue's mechanical properties, resulting in different damage mechanisms from those observed on hard materials. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. Hokkaido Univ Educ, Fac Educ, Hakodate, Hokkaido 0408567, Japan. RP Kodama, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, 55 Fruit St,WEL 224, Boston, MA 02114 USA. OI kodama, tetsuya/0000-0003-4727-9558 NR 54 TC 99 Z9 105 U1 2 U2 33 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0946-2171 J9 APPL PHYS B-LASERS O JI Appl. Phys. B-Lasers Opt. PD JAN PY 2000 VL 70 IS 1 BP 139 EP 149 DI 10.1007/s003400050022 PG 11 WC Optics; Physics, Applied SC Optics; Physics GA 273HF UT WOS:000084701300022 ER PT J AU Sugerman, PB Bigby, M AF Sugerman, PB Bigby, M TI Preliminary functional analysis of human epidermal T cells SO ARCHIVES OF DERMATOLOGICAL RESEARCH LA English DT Article DE epidermal T cells; function; human ID NORMAL HUMAN-SKIN; RECEPTOR-GAMMA-DELTA; HUMAN KERATINOCYTES; THY-1 ANTIGEN; IMMUNE-SYSTEM; LYMPHOCYTES; EXPRESSION; TRANSFORMATION; IL-8 AB The function of human epidermal T cells (ETC) is unknown, In the present study, dermal T cells (DTC), ETC and keratinocytes were cultured from normal human skin, DTC and ETC lines were expanded in medium containing interleukin 2, The autologous keratinocytes were transfected with a human papillomavirus 16 E6 and E7 plasmid to produce an immortal keratinocyte line "HEK001", Lymphocyte migration and adhesion to HEK001 was assessed in calcein fluorimetric assays, ETC migrated towards HEK001 three to four times more than DTC, ETC adhered to HEK001 two to four times more than DTC, The proportion of ETC expressing the cutaneous lymphocyte-associated antigen was greater than that of DTC (26% and 1%, respectively), The keratinocyte line HEK001 expressed ICAM-1 following stimulation with TNF-alpha or IFN-gamma and following coculture with autologous cutaneous T cells, A blocking anti-ICAM-1 antibody reduced DTC and ETC adhesion to HEK001 by 30% and 50%, respectively, Therefore, cutaneous T cells may upregulate keratinocyte ICAM-1 expression which mediates adhesion to autologous keratinocytes. These results are consistent with the hypothesis that the ETC and DTC populations are distinct, Both directed migration (epidermotropism) and selective retention may be involved in the development and maintenance of the ETC population in normal human skin. C1 Univ Queensland, St Lucia, Qld 4072, Australia. Harvard Univ, Sch Med, Dept Dermatol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Sugerman, PB (reprint author), Univ Queensland, St Lucia, Qld 4072, Australia. NR 24 TC 6 Z9 7 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-3696 J9 ARCH DERMATOL RES JI Arch. Dermatol. Res. PD JAN PY 2000 VL 292 IS 1 BP 9 EP 15 DI 10.1007/PL00007461 PG 7 WC Dermatology SC Dermatology GA 279UD UT WOS:000085062800002 PM 10664009 ER PT J AU Greenberg, SM Tennis, MK Brown, LB Gomez-Isla, T Hayden, DL Schoenfeld, DA Walsh, KL Corwin, C Daffner, KR Friedman, P Meadows, ME Sperling, RA Growdon, JH AF Greenberg, SM Tennis, MK Brown, LB Gomez-Isla, T Hayden, DL Schoenfeld, DA Walsh, KL Corwin, C Daffner, KR Friedman, P Meadows, ME Sperling, RA Growdon, JH TI Donepezil therapy in clinical practice - A randomized crossover study SO ARCHIVES OF NEUROLOGY LA English DT Article; Proceedings Paper CT 123rd Annual Meeting of the American-Neurological-Association CY OCT 18-21, 1998 CL MONTREAL, CANADA SP Amer Neurol Assoc ID APOLIPOPROTEIN-E GENOTYPE; PLACEBO-CONTROLLED TRIAL; ALZHEIMERS-DISEASE; DOUBLE-BLIND; CHOLINERGIC SYSTEM; MEMORY; TACRINE; DIAGNOSIS; DEFICITS; IMPROVES AB Objective: To determine the efficacy of donepezil hydrochloride for the treatment of Alzheimer disease in patients drawn from clinical practice. Design: Two-center, randomized, placebo-controlled, double-masked crossover study. Setting: Memory disorders units at Massachusetts General and Brigham and Women's hospitals, Boston. Patients: Sixty individuals (30 men and 30 women; mean +/- SD age, 75.0 +/- 9.5 years) with probable Alzheimer disease and scores of 20 or less on the information-memory-concentration subscale of the Blessed Dementia Scale. Interventions: Placebo wash-in, followed in randomized sequence by (1) donepezil hydrochloride therapy, 5 mg/d, for 6 weeks, followed by placebo washout for 6 weeks and (2) placebo treatment for 6 weeks. Primary Outcome Measure: Change in Alzheimer's Disease Assessment Scale cognitive subscale scores from the beginning to the end of the two 6-week treatment periods. Results: Among patients completing treatment and testing for both periods (n = 48), subscale scores improved (mean +/- SEM) 2.17 +/- 0.98 points (95% confidence interval, 0.20-4.10 points) during donepezil therapy relative to placebo therapy (P = .04). Scores returned toward baseline within 3 weeks of drug washout. There was no associated change in caregiver-rated global impression (donepezil vs placebo: proportion improved, 0.24 vs 0.22; proportion worsened, 0.27 vs 0.35; P = .34) or on specific tests of explicit memory or verbal fluency. Contrary to studies with tacrine, the presence of the apolipoprotein E epsilon 4 allele did not predict donepezil treatment failure. Most common adverse events related to donepezil therapy were nausea (5 patients), diarrhea (3 patients), and agitation (3 patients). Serious events possibly related to drug use were seizure, pancreatitis, and syncope (1 patient each). Conclusion: This independent confirmation of data from phase 3 trials suggests that donepezil therapy modestly improves cognition in patients with Alzheimer disease who are encountered in clinical practice. C1 Massachusetts Gen Hosp, Neurol Clin Trials Unit, Dept Neurol, Partners HealthCare Inc, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Neurol Clin Trials Unit, Dept Neurol, Partners HealthCare Inc, Wang ACC 836, Boston, MA 02114 USA. FU NCRR NIH HHS [MO1-RR01066]; NIA NIH HHS [5P50 AG05134-14] NR 24 TC 117 Z9 123 U1 2 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JAN PY 2000 VL 57 IS 1 BP 94 EP 99 DI 10.1001/archneur.57.1.94 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 272QD UT WOS:000084661700027 PM 10634454 ER PT J AU Tolentino, MJ Husain, D Theodosiadis, P Gragoudas, ES Connolly, E Kahn, J Cleland, J Adamis, AP Cuthbertson, A Miller, JW AF Tolentino, MJ Husain, D Theodosiadis, P Gragoudas, ES Connolly, E Kahn, J Cleland, J Adamis, AP Cuthbertson, A Miller, JW TI Angiography of fluoresceinated anti-vascular endothelial growth factor antibody and dextrans in experimental choroidal neovascularization SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID PROLIFERATIVE DIABETIC-RETINOPATHY; PIGMENT EPITHELIAL-CELLS; RETINAL NEOVASCULARIZATION; MACULAR DEGENERATION; PERMEABILITY FACTOR; PRIMATE MODEL; INHIBITION; EXPRESSION; MEMBRANES; ISCHEMIA AB Objective: To determine if anti-vascular endothelial growth factor antibody and a range of dextrans with varying diffusion radii and molecular weights are permeable through experimental choroidal neovascularization (CNV). Methods: Choroidal neovascularization was induced in 10 cynomolgus monkey retinas by means of argon laser injury. Digital fundus fluorescein angiograms were performed with fluorescein sodium: fluoresceinated IgG antibodies (anti-vascular endothelial growth factor and a control antibody), and fluoresceinated dextrans with molecular weights of 4, 20, 40, 70 and 150 kd. The 40- and 70-kd dextrans straddle the effective diffusion radius of IgG. For each reagent, early and late angiograms were performed in a standardized fashion, with follow-up images obtained to monitor residual fluorescence. Results: Perfusion of retinal vessels and choroidal vasculature was seen with all reagents. Fluorescein and 4-and 20-kd dextran leaked rapidly from the CNV within the first minute. Angiography with the use of 40-kd dextran and fluoresceinated antibody, either anti-vascular endothelial growth factor or control IgG, showed fluorescence within the CNV that increased during the first 1 to 5 hours, with mild leakage from the CNV. By 24 hours, fluorescence in the CNV was minimal, although in some cases persistent fluorescence in the surrounding tissue was evident up to 2 weeks. The 70-kd dextran showed fluorescence within the CNV and leakage in 1 of 3 eyes, The 150-kd dextran showed fluorescence within the CNV but did not demonstrate leakage. Conclusions: Fluoresceinated antibodies and dextran with smaller effective diffusion radii showed CNV perfusion and leakage. Dextrans with larger effective diffusion radii (70 kd and 150 kd) perfused into CNV but did not show leakage consistently. Clinical Relevance: Determining the permeablity of antibodies and molecules of similar size through CNV can help ascertain the feasibility of using intravenously administered antibodies against angiogenic growth factors as a future treatment for choroidal neovascularization. C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Surg Res Labs, Childrens Hosp, Boston, MA USA. Genentech Inc, S San Francisco, CA 94080 USA. RP Miller, JW (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. NR 25 TC 32 Z9 37 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JAN PY 2000 VL 118 IS 1 BP 78 EP 84 PG 7 WC Ophthalmology SC Ophthalmology GA 276AF UT WOS:000084852900013 PM 10636419 ER PT J AU Hammond, MEH Compton, CC AF Hammond, MEH Compton, CC CA Coll Amer Pathologists TI Protocols for the examination of tumors of diverse sites - Introduction SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID OF-AMERICAN-PATHOLOGISTS; UPPER AERODIGESTIVE TRACT; CANCER-COMMITTEE; COLORECTAL-CARCINOMA; HISTOLOGIC GRADE; LUNG-CANCER; SPECIMENS; CHECKLISTS; SURVIVAL; STAGE AB This issue of the ARCHIVES includes previously unpublished protocols for the examination of specimens removed from patients with cancer of diverse sites. We provide a historical context for the development of these protocols and describe the process of development and approval. General information about the structure and content of the protocols is also provided. Cancer protocol development is an important step in the process of standardized cancer reporting. The value of such standardized reporting is discussed. C1 Univ Utah, Sch Med, Dept Pathol, LDS Hosp, Salt Lake City, UT USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Hammond, MEH (reprint author), Care of Schramm J, Coll Amer Pathologists, 325 Waukegan Rd, Northfield, IL 60093 USA. NR 46 TC 5 Z9 5 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 2000 VL 124 IS 1 BP 13 EP 16 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 276CB UT WOS:000084857100003 PM 10629124 ER PT J AU Rickert, RR Compton, CC AF Rickert, RR Compton, CC CA Coll Amer Pathologists TI Protocol for the examination of specimens from patients with carcinomas of the anus and anal canal - A basis for checklists SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID HUMAN PAPILLOMAVIRUS INFECTION; INSITU HYBRIDIZATION; NEOPLASIA; CANCER; ADENOCARCINOMA; PRECURSORS; WOMEN; DNA C1 St Barnabas Med Ctr, Livingston, NJ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rickert, RR (reprint author), Care of Schramm J, Coll Amer Pathologists, 325 Waukegan Rd, Northfield, IL 60093 USA. NR 25 TC 7 Z9 7 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 2000 VL 124 IS 1 BP 21 EP 25 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 276CB UT WOS:000084857100005 PM 10629126 ER PT J AU Henson, DE Albores-Saavedra, J Compton, CC AF Henson, DE Albores-Saavedra, J Compton, CC CA Coll Amer Pathologists TI Protocol for the examination of specimens from patients with carcinomas of the extrahepatic bile ducts, exclusive of sarcomas and carcinoid tumors - A basis for checklists SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID BILIARY-TRACT; PROGNOSTIC FACTORS; INVASION C1 NCI, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Henson, DE (reprint author), Care of Schramm J, Coll Amer Pathologists, 325 Waukegan Rd, Northfield, IL 60093 USA. NR 20 TC 7 Z9 7 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 2000 VL 124 IS 1 BP 26 EP 29 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 276CB UT WOS:000084857100006 PM 10629127 ER PT J AU Compton, CC AF Compton, CC CA Coll Amer Pathologists TI Protocol for the examination of specimens from patients with endocrine tumors of the pancreas, including those with mixed endocrine and acinar cell differentiation - A basis for checklists SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID ZOLLINGER-ELLISON SYNDROME; HUMAN CHORIONIC-GONADOTROPIN; ISLET-CELL; CARCINOID-TUMORS; PREDICT MALIGNANCY; NUCLEAR ANTIGEN; POLYPEPTIDE; MANAGEMENT; SUBUNITS; IMMUNOREACTIVITY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Compton, CC (reprint author), Care of Schramm J, Coll Amer Pathologists, 325 Waukegan Rd, Northfield, IL 60093 USA. NR 59 TC 5 Z9 5 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 2000 VL 124 IS 1 BP 30 EP 36 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 276CB UT WOS:000084857100007 PM 10629128 ER PT J AU Henson, DE Albores-Saavedra, J Compton, CC AF Henson, DE Albores-Saavedra, J Compton, CC CA Coll Amer Pathologists TI Protocol for the examination of specimens from patients with carcinomas of the gallbladder, including those showing focal endocrine differentiation - A basis for checklists SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID OAT-CELL CARCINOMA; PROGNOSTIC FACTORS; HYPERPLASIA; INSITU C1 NCI, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Henson, DE (reprint author), Care of Schramm J, Coll Amer Pathologists, 325 Waukegan Rd, Northfield, IL 60093 USA. NR 26 TC 6 Z9 7 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 2000 VL 124 IS 1 BP 37 EP 40 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 276CB UT WOS:000084857100008 PM 10629129 ER PT J AU Wanebo, HJ Glicksman, AS Vezeridis, MP Clark, J Tibbetts, L Koness, RJ Levy, A AF Wanebo, HJ Glicksman, AS Vezeridis, MP Clark, J Tibbetts, L Koness, RJ Levy, A TI Preoperative chemotherapy, radiotherapy, and surgical resection of locally advanced pancreatic cancer SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 50th Annual Meeting of the Society-of-Surgical-Oncology CY MAR 20-23, 1997 CL CHICAGO, ILLINOIS SP Soc Surg Oncol ID PHASE-II TRIAL; RADIATION-THERAPY; ADENOCARCINOMA; CARCINOMA; CHEMORADIOTHERAPY; IRRADIATION; PANCREATICODUODENECTOMY; CHEMORADIATION; GEMCITABINE; EXPERIENCE AB Hypothesis: Neoadjuvant therapy has the potential to induce regression of high-risk, locally advanced cancers and render them resectable. Preoperative chemoradiotherapy is proposed as a testable treatment concept for locally advanced pancreatic cancer. Design: Fourteen patients (8 men, 6 women) with locally advanced pancreatic cancer were surgically explored to exclude distant spread of disease, to perform bypass of biliary and/or gastric obstruction, and to provide a jejunostomy feeding tube for long-term nutritional support. A course of chemotherapy with fluorouracil and cisplatin plus radiotherapy was then initiated. Reexploration and resection were planned subsequent to neoadjuvant therapy. Main Outcome Measures: Tumor regression and survival. Interventions: Surgically staged patients with locally advanced pancreatic cancer were treated by preoperative chemotherapy with bolus fluorouracil, 400 mg/m(2), on days 1 through 3 and 28 through 30 accompanied by a 3-day infusion of cisplatin, 25 mg m(2), on days 1 through 3 and 28 through 30 and concurrent radiotherapy, 45 Gy. Enteral nutritional support was maintained via jejunostomy tube. Results: Of 14 patients who enrolled in the protocol and were initially surgically explored, 3 refused the second operation and 11 were reexplored; 2 showed progressive disease and were unresectable and 9 (81%) had definitive resection. Surgical pathologic stages of the resected patients were: Ib (2 patients), II (2 patients), and III (5 patients). Pancreatic resection included standard Whipple resection in 1 patient, resection of body and neck in 1 patient, and extended resection in 6 patients (portal vein resection in 6, arterial resection in 4). One patient who was considered too frail for resection had core biopsies of the pancreatic head, node dissection, and an interstitial implant of the tumorous head. Pathologic response: 2 patients had apparent complete pathologic response; 1 patient had no residual cancer in the pancreatectomy specimen, the other patient who had an iridium 192 interstitial implant had normal core biopsies of the pancreatic head. Five patients had minimal residual cancer in the resected pancreas or microscopic foci only with extensive fibrosis, and 2 patients had fully viable residual cancer. Lymph node downstaging occurred in 2 of 4 patients who had positive peripancreatic nodes at the initial surgical staging. There was 1 postoperative death at 10 days. Sepsis, prolonged ileus, and failure to thrive were major complications. In the definitive surgery group the median survival was 19 months after beginning chemoradiotherapy and 16 months after definitive surgery. The absolute 5-year survival was 11% of 9 patients, 1 is surviving 96 months (with no evidence of disease) after chemoradiotherapy and extended pancreatic resection including resection of the superior mesenteric artery and the portal vein for stage III cancer. In the nonresected group the mean survival was 9 months (survial range, 7-12 months) after initiation of chemoradiotherapy. Conclusion: A pilot study of preoperative chemoradiotherapy with infusional cisplatin and radiation induced a high rate of clinical pathologic response in patients with locally advanced pancreatic cancer and merits further study in these high-risk patients. C1 Boston Univ, Roger Williams Med Ctr, Sch Med, Div Surg Oncol, Providence, RI 02908 USA. Boston Univ, Sch Med, Dept Surg, Providence, RI USA. Boston Univ, Sch Med, Dept Radiat Therapy, Providence, RI USA. Boston Univ, Sch Med, Dept Pathol, Providence, RI USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med Med Oncol, Boston, MA USA. RP Wanebo, HJ (reprint author), Boston Univ, Roger Williams Med Ctr, Sch Med, Div Surg Oncol, Providence, RI 02908 USA. NR 25 TC 93 Z9 95 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD JAN PY 2000 VL 135 IS 1 BP 81 EP 87 DI 10.1001/archsurg.135.1.81 PG 7 WC Surgery SC Surgery GA 270UH UT WOS:000084555100018 PM 10636353 ER PT J AU Lee, SK Pestano, GA Riley, J Hasan, AS Pezzano, M Samms, M Park, KJ Guyden, J Boto, WMO AF Lee, SK Pestano, GA Riley, J Hasan, AS Pezzano, M Samms, M Park, KJ Guyden, J Boto, WMO TI A single point mutation in HIV-1V3 loop alters the immunogenic properties of rgp120 SO ARCHIVES OF VIROLOGY LA English DT Article ID T-LYMPHOCYTE ACTIVITY; AMINO-ACID-SEQUENCE; SUBTYPE-A; V3 LOOP; NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODY; STRUCTURAL ELEMENTS; ANTIGENIC EPITOPES; TYPE-1 INFECTION; ENVELOPE PROTEIN AB The results of the study presented in this report show that clones of env derived from genetically divergent HIV-1 field isolates fall into two major subsets based on the predicted secondary structure of the V3 region in gp120. One subset exemplified by the clones A-UG06c, B-RT3.12 and C-UG045 is predicted to assume a beta -turn conformation in the V3 loop and comprises the GPG (X) under bar residues. The other subset exemplified by the clones D-UG23c and D-UG042 (G (X) under barG (X) under bar are deficient in the expression of the beta -turn in the loop. Since secondary conformations are highly likely to confer antigenic properties in a protein backbone at least for B cells, we have used nucleic acid immunization to test the effect of the beta -turn deficiency on the immunogenic potential of rgp 120 encoded in these field isolates. As hypothesized, inoculation of BALB/c mice with the env plasmid encoding the beta -turn expressing rgp120 molecules resulted in the development of a vigorous antibody response to the homologous V3 loop peptides. In contrast, immunization with an rgp120 clone deficient in the beta -turn in the V3 loop showed no evidence of antibody development to the V3 loop. Instead, the latter clones triggered T cell proliferative responses and markedly increased the level of IL-2 and IFN-gamma production by T cells. Significantly, reconstitution of the beta -turn conformation by site-directed mutagenesis of a single V3 loop residue yielded rgp120 molecules which restored antibody production while diminishing the cell-mediated immune (CMI) responses to the V3 residue. These observations demonstrate the marked impact of a single amino acid substitution on the immunogenic properties of V3 region in gp120 encoded by divergent HIV-I, field isolates. C1 CUNY City Coll, Dept Biol, New York, NY 10031 USA. CUNY, Biol Doctoral Program, New York, NY 10021 USA. Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA USA. CUNY, Biochem Doctoral Program, New York, NY 10021 USA. RP Boto, WMO (reprint author), CUNY City Coll, Dept Biol, 138Th St & Convent Ave, New York, NY 10031 USA. FU FIC NIH HHS [T37TW00029]; NCRR NIH HHS [RR/AI03060] NR 38 TC 9 Z9 9 U1 2 U2 3 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 2000 VL 145 IS 10 BP 2087 EP 2103 DI 10.1007/s007050070041 PG 17 WC Virology SC Virology GA 366PT UT WOS:000090014300007 PM 11087093 ER PT J AU Choi, HK Lamprecht, P Niles, JL Gross, WL Merkel, PA AF Choi, HK Lamprecht, P Niles, JL Gross, WL Merkel, PA TI Subacute bacterial endocarditis with positive cytoplasmic antineutrophil cytoplasmic antibodies and anti-proteinase 3 antibodies SO ARTHRITIS AND RHEUMATISM LA English DT Article ID INFECTIOUS ENDOCARDITIS; ANCA; VASCULITIS; GLOMERULONEPHRITIS; AUTOANTIBODIES AB Objective. To report a potentially important limitation of antineutrophil cytoplasmic antibody (ANCA) testing: positive results in patients,vith subacute bacterial endocarditis (SBE), Methods, We describe 3 patients with SEE who presented with features mimicking ANCA-associated vasculitis (AAV) and positive findings on tests for cytoplasmic ANCA (cANCA) by indirect immunofluorescence and for anti-proteinase 3 (anti-PR3) antibodies by antigen-specific enzyme-linked immunosorbent assay (ELISA). We also reviewed the published literature describing infectious diseases with (misinterpreted) positive ANCA results through a Medline search of English-language articles published between 1966 and January 1999, These previously reported cases were reinterpreted using an ANCA scoring system that combines the findings of immunofluorescence and antigen-specific ELISA testing. Results. We are now aware of a total of 7 cases of SEE with positive cANCA and anti-PR3 antibodies. We are not aware of any cases of SEE associated with antimyeloperoxidase/perinuclear ANCA, Clinical manifestations mimicking AAV included glomerulonephritis, purpura, epistaxis, or sinus symptoms in 6 of the patients. Streptococcal species were identified in 5 patients, and cardiac valvular abnormalities were demonstrated in 6, All patients except 1, who died of a complication of SEE, recovered with antibiotic therapy. Conclusion. Findings of tests for anti-PR3/ cANCA antibodies may be positive in patients with SBE. When encountering ANCA positivity in patients suspected of having systemic vasculitis, physicians should take appropriate steps to rule out infectious diseases, including SEE, before committing the patient to longterm, aggressive immunosuppressive therapy. C1 Massachusetts Gen Hosp, Arthrit Unit, Boston, MA 02114 USA. Univ Lubeck, D-2400 Lubeck, Germany. Rheumaclin Bad Bramstedt, Bad Bramstedt, Germany. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Choi, HK (reprint author), Massachusetts Gen Hosp, Arthrit Unit, Bulfinch 165,Fruit St, Boston, MA 02114 USA. RI Gross, Wolfgang Ludwig/C-8733-2011; Lamprecht, Peter/F-1063-2013 OI Lamprecht, Peter/0000-0001-5929-868X NR 18 TC 101 Z9 106 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JAN PY 2000 VL 43 IS 1 BP 226 EP 231 DI 10.1002/1529-0131(200001)43:1<226::AID-ANR27>3.0.CO;2-Q PG 6 WC Rheumatology SC Rheumatology GA 274UD UT WOS:000084782700027 PM 10643719 ER PT J AU Benoist, C Mathis, D AF Benoist, C Mathis, D TI A revival of the B cell paradigm for rheumatoid arthritis pathogenesis? SO ARTHRITIS RESEARCH LA English DT Review DE B lymphocyte; immunoglobulin; major histocompatibility complex; T lymphocyte; transgenic ID T-CELL; AUTOIMMUNITY; RECOGNITION; SYNOVITIS; DISEASE AB Dominant paradigms for the understanding of rheumatoid arthritis (RA) pathogenesis have changed over the years. A predominant role of B lymphocytes, and perhaps of the rheumatoid factor they produced, was initially invoked. In more recent years, recognition of antigens in the joint by T cells sparking an inflammatory cascade has been a more favored interpretation. Here, we re-examine some of the arguments that underpin this proposed role of joint T cells, in light of recent results from transgenic mice in which a self-reactive T-cell receptor provokes disease, but from outside the joint and indirectly via B lymphocytes and immunoglobulins. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Mathis, D (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. NR 25 TC 35 Z9 37 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1465-9913 J9 ARTHRITIS RES JI Arthritis Res. PY 2000 VL 2 IS 2 BP 90 EP 94 DI 10.1186/ar73 PG 5 WC Rheumatology SC Rheumatology GA 408ZP UT WOS:000167357300002 PM 11094418 ER PT J AU Goldbach-Mansky, R Lee, J McCoy, A Hoxworth, J Yarboro, C Smolen, JS Steiner, G Rosen, A Zhang, C Menard, HA Zhou, ZJ Palosuo, T Van Venrooij, WJ Wilder, RL Klippel, JH Schumacher, HR El-Gabalawy, HS AF Goldbach-Mansky, R Lee, J McCoy, A Hoxworth, J Yarboro, C Smolen, JS Steiner, G Rosen, A Zhang, C Menard, HA Zhou, ZJ Palosuo, T Van Venrooij, WJ Wilder, RL Klippel, JH Schumacher, HR El-Gabalawy, HS TI Rheumatoid arthritis associated autoantibodies in patients with synovitis of recent onset SO ARTHRITIS RESEARCH LA English DT Review DE autoantibodies; early synovitis; human leukocyte antigen; rheumatoid arthritis; spondylarthropathy ID HUMAN EPIDERMIS FILAGGRIN; ANTIKERATIN ANTIBODIES; ANTIFILAGGRIN AUTOANTIBODIES; ANTIPERINUCLEAR FACTOR; MARKER; PURIFICATION; DISEASE; SERA; RA33 AB An inception cohort of 238 patients having peripheral joint synovitis of less than 12 months duration was evaluated clinically and followed prospectively for 1 year to determine the clinical significance of a number of rheumatoid arthritis (RA) associated autoantibodies. Serum samples collected at the time of the initial evaluation were tested for rheumatoid factor (RF) and antibodies to Sa (anti-Sa), RA-33, (pro) filaggrin [antifilaggrin antibody (AFA)], cyclic citrullinated peptide (anti-CCP), calpastatin, and keratin [antikeratin antibody (AKA)]. RF had a sensitivity of 66% and a specificity of 87% for RA. Anti-Sa, AFA, and anti-CCP all had a specificity of more than 90%, but a sensitivity of less than 50% for this diagnosis. Overall, there was a high degree of correlation between AFA, AKA, anti-Sa or anti-CCP, this being highest between anti-Sa and anti-CCP (odds ratio, 13.3; P < 0.001). Of the 101 patients who were positive for at least one of these four autoantibodies, 57% were positive for only one. Finally, anti-Sa identified a subset of predominantly male RA patients with severe, erosive disease. Anti-Sa, AFA and anti-CCP are all specific for early RA but, overall, have little additional diagnostic value over RF alone. Although these antibodies may preferentially recognize citrullinated antigens, the modest degree of concordance between them in individual patient sera suggests that it is unlikely a single antigen is involved in generating these responses. C1 Univ Vienna, Dept Med, Div Rheumatol, Vienna, Austria. Johns Hopkins Sch Med, Dept Med, Div Rheumatol, Baltimore, MD USA. Univ Sherbrooke, Ctr Univ Sante Estrie, Div Rheumatol, Sherbrooke, PQ J1K 2R1, Canada. Natl Publ Hlth Inst, Immunobiol Lab, Helsinki, Finland. Katholieke Univ Nijmegen, Nijmegen, Netherlands. Univ Penn, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP El-Gabalawy, HS (reprint author), NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. OI Hoxworth, Joseph/0000-0002-7179-5846 NR 30 TC 246 Z9 278 U1 0 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1465-9913 J9 ARTHRITIS RES JI Arthritis Res. PY 2000 VL 2 IS 3 BP 236 EP 243 DI 10.1186/ar93 PG 8 WC Rheumatology SC Rheumatology GA 408ZU UT WOS:000167357700013 PM 11056669 ER PT J AU Ticker, JB Beim, GM Warner, JJP AF Ticker, JB Beim, GM Warner, JJP TI Recognition and treatment of refractory posterior capsular contracture of the shoulder SO ARTHROSCOPY LA English DT Article DE shoulder; impingement; adhesive capsulitis; arthroscopy; capsular release; kinematics ID IMPINGEMENT; RELEASE AB Limitation of internal rotation has-been reported in conjunction with impingement syndrome of the shoulder. A group of 9 patients was identified who had discrete, painful loss of internal rotation associated with refractory impingement syndrome. The duration of symptoms averaged 18 months (range, 11 to 33 months), and all patients failed a course of physical-therapy specifically addressing loss of internal rotation. Six patients reported traction as the mechanism of injury, and 3 developed motion loss and pain following a posterior capsular shift procedure. All patients underwent arthroscopy, and were observed to have a thickened posterior capsule. An arthroscopic release of the posterior capsule improved motion in all patients, with substantial relief of pain. At an average of 19 months follow-up (range, 11 to 35 months), internal rotation in 90 degrees of abduction improved from 10 degrees preoperatively to 47 degrees postoperatively, and there were no complications related to the procedure. We Conclude that chronic loss of internal rotation secondary to posterior capsular contracture may be an explanation for refractory pain in some patients with an initial diagnosis of impingement syndrome. This condition appears to be amenable to arthroscopic posterior capsular release. C1 Isl Orthopaed & Sports Med PC, Massapequa, NY USA. Hughston Clin PC, Mt Crested Butte, CO USA. Massachusetts Gen Hosp, Harvard Shoulder Serv, Boston, MA 02114 USA. RP Warner, JJP (reprint author), Harvard Shoulder Serv, 275 Cambridge,4th Floor, Boston, MA 02114 USA. NR 36 TC 40 Z9 41 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 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD JAN-FEB PY 2000 VL 16 IS 1 BP 27 EP 34 DI 10.1016/S0749-8063(00)90124-5 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 272HB UT WOS:000084643500008 PM 10627342 ER PT J AU Sodian, R Hoerstrup, SP Sperling, JS Martin, DP Daebritz, S Mayer, JE Vacanti, JP AF Sodian, R Hoerstrup, SP Sperling, JS Martin, DP Daebritz, S Mayer, JE Vacanti, JP TI Evaluation of biodegradable, three-dimensional matrices for tissue engineering of heart valves SO ASAIO JOURNAL LA English DT Article ID IN-VITRO; PROSTHESES AB A crucial factor in tissue engineering of heart valves is the type of scaffold material. In the following study, we tested three different biodegradable scaffold materials, polyglycolic acid (PCA), polyhydroxyalkanoate (PHA), and poly-4-hydroxybutyrate (P4HB), as scaffolds for tissue engineering of heart valves. We modified PHA and P4HB by a salt leaching technique to create a porous matrix. We constructed trileaflet heart valve scaffolds from each polymer and tested them in a pulsatile flow bioreactor. In addition, we evaluated the cell attachment to our polymers by creating four tubes of each material (length equals 4 cm; inner diameter, 0.5 cm), seeding each sample with 8,000,000 ovine vascular cells, and incubating the cell-polymer construct for 8 days (37 degreesC and 5% CO2). The seeded vascular constructs were exposed to continuous flow for 1 hour. Analysis of samples included DNA assay before and after flow exposure, 4-hydroxyproline assay, and environmental scanning electron microscopy (ESEM). We fabricated trileaflet heart valve scaffolds from porous PHA and porous P4HB, which opened and closed synchronously in a pulsatile bioreactor. It was not possible to create a functional trileaflet heart valve scaffold from PCA. After seeding and incubating the PGA-, PHA-, and P4HB-tubes, there were significantly (p < 0.001) more cells on PCA compared with PHA and P4HB. There were no significant differences among the materials after flow exposure, but there was a significantly higher collagen content (p < 0.017) on the PGA samples compared with P4HB and PHA. Cell attachment and collagen content was significantly higher on PCA samples compared with PHA and P4HB. However, PHA and P4HB also demonstrate a considerable amount of cell attachment and collagen development and share the major advantage that both materials are thermoplastic, making it possible to mold them into the shape of a functional scaffold for tissue engineering of heart valves. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Cardiac Res, Boston, MA 02115 USA. Metabolix Inc, Cambridge, MA USA. RP Sodian, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 18 TC 112 Z9 120 U1 1 U2 28 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD JAN-FEB PY 2000 VL 46 IS 1 BP 107 EP 110 DI 10.1097/00002480-200001000-00025 PG 4 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 392UK UT WOS:000166430800025 PM 10667727 ER PT J AU Ratcliffe, MB Hong, J Salahieh, A Wallace, AW AF Ratcliffe, MB Hong, J Salahieh, A Wallace, AW TI The effect of diastolic stiffness on ventricular function after partial ventriculectomy: A finite element simulation SO ASAIO JOURNAL LA English DT Article ID DILATED CARDIOMYOPATHY; REDUCTION SURGERY; SARCOMERE-LENGTH; HEART; PERFORMANCE; TRABECULAE AB Partial ventriculectomy (PV) has been proposed by Batista and colleagues to improve cardiac function in patients with dilated cardiomyopathy (DCM); however, results have been mixed. We tested the hypothesis that preoperative diastolic function affects the stroke volume/end-diastolic pressure (Starling) relationship after PV. A previously described finite element simulation of DCM and PV was used. Diastole and end systole were represented by separate elastic finite element models with different unloaded shapes and nonlinear material properties. Left ventricular (LV) end-systolic elastance (E-ES), diastolic compliance (DC), and Starling relationships were calculated. DC was varied by changing Ogden material property alpha (i) from 12 (compliant) to 20 (stiff). PV was simulated at 20% LV mass reduction. The slope of the Starling relationship increased from 1.82 to 1.21 as alpha (i) increased from 12 to 20. Partial ventriculectomy increased the Starling relationship in each case from 1.34 to 1.01 respectively. However, the net result in each case is a decrement in the Starling relationship with resection, and the smallest decrement was associated with the highest diastolic stiffness (alpha (i) = 20). Partial ventriculectomy depressed the Starling relationship for all values of diastolic compliance. It is expected that patients with a higher diastolic stiffness should do better. C1 San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Sch Med, Div Cardiothorac Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Dept Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Dept Anesthesia, San Francisco, CA 94143 USA. RP Ratcliffe, MB (reprint author), San Francisco Vet Affairs Med Ctr, 112D,4150 Clement St, San Francisco, CA 94121 USA. NR 34 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD JAN-FEB PY 2000 VL 46 IS 1 BP 111 EP 116 DI 10.1097/00002480-200001000-00026 PG 6 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 392UK UT WOS:000166430800026 PM 10667728 ER PT J AU Cooper, RA Rentschler, AJ O'Connor, TJ Ster, JF AF Cooper, RA Rentschler, AJ O'Connor, TJ Ster, JF TI Wheelchair armrest strength testing SO ASSISTIVE TECHNOLOGY LA English DT Article DE wheelehair; fatigue testing; wheclchair standards; strength testing ID MANUAL WHEELCHAIRS; UNITED-STATES; ACCIDENTS; LIFE AB There are about 1.4 million manual wheelchair users, 100,000 electric-powered wheelchair users, and 60,000 electric-powered scooter users. The current study was undertaken to determine if the fasteners of a clamp-type armrest receiver were prone to failure. The first test was used to examine the potential misalignment of the armrest receiver components that attach it to the frame. The second test was to evaluate the entire armrest using the American National Standards Institute/Rehabilitation Engineering and Assistive Technology Society of North America armrest static strength standard. Finally, we conducted three fatigue tests. The first fatigue test was performed by repeating the static stability tests multiple times. The last two tests were a modified version of the double-drum wheelchair fatigue test used to apply repeated loading and vibration simultaneously. A paired t-test showed that there is no statistically significant difference (p = 0.08), with a confidence of 95%, between critical alignment measurements. The armrest including the receiver passed the standard requirement of a force of 760 N being applied outward at 15 degrees. During fatigue testing, we found that armrests did not exhibit any visible or functional damage. Upon completion of the tests, the armrests and receivers functioned properly. At about 100,289 cycles on a double-drum test machine, three bolts failed on each armrest receiver when the screws were loosened to have only five threads engaged prior to commencing the test. The design of the armrest tested was in compliance with existing national and international standards. Currently, both International Standards Organization and American National Standards Institute/Rehabilitation Engineering and Assistive Technology Society committees are developing standards for seating systems that will include static, impact, and fatigue strength testing of devices like lateral torso supports, lateral hip support, etc. Methods similar to those explored in this study should be considered. This study may help manufacturers when designing products and purchasers or regulatory agencies when attempting to evaluate the safety and quality of armrest assemblies. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151R1, VA Rehabil Res & Dev Ctr Wheelchairs & Related Te, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. Univ Pittsburgh, Dept Orthopaed Surg, Div Phys Med & Rehabil, Pittsburgh, PA USA. Calif State Univ Sacramento, Sch Engn & Comp Sci, Sacramento, CA 95819 USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151R1, VA Rehabil Res & Dev Ctr Wheelchairs & Related Te, 7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 15 TC 2 Z9 2 U1 4 U2 5 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PY 2000 VL 12 IS 2 BP 106 EP 115 PG 10 WC Rehabilitation SC Rehabilitation GA 434WV UT WOS:000168839600003 PM 11508400 ER PT S AU Luscinskas, FW Gerszten, RE Garcia-Zepeda, EA Lim, YC Yoshida, M Ding, HA Gimbrone, MA Luster, AD Rosenzweig, A AF Luscinskas, FW Gerszten, RE Garcia-Zepeda, EA Lim, YC Yoshida, M Ding, HA Gimbrone, MA Luster, AD Rosenzweig, A BE Numano, F Gimbrone, MA TI C-C and C-X-C chemokines trigger firm adhesion of monocytes to vascular endothelium under flow conditions SO ATHEROSCLEROSIS V: THE FIFTH SARATOGA CONFERENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 5th Saratoga International Conference on Atherosclerosis CY MAY 18-20, 1999 CL BARCELONA, SPAIN SP Japan Arteriosclerosis Res Fdn, Japan Atherosclerosis Soc, Japan Circulat Soc, Japanese Coll Angiol ID IN-VITRO; CELLS; SELECTIN; MECHANISMS C1 Brigham & Womens Hosp, Dept Pathol, Div Vasc Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Tokyo Med & Dent Univ, Med Res Inst, Tokyo, Japan. RP Luscinskas, FW (reprint author), Div Vasc Res, 221 Longwood Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL54202, HL03348]; NIAID NIH HHS [AI40970] NR 16 TC 34 Z9 34 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-246-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 902 BP 288 EP 293 PG 6 WC Multidisciplinary Sciences; Peripheral Vascular Disease SC Science & Technology - Other Topics; Cardiovascular System & Cardiology GA BQ53G UT WOS:000088670700030 PM 10865849 ER PT S AU Reid, RR Woodcock, S Prodeus, AP Austen, J Kobzik, L Hechtman, H Moore, FD Carroll, MC AF Reid, RR Woodcock, S Prodeus, AP Austen, J Kobzik, L Hechtman, H Moore, FD Carroll, MC BE Potter, M Melchers, F TI The role of complement receptors CD21/CD35 in positive selection of B-l cells SO B 1 LYMPHOCYTES IN B CELL NEOPLASIA SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT 16th Workshop on the Mechanisms of B Cell Neoplasia CY OCT 28-29, 1999 CL NIH, NATL LIB MED, BETHESDA, MARYLAND SP NCI, Lab Genet, Div Basic Sci HO NIH, NATL LIB MED ID T-CELL; MICE; IMMUNITY; ANTIGEN; B-1; DIFFERENTIATION; LYMPHOCYTES; REPERFUSION; TYPE-1; INJURY C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Reid, RR (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. NR 25 TC 9 Z9 12 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-67567-1 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2000 VL 252 BP 57 EP 65 PG 9 WC Immunology; Microbiology SC Immunology; Microbiology GA BR65E UT WOS:000167097400007 PM 11187085 ER PT J AU Hasirci, V Lewandrowski, KU Bondre, SP Gresser, JD Trantolo, DJ Wise, DL AF Hasirci, V Lewandrowski, KU Bondre, SP Gresser, JD Trantolo, DJ Wise, DL TI High strength bioresorbable bone plates: preparation, mechanical properties and in vitro analysis SO BIO-MEDICAL MATERIALS AND ENGINEERING LA English DT Article DE semi-interpenetrating network; bioresorbable; bone plates; poly(lactide-co-glycolide); polypropylene fumarate ID FIXATION; PLLA AB Biodegradable bone plates were prepared as semi-interpenetrating networks (SIPN) of crosslinked polypropylene fumarate (PPF) within a host matrix of either poly(lactide-co-glycolide) - 85 : 15 (PLGA) or poly(l-lactide-co-d,l-lactide) - 70 : 30 (PLA) using N-vinylpyrrolidone (NVP), ethylene glycol dimethacrylate (EGDMA), 2-hydroxyethyl methacrylate (HEMA), and methyl methacrylate (MMA) as crosslinking agents. Hydroxyapatite (HAP), an inorganic filler material, was used to further augment mechanical strength. The control crosslinking agent (NVP) was replaced partially and totally with other crosslinking agents. The amount of crosslinking agent lost, the characterization change in the mechanical properties and the dimensional stability of the bone plates after in vitro treatment was calculated. The optimum crosslinking agent was selected on the basis of low in vitro release of NVP from SIPN matrix. Bone plates were then prepared using this crosslinking agent at 5 MPa pressure and at temperatures between 100-140 degrees C to determine if there was any augmentation of mechanical properties in the presence of the crosslinked network. In vitro analysis showed that 90% of the crosslinking agent was lost on plates using NVP as a crosslinking agent. This loss was reduced to 50% when NVP was partially replaced with EGDMA or MMA. EGDMA was determined to be superior because (1) its low release as a crosslinking agent, (2) flexural plate strength of 50-67 MPa, (3) flexural modulus of 7-13 GPa, and (4) manufacturability stiffness of 300-600 N/m. HAP-loading resulted in an additional increase in values of mechanical parameters. Substituting PLGA with PLA in the PPF-SIPN did not show any additional improvement of mechanical properties. C1 Cambridge Sci Inc, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. Middle E Tech Univ, Dept Biol Sci, Biotechnol Res Unit, TR-06531 Ankara, Turkey. RP Wise, DL (reprint author), Cambridge Sci Inc, 180 Fawcett St, Cambridge, MA 02138 USA. FU NIAMS NIH HHS [AR 45062] NR 16 TC 9 Z9 10 U1 0 U2 6 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0959-2989 J9 BIO-MED MATER ENG JI Bio-Med. Mater. Eng. PY 2000 VL 10 IS 1 BP 19 EP 29 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 332ZM UT WOS:000088104300003 PM 10950204 ER PT J AU Vasconcelles, MJ Bernardo, MVP King, C Weller, EA Antin, JH AF Vasconcelles, MJ Bernardo, MVP King, C Weller, EA Antin, JH TI Aerosolized pentamidine as pneumocystis prophylaxis after bone marrow transplantation is inferior to other regimens and is associated with decreased survival and an increased risk of other infections SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE bone marrow transplantation; pneumocystis carinii pneumonia; prophylaxis ID TRIMETHOPRIM-SULFAMETHOXAZOLE PROPHYLAXIS; VERSUS-HOST DISEASE; CARINII PNEUMONIA; CONTROLLED TRIAL; HEMATOLOGIC MALIGNANCIES; COTRIMOXAZOLE; PREVENTION; DAPSONE; BACTERIAL; PYRIMETHAMINE AB Pneumocystis carinii pneumonia (PCP) is a life-threatening but preventable infection that may occur after bone marrow transplantation (BMT). Although various prophylactic regimens have been used in this setting to prevent active infection, their efficacy, toxicity profile, and impact on outcomes are poorly described in this patient group. We undertook a retrospective cohort study in which we reviewed the records of 451 adult patients who underwent BMT for hematologic malignancies, aplastic anemia, or myelodysplasia over a 7-year period at the Brigham and Women's Hospital. Post-BMT PCP prophylaxis consisted of aerosolized pentamidine (AP) 150 mg every 2 weeks or 300 mg per month, trimethoprim/sulfamethoxazole (TMP/SMX) 160/800 mg orally b.i.d. 3 times per week, or dapsone 100 mg orally each day. Prophylaxis was continued for 1 year post-BMT in all patients when clinically feasible. One hundred twenty-one patients were unevaluable because of death or relapse <60 days after BMT (n = 89), loss to follow-up upon hospital discharge (n = 20), or other reasons (n = 12). Three eligible patients did not receive any prophylaxis and were not further evaluated. Of the 327 patients analyzed, 133 underwent autologous BMT, 4 syngeneic BMT, 159 related allogeneic BMT, and 31 unrelated allogeneic BMT. Graft-versus-host disease prophylaxis in the 190 patients receiving allogeneic BMT consisted of T-cell depletion with anti-CD5 and complement in 58 patients and cyclosporine/methotrexate or FK506 with or without steroids in 132 patients. Eight of 327 (2.4%) documented PCP cases were identified, 0 of 105 in patients receiving only TMP/SMX. Four cases occurred in patients receiving only AP (4/44, 9.1%; odds ratio [OR] relative to TMP/SMX 23.4, 95% confidence interval [CI] 1.2, 445.2); 1 in patients receiving only dapsone (1/31, 3.2%; OR not significant); 2 in patients receiving more than 1 prophylactic regimen (2/147 1.4%; OR not significant); and 1 >1 year post-BMT in a patient who was off PCP prophylaxis. Although the patients receiving only AP had a significantly lower probability of treatment-related toxicity than those receiving TMP/SMX (OR 0.19 [95% CI 0.04, 0.85]), the probability of their acquiring other serious non-PCP infections was increased (OR 2.2 [95% CI 1.0, 4.6]), and the probability of their dying by 1 year post-BMT was significantly higher (OR 5.2 [95% CI 2.4, 26.6]), even when adjusted for variables such as type of BMT (autologous versus allogeneic; high versus low risk) and sex. Although AP is associated with fewer toxicities, the data show that it is inferior to TMP/SMX in preventing PCP in the post-BMT setting and is associated with an increased risk of other infections and a higher mortality at 1 year after BMT. C1 Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Antin, JH (reprint author), Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [T32 HL07623] NR 36 TC 60 Z9 64 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PY 2000 VL 6 IS 1 BP 35 EP 43 DI 10.1016/S1083-8791(00)70050-4 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 366UB UT WOS:000090022000004 PM 10707997 ER PT J AU Weilbaecher, KN AF Weilbaecher, KN TI Mechanisms of osteoporosis after hematopoietic cell transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE bone marrow transplantation; osteoporosis; osteoclast ID BONE-MARROW TRANSPLANTATION; COLONY-STIMULATING FACTOR; ACUTE LYMPHOBLASTIC-LEUKEMIA; TOTAL-BODY IRRADIATION; BREAST-CANCER PATIENTS; FORMATION IN-VITRO; OP OP MOUSE; OSTEOCLAST DIFFERENTIATION; OSTEOPROTEGERIN LIGAND; MINERAL DENSITY AB Osteopenia and osteoporosis are common complications of bone marrow and peripheral blood stem cell transplantation. Bone loss occurs in 50% to 60% of patients treated with the most common preparatory regimens. The major causes of transplant-related bone loss are primary hypogonadism (low estrogen and testosterone), secondary hyperparathyroidism due to low serum calcium, and posttransplant steroid therapy. Other transplant-related treatments that induce bone loss are discussed. Trabecular bone is particularly vulnerable to transplant-related therapies. The spine and hip contain 50% to 75% trabecular bone and are most at risk for fracture after hematopoietic cell transplantation (HCT). The structure of bone and the bone cells that are involved in maintaining skeletal integrity are discussed, followed by a discussion of the transplant-related therapies that have been shown to cause damage to bone and lead to bone loss. Recommendations for patients undergoing HCT include (1) evaluation of bone mineral density either shortly before or shortly after transplantation and appropriate intervention and monitoring based on the results; and (2) evaluation of estrogen and testosterone levels after HCT and replacement when appropriate; and (3) administration of bisphosphonate therapy to all patients on steroids for >2 months. Early intervention and prevention of bone loss can have a tremendous clinical impact for patients undergoing HCT because once significant bone loss has occurred, it is difficult to reverse. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Cambridge, MA 02138 USA. RP Weilbaecher, KN (reprint author), Washington Univ, Sch Med, Div Oncol, 660 S Euclid,Box 8056, St Louis, MO 63110 USA. RI huang, hongqi/N-1473-2014 NR 75 TC 53 Z9 55 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PY 2000 VL 6 IS 2A BP 165 EP 174 DI 10.1016/S1083-8791(00)70039-5 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 366UD UT WOS:000090022200001 PM 10816024 ER PT J AU Ladetto, M Donovan, JW Harig, S Weller, E Trojan, A Poor, C Schlossman, R Anderson, KC Gribben, JG AF Ladetto, M Donovan, JW Harig, S Weller, E Trojan, A Poor, C Schlossman, R Anderson, KC Gribben, JG TI Real-time polymerase chain reaction of immunoglobulin rearrangements for quantitative evaluation of minimal residual disease in multiple myeloma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE PCR; consensus probe; IgH rearrangement; tumor burden ID BONE-MARROW TRANSPLANTATION; DOSE SEQUENTIAL CHEMORADIOTHERAPY; ACUTE LYMPHOBLASTIC-LEUKEMIA; PERIPHERAL-BLOOD; MALIGNANT-CELLS; GENE USAGE; PCR ASSAY; RT-PCR; CHEMOTHERAPY; THERAPY AB The majority of patients with multiple myeloma (il IM) have persistence of minimal residual disease (MRD), as determined by polymerase chain reaction (PCR) detection of clonal immunoglobulin H (IgH) gene rearrangements. As a result, PCR analysis has not provided clinically useful prognostic information in myeloma patients. Instead, quantitative PCR approaches are required to predict patient outcomes and assess response to novel treatment strategies. We adapted real-time PCR technology to quantify myeloma cells using the IgH rearrangement and then assessed the utility of this approach in 29 patients with myeloma who had undergone autologous stem cell transplantation. Because of the high cost of producing a specific reporting probe for each patient, H-chain V-region family-specific consensus probes were used in association with allele-specific oligonucleotides for PCR amplification. Because of the high frequency with which somatic hypermutation at the immunoglobulin locus occurs in MM, a number of mismatches occurred between the patient sequences and the consensus probe. However, construction of a limited number of probes allowed real-time PCR with a sensitivity of 10(-4) to 10(-5). To validate this method, we extensively evaluated assay accuracy and reproducibility. Results indicate that real-time PCR using consensus probes provides a feasible, accurate, and reproducible method for evaluating MRD in MM and possibly in other differentiated B-cell malignancies, and one that is less expensive than the use of patient-specific probes. This technique is being used to assess tumor depletion after immunologic purging and changes in tumor burden in patients undergoing stem cell transplantation and novel treatment approaches. 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 Biostat, Boston, MA 02115 USA. RP Gribben, JG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. OI LADETTO, Marco/0000-0002-8283-2681 FU NCI NIH HHS [P01 CA78378] NR 46 TC 61 Z9 61 U1 1 U2 3 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PY 2000 VL 6 IS 3 BP 241 EP 253 DI 10.1016/S1083-8791(00)70006-1 PG 13 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 366UE UT WOS:000090022300004 PM 10871149 ER PT J AU Spitzer, TR McAfee, S Sackstein, R Colby, C Multani, P Saidman, S Weymouth, D Preffer, F Poliquin, C Foley, A Cox, B Andrews, D Sachs, DH Sykes, M AF Spitzer, TR McAfee, S Sackstein, R Colby, C Multani, P Saidman, S Weymouth, D Preffer, F Poliquin, C Foley, A Cox, B Andrews, D Sachs, DH Sykes, M TI Intentional induction of mixed chimerism and achievement of antitumor responses after nonmyeloablative conditioning therapy and HLA-matched donor bone marrow transplantation for refractory hematologic malignancies SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE mixed chimerism; allogeneic; bone marrow transplantation; nonmyeloablative; hematologic malignancies ID VERSUS-HOST DISEASE; CHRONIC MYELOID-LEUKEMIA; TOTAL-BODY IRRADIATION; POLYMERASE CHAIN-REACTION; ALLOGENEIC MARROW; MYELOABLATIVE THERAPY; CELL TRANSPLANTATION; APLASTIC-ANEMIA; TOLERANCE; CHEMOTHERAPY AB Mixed lymphohematopoietic chimerism can be induced in mice with bone marrow transplantation (BMT) after a nonmyeloablative preparative regimen that includes cyclophosphamide, anti-T-cell antibody therapy, and thymic irradiation. These mixed chimeras are resistant to the induction of graft-versus-host disease (GVHD) after delayed donor leukocyte infusions (DLIs), despite a potent lymphohematopoietic graft-versus-host reaction that converts the mixed chimeric state to a full donor one. Based on this animal model, we initiated a trial of nonmyeloablative therapy with HLA-matched or -mismatched donor BMT and DLI for refractory hematologic malignancies. Twenty-one of 36 patients enrolled in this trial received a genotypically (n = 20) or phenotypically (n = 1) HLA-matched donor transplant; results reported here are for those patients only. Preparative therapy consisted of cyclophosphamide in doses of 150 to 200 mg/kg; peritransplant antithymocyte globulin; thymic irradiation (in patients who had not received previous mediastinal radiation therapy); and cyclosporine. Eighteen of 20 evaluable patients developed persistent mixed lymphohematopoietic chimerism as defined by >1% donor peripheral white blood cells until at least day 35 posttransplantation. Ten patients received prophylactic DLI beginning 5 to 6 weeks after BMT for conversion of mixed chimerism to full donor hematopoiesis and to optimize a graft-versus-leukemia effect. Fourteen of 20 evaluable patients (70%) achieved an antitumor response; 8 of these responses were complete, and 6 were partial. Of the 8 evaluable patients who received prophylactic DLI, 6 showed conversion to full donor chimerism. Five of the 9 evaluable patients (56%) who received prophylactic DLI achieved a complete response, compared with 3 of 11 patients (27%) who did not receive prophylactic DLI. Currently 11 patients are alive, and 7 of these are free of disease progression at a median follow-up time of 445 days (range, 105-548 days) posttransplantation. Transplantation-related complications included cyclophosphamide-induced cardiac toxicity in 3 of 21 patients (14%) and grade II or greater GVHD in 6 patients (29%). One patient (5%) died from a complication of BMT, and 1 patient (5%) died from GVHD after 2 prophylactic DLIs were given for conversion of chimerism. In summary, mixed lymphohematopoietic chimerism was reproducibly induced after a novel nonmyeloablative preparative regimen incorporating chemotherapy, peritransplant antithymocyte globulin, and thymic irradiation, allowing for early administration of DLI in 10 of 21 patients. After treatment, striking antitumor responses were observed in the majority of patients with chemotherapy-refractory hematologic malignancies. C1 Massachusetts Gen Hosp, Bone Marrow Transplant Program, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Spitzer, TR (reprint author), Massachusetts Gen Hosp, Bone Marrow Transplant Program, Dept Med, Cox 640,55 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [1R01 CA79986-01A1, 1R01 CA79988-01A1, 1R01 CA79989-01A1] NR 38 TC 188 Z9 193 U1 2 U2 2 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PY 2000 VL 6 IS 3A BP 309 EP 320 DI 10.1016/S1083-8791(00)70056-5 PG 12 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 366UG UT WOS:000090022500003 PM 10905768 ER PT J AU Orsini, E Alyea, EP Chillemi, A Schlossman, R McLaughlin, S Canning, C Soiffer, RJ Anderson, KC Ritz, J AF Orsini, E Alyea, EP Chillemi, A Schlossman, R McLaughlin, S Canning, C Soiffer, RJ Anderson, KC Ritz, J TI Conversion to full donor chimerism following donor lymphocyte infusion is associated with disease response in patients with multiple myeloma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE multiple myeloma; chimerism; bone marrow transplantation; donor lymphocyte infusion; T-cell repertoire ID BONE-MARROW TRANSPLANTATION; CYTOTOXIC T-LYMPHOCYTES; GRAFT-VERSUS-LEUKEMIA; MINOR HISTOCOMPATIBILITY ANTIGENS; CHRONIC MYELOGENOUS LEUKEMIA; LEUKOCYTE INFUSIONS; CELL REPERTOIRE; HOST DISEASE; IN-VIVO; RELAPSE AB Donor lymphocyte infusions (DLIs) have been demonstrated to induce clinical responses in patients with relapsed multiple myeloma after allogeneic bone marrow transplantation but the immunologic mechanisms involved have not been well characterized. In patients with chronic myelocytic leukemia (CML), remissions following DLI are invariably associated with conversion to complete donor hematopoiesis, suggesting that the target antigens of this response are expressed on both normal and CML-derived hematopoietic stem cells. In the present study, we examined hematopoietic chimer sm and the complexity of the T-cell receptor (TCR) repertoire in 4 patients with relapsed multiple myeloma who received infusions of donor CD4(+) lymphocytes. Three of 4 patients had a clinical response that began 1 to 2 months after DLI. All 3 responding patients developed lymphocytosis at the initiation of response that was due to a 2- to 4.5-fold increase in the number of CD3(+) T cells. In 1 patient, this was due primarily to increases in CD3(+) and CD8(+) cells; in 2 patients, to increased numbers of CD3(+) and CD8(+) and CD3(+) and CD4(+) T cells. In all responding patients, conversion to complete donor hematopoiesis occurred in the first 2 months after DLI. The single nonresponding patient remained at 100% recipient hematopoiesis. The TCR repertoire complexity was examined by polymerase chain reaction amplification of complementary-determining region 3 (CDR3) derived from 24 V beta gene subfamilies. In 2 patients, the initiation of myeloma response and conversion to complete donor hematopoiesis was associated with normalization of TCR complexity. Complete donor chimerism and normal TCR complexity remained stable in all patients and did not change with subsequent relapse or development of graft-versus-host disease (GVHD). Thus, conversion to full donor chimerism was temporally associated with the antimyeloma effect of DLI but not with the development of GVHD. Nevertheless, the maintenance of stable donor hematopoiesis did not prevent disease relapse and was not associated with prolonged remission. The selective relapse of myeloma cells without concomitant return of mixed hematopoietic chimerism suggests that myeloma tumor cells in some patients develop resistance to immune destruction. C1 Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, Ctr Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA78378]; NIAID NIH HHS [AI29530] NR 33 TC 43 Z9 44 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PY 2000 VL 6 IS 4 BP 375 EP 386 DI 10.1016/S1083-8791(00)70014-0 PG 12 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 366UJ UT WOS:000090022700004 PM 10917573 ER PT J AU Nieto, Y Champlin, RE Wingard, JR Vredenburgh, JJ Elias, AD Richardson, PR Glaspy, J Jones, RB Stiff, PJ Bearman, SI Cagnoni, PJ McSweeney, PA LeMaistre, CF Pecora, AL Shpall, EJ AF Nieto, Y Champlin, RE Wingard, JR Vredenburgh, JJ Elias, AD Richardson, PR Glaspy, J Jones, RB Stiff, PJ Bearman, SI Cagnoni, PJ McSweeney, PA LeMaistre, CF Pecora, AL Shpall, EJ TI Status of high-dose chemotherapy for breast cancer: A review SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE breast cancer; high-dose chemotherapy; stem cell transplantation ID BONE-MARROW SUPPORT; STEM-CELL SUPPORT; PHASE-I TRIAL; PROSPECTIVE RANDOMIZED TRIAL; PROGRESSION-FREE SURVIVAL; POLYMERASE CHAIN-REACTION; SURGICAL ADJUVANT BREAST; HER2/NEU-OVEREXPRESSING METASTATIC BREAST; COMBINATION ALKYLATING-AGENTS; AXILLARY LYMPH-NODES AB The purpose of this review is to analyze the current status of high-dose chemotherapy (HDCT) with autologous stem cell transplantation for patients with breast cancer. Current results from the major prospective phase 2 and phase 3 trials in metastatic breast cancer (MBC) and high-risk primary breast cancer (HRPBC) are reviewed. Prognostic factors and future research directions are also discussed. The encouraging results of phase 2 trials suggested a benefit for HDCT in HRPBC and some categories of patients with MBC. Some investigators have argued that patient selection might have been a critical factor in those studies. Recently reported randomized trials in patients with chemosensitive MBC have included only small numbers of patients in complete remission and thus have not adequately addressed the relative value of HDCT versus maintenance standard-dose chemotherapy in this patient subset. Although initial results of 2 studies have been reported, most randomized phase 3 studies of HDCT in HRPBC require longer follow-up before definitive conclusions can be made about its efficacy in this setting: We conclude that the role of HDCT for HRPBC or MBC patients has not yet been fully defined. Longer follow-up of the ongoing randomized trials is necessary, and their mature results will help clarify this important question. In the meantime, it is imperative that research continues, to enhance the efficacy of the procedure. This may come through incorporating more active drugs into HDCT regimens and combining HDCT with novel strategies aimed at eradication of posttransplantation minimal residual disease. C1 Univ Colorado, Hlth Sci Ctr, Bone Marrow Transplant Program, Denver, CO 80262 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Florida, Bone Marrow Transplant Program, Gainesville, FL 32611 USA. Duke Univ, Bone Marrow Transplant Program, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Loyola Univ, Chicago, IL 60611 USA. S Texas Canc Inst, San Antonio, TX USA. No New Jersey Canc Associates, Hackensack, NJ USA. RP Nieto, Y (reprint author), Univ Colorado, Hlth Sci Ctr, Bone Marrow Transplant Program, B 190,4200 E 9th Ave, Denver, CO 80262 USA. NR 177 TC 16 Z9 15 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PY 2000 VL 6 IS 5 BP 476 EP 495 DI 10.1016/S1083-8791(00)70019-X PG 20 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 367EX UT WOS:000090049700002 PM 11063377 ER PT J AU Dykewicz, CA Jaffe, HW Kaplan, JE AF Dykewicz, CA Jaffe, HW Kaplan, JE CA CDC Infect Dis Soc Amer Amer Soc Blood Marrow Transplation TI Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients - Recommendations of CDC, the Infectious Diseases Society of America, and the American Society of Blood and Marrow Transplation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review ID VERSUS-HOST DISEASE; PNEUMOCYSTIS-CARINII PNEUMONIA; RESPIRATORY SYNCYTIAL VIRUS; HERPES-SIMPLEX-VIRUS; CYTOMEGALOVIRUS PP65 ANTIGENEMIA; HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; LIPOSOMAL AMPHOTERICIN-B; HLA-IDENTICAL SIBLINGS; VARICELLA-ZOSTER VIRUS AB CDC, the Infectious Diseases Society of America, and the American Society of Blood and Marrow Transplantation have cosponsored these guidelines for preventing opportunistic infections (OIs) among hematopoietic stem cell transplant (HSCT) recipients. The guidelines were drafted with the assistance of a working group of experts in infectious diseases, transplantation, and public health. For the purposes of this report, HSCT is defined as any transplantation of blood- or marrow-derived hematopoietic stem cells, regardless of transplant type (i.e., allogeneic or autologous) or cell source (i.e., bone marrow, peripheral blood, or placental or umbilical cord blood). Such OIs as bacterial, viral, fungal, protozoal, and helminth infections occur with increased frequency or severity among HSCT recipients. These evidence-based guidelines contain information regarding preventing OIs, hospital infection control, strategies for safe living after transplantation, vaccinations, and hematopoietic stem cell safety. The disease-specific sections address preventing exposure and disease for pediatric and adult and autologous and allogeneic HSCT recipients. The goal of these guidelines is twofold: to summarize current data and provide evidence-based recommendations regarding preventing OIs among HSCT patients. The guidelines were developed for use by HSCT recipients, their household and close contacts, transplant and infectious diseases physicians, HSCT center personnel, and public health professionals. For all recommendations, prevention strategies are rated by the strength of the recommendation and the quality of the evidence supporting the recommendation. Adhering to these guidelines should reduce the number and severity of OIs among HSCT recipients. C1 CDC, Div AIDS STD & TB Lab Res, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. CDC, Div HIV AIDS Prevent Surveillance & Epidemiol, Natl Ctr HIV STD & TB Prevent, Atlanta, GA 30333 USA. CDC, Hosp Infect Program, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. CDC, Epidemiol & Surveillance Div, Natl Immunizat Program, Atlanta, GA 30333 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Duke Univ, Durham, NC USA. Indiana Univ, Indianapolis, IN 46204 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Med Coll Wisconsin, Int Bone Marrow Transplant Registry, Autologous Blood & Marrow Transplant Registry, Milwaukee, WI 53226 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Florida, Gainesville, FL USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. US FDA, Rockville, MD 20857 USA. Univ Pittsburgh, Pittsburgh, PA USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Univ Colorado, Denver, CO 80202 USA. Johns Hopkins Univ, Baltimore, MD USA. Kaiser Permanente Med Ctr, Santa Rosa, CA USA. RP Dykewicz, CA (reprint author), CDC, Div AIDS STD & TB Lab Res, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. NR 401 TC 86 Z9 86 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PY 2000 VL 6 IS 6A BP 659 EP + PG 67 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 378DR UT WOS:000165570200001 ER PT S AU Mannick, J Hausladen, A Liu, LM Hess, D Zeng, M Miao, Q Kane, L Gow, A Stamler, J AF Mannick, J Hausladen, A Liu, LM Hess, D Zeng, M Miao, Q Kane, L Gow, A Stamler, J BE Moncada, S Gustafsson, LE Wiklund, NP Higgs, EA TI Caspase denitrosylation during Fas-induced apoptosis SO BIOLOGY OF NITRIC OXIDE, PT 7 SE PORTLAND PRESS PROCEEDINGS LA English DT Proceedings Paper CT 6th International Meeting on Biology of Nitric Oxide CY SEP 05-08, 1999 CL STOCKHOLM, SWEDEN C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Mannick, J (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU PORTLAND PRESS LTD PI LONDON PA 59 PORTLAND PL, LONDON W1N 3AJ, ENGLAND SN 0966-4068 BN 1-85578-142-5 J9 PORTL PR P PY 2000 VL 16 BP 18 EP 18 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA BT52N UT WOS:000173244100018 ER PT J AU Hansen, TR Pru, JK Rueda, BR Austin, KJ Guzeloglu, A Thatcher, WW AF Hansen, TR Pru, JK Rueda, BR Austin, KJ Guzeloglu, A Thatcher, WW TI Interferon-tau suppresses prostaglandin F-2 alpha release through a MAP kinase- and NF kappa B-independent mechanism. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Univ Wyoming, Dept Anim Sci, Laramie, WY 82071 USA. Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Univ Florida, Dept Dairy & Poultry Sci, Gainesville, FL 32611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2000 VL 62 SU 1 MA 32 BP 118 EP 118 PG 1 WC Reproductive Biology SC Reproductive Biology GA 328QV UT WOS:000087862300099 ER PT J AU Jurisicova, A Perez, GI Casper, RF Tilly, JL AF Jurisicova, A Perez, GI Casper, RF Tilly, JL TI Cellular fragmentation and DNA cleavage are independent events during oocyte apoptosis in vitro SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol,Dept OB GYN, Cambridge, MA 02138 USA. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2000 VL 62 SU 1 MA 67 BP 132 EP 132 PG 1 WC Reproductive Biology SC Reproductive Biology GA 328QV UT WOS:000087862300134 ER PT J AU Perez, GI Trbovich, AM Jurisicova, A Casper, RF Tilly, JL AF Perez, GI Trbovich, AM Jurisicova, A Casper, RF Tilly, JL TI Further studies on the role of mitochondria in controlling oocyte apoptosis. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet Gynecol,Vincent Ctr Reprod Biol, Boston, MA 02115 USA. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2000 VL 62 SU 1 MA 66 BP 132 EP 132 PG 1 WC Reproductive Biology SC Reproductive Biology GA 328QV UT WOS:000087862300133 ER PT J AU Carambula, SF Matikainen, T Tilly, JL Rueda, BR AF Carambula, SF Matikainen, T Tilly, JL Rueda, BR TI Culture of individual murine corpora lutea to study apoptosis during luteolysis: Development of the model. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol,Dept OB GYN, Cambridge, MA 02138 USA. Univ Kansas, Sch Med, Womens Res Inst, Wichita, KS 67214 USA. Univ Kansas, Sch Med, Dept OB GYN, Wichita, KS 67214 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2000 VL 62 SU 1 MA 69 BP 133 EP 133 PG 1 WC Reproductive Biology SC Reproductive Biology GA 328QV UT WOS:000087862300136 ER PT J AU Matikainen, T Perez, GI Jurisicova, A Mann, KK Schlezinger, J Korsmeyer, SJ Casper, RF Sherr, DH Tilly, JL AF Matikainen, T Perez, GI Jurisicova, A Mann, KK Schlezinger, J Korsmeyer, SJ Casper, RF Sherr, DH Tilly, JL TI Aryl hydrocarbon receptor (AhR)-dependent induction of Bax gene expression is required for oocyte apoptosis caused by polycyclic aromatic hydrocarbons. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol,Dept Ob Gyn, Boston, MA USA. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. Boston Univ, Sch Med, Dept Environm Hlth, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2000 VL 62 SU 1 MA 237 BP 200 EP 201 PG 2 WC Reproductive Biology SC Reproductive Biology GA 328QV UT WOS:000087862300303 ER PT J AU Mosier, J Olesen, CEM Voyta, JC Bronstein, I AF Mosier, J Olesen, CEM Voyta, JC Bronstein, I TI Immunoassay protocol for quantitation of protein kinase activities SO BIOLUMINESCENCE AND CHEMILUMINESCENCE, PT C SE METHODS IN ENZYMOLOGY LA English DT Review ID LINKED-IMMUNOSORBENT-ASSAY; TYROSINE KINASE; ENZYME-IMMUNOASSAY; SUBSTRATE C1 Ctr Blood Res, Boston, MA 02115 USA. Tropix Inc, Bedford, MA 01730 USA. RP Mosier, J (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. NR 18 TC 3 Z9 3 U1 0 U2 0 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 2000 VL 305 BP 410 EP 416 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BQ22L UT WOS:000087601600029 PM 10812616 ER PT J AU Olesen, CEM Mosier, J Voyta, JC Bronstein, I AF Olesen, CEM Mosier, J Voyta, JC Bronstein, I TI Chemiluminescent immunodetection protocols with 1,2-dioxetane substrates SO BIOLUMINESCENCE AND CHEMILUMINESCENCE, PT C SE METHODS IN ENZYMOLOGY LA English DT Review ID NERVE GROWTH-FACTOR; HAIR BUNDLES; PROTEINS; CELLS; ACTIVATION; IDENTIFICATION; APOPTOSIS; BINDING; FAMILY C1 Tropix Inc, Bedford, MA 01730 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Olesen, CEM (reprint author), Tropix Inc, Bedford, MA 01730 USA. NR 27 TC 8 Z9 8 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 2000 VL 305 BP 417 EP 427 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BQ22L UT WOS:000087601600030 PM 10812617 ER PT J AU Olesen, CEM Martin, CS Mosier, J Liu, B Voyta, JC Bronstein, I AF Olesen, CEM Martin, CS Mosier, J Liu, B Voyta, JC Bronstein, I TI Chemiluminescent reporter gene assays with 1,2-dioxetane enzyme substrates SO BIOLUMINESCENCE AND CHEMILUMINESCENCE, PT C SE METHODS IN ENZYMOLOGY LA English DT Review ID PLACENTAL ALKALINE-PHOSPHATASE; SIMIAN IMMUNODEFICIENCY VIRUS; MAMMALIAN-CELL LINES; SMOOTH-MUSCLE CELLS; NF-KAPPA-B; BETA-GALACTOSIDASE; FIREFLY LUCIFERASE; TRANSGENIC MICE; IN-VIVO; SENSITIVE DETECTION C1 Tropix Inc, Bedford, MA 01730 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Olesen, CEM (reprint author), Tropix Inc, Bedford, MA 01730 USA. NR 70 TC 7 Z9 7 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 2000 VL 305 BP 428 EP 450 PG 23 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BQ22L UT WOS:000087601600031 PM 10812618 ER PT B AU Liu, AK Sereno, MI Rosen, BR Belliveau, JW Dale, AM AF Liu, AK Sereno, MI Rosen, BR Belliveau, JW Dale, AM BE Aine, CJ Okada, Y Stroink, G Swithenby, SJ Wood, CC TI fMRI constrained linear estimation of cortical activity from MEG measurements: A model study SO BIOMAG 96: PROCEEDINGS OF THE TENTH INTERNATIONAL CONFERENCE ON BIOMAGNETISM, VOLS I & II LA English DT Proceedings Paper CT 10th International Conference on Biomagnetism CY 1999 CL SANTA FE, NM ID HUMAN BRAIN C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA USA. RP Liu, AK (reprint author), Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-98915-3 PY 2000 BP 1142 EP 1145 PG 4 WC Biophysics; Engineering, Biomedical; Instruments & Instrumentation SC Biophysics; Engineering; Instruments & Instrumentation GA BQ47L UT WOS:000088437300279 ER PT S AU Doukas, AG Lee, S AF Doukas, AG Lee, S BE Oraevsky, AA TI Photomechanical drug delivery SO BIOMEDICAL OPTOACOUSTICS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Biomedical Optoacoustics CY JAN 25-27, 2000 CL SAN JOSE, CA SP SPIE, Int Biomed Opt Soc DE ablation; drug delivery; membrane permeability; photoacoustics; photomechanical effects; pressure waves; shock waves; stress waves; trandermal delivery ID GENERATED STRESS WAVES; INDUCED SHOCK-WAVES; IN-VITRO; CELL-MEMBRANE; LASER-PULSES; SKIN; DAMAGE; INJURY; TISSUE; CAVITATION AB Photomechanical waves (PW) are generated by Q-switched or mode-locked lasers. Ablation is a reliable method for generating PWs with consistent characteristics. Depending on the laser wavelength and target material, PWs with different parameters can be generated which allows the investigation of the interactions of PWs with cells and tissue. PWs have been shown to permeabilize the stratum corneum (SC) in vivo and facilitate the transport of drugs into the skin. Once a drug has diffused into the dermis it can enter the vasculature, thus producing a systemic effect. Fluorescence microscopy of biopsies show that 40-kDa molecules can be delivered to a depth of >300 mu m into the viable skin of rats. Many important drugs such as insulin (6 kDa), and erythropoetin (48 kDa) are smaller or comparable in size, making the PWs attractive for transdermal drug delivery. There are three possible pathways through the SC: Transappendageal via hair follicles or other appendages, transcellular through the corneocytes, and intercellular via the extracellular matrix. The intercellular route appears to be the most likely pathway of drug delivery through the SC. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. RP Doukas, AG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. EM doukas@helix.mgh.harvard.edu NR 51 TC 2 Z9 2 U1 1 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 0-8194-3532-5 J9 PROC SPIE PY 2000 VL 3916 BP 188 EP 197 DI 10.1117/12.386322 PG 10 WC Acoustics; Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BQ31N UT WOS:000087915300022 ER PT S AU Li, XD Gold, H Weissman, N Pitris, C Saunders, K Ghanti, R Fujimoto, J Brezinski, M AF Li, XD Gold, H Weissman, N Pitris, C Saunders, K Ghanti, R Fujimoto, J Brezinski, M GP OSA OSA TI In vivo intravascular imaging with OCT: Comparison with ultrasound SO BIOMEDICAL TOPICAL MEETINGS, TECHNICAL DIGEST SE OSA TRENDS IN OPTICS AND PHOTONICS LA English DT Proceedings Paper CT Biomedical Topical Meeting CY APR 02-05, 2000 CL MIAMI BEACH, FL ID OPTICAL COHERENCE TOMOGRAPHY AB A true clinical need exists for a high resolution imaging modality to characterize coronary microstructure. In this study, OCT imaging was performed of,the in in vivo rabbit aorta examining clot, atherosclerosis, and intravascular stents. The performance of OCT was superior to that of high frequency ultrasound. C1 Massachusetts Gen Hosp, Cardiol Unit, Boston, MA 02114 USA. RP Li, XD (reprint author), Massachusetts Gen Hosp, Cardiol Unit, Fruit St, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU OPTICAL SOC AMERICA PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-5695 BN 1-55752-632-X J9 OSA TRENDS OPT PHOTO PY 2000 VL 38 BP 32 EP 34 PG 3 WC Optics; Spectroscopy SC Optics; Spectroscopy GA BU51D UT WOS:000176203200009 ER PT S AU Bouma, BE Tearney, GJ Compton, CC Brand, S Poneros, J Schlendorf, K Asimellis, G Puricelli, WP Nishioka, NS AF Bouma, BE Tearney, GJ Compton, CC Brand, S Poneros, J Schlendorf, K Asimellis, G Puricelli, WP Nishioka, NS GP OSA OSA TI Optical coherence tomography for upper gastrointestinal tract diagnosis SO BIOMEDICAL TOPICAL MEETINGS, TECHNICAL DIGEST SE OSA TRENDS IN OPTICS AND PHOTONICS LA English DT Proceedings Paper CT Biomedical Topical Meeting CY APR 02-05, 2000 CL MIAMI BEACH, FL AB A high speed, power-efficient, catheter-based optical coherence tomography system has been used to image the esophagus and stomach in over 90 patients and can differentiate normal tissue from Barrett's esophagus and esophageal adenocarcinoma. (C) 1999 Optical Society of America. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Ctr Innovat Minimally Invas Therapy, Boston, MA 02114 USA. RP Bouma, BE (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Ctr Innovat Minimally Invas Therapy, Boston, MA 02114 USA. NR 11 TC 0 Z9 0 U1 0 U2 2 PU OPTICAL SOC AMERICA PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-5695 BN 1-55752-632-X J9 OSA TRENDS OPT PHOTO PY 2000 VL 38 BP 41 EP 43 PG 3 WC Optics; Spectroscopy SC Optics; Spectroscopy GA BU51D UT WOS:000176203200012 ER PT S AU Rajadhyaksha, M Henrichs, M Ananth, KP Chang, HT Gonzalez, S AF Rajadhyaksha, M Henrichs, M Ananth, KP Chang, HT Gonzalez, S GP OSA OSA TI Reflectance and fluorescent contrast agents for real-time in vivo confocal imaging SO BIOMEDICAL TOPICAL MEETINGS, TECHNICAL DIGEST SE OSA TRENDS IN OPTICS AND PHOTONICS LA English DT Proceedings Paper CT Biomedical Topical Meeting CY APR 02-05, 2000 CL MIAMI BEACH, FL ID SCANNING LASER MICROSCOPY; IN-VIVO; HUMAN SKIN AB Reflectance (liposomes, intralipid, microparticles) and fluorescence (polymer- and cosmetic oil-tagged fluorescein and rhodamine) agents enhance contrast in real-time confocal images of skin in vivo. Quantitative analysis (signal versus contrast agent properties) and images are presented. (C) 2000 Optical Society of America. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Rajadhyaksha, M (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Bartlett Hall Ext 630, Boston, MA 02114 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU OPTICAL SOC AMERICA PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-5695 BN 1-55752-632-X J9 OSA TRENDS OPT PHOTO PY 2000 VL 38 BP 182 EP 184 PG 3 WC Optics; Spectroscopy SC Optics; Spectroscopy GA BU51D UT WOS:000176203200052 ER PT S AU Saunders, K Jesser, C Ghanta, R Pitris, C Fujimoto, J Brezinski, MD AF Saunders, K Jesser, C Ghanta, R Pitris, C Fujimoto, J Brezinski, MD GP OSA OSA TI Increasing OCT penetration through blood with index matching SO BIOMEDICAL TOPICAL MEETINGS, TECHNICAL DIGEST SE OSA TRENDS IN OPTICS AND PHOTONICS LA English DT Proceedings Paper CT Biomedical Topical Meeting CY APR 02-05, 2000 CL MIAMI BEACH, FL ID OPTICAL COHERENCE TOMOGRAPHY AB Blood substantially reduces image quality during intravascular OCT imaging. In this preliminary work, increasing the refractive index of the serum to that near the cytoplasm, or index matching, was used to increase penetration through blood. The hypothesis was tested by adding compounds to blood in an in vitro system. Increased penetration was noted for dextran and IV contrast which could not be explained by changes in hematocrit or hemoglobin. This study demonstrates the feasibility of index matching for dealing with the blood problem associated with intravascular OCT imaging. C1 Massachusetts Gen Hosp, Cardiol Unit, Boston, MA 02114 USA. RP Saunders, K (reprint author), Massachusetts Gen Hosp, Cardiol Unit, Fruit St, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU OPTICAL SOC AMERICA PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-5695 BN 1-55752-632-X J9 OSA TRENDS OPT PHOTO PY 2000 VL 38 BP 185 EP 187 PG 3 WC Optics; Spectroscopy SC Optics; Spectroscopy GA BU51D UT WOS:000176203200053 ER PT S AU Dunn, A Boas, D AF Dunn, A Boas, D GP OSA OSA TI Considerations for image reconstruction with small source detector separations SO BIOMEDICAL TOPICAL MEETINGS, TECHNICAL DIGEST SE OSA TRENDS IN OPTICS AND PHOTONICS LA English DT Proceedings Paper CT Biomedical Topical Meeting CY APR 02-05, 2000 CL MIAMI BEACH, FL ID TOMOGRAPHY AB Imaging at length scales comparable to the scattering mean free path can potentially provide images not attainable with either diffuse or microscopic imaging methods. However,consideration must be given to the description of the forward problem in order to obtain the best images. (C) 1999 Optical Society of America. C1 Harvard Univ, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. RP Dunn, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU OPTICAL SOC AMERICA PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-5695 BN 1-55752-632-X J9 OSA TRENDS OPT PHOTO PY 2000 VL 38 BP 191 EP 193 PG 3 WC Optics; Spectroscopy SC Optics; Spectroscopy GA BU51D UT WOS:000176203200055 ER PT S AU Grant, PE Zourabian, A Boas, DA AF Grant, PE Zourabian, A Boas, DA GP OSA OSA TI Functional optical imaging of visual stimulation in neonates with brain injury SO BIOMEDICAL TOPICAL MEETINGS, TECHNICAL DIGEST SE OSA TRENDS IN OPTICS AND PHOTONICS LA English DT Proceedings Paper CT Biomedical Topical Meeting CY APR 02-05, 2000 CL MIAMI BEACH, FL ID INFANTS; MRI AB Currently, outcomes in perinatal brain injury are difficult to predict. Diffuse Optical Imaging enables longitudingal assessment of regional blood flow in response to neurological stimulii. Such functional information may improve our predictive ability and guide interventions. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. RP Grant, PE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, 13th St Bldg 149, Charlestown, MA 02129 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU OPTICAL SOC AMERICA PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-5695 BN 1-55752-632-X J9 OSA TRENDS OPT PHOTO PY 2000 VL 38 BP 253 EP 255 PG 3 WC Optics; Spectroscopy SC Optics; Spectroscopy GA BU51D UT WOS:000176203200075 ER PT S AU Boas, DA Cheng, XF Mandeville, JB AF Boas, DA Cheng, XF Mandeville, JB GP OSA OSA TI Quantifying tissue hemodynamics by NIRS versus DOT: Global versus focal changes in cerebral hemodynamics SO BIOMEDICAL TOPICAL MEETINGS, TECHNICAL DIGEST SE OSA TRENDS IN OPTICS AND PHOTONICS LA English DT Proceedings Paper CT Biomedical Topical Meeting CY APR 02-05, 2000 CL MIAMI BEACH, FL AB NIRS is unable to accurately quantify absolute focal changes in oxy- and deoxy-hemoglobin as well as relative changes. This is due to differential wavelength sensitivity to the focal region not accounted by the NIRS theory. (C) 1999 Optical Society of America. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Charlestown, MA 02129 USA. RP Boas, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, 13th St Bldg 149, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OPTICAL SOC AMERICA PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-5695 BN 1-55752-632-X J9 OSA TRENDS OPT PHOTO PY 2000 VL 38 BP 455 EP 456 PG 2 WC Optics; Spectroscopy SC Optics; Spectroscopy GA BU51D UT WOS:000176203200142 ER PT S AU Shishkov, M Bouma, BE Jang, IK Kang, DH Aretz, HT Houser, SL Brady, TJ Schlendorf, K Tearney, GJ AF Shishkov, M Bouma, BE Jang, IK Kang, DH Aretz, HT Houser, SL Brady, TJ Schlendorf, K Tearney, GJ GP OSA OSA TI Optical coherence tomography of porcine coronary arteries in vivo SO BIOMEDICAL TOPICAL MEETINGS, TECHNICAL DIGEST SE OSA TRENDS IN OPTICS AND PHOTONICS LA English DT Proceedings Paper CT Biomedical Topical Meeting CY APR 02-05, 2000 CL MIAMI BEACH, FL ID INTRAVASCULAR ULTRASOUND; BIOPSY AB A catheter-based OCT system was developed and tested for feasibility of coronary artery imaging in five living swine. In this study, OCT provided high-resolution imaging of coronary vessel wall structure, dissections, and stent deployment. (C) 1999 Optical Society of America. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Shishkov, M (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU OPTICAL SOC AMERICA PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-5695 BN 1-55752-632-X J9 OSA TRENDS OPT PHOTO PY 2000 VL 38 BP 501 EP 503 PG 3 WC Optics; Spectroscopy SC Optics; Spectroscopy GA BU51D UT WOS:000176203200156 ER PT S AU Pfefer, TJ Paithankar, DY Poneros, JM Schomacker, KT Nishioka, NS AF Pfefer, TJ Paithankar, DY Poneros, JM Schomacker, KT Nishioka, NS GP OSA OSA TI Time- and wavelength-resolved fluorescence Spectroscopy for endoscopic detection of esophageal dysplasia SO BIOMEDICAL TOPICAL MEETINGS, TECHNICAL DIGEST SE OSA TRENDS IN OPTICS AND PHOTONICS LA English DT Proceedings Paper CT Biomedical Topical Meeting CY APR 02-05, 2000 CL MIAMI BEACH, FL ID ADENOCARCINOMA AB Time-resolved and steady-state autofluorescence were measured in 41 patients with Barrett's esophagus using excitation wavelengths of 337 and 400 nm. Statistical analysis of the data indicates the clinical potential of this approach for detecting esophageal dysplasia. (C) 2000 Optical Society of America. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Pfefer, TJ (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, 55 Fruit St,Bartlett 722, Boston, MA 02114 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU OPTICAL SOC AMERICA PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-5695 BN 1-55752-632-X J9 OSA TRENDS OPT PHOTO PY 2000 VL 38 BP 504 EP 506 PG 3 WC Optics; Spectroscopy SC Optics; Spectroscopy GA BU51D UT WOS:000176203200157 ER PT J AU Klar, N Lipsitz, SR Ibrahim, JG AF Klar, N Lipsitz, SR Ibrahim, JG TI An estimating equations approach for modelling kappa SO BIOMETRICAL JOURNAL LA English DT Article DE generalized estimating equations; common correlation model; maximum likelihood estimation; inter-rater agreement ID BIVARIATE LOGISTIC-REGRESSION; INTERRATER AGREEMENT; BINARY; ASSOCIATION; STATISTICS AB Agreement between raters for binary outcome data is typically assessed using the kappa coefficient. There has been considerable recent work extending logistic regression to provide summary estimates of interrater agreement adjusted for covariates predictive of the marginal probability of classification by each rater. We propose an estimating equations approach which can also be used to identify covariates predictive of kappa. Models may include an arbitrary and variable number of raters per subject and yet do not require any stringent parametric assumptions. Examples used to illustrate this procedure include an investigation of factors affecting agreement between primary and proxy respondents from a case-control study and a study of the effects of gender and zygosity on twin concordance for smoking history. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. NR 20 TC 27 Z9 27 U1 0 U2 0 PU AKADEMIE VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 2000 VL 42 IS 1 BP 45 EP 58 DI 10.1002/(SICI)1521-4036(200001)42:1<45::AID-BIMJ45>3.3.CO;2-R PG 14 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 289NB UT WOS:000085627900004 ER PT J AU Geys, H Molenberghs, G Declerck, L Ryan, L AF Geys, H Molenberghs, G Declerck, L Ryan, L TI Flexible quantitative risk assessment for developmental toxicity based on fractional polynomial predictors SO BIOMETRICAL JOURNAL LA English DT Article DE benchmark dose; clustering; conditional model; dose-response model; effective dose ID CLUSTERED BINARY DATA; LIKELIHOOD; TRANSFORMATION; TOXICOLOGY; RESPONSES; RATS; MICE AB Risk assessment for developmental toxicity studies in rodents is faced with the fairly involved data structure of clustered multivariate binary outcomes. While likelihood methods for this setting do not abound, we show that a conditional model, combined with pseudo-likelihood inference and fractional polynomial predictor functions, as proposed by ROYSTON and ALTMAN (1994), are a promising way forward. The methods are illustrated using teratology data collected under the National Toxicology Program. C1 Limburgs Univ Ctr, Ctr Stat, B-3590 Diepenbeek, Belgium. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 26 TC 0 Z9 0 U1 0 U2 0 PU AKADEMIE VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 2000 VL 42 IS 3 BP 279 EP 302 PG 24 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 329TE UT WOS:000087923500002 ER PT J AU Addona, GH Maggio, JE Miller, KW AF Addona, GH Maggio, JE Miller, KW TI Topographical investigation of the substance P antibody binding site by site-directed spin-labeling SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Univ Cincinnati, Coll Med, Dept Pharmacol & Biophys, Cincinnati, OH 45221 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 218POS BP 38A EP 38A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300219 ER PT J AU Lader, AS Wang, Y Jackson, RG Borkan, SC Cantiello, HF AF Lader, AS Wang, Y Jackson, RG Borkan, SC Cantiello, HF TI CFTR is associated with a cyclic-amp stimulated ATP release pathway in neonatal mouse cardiac myocytes. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Boston Univ, Med Ctr, Boston, MA 02118 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1558Plat BP 264A EP 264A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301538 ER PT J AU Arystarkhova, E Wetzel, RK Rael, EL Asinovski, NK Sweadner, KJ AF Arystarkhova, E Wetzel, RK Rael, EL Asinovski, NK Sweadner, KJ TI The Na,K-ATPase gamma subunit modulates Na+ and K+ affinity SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1649Plat BP 279A EP 279A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301631 ER PT J AU Forman, SA Zhou, Q AF Forman, SA Zhou, Q TI Curare agonism in nAChR: Asymmetric forces on M2 domains SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2118Pos BP 359A EP 359A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302097 ER PT J AU Pratt, MB Husain, SS Miller, KW Cohen, JB AF Pratt, MB Husain, SS Miller, KW Cohen, JB TI Localization of the [H-3]3-azioctanol binding site in the nicotinic acetylcholine receptor SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2124Pos BP 360A EP 360A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302103 ER PT J AU Corey, DP AF Corey, DP TI Dancing on the head of a pin: Motor proteins in hair-cell adaptation. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, HHMI, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2285Symp BP 388A EP 388A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302262 ER PT J AU Lader, AS del Monte, F Hajjar, RJ Cantiello, HF AF Lader, AS del Monte, F Hajjar, RJ Cantiello, HF TI ATP-permeable electrodifusional pathway in adult human cardiac myocytes. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2749Pos BP 467A EP 467A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302723 ER PT J AU Melichar, H Bosch, I Molnar, GM Huang, L Pardee, AB AF Melichar, H Bosch, I Molnar, GM Huang, L Pardee, AB TI Detection of eukaryotic cDNA in differential display is enhanced by the addition of E-coli RNA SO BIOTECHNIQUES LA English DT Article ID TRANSFORMED-CELL DIFFERENTIATION; MESSENGER-RNA; INDUCERS; PCR AB We describe a method to enhance the sensitivity of eukaryotic cDNA detection in differential display (DD). Typically, DD protocols require between 200 and 500 ng RNA for each reverse transcription reaction. The addition of Escherichia coli RNA before reverse transcription of eukaryotic RNA increases the detection of DD patterns more than tenfold. The method broadens the applicability of DD mid allows the identification of genes that are differentially expressed when the amount of eukaryotic RNA is limited. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Biol, Boston, MA 02115 USA. RP Pardee, AB (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Biol, 44 Binney St, Boston, MA 02115 USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JAN PY 2000 VL 28 IS 1 BP 76 EP + PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 273QE UT WOS:000084717700014 PM 10649774 ER PT J AU Galy, A Christopherson, I Ferlazzo, G Liu, G Spits, H Georgopoulos, K AF Galy, A Christopherson, I Ferlazzo, G Liu, G Spits, H Georgopoulos, K TI Distinct signals control the hematopoiesis of lymphoid-related dendritic cells SO BLOOD LA English DT Article ID COLONY-STIMULATING-FACTOR; CORD-BLOOD DIFFERENTIATE; NECROSIS-FACTOR-ALPHA; LIGAND-TREATED MICE; NATURAL-KILLER; FLT3 LIGAND; STEM-CELLS; PROGENITOR CELLS; IKAROS GENE; T-CELLS AB The molecular and cellular requirements for the development of different populations of human dendritic cells (DC) were studied. Conditions were defined that support DC production from lymphoid progenitors but that fail to induce DC formation from peripheral monocytes. The production of these lymphoid-related DC was severely blocked when hematopoietic progenitors overexpressed Ik7, a mutant dominant-negative Ikaros protein. In contrast, Ik7 did not block the formation of DC in conditions supporting the development of monocyte-derived DC. Furthermore, Ik7 did not block the formation of monocyte/macrophages and enhanced granulopoiesis. One of the molecular mechanisms mediated by Ik7 appears to be down-regulation of the flt3-receptor mRNA, Thus, distinct signals control the formation of DC demonstrating that some aspects of DC diversity are determined in part by distinct molecular cues at the hematopoietic level. (C) 2000 by The American Society of Hematology. C1 Wayne State Univ, Barbara Ann Karmanos Canc Inst, Detroit, MI 48201 USA. Netherlands Canc Inst, Amsterdam, Netherlands. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. RP Galy, A (reprint author), Wayne State Univ, Barbara Ann Karmanos Canc Inst, 110 Warren Ave, Detroit, MI 48201 USA. RI Galy, Anne/J-4439-2013 OI Galy, Anne/0000-0002-0153-4392 NR 50 TC 40 Z9 42 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 2000 VL 95 IS 1 BP 128 EP 137 PG 10 WC Hematology SC Hematology GA 270MB UT WOS:000084538600019 PM 10607695 ER PT J AU Wu, CJ Chillemi, A Alyea, EP Orsini, E Neuberg, D Soiffer, RJ Ritz, J AF Wu, CJ Chillemi, A Alyea, EP Orsini, E Neuberg, D Soiffer, RJ Ritz, J TI Reconstitution of T-cell receptor repertoire diversity following T-cell depleted allogeneic bone marrow transplantation is related to hematopoietic chimerism SO BLOOD LA English DT Article ID VERSUS-HOST DISEASE; MINOR HISTOCOMPATIBILITY ANTIGENS; POLYMERASE CHAIN-REACTION; PERIPHERAL-BLOOD; MIXED CHIMERISM; RECIPIENTS; SELECTION; AMPLIFICATION; REGENERATION; PHENOTYPE AB CDR3 spectratyping was used to analyze the complexity of the T-cell repertoire and to define the mechanisms and kinetics of the reconstitution of T-cell immunity after allogeneic bone marrow transplantation (BMT), This method, which is based on polymerase chain reaction amplification of all CDR3 regions using the T-cell receptor (TCR) VP genes, was used to examine serial samples of peripheral blood lymphocytes from 11 adult patients with chronic myelogenous leukemia (CML) who underwent T-cell-depleted allogeneic BMT In contrast to 10 normal donors who display highly diverse and polyclonal spectratypes, patient samples before and early after BMT revealed markedly skewed repertoires, consisting of absent, monoclonal, or oligoclonal profiles for the majority of VP subfamilies. To quantify changes in TCR repertoire over time, we established an 8-point scoring system for each vp subfamily. The mean complexity score for patient samples before transplant (130.8) was significantly lower than that for normal donors (183; P= 0.0007), TCR repertoire complexity was abnormal in all patients at 3 months after BMT (mean score = 87), Normalization of repertoire began in 4 patients at 6 months after BMT, but the majority of patients continued to display abnormal repertoires for up to 3 years after BMT. To determine whether the reconstituted T-cell repertoire was derived from the donor or recipient, unique microsatellite loci were examined to establish chimeric status. At 3 months after BMT, 7 patients demonstrated mixed chimerism; 4 had complete donor hematopoiesis (CDH), CDH strongly correlated with likelihood of restoration of T-cell repertoire complexity (P = 0.003), In contrast, patients who demonstrated persistence of recipient hematopoiesis failed to reconstitute a diverse TCR repertoire. These findings suggest that the reconstitution of a normal T-cell repertoire from T-cell progenitors in adults is influenced by interactions between recipient and donor hematopoietic cells. (C) 2000 by The American Society of Hematology. C1 Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, Ctr Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NIAID NIH HHS [AI29530] NR 41 TC 116 Z9 124 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 2000 VL 95 IS 1 BP 352 EP 359 PG 8 WC Hematology SC Hematology GA 270MB UT WOS:000084538600048 PM 10607724 ER PT J AU Bliziotes, M McLoughlin, S Gunness, M Fumagalli, F Jones, SR Caron, MG AF Bliziotes, M McLoughlin, S Gunness, M Fumagalli, F Jones, SR Caron, MG TI Bone histomorphometric and biomechanical abnormalities in mice homozygous for deletion of the dopamine transporter gene SO BONE LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 10-14, 1997 CL CINCINNATI, OHIO SP Amer Soc Bone & Mineral Res DE dopamine transporter; osteoporosis; biomechanics; neurotransmitter; bone histomorphometry; transgenic mice ID PARATHYROID-HORMONE; BODY CONFORMATION; DEFICIENT MICE; LACKING; RUNNERS; COCAINE; TRAITS; MOUSE; RATS AB Dopamine (DA) has been reported to have effects on calcium and phosphorus metabolism. The dopamine transporter (DAT) is believed to control the temporal and spatial activity of released DA by rapid uptake of the neurotransmitter into presynaptic terminals. We have evaluated the histologic and biomechanical properties of the skeleton in mice homozygous for deletion of the DA transporter gene (DAT) to help delineate the role of DA in bone biology. We have demonstrated that DAT(-/-) mice have reduced bone mass and strength. DAT(-/-) animals had shorter femur length and dry weight. Ash calcium content of the femur was 32% lower in the DAT(-/-) mice than in the wild-type animals. Cancellous bone volume in the proximal tibial metaphysis was significantly lower in the DAT(-/-) animals (p, < 0.04). There was a 32% reduction in trabecular thickness (p = NS), For the vertebrae, cancellous bone volume was again lower in the DAT(-/-) animals compared with wild-type as a consequence of increased trabecular spacing (p < 0.05) and reduced trabecular number (p < 0.05). Cortical thickness and bone area in the femoral diaphysis were reduced in the DAT(-/-) animals. The ultimate bending load (femoral strength) for the DAT(-/-) mice was 30% lower than the wild-type mice (p = 0.004). Thus, deletion of the DAT gene results in deficiencies in skeletal structure and integrity. (C) 2000 by Elsevier Science Inc. All rights reserved. C1 Portland VA Med Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Duke Univ, Med Ctr, Howard Hughes Med Inst Labs, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. RP Bliziotes, M (reprint author), Portland VA Med Ctr, P-3-ENDO, Portland, OR 97201 USA. RI Fumagalli, Fabio/E-8992-2012; Jones, Sara/K-4816-2014; OI Jones, Sara/0000-0002-3424-7576; Fumagalli, Fabio/0000-0002-8814-7706 FU NINDS NIH HHS [NS-19576] NR 33 TC 34 Z9 37 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 8756-3282 J9 BONE JI Bone PD JAN PY 2000 VL 26 IS 1 BP 15 EP 19 DI 10.1016/S8756-3282(99)00232-X PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 268CD UT WOS:000084396000003 PM 10617152 ER PT J AU Toh, HC McAfee, SL Sackstein, R Multani, P Cox, BF Garcia-Carbonero, R Colby, C Spitzer, TR AF Toh, HC McAfee, SL Sackstein, R Multani, P Cox, BF Garcia-Carbonero, R Colby, C Spitzer, TR TI High-dose cyclophosphamide plus carboplatin and interleukin-2 (IL-2) activated autologous stem cell transplantation followed by maintenance IL-2 therapy in metastatic breast carcinoma - a phase II study SO BONE MARROW TRANSPLANTATION LA English DT Article DE high dose chemotherapy and stem cell transplantation; metastatic breast cancer; interleukin-2; graft-versus-tumor effect; adoptive immunotherapy ID BONE-MARROW; CANCER; GRAFT AB While high-dose chemotherapy and stem cell transplantation is associated with higher complete response rates than conventional chemotherapy in patients with metastatic breast cancer (MBC), its role in conferring a survival advantage is unproven. We report the results of a prospective phase II trial of 33 patients accrued between 1996 to 1998 with chemosensitive MBC, who received cyclophosphamide (Cy) 2000 mg/m(2)/day and carboplatin (Cb) 600 mg/m(2)/day for 3 consecutive days, followed by infusion of peripheral blood stem cells cultured in IL-2 for 24 h on day 0 as adoptive immunotherapy, Low-dose interleukin-2 (IL-2) was administered from day 0 to +4 and/or +7 to +11, +14 to +18, +21 to +25, then 5 days per month for 11 months to augment a graft-versus-tumor effect. The results of this study were compared to those of a historical control group treated with an identical high-dose Cb + Cy regimen with SCT but without IL-2 treatment. Only gastrointestinal (GI) toxicity was more frequent in the IL-2 cohort (P = 0.0031). At a median follow-up of 18.6 months, the median progression-free survival (PFS) is 9 months (2.4-40) and the median OS has not been reached yet. The Kaplan-Meier estimated 2 year PFS is 35%, compared with 17% in the control arm (P = 0.73), and the estimated 2 year OS is 78%, compared with 61% in the control arm (P = 0.22). Multivariate analysis showed that ER status was an independent predictor for OS and PFS, and less chemotherapy prior to HDCSCT predicted for a better PFS, These results show that augmenting HDC with IL-2 activated SCT is well-tolerated. Whether a therapeutic advantage is achievable in patients with MBC remains to be determined. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplant Program, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Spitzer, TR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplant Program, Cox 640,100 Blossom St, Boston, MA 02114 USA. NR 22 TC 12 Z9 12 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JAN PY 2000 VL 25 IS 1 BP 19 EP 24 DI 10.1038/sj.bmt.1702091 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 282HV UT WOS:000085213100004 PM 10654009 ER PT J AU Kozlowski, T Sablinski, T Basker, M Kitamura, H Spitzer, TR Fishman, J Sykes, M Cooper, DKC Sachs, DH AF Kozlowski, T Sablinski, T Basker, M Kitamura, H Spitzer, TR Fishman, J Sykes, M Cooper, DKC Sachs, DH TI Decreased graft-versus-host disease after haplotype mismatched bone marrow allografts in miniature swine following interleukin-2 treatment SO BONE MARROW TRANSPLANTATION LA English DT Article DE GVHD; interleukin-2; bone marrow transplantation; miniature swine ID T-CELL DEPLETION; TRANSPLANTATION; LEUKEMIA; ALLOENGRAFTMENT; ENGRAFTMENT; RECIPIENTS AB Graft-versus-host disease (GVHD) is an important complication of bone marrow transplantation after transplants between HLA-mismatched donor/recipient pairs, In mice, giving IL-2 post transplant decreases GVHD in this setting. We studied high-dose IL-2 therapy in pigs. Transplants were carried out after conditioning with fractionated total body radiation and cyclophosphamide, Fourteen pigs received a fully mismatched bone marrow transplant (six with IL-2; eight without IL-2), and six received a single haplotype class II mismatched transplant (three with IL-2; three without IL-2), GVHD was evaluated by skin histology, All fully mismatched recipients had severe GVHD (grade 2-3) and died within 13 to 51 days whether or not they received IL-2. Pigs receiving a one haplotype class II mismatched transplant without IL-2 developed severe skin GVHD lasting for 8-45 days; all died within 57 days. Similar pigs receiving IL-2 post transplant had no or only mild skin GVHD for less than 15 days; two are long-term survivors. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Pathol, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Hematol Oncol Unit, Transplantat Biol Res Ctr,Dept Med, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Infect Dis, Boston, MA 02129 USA. RP Sachs, DH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Pathol, MGH-E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NCI NIH HHS [1R01CA61537] NR 22 TC 10 Z9 11 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JAN PY 2000 VL 25 IS 1 BP 47 EP 52 DI 10.1038/sj.bmt.1702083 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 282HV UT WOS:000085213100009 PM 10654014 ER PT J AU Vescio, RA Wu, CH Zheng, L Sheen, D Ma, H Liu, J Stewart, AK Ballester, O Noga, SJ Rugo, H Freytes, C Stadtmauer, E Sahebi, F Tarantolo, S Stiff, P Schiller, GJ White, M Jacobs, C DiPersio, J Anderson, KC Berenson, JR AF Vescio, RA Wu, CH Zheng, L Sheen, D Ma, H Liu, J Stewart, AK Ballester, O Noga, SJ Rugo, H Freytes, C Stadtmauer, E Sahebi, F Tarantolo, S Stiff, P Schiller, GJ White, M Jacobs, C DiPersio, J Anderson, KC Berenson, JR TI Human herpesvirus 8 (KSHV) contamination of peripheral blood and autograft products from multiple myeloma patients SO BONE MARROW TRANSPLANTATION LA English DT Article DE human herpesvirus 8; Kaposi's sarcoma-associated herpesvirus; multiple myeloma; pathogenesis; autologous transplantation; leukapheresis ID SARCOMA-ASSOCIATED HERPESVIRUS; STEM-CELL TRANSPLANTATION; KAPOSIS-SARCOMA; DENDRITIC CELLS; BONE-MARROW; DNA-SEQUENCES; AIDS; INFECTION; THERAPY; DISEASE AB Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), has recently been identified within the bone marrow dendritic cells of multiple myeloma (MM) patients. This virus contains homologues to human cytokines such as IL-6 that could potentially stimulate myeloma cell growth and contribute to disease pathogenesis. Since mobilization chemotherapy may increase circulating dendritic cell numbers, we searched for HHV-8 in peripheral blood mononuclear cells (PBMCs) before and after mobilization chemotherapy given to MM patients. Furthermore, we determined if autograft purging using the CEPRATE SC device would reduce the percentage of HHV-8 infected stem cell products. Only two of the 39 PBMC samples collected prior to mobilization chemotherapy contained PCR detectable virus, yet nine of 37 PBMCs collected on the first day of leukapheresis had detectable HHV-8 (P = 0.016), HHV-8 was more frequently identified in autograft products before vs after Ceprate SC selection (40% vs 15%, P = 0.016), Although the role HHV-8 plays in myeloma pathogenesis remains unclear, these results imply that mobilization chemotherapy increases the numbers of circulating HHV-8-infected dendritic cells within the peripheral blood, In addition, CD34 selection of autograft products in MM patients may reduce the reintroduction of virally infected cells following high-dose chemotherapy. C1 Univ Calif Los Angeles, H W LA VAMC 111, Los Angeles, CA 90073 USA. Toronto Hosp, Toronto, ON M5T 2S8, Canada. Univ S Florida, Miami, FL USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. Univ Penn, Philadelphia, PA 19104 USA. So Calif Kaiser Permanente Grp, Los Angeles, CA USA. Univ Nebraska, Omaha, NE 68182 USA. Loyola Univ, Chicago, IL 60611 USA. CellPro Inc, Bothell, WA USA. Washington Univ, Sch Med, St Louis, MO USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Vescio, RA (reprint author), Univ Calif Los Angeles, H W LA VAMC 111, 1301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 45 TC 1 Z9 2 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JAN PY 2000 VL 25 IS 2 BP 153 EP 160 DI 10.1038/sj.bmt.1702113 PG 8 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 282YG UT WOS:000085248900006 PM 10673673 ER PT J AU McNeil, MR Doyle, PJ AF McNeil, MR Doyle, PJ TI Reconsidering the hegemony of linguistic explanations in aphasia: The challenge for the beginning of the millennium SO BRAIN AND LANGUAGE LA English DT Article C1 Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. GRECC, VA Pittsburgh Healthcare Syst, Aphasia Rehabil Res Lab & Clin, Pittsburgh, PA USA. Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA 15260 USA. RP McNeil, MR (reprint author), Univ Pittsburgh, Dept Commun Sci & Disorders, 4033 Forbes Tower, Pittsburgh, PA 15260 USA. NR 10 TC 9 Z9 9 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD JAN PY 2000 VL 71 IS 1 BP 154 EP 156 DI 10.1006/brln.1999.2238 PG 3 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 291GK UT WOS:000085725600044 PM 10716833 ER PT S AU Mueller, E Wietzorrek, J Ringel, F Guretzki, S Baethmann, A Plesnila, N AF Mueller, E Wietzorrek, J Ringel, F Guretzki, S Baethmann, A Plesnila, N BE Mendelow, AD Baethmann, A Czernick, Z Hoff, JT Ito, U James, HE Kuroiwa, T Marmarou, A Marshall, LF Reulen, HJ TI Influence of hypothermia on cell volume and cytotoxic swelling of glial cells in vitro SO BRAIN EDEMA XI SE ACTA NEUROCHIRURGICA SUPPLEMENTA LA English DT Proceedings Paper CT 11th International Brain Oedema Symposium CY JUN 06-10, 1999 CL NEWCASTLE TYNE, ENGLAND DE hypothermia; cell swelling; glial cells; Na+/H+-antiporter ID MILD INTRAISCHEMIC HYPOTHERMIA; BRAIN INJURY; MODERATE HYPOTHERMIA; DAMAGE; TEMPERATURE; ACIDOSIS; RATS AB In view of the increasing significance of mild hypothermia (32 degreesC) as an efficient procedure of neuroprotection, the present study was performed to examine the influence of this level of hypothermia on the volume of glial cells under physiological as well as under pathological conditions. The influence of mild (32 degreesC) and moderate (27 degreesC) hypothermia on cell volume and cell viability of C6 glioma cells was studied for 60 minutes in vitro. Cells were suspended in an incubation chamber under continuous control of temperature, pH and PO2. Cell Volume was measured by an advanced Coulter system. Hypothermia itself was causing significant cell swelling in a dose-dependent manner, which could be prevented by omission of Na+-ions from the suspension medium, while the replacement of Cl--ions failed to prevent cell swelling from hypothermia. Inhibition of the Na+/H+-antiporter with EIPA (5N-ethyl-n-isopropyl-amiloride, 50 muM) was significantly reducing the hypothermia induced cell swelling, indicating activation of the Na+/H+-antiporter. Conversely, mild or moderate hypothermia failed to prevent cell swelling from lactic acid, arachidonic acid or glutamate, i.e. agents which are mediating the development of cytotoxic brain edema in vivo in cerebral trauma, ischemia and other acute insults. The findings indicate that cerebral protection by hypothermia in vivo is most likely not attributable to an inhibition of cytotoxic brain edema. Further investigations, however, are required in vivo and in vitro to elucidate the hypothermia-induced swelling of glial cells in more detail, e.g. as to the role of the Na+/H+-antiporter. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regenerat Lab, Charlestown, MA 02139 USA. RP Plesnila, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regenerat Lab, 149 13th St,CNY 6403, Charlestown, MA 02139 USA. NR 13 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA SN 0065-1419 BN 3-211-83561-X J9 ACT NEUR S JI Acta Neurochir. Suppl. PY 2000 VL 76 BP 551 EP 555 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA BS52G UT WOS:000170202700115 PM 11450089 ER EF